Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults.

PubMed

Meng, Lina; Nguyen, Cherwyn M; Patel, Samit; Mlynash, Michael; Caulfield, Anna Finley

2018-03-01

One institution's experience with use of peripheral i.v. (PIV) catheters for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr is described. A prospective, observational, 13-month quality assurance project was conducted at an academic medical center to evaluate frequencies of patient and catheter phlebitis among adult inpatients who received both an infusion of 3% sodium chloride injection for a period of ≥4 hours through a dedicated PIV catheter and infusions of routine-care solutions (RCSs) through separate PIV catheters during the same hospital stay. Sixty patients received PIV infusions through a total of 291 catheters during the study period. The majority of patients (78%) received infusions of 3% sodium chloride injection for intracranial hypertension, with 30% receiving such infusions in the intensive care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium chloride and 26 patients (43%) during RCS infusions ( p = 0.19). Catheter phlebitis occurred in 73 catheters (25%), with no significant difference in the frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16). Patient and catheter phlebitis rates were not significantly different with infusions of 3% sodium chloride injection versus RCSs, suggesting that an osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic saline solutions may not be warranted. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Unintentional Infusion of Phenylephrine into the Epidural Space.

PubMed

Townley, Kress R; Lane, Jason; Packer, Robyn; Gupta, Rajnish K

2016-03-01

We describe a patient who received an unintentionally prolonged epidural infusion of phenylephrine. The patient experienced no major morbidity. However, this case highlights the continuing problem of wrong-route drug administration and the urgent need to adopt route-specific connections.

Use of nitroglycerin by bolus prevents intensive care unit admission in patients with acute hypertensive heart failure.

PubMed

Wilson, Suprat Saely; Kwiatkowski, Gregory M; Millis, Scott R; Purakal, John D; Mahajan, Arushi P; Levy, Phillip D

2017-01-01

The purpose of this study was to compare health care resource utilization among patients who were given intravenous nitroglycerin for acute heart failure (AHF) in the emergency department (ED) by intermittent bolus, continuous infusion, or a combination of both. We retrospectively identified 395 patients that received nitroglycerin therapy in the ED for the treatment of AHF over a 5-year period. Patients that received intermittent bolus (n=124) were compared with continuous infusion therapy (n=182) and combination therapy of bolus and infusion (n=89). The primary outcomes were the frequency of intensive care unit (ICU) admission and hospital length of stay (LOS). On unadjusted analysis, rates of ICU admission were significantly lower in the bolus vs infusion and combination groups (48.4% vs 68.7% vs 83%, respectively; P<.0001) and median LOS (interquartile range) was shorter (3.7 [2.5-6.2 days]) compared with infusion (4.7 [2.9-7.1 days]) and combination (5.0 [2.9-6.7 days]) groups; P=.02. On adjusted regression models, the strong association between bolus nitroglycerin and reduced ICU admission rate remained, and hospital LOS was 1.9 days shorter compared with infusion therapy alone. Use of intubation (bolus [8.9%] vs infusion [8.8%] vs combination [16.9%]; P=.096) and bilevel positive airway pressure (bolus [26.6%] vs infusion [20.3%] vs combination [29.2%]; P=.21) were similar as was the incidence of hypotension, myocardial injury, and worsening renal function. In ED patients with AHF, intravenous nitroglycerin by intermittent bolus was associated with a lower ICU admission rate and a shorter hospital LOS compared with continuous infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracerebroventricular morphine for refractory cancer pain: transitioning to the home setting.

PubMed

Adolph, Michael D; Stretanski, Michael F; McGregor, John M; Rawn, Bonnie L; Ross, Patrick M; Benedetti, Costantino

2010-08-01

Refractory cancer pain may be effectively controlled by titrating intracerebroventricular (ICV) preservative-free opioid. In this case report, a continuous infusion of ICV morphine permitted our patient with lung cancer and painful spinal metastases to be discharged to home hospice with family. The approach exploits the high potency of morphine injected into cerebrospinal fluid (CSF). Sterile, injectable, preservative-free morphine is directly infused into CSF through a subcutaneous Ommaya reservoir placed under the scalp by a neurosurgeon, with an attached catheter passed through a burr hole in the skull with its tip in a cerebral ventricle. Although investigators have described home care of patients receiving intraspinal analgesics, no report describes the process of transitioning the patient receiving continuous ICV morphine infusion to the home setting.

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

[Ambulatory continuous intravenous infusion of fluorouracil: a feasible palliative form of chemotherapy].

PubMed

van Hoef, M E; Zonnenberg, B A; de Graeff, A; van Milligen de Wit, A W; Tjia, P; Neijt, J P

1991-03-30

A study to evaluate the feasibility and toxicity of outpatient continuous intravenous infusion of fluorouracil (5-FU) was initiated at the department of Medical Oncology of the University Hospital of Utrecht. To this purpose a subcutaneous drug delivery system (Port-a-Cath) was implanted in 36 patients with various advanced cancers. Of these patients 83% had received prior chemotherapy (including 5-FU in 62%). Ambulatory continuous-infusion pumps were used to administer 5-FU in a dosage of 300 mg/m2/24 h. The treatment was continued until tumour progression was seen, and it was interrupted in case of toxicity grade 2 or more (WHO criteria). A Port-a-Cath was implanted 37 times in the 36 patients. The main complications of this infusion system were pneumothorax (2/37), arrhythmia (1/37), catheter sepsis (2/37) and thrombosis (2/37); they were easily managed. The toxicity and feasibility of this treatment were evaluable in 30 patients. They received a median of 44 g 5-FU (range 11-136, 5 g, mean 281 mg/m2/24 h) during a median infusion time of 12 weeks (range 4-32 w). Side effects were encountered in 70% of the patients and consisted of the hand-foot syndrome (14/30), nausea and vomiting (8/30), diarrhoea (8/30) and stomatitis (7/30). The toxicity was completely reversible after a short interruption of the chemotherapy. The treatment was tolerated well, and good palliation was attained in 22 of 30 patients. The best response was seen in patients with colon and breast cancer. We conclude that continuous infusion of 5-FU is a reliable outpatient chemotherapy even in this category of patients.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

PubMed

Bele, Sylvia; Proescholdt, Martin A; Hochreiter, Andreas; Schuierer, Gerhard; Scheitzach, Judith; Wendl, Christina; Kieninger, Martin; Schneiker, Andre; Bründl, Elisabeth; Schödel, Petra; Schebesch, Karl-Michael; Brawanski, Alexander

2015-12-01

Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Continuous intravenous morphine infusion for postoperative analgesia following posterior spinal fusion for idiopathic scoliosis.

PubMed

Poe-Kochert, Connie; Tripi, Paul A; Potzman, Jennifer; Son-Hing, Jochen P; Thompson, George H

2010-04-01

A retrospective study of postoperative pain management. Evaluate the efficacy and safety of continuous intravenous morphine infusion for postoperative pain management in patients with idiopathic scoliosis (IS) undergoing posterior spinal fusion (PSF) and segmental spinal instrumentation (SSI). Postoperative pain is a common problem following surgery for IS. There are no published reports regarding the use of a continuous intravenous morphine infusion for this patient population. We retrospectively reviewed data regarding 339 consecutive patients with IS who underwent PSF and SSI between 1992 and 2006. All patients received intrathecal morphine after the induction of general anesthesia. Following surgery, preordered morphine infusion (0.01 mg/kg/h) was started at first reported pain. The infusion rate was titrated based on vital signs, visual analog scale (VAS) pain scores (0-10), and clinical status. It was continued until patients were able to take oral analgesics. We reviewed intrathecal morphine dosage, VAS pain scores through the third postoperative day, interval to start of morphine infusion, total morphine requirements in the first 48 hours, and any adverse reactions (nausea/vomiting, pruritus, respiratory depression, and pediatric intensive care unit admission). Mean intrathecal morphine dose was 15.5 +/- 3.9 microg/kg and mean interval to start of the intravenous morphine infusion was 17.5 +/- 5 hours. Mean VAS pain scores were 3.1, 4.5, 4.5, and 4.6 at 12 hours, 1, 2, and 3 days after surgery, respectively.The total mean morphine dose in the first 48 hours postoperatively was 0.03 +/- 0.01 mg/kg/h. Total morphine received was 1.44 +/- 0.5 mg/kg. Nausea/vomiting and pruritus, related to the morphine infusion occurred in 45 patients (13.3%) and 14 patients (4.1%), respectively. No patients had respiratory depression or required Pediatric Intensive Care Unit admission. A low frequency of adverse events and a mean postoperative VAS pain score of 5 or less demonstrate that a continuous postoperative morphine infusion is a safe and effective method of pain management in patients with IS following PSF and SSI.

Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial.

PubMed

Loisa, Pekka; Parviainen, Ilkka; Tenhunen, Jyrki; Hovilehto, Seppo; Ruokonen, Esko

2007-01-01

Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach. In this prospective randomized study, we compared the blood glucose profiles, insulin requirements, amount of nursing workload needed, and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose (200 mg/day). Duration of hydrocortisone treatment was five days. The mean blood glucose levels were similar in the two groups, but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy (15.7 +/- 8.5 versus 10.5 +/- 8.6 episodes per patient, p = 0.039). Also, more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group (4.7 +/- 2.2 versus 3.4 +/- 1.9 adjustments per patient per day, p = 0.038). Hypoglycemic episodes were rare in both groups. No difference was seen in shock reversal. Strict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion. This approach also reduces nursing workload needed to maintain tight blood glucose control.

Continuous subcutaneous infusion of morphine in children with cancer.

PubMed

Miser, A W; Davis, D M; Hughes, C S; Mulne, A F; Miser, J S

1983-04-01

Seventeen children with severe pain due to malignant neoplasm were successfully treated with a subcutaneous infusion of morphine sulfate using a syringe pump. Pain relief was adequate in every case without major side effects. The median dosage required was 0.06 mg/kg/hr (range, 0.025 to 1.79 mg/kg/hr). Three patients received the subcutaneous infusion at home. No patient required an intravenous line for pain control.

Comparison of Propofol-Remifentanil Versus Propofol-Ketamine Deep Sedation for Third Molar Surgery

PubMed Central

Kramer, Kyle J.; Ganzberg, Steven; Prior, Simon; Rashid, Robert G.

2012-01-01

This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting. PMID:23050750

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

PubMed

Moulin, D E; Kreeft, J H; Murray-Parsons, N; Bouquillon, A I

1991-02-23

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

Continuous versus short-term infusion of cefuroxime: assessment of concept based on plasma, subcutaneous tissue, and bone pharmacokinetics in an animal model.

PubMed

Tøttrup, Mikkel; Bibby, Bo M; Hardlei, Tore F; Bue, Mats; Kerrn-Jespersen, Sigrid; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

2015-01-01

The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparative total and unbound pharmacokinetics of cefazolin administered by bolus versus continuous infusion in patients undergoing major surgery: a randomized controlled trial.

PubMed

Naik, B I; Roger, C; Ikeda, K; Todorovic, M S; Wallis, S C; Lipman, J; Roberts, J A

2017-06-01

Perioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probability of target attainment (PTA) and fractional target attainment (FTA) than intermittent dosing. Patients undergoing major surgery received cefazolin 2 g before surgical incision. They were subsequently randomized to receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500 mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total and unbound cefazolin concentrations using a validated chromatographic method. Population pharmacokinetic modelling was performed using Pmetrics ® software. Calculations of PTA and FTA were performed for common pathogens. Ten patients were enrolled in each arm. A two-compartment linear model best described the time course of the total plasma cefazolin concentrations. The covariates that improved the model were body weight and creatinine clearance. Protein binding varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd ) central volume of distribution was 5.73 (2.42) litres, and total cefazolin clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin consistently achieved better drug exposures and FTA for different weight and creatinine clearances, particularly for less susceptible pathogens. Our study demonstrates that intraoperative continuous infusions of cefazolin increase the achievement of target plasma concentrations, even with lower infusion doses. Renal function and body weight are important when considering the need for alternative dosing regimens. NCT02058979. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

PubMed

O'Scanaill, P; Keane, S; Wall, V; Flood, G; Buggy, D J

2018-04-01

Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h -1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. AUC moving was mean (SD) 71 (34) mm h -1 vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. NCT 03024697. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Comparison of analgesic efficacy of four-quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open-label, randomised, non-inferiority trial.

PubMed

Niraj, G; Kelkar, A; Hart, E; Horst, C; Malik, D; Yeow, C; Singh, B; Chaudhri, S

2014-04-01

Posterior transversus abdominis plane blocks have been reported to be an effective method of providing analgesia after lower abdominal surgery. We compared the efficacy of a novel technique of providing continuous transversus abdominis plane analgesia with epidural analgesia in patients on an enhanced recovery programme following laparoscopic colorectal surgery. A non-inferiority comparison was used. Adult patients undergoing elective laparoscopic colorectal surgery were randomly assigned to receive continuous transversus abdominis plane analgesia (n = 35) vs epidural analgesia (n = 35), in addition to a postoperative analgesic regimen comprising regular paracetamol, regular diclofenac and tramadol as required. Sixty-one patients completed the study. The transversus group received four-quadrant transversus abdominis plane blocks and bilateral posterior transversus abdominis plane catheters that were infused with levobupivacaine 0.25% for 48 h. The epidural group received an infusion of bupivacaine and fentanyl. The primary outcome measure was visual analogue scale pain score on coughing at 24 h after surgery. We found no significant difference in median (IQR [range]) visual analogue scores during coughing at 24 h between the transversus group 2.5 (1.0-3.0 [0-5.5]) and the epidural group 2.5 (1.0-5.0 [0-6.0]). The one-sided 97.5% CI was a 0.0 (∞-1.0) difference in means, establishing non-inferiority. There were no significant differences between the groups for tramadol consumption. Success rate was 28/30 (93%) in the transversus group vs 27/31 (87%) in the epidural group. Continuous transversus abdominis plane infusion was non-inferior to epidural infusion in providing analgesia after laparoscopic colorectal surgery. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

The costs of fluid overload in the adult intensive care unit: is a small-volume infusion model a proactive solution?

PubMed Central

Child, Debra L; Cao, Zhun; Seiberlich, Laura E; Brown, Harold; Greenberg, Jordan; Swanson, Anne; Sewall, Martha R; Robinson, Scott B

2015-01-01

Purpose Fluid overload (FO) in critically ill patients remains a challenging clinical dilemma, and many continuous intravenous (IV) medications in the US are being delivered as a dilute solution, adding significantly to a patient’s daily intake. This study describes the costs and outcomes of FO in patients receiving multiple continuous infusions. Materials and methods A retrospective study was conducted using a hospital administrative database covering >500 US hospitals. An FO cohort included adult intensive care unit (ICU) patients with a central line receiving IV loop diuretics and 2+ continuous IV infusions on 50%+ of their ICU days; a directly matched non-FO cohort included patients without IV diuretic use. The primary outcome of the study was total hospitalization costs per visit. Additional outcomes were ICU costs, mortality, total and ICU length of stay (LOS), 30-day readmission rates, and ventilator use. Unadjusted descriptive analysis was performed using chi-squared or paired t-tests to compare outcomes between the two cohorts. Results A total of 63,974 patients were identified in each cohort. The total hospitalization cost per visit for the FO cohort was US$15,344 higher than the non-FO cohort (US$42,386 vs US$27,042), and the ICU cost for the FO cohort was US$5,243 higher than the non-FO cohort (US$10,902 vs US$5,659). FO patients had higher mortality (20% vs 16.8%), prolonged LOS (11.5 vs 8.0 days), longer ICU LOS (6.2 vs 3.6 days), higher risk of 30-day readmission (21.8% vs 21.3%), and ventilator usage (47.7% vs 28.3%) than the non-FO cohort (all P<0.05). Conclusion In patients receiving multiple continuous infusions, FO is associated with increased health care resources and costs. Maximally concentrating medications and proactively providing continuous medications in small-volume infusions (SVI) could be a potential solution to prevent iatrogenic FO in critically ill patients. Further prospective research is warranted to assess the impact of the SVI dispensing model on patient outcomes and health care costs. PMID:25548524

A randomized comparison of ropivacaine 0.1% and 0.2% for continuous interscalene block after shoulder surgery.

PubMed

Yang, Chun Woo; Jung, Sung Mee; Kang, Po Soon; Kwon, Hee Uk; Cho, Choon Kyu; Lee, Younsuk; Kim, Chul Woung; Kim, Su Young

2013-03-01

The optimal concentration of ropivacaine for continuous interscalene block after shoulder surgery is currently unknown. Fifty-six patients received a perineural infusion of either ropivacaine 0.1% or 0.2% for 48 hours after shoulder surgery. We assessed pain scores as primary end points and supplemental analgesia, ropivacaine consumption, motor block, side effects, and patient satisfaction as secondary end points. Pain scores were not statistically different during the infusion periods; however, supplemental analgesia consumption was higher in the group receiving ropivacaine 0.1% during the first 24 hours (64% vs 28%, P = 0.022). Other secondary end points were statistically inconclusive. These results suggest that ropivacaine 0.2% provides more effective analgesia than ropivacaine 0.1% during the first 24 hours for continuous interscalene block after shoulder surgery.

Seizure and electroencephalographic changes in the newborn period induced by opiates and corrected by naloxone infusion.

PubMed

da Silva, O; Alexandrou, D; Knoppert, D; Young, G B

1999-03-01

To describe the association between opioid administration in the newborn period and neurologic abnormalities. Case reports of two infants who presented with seizure activity and abnormal electroencephalograms associated with opiate administration, and reversed by naloxone. The first was a preterm infant who developed a burst-suppression pattern on the electroencephalogram while receiving a continuous infusion of morphine and muscle paralysis. Naloxone injection during the electroencephalogram recording reversed the burst-suppression pattern. The second was a term infant receiving fentanyl infusion for pain control following surgery, who presented with motor seizure that was only partially controlled with barbiturates. An abnormal electroencephalogram recording during the opiate infusion improved with naloxone administration. Our observations indicate a potential for neurologic abnormalities, including induction of seizure activity and electroencephalogram abnormalities, suggesting caution when opiates are used for sedation and/or pain control in the newborn period.

Drug withdrawal symptoms in children after continuous infusions of fentanyl.

PubMed

French, J P; Nocera, M

1994-04-01

The purpose of this research was to determine the extent to which critically ill infants exhibited signs and symptoms of narcotic withdrawal after receiving continuous infusions of fentanyl. The convenience sample consisted of 12 pediatric intensive care unit (PICU) patients under 25 months of age who received fentanyl infusions for at least 24 hours. Drug withdrawal symptoms were monitored using the Neonatal Abstinence Score Tool (NAST), which assigns a score to each behavior indicative of withdrawal. A score of 8 or greater indicates Neonatal Abstinence Syndrome (NAS). Scoring began 4 hours after discontinuation of fentanyl and was conducted once per hour for 8 hours. Six subjects had a NAST score exceeding 8; these infants frequently exhibited tremors with or without stimulation, increased muscle tone, insomnia, and increased respiratory rate and effort. There were significant correlations between fentanyl dosage and NAST score (r = .76, p < 0.01), between length of infusion of fentanyl and NAST score (r = .70, p < 0.05), and between chloral hydrate dosage and NAST score (r = .62, p < 0.05). These findings suggest the need for an observation protocol and a possible weaning regimen after fentanyl is discontinued.

Comparison between analgesic effect of bupivacaine thoracic epidural and ketamine infusion plus wound infiltration with local anesthetics in open cholecystectomy.

PubMed

Megahed, Nagwa Ahmed Ebrahim; Ellakany, Mohamed; Elatter, Ahmed Mohammed Ibrahim; Moustafa Teima, Mohamed Ahmed Ali

2014-01-01

Neuraxial blocks result in sympathetic block, sensory analgesia and motor block. Continuous epidural anesthesia through a catheter offers several options for perioperative analgesia. Local anesthetic boluses or infusions can provide profound analgesia. Although the role of low-dose ketamine (<2 mg/kg intramuscular, <1 mg/kg intravenous [IV] or ≤ 20 μg/kg/min by IV infusion) in the treatment of post-operative pain is controversial, perioperative administration of a small dose of ketamine may be valuable to a multimodal analgesic regimen. A local anesthetic can be used for wound infiltration intra-operative to minimized the surgical pain. A prospective randomized study was performed in which 40 patients scheduled for elective open cholecystectomy under general anesthesia admitted to the Medical Research Institute were included and further subdivided into two groups, group A, received thoracic epidural catheter at T7-8, activation was done 20 min before induction of anesthesia with plain bupivacaine at a concentration of 0.25% at a volume of 1 ml/segment aiming to block sensory supply from T4-L2, then received continuous thoracic epidural infusion intra and postoperatively with plain bupivacaine at a concentration of 0.125% at a rate of 5 ml/h for 24 h, group B received 0.3 mg/kg bolus of ketamine at the time of induction then 0.1 mg/kg/h ketamine IV infusion during surgery followed by wound infiltration with 15 ml of plain bupivacaine 0.5% at the time of skin closure. Bupivacaine thoracic epidural analgesia had better control on heart rate and mean arterial blood pressure than ketamine infusion plus wound infiltration with local anesthetic in patients undergoing open cholecystectomy. Thoracic epidural analgesia had better control on hemodynamic changes intra-and postoperatively than ketamine infusion with local wound infiltration in open cholecystectomy.

The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease.

PubMed

Sanjay, Srinivas; Annigeri, Rajeev A; Seshadri, Rajagopalan; Rao, Budithi Subba; Prakash, Kowdle C; Mani, Muthu Krishna

2008-06-01

To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuous versus bolus intravenous furosemide administration in patients with chronic renal insufficiency. In a prospective randomized cross-over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed. Mean age was 53.6 +/- 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 +/- 17 mL/min per 1.73 m(2). The urinary excretion of sodium in intravenous bolus and infusion was 98.1 +/- 78 and 114.4 +/- 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 +/- 627 and 1170 +/- 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 +/- 16.6) and infusion (14.3 +/- 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 +/- 16.1) than bolus administration (12.87 +/- 9) of furosemide (P = 0.016). Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.

Plasma concentrations of midazolam during continuous subcutaneous administration in palliative care.

PubMed

Bleasel, M D; Peterson, G M; Dunne, P F

1994-01-01

We have investigated the steady-state plasma concentrations of midazolam during continuous subcutaneous administration in palliative care. Using a sensitive gas chromatography with electron capture detector assay, plasma concentrations of midazolam were measured in 11 patients (median age 68 years; range 47-82 years; six females) receiving the drug by continuous subcutaneous infusion (median rate 20 mg/day; range 10-60 mg/day). While not significant, the infusion rate tended to decrease with increasing age of the patient (Spearman's p = -0.51; p = 0.11). The steady-state plasma concentration range was 10-147 ng/ml, with a median of 30 ng/ml. Infusion rates and plasma concentrations of midazolam were correlated (Spearman's p = 0.71; p < 0.05). No other significant relationships were found between plasma concentrations and the variables of age, sex and liver function.

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

Chloral hydrate enteral infusion for sedation in ventilated children: the CHOSEN pilot study.

PubMed

Joffe, Ari R; Hogan, Jessica; Sheppard, Cathy; Tawfik, Gerda; Duff, Jonathan P; Garcia Guerra, Gonzalo

2017-11-26

We aimed to test a novel method of delivery of chloral hydrate (CH) sedation in ventilated critically ill young children. Children < 12 years old, within 72 hours of admission, who were ventilated, receiving enteral tube-feeds, with intermittent CH ordered were enrolled after signed consent. Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases were compared to historical controls matched for age group and Pediatric Risk of Mortality score (PRISM) category, using Fisher's exact test and the t test. The primary outcome was feasibility, defined as the use of an enteral CH continuous infusion without discontinuation attributable to a pre-specified potential harm. There were 21 patients enrolled, at age 11.4 (12.1) months, with bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD) score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5 (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients, with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8 (IQR 7, 9). Days to titration of adequate sedation (defined as ≤ 3 PRN doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5 (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2 (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p = 0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically significant differences between cases and controls in inotrope scores, signs or treatment of withdrawal, or PICU days. Delivering CH by continuous enteral infusion is feasible, effective, and may be associated with less positive fluid balance. Whether there is a risk of duodenal perforation requires further study.

Epidural Baclofen for the Management of Postoperative Pain in Children With Cerebral Palsy.

PubMed

Nemeth, Blaise A; Montero, Robert J; Halanski, Matthew A; Noonan, Kenneth J

2015-09-01

Children with cerebral palsy undergoing soft tissue and bony procedures often experience pain and spasticity postoperatively. Differentiation of pain from spasticity complicates management, so controlling spasticity with a continuous infusion of baclofen, an antispasmodic, through an already present indwelling epidural catheter holds interest. A retrospective chart review was performed of patients with cerebral palsy undergoing single event, multilevel lower extremity surgery at a single institution who received epidural analgesia with or without continuous baclofen infusion. Primary outcomes included need for supplemental narcotic analgesics and benzodiazepines postoperatively. Duration of hospitalization, pain scores, and complications were also evaluated. Forty-four patients were identified, ranging in age from 3 to 17 years, 19 of whom received epidural baclofen. No differences were found in use of supplemental narcotic analgesia, benzodiazepines, or duration of hospitalization. Differences in pain scores were not statistically significant (0.82±0.95 for baclofen vs. 1.48±0.99 for controls) (P=0.391). Mean arterial pressure was lower in patients receiving baclofen (P=0.004). No potential side effects attributable to baclofen were noted. Continuous epidural baclofen infusion seems unlikely to alter the pain-spasm cycle experienced by patients with cerebral palsy following orthopaedic surgery to a clinically significant degree. More effective, and cost-effective, measures at assessing and controlling pain and muscle spasm should be explored to benefit cerebral palsy patients postoperatively. Level III-therapeutic study.

Continuous intra-articular infusion anesthesia for pain control after total knee arthroplasty: study protocol for a randomized controlled trial.

PubMed

Guo, Da; Cao, Xue-Wei; Liu, Jin-Wen; Ouyang, Wen-Wei; Pan, Jian-Ke; Liu, Jun

2014-06-23

Postoperative pain control after total knee arthroplasty (TKA) remains a great challenge. The management of pain in the immediate postoperative period is one of the most critical aspects to allow speedier rehabilitation and reduce the risk of postoperative complications. Recently, periarticular infiltration anesthesia has become popular, but the outcome is controversial. Some studies have shown transient effects, "rebound pain", or no effectiveness in pain control. Continuous intra-articular infusion technique has been introduced to improve these transient effects, but more clinical studies are needed. Furthermore, the potential risk of early periprosthetic joint infection is causing concerning. We plan to compare continuous intra-articular infusion anesthesia with epidural infusion anesthesia after TKA to assess the effectiveness of this technique in reducing pain, in improving postoperative function, and to look at the evidence for risk of early infection. This trial is a randomized, controlled study. Patients (n = 214) will be randomized into two groups: to receive continuous intra-articular infusion anesthesia (group C); and epidural infusion anesthesia (group E). For the first 3 postoperative days, pain at rest, active range of motion (A-ROM), rescue analgesia and side effects will be recorded. At 3-month and 6-month follow-up, A-ROM, C-reactive protein, erythrocyte sedimentation rate, and synovial fluid cell count and culture will be analyzed. The results from this study will provide clinical evidence on the efficacy of a continuous intra-articular infusion technique in reducing pain, postoperative functional improvement and safety. It will be the first randomized controlled trial to investigate infection risk with local anesthesia after TKA. ClinicalTrials.gov identifier: ChiCTR-TRC-13003999.

Circadian rhythm of energy expenditure and oxygen consumption.

PubMed

Leuck, Marlene; Levandovski, Rosa; Harb, Ana; Quiles, Caroline; Hidalgo, Maria Paz

2014-02-01

This study aimed to evaluate the effect of continuous and intermittent methods of enteral nutrition (EN) administration on circadian rhythm. Thirty-four individuals, aged between 52 and 80 years, were fed through a nasoenteric tube. Fifteen individuals received a continuous infusion for 24 hours/d, and 19 received an intermittent infusion in comparable quantities, every 4 hours from 8:00 to 20:00. In each patient, 4 indirect calorimetric measurements were carried out over 24 hours (A: 7:30, B: 10:30, C: 14:30, and D: 21:30) for 3 days. Energy expenditure and oxygen consumption were significantly higher in the intermittent group than in the continuous group (1782 ± 862 vs 1478 ± 817 kcal/24 hours, P = .05; 257 125 vs 212 117 ml/min, P = .048, respectively). The intermittent group had higher levels of energy expenditure and oxygen consumption at all the measured time points compared with the continuous group. energy expenditure and oxygen consumption in both groups were significantly different throughout the day for 3 days. There is circadian rhythm variation of energy expenditure and oxygen consumption with continuous and intermittent infusion for EN. This suggests that only one indirect daily calorimetric measurement is not able to show the patient's true needs. Energy expenditure is higher at night with both food administration methods. Moreover, energy expenditure and oxygen consumption are higher with the intermittent administration method at all times.

A North Central Cancer Treatment Group Phase II trial of 9-aminocamptothecin in previously untreated patients with measurable metastatic colorectal carcinoma.

PubMed

Pitot, H C; Knost, J A; Mahoney, M R; Kugler, J; Krook, J E; Hatfield, A K; Sargent, D J; Goldberg, R M

2000-10-15

Topoisomerase I inhibitors have demonstrated clinical activity in patients with metastatic colorectal carcinoma. The authors performed a Phase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated patients with measurable recurrent metastatic colorectal carcinoma. Fifty-one patients were registered. One schedule evaluated 9-AC given at 1100 microgram/m(2)/24 hours by continuous infusion for 72 hours along with granulocyte-colony stimulating factor at 5 microgram/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 microgram/m(2)/24 hours by continuous infusion for 120 hours on Days 1, 8, and 15 given every 4 weeks. Forty-eight of 51 patients (94%) were evaluable (28 patients who received 72-hour infusion and 20 patients who received 120-hour infusion) for response and toxicity. Significant hematologic toxicities were encountered, especially with the 72-hour infusion schedule, in which 43% (12 of 28) and 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxicity Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutropenia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on the 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. Seventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencing Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedule. Three patients died of chemotherapy-related toxicity. One response was observed in 48 evaluable patients (2%). 9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic colorectal carcinoma. Copyright 2000 American Cancer Society.

Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion

PubMed Central

Jun, Na Hyung; Shim, Jae Kwang; Choi, Yong Sun; An, Seung Ho

2011-01-01

Background An appropriate level of sedation and pharmacological assist are essential during percutaneous transluminal balloon angioplasty (PTA). Ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability with an opioid sparing effect suggesting that it would be ideal in combination with remifentanil and midazolam in spontaneously breathing patients. We evaluated the effect of a small dose of ketamine added to midazolam and remifentanil on analgesia/sedation for PTA procedures. Methods Sixty-four patients receiving PTA were enrolled. The Control group received midazolam 1.0 mg i.v. and continuous infusion of remifentanil 0.05 µg/kg/min. The Ketamine group received, in addition, an intravenous bolus of 0.5 mg/kg ketamine. Patients' haemodynamic data were monitored before remifentanil infusion, 5 min after remifentanil infusion, at 1, 3, 5, 30 min after incision, and at admission to the recovery room. Verbal numerical rating scales (VNRS) and sedation [OAA/S (Observer's Assessment of Alertness/Sedation)] scores were also recorded. Results The VNRS values at 1, 3, and 5 min after incision and OAA/S scores at 5 min after remifentanil infusion, and 1, 3, and 5 min after incision were lower in the Ketamine group than in the Control group. In the Control group, the VNRS value at 1 min after incision significantly increased and OAA/S values at 3, 5, and 30 min after incision significantly decreased compared to baseline values, while there were no significant changes in the ketamine group. Conclusions A small dose of ketamine as an adjunct sedative to the combination of midazolam and remifentanil produced a better quality of sedation and analgesia than without ketamine and provided stable respiration without cardiopulmonary deterioration. PMID:22110884

Pre-emptive multimodal analgesia with tramadol and ketamine-lidocaine infusion for suppression of central sensitization in a dog model of ovariohysterectomy.

PubMed

Kaka, Ubedullah; Rahman, Nor-Alimah; Abubakar, Adamu Abdul; Goh, Yong Meng; Fakurazi, Sharida; Omar, Mohamed Ariff; Chen, Hui Cheng

2018-01-01

The effects of pre-emptive infusion of ketamine-lidocaine with tramadol on the suppression of central sensitization were investigated in a dog ovariohysterectomy model. Twelve dogs were randomly assigned to two groups: ketamine-lidocaine-tramadol (KLT) and tramadol (T) groups. Both groups received intravenous tramadol 4 mg/kg body weight as premedication. Immediately after induction, the KLT group received ketamine and lidocaine at 0.5 and 2 mg/kg loading dose, followed by continuous rate infusion of 50 and 100 µg/kg/min, respectively, for 2 hours. Dogs in T group received saline bolus and continuous rate infusion at equi-volume. Intraoperatively, hemodynamic responses to surgical stimulation were recorded, whereas postoperative pain was evaluated using an algometer and short form of the Glasgow composite measure pain scale. Intraoperatively, hemodynamic responses to surgical stimulation were obtunded to a greater degree in KLT compared to T group. Postoperatively, the pain scores increased only for the first hour in KLT group, compared to 12 hours in T group. Mechanical thresholds at the abdomen decreased postoperatively between 12 and 60 hours in KLT group versus the entire 72 hours in T group. Thresholds at tibia and radius in both groups increased in the immediate 1 hour postoperatively, but decreased thereafter. Significant decrement of thresholds from baseline were detected in the tibia at 24, 42, and 60 hours in KLT group compared to 24-72 hours in T group, and in the radius between 36 and 48 hours in T group, but none in KLT group. Addition of pre-emptive ketamine-lidocaine infusion to single intravenous dose of tramadol enhanced attenuation of central sensitization and improved intra- and postoperative analgesia.

Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

PubMed

Pasternak, Amy L; Link, Nicholas A; Richardson, Carolyn M; Rose, Peter G

2016-07-01

To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. Retrospective chart review. Large integrated health system. A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed to the triple premedication regimen received more frequently in patients in the extended-infusion group. © 2016 Pharmacotherapy Publications, Inc.

A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery.

PubMed

Su, Felice; Nicolson, Susan C; Zuppa, Athena F

2013-06-01

To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery. Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study. Tertiary pediatric cardiac ICU. Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation. Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours. Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure. Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

PubMed

Lockwood, Geoff G; Cabreros, Leilani; Banach, Dorota; Punjabi, Prakash P

2017-10-01

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg -1 .hr -1 ) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l -1 . There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats

PubMed Central

Kirsch, Michael; Petrat, Frank

2017-01-01

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats. PMID:28817064

Safety and efficacy of intravenous labetalol for hypertensive crisis in infants and small children.

PubMed

Thomas, Christopher A; Moffett, Brady S; Wagner, Jeffrey L; Mott, Antonio R; Feig, Daniel I

2011-01-01

To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age. Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression. A 737-bed pediatric teaching institution. Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency. None. The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation. Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

PubMed Central

Weng, Xiao-chuan; Zhou, Liang; Fu, Yin-yan; Zhu, Sheng-mei; He, Hui-liang; Wu, Jian

2005-01-01

Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167) mg/(kg·h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303±0.134) mg/(kg·h) and returned to the initial values at the neohepatic period ((0.429±0.130) mg/(kg·h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT. PMID:16130187

Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs.

PubMed

Favarato, E S; Souza, M V; Costa, P R S; Favarato, L S C; Nehme, R C; Monteiro, B S; Bonfá, L P

2012-08-01

This research aimed to evaluate the effect of metoclopramide and ranitidine in the prevention of gastroesophageal reflux episodes during anesthetic procedures. Ninety healthy female dogs were submitted to elective ovariosalpingohisterectomy, randomly divided into three groups of 30 animals. The control group received only the anesthetic protocol. The metoclopramide group received an intravenous bolus of 1mg/kg, and continuous infusion (1 mg/kg/h intravenously) immediately after anesthetic induction. The ranitidine group received an intravenous bolus of 2 mg/kg, 6 h before anesthesia. Anesthesia (acepromazine, propofol and isofluorane) was standardized and the esophageal pH variations were recorded. Esophagoscopy was carried out after surgery. No difference (p<0.05) was verified in the reflux episodes between the groups. Seven animals presented reflux. Metoclopramide in bolus and continuous infusion, as well as ranitidine, 6 h before anesthesia, did not influence the reduction of the incidence of gastroesophageal reflux. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

PubMed

Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

2014-01-01

Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under ultrasound guidance after shoulder surgery, automated boluses of local anesthetic combined with PRN boluses did not provide any reduction in local anesthetic consumption or rescue analgesia, compared with continuous infusion combined with PRN boluses.

Controlled hypotension for middle ear surgery: a comparison between remifentanil and magnesium sulphate.

PubMed

Ryu, J-H; Sohn, I-S; Do, S-H

2009-10-01

This prospective, randomized study was designed to compare remifentanil and magnesium sulphate during middle ear surgery in terms of postoperative pain and other complications. Eighty patients undergoing middle ear surgery were enrolled in the study. Patients were randomized into two groups of 40 to receive remifentanil (Group R) or magnesium sulphate (Group M) infusion. Propofol 2 mg kg(-1) was administered to induce anaesthesia, which was maintained using sevoflurane. Group R received a continuous infusion of remifentanil titrated between 3 and 4 ng ml(-1) using target-controlled infusion, whereas Group M received an i.v. magnesium sulphate bolus of 50 mg kg(-1) followed by a 15 mg kg(-1) h(-1) continuous infusion to maintain a mean arterial pressure (MAP) between 60 and 70 mm Hg. Haemodynamic variables, surgical conditions, postoperative pain, and adverse effects, such as postoperative nausea and vomiting (PONV) and shivering, were recorded. Controlled hypotension was well maintained in both groups. MAP and heart rate were higher in Group R than in Group M after operation. Surgical conditions were not different between the two groups. Postoperative pain scores were significantly lower in Group M than in Group R (P<0.05). Seventeen patients in Group R (43%) and seven patients in Group M (18%) developed PONV (P=0.01). Both magnesium sulphate and remifentanil when combined with sevoflurane provided adequate controlled hypotension and proper surgical conditions for middle ear surgery. However, patients administered magnesium sulphate had a more favourable postoperative course with better analgesia and less shivering and PONV.

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

PubMed

Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

2016-07-01

Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

APA national audit of pediatric opioid infusions.

PubMed

Morton, Neil S; Errera, Agata

2010-02-01

A prospective audit of neonates, infants, and children receiving opioid infusion techniques managed by pediatric acute pain teams from across the United Kingdom and Eire was undertaken over a period of 17 months. The aim was to determine the incidence, nature, and severity of serious clinical incidents (SCIs) associated with the techniques of continuous opioid infusion, patient-controlled analgesia, and nurse-controlled analgesia in patients aged 0-18. The audit was funded by the Association of Paediatric Anaesthetists (APA) and performed by the acute pain services of 18 centers throughout the United Kingdom. Data were submitted weekly via a web-based return form designed by the Document Capture Company that documented data on all patients receiving opioid infusions and any SCIs. Eight categories of SCI were identified in advance, and the reported SCIs were graded in terms of severity (Grade 1 (death/permanent harm); Grade 2 (harm but full recovery and resulting in termination of the technique or needing significant intervention); Grade 3 (potential but no actual harm). Data were collected over a period of 17 months (25/06/07-25/11/08) and stored on a secure server for analysis. Forty-six SCIs were reported in 10 726 opioid infusion techniques. One Grade 1 incident (1 : 10,726) of cardiac arrest occurred and was associated with aspiration pneumonitis and the underlying neurological condition, neurocutaneous melanosis. Twenty-eight Grade 2 incidents (1 : 383) were reported of which half were respiratory depression. The seventeen Grade 3 incidents (1 : 631) were all drug errors because of programming or prescribing errors and were all reported by one center. The overall incidence of 1 : 10,000 of serious harm with opioid infusion techniques in children is comparable to the risks with pediatric epidural infusions and central blocks identified by two recent UK national audits (1,2). Avoidable factors were identified including prescription and pump programming errors, use of concurrent sedatives or opioids by different routes and overgenerous dosing in infants. Early respiratory depression in patients with specific risk factors, such as young age, neurodevelopmental, respiratory, or cardiac comorbidities, who are receiving nurse-controlled analgesia or continuous opioid infusion suggests that closer monitoring for at least 2 h is needed for these cases. As a result of this audit, we can provide parents with better information on relative risks to help the process of informed consent.

Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial.

PubMed

Ferrer, Leopoldo E; Romero, David J; Vásquez, Oscar I; Matute, Ednna C; Van de Velde, Marc

2017-11-01

Continuous epidural infusion and programmed intermittent epidural boluses are analgesic techniques routinely used for pain relief in laboring women. We aimed to assess both techniques and compare them with respect to labor analgesia and obstetric outcomes. After Institutional Review Board approval, 132 laboring women aged between 18 and 45 years were randomized to epidural analgesia of 10 mL of a mixture of 0.1% bupivacaine plus 2 µg/mL of fentanyl either by programmed intermittent boluses or continuous infusion (66 per group). Primary outcome was quality of analgesia. Secondary outcomes were duration of labor, total drug dose used, maternal satisfaction, sensory level, motor block level, presence of unilateral motor block, hemodynamics, side effects, mode of delivery, and newborn outcome. Patients in the programmed intermittent epidural boluses group received statistically less drug dose than those with continuous epidural infusion (24.9 vs 34.4 mL bupivacaine; P = 0.01). There was no difference between groups regarding pain control, characteristics of block, hemodynamics, side effects, and Apgar scores. Our study evidenced a lower anesthetic consumption in the programmed intermittent boluses group with similar labor analgesic control, and obstetric and newborn outcomes in both groups.

Parenterally fed neonatal piglets have a low rate of endogenous arginine synthesis from circulating proline.

PubMed

Urschel, Kristine L; Evans, Amanda R; Wilkinson, Craig W; Pencharz, Paul B; Ball, Ronald O

2007-03-01

Parenterally fed neonatal piglets cannot synthesize sufficient arginine to maintain arginine status, presumably due to the intestinal atrophy that occurs with parenteral feeding. Parenteral feeding-induced atrophy can be reduced by the infusion of glucagon-like peptide 2 (GLP-2). GLP-2 infusion was hypothesized to increase the rate of endogenous arginine synthesis from proline, the major arginine precursor, in parenterally fed piglets receiving an arginine-deficient diet. Male piglets, fitted with jugular vein catheters for diet and isotope infusion, and femoral vein catheters for blood sampling (d 0), were allocated to a continuous infusion of either GLP-2 (n = 5; 10 nmol x kg(-1) x d(-1)) or saline (n = 5) for 7 d. Piglets received 2 d of a complete diet, followed by 5 d of an arginine-deficient [0.60 g x kg(-1) x d(-1)] diet. Piglets received primed, constant infusions of [guanido-(14)C]arginine to measure arginine flux (d 6) and [U-(14)C]proline (d 7) to measure proline conversion to arginine. Plasma arginine concentrations and arginine fluxes indicated a similar whole-body arginine status. Piglets receiving GLP-2 showed improvements in intestinal variables, including mucosal mass (P < 0.01) and villus height (P < 0.001), and a greater rate of arginine synthesis (micromol x kg(-1) x h(-1)) from proline (11.6 vs. 6.3) (P = 0.03). Mucosal mass (R(2) = 0.71; P = 0.002) and villus height were correlated (R(2) = 0.66; P = 0.004) with arginine synthesis. This study was the first to quantitate arginine synthesis in parenterally fed neonates and showed that although GLP-2 infusion increased arginine synthesis in a manner directly related to mucosal mass, this increased arginine synthesis was insufficient to improve whole-body arginine status in piglets receiving a low arginine diet.

Once-weekly exenatide as adjunct treatment of type 1 diabetes mellitus in patients receiving continuous subcutaneous insulin infusion therapy.

PubMed

Traina, Andrea N; Lull, Melinda E; Hui, Adrian C; Zahorian, Toni M; Lyons-Patterson, Jane

2014-08-01

The use of once-weekly exenatide in type 2 diabetes mellitus is well supported, but little is known about its effectiveness in type 1 diabetes. The objective of this study was to determine the clinical efficacy of once-weekly exenatide on glycemic control in patients with type 1 diabetes when added to basal-bolus insulin therapy. For this retrospective study, patients with type 1 diabetes, aged 18 years and older, receiving continuous subcutaneous insulin infusion, using a continuous glucose monitoring device or regularly measuring blood glucose levels and receiving 2 mg of exenatide once weekly for at least 3 months were included. Demographic information, glycated hemoglobin (A1C), body weight, body mass index, systolic and diastolic blood pressures, total daily insulin dose, basal and bolus insulin doses, 28-day continuous subcutaneous insulin infusion glucose average and incidence of hypoglycemia were collected at baseline and 3 months after beginning therapy with once-weekly exenatide. An electronic medical record search identified 11 patients with type 1 diabetes who met the inclusion criteria. Comparing baseline and 3 months after initiation of once-weekly exenatide revealed reductions of 0.6% in A1C (p=0.013), 3.7% in body weight (p=0.008), 1.7 kg/m(2) in body mass index (p=0.003), 13% in total daily insulin dose (p=0.011) and 9.3 units in bolus insulin dose (p=0.015). This study revealed that the addition of once-weekly exenatide to insulin therapy for type 1 diabetes patients leads to significant improvements in A1C, body weight, body mass index and insulin doses. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Incontinence Morbidity Following Radical Prostatectomy: Psychosocial Impact on African American and White Men

DTIC Science & Technology

2005-07-01

continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study. (Review) ONS Nursing Scan in Oncology, 2 (6...teaching, medical, nursing , psychosocial, and follow-up care . Thus, in contrast to many of the men in the larger cohort, they believed they were...informed about their treatment decision and spoke very highly of the caring , professional, medical and nursing care they received. Two men who underwent the

Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American rattlesnake bite patients.

PubMed

Bush, Sean P; Seifert, Steven A; Oakes, Jennifer; Smith, Susan D; Phan, Tammy H; Pearl, Sarah R; Reibling, Ellen T

2013-07-01

In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Severe hypertriglyceridaemia in Type 2 diabetes mellitus: beneficial effect of continuous insulin infusion.

PubMed

Henderson, S R; Maitland, R; Mustafa, O G; Miell, J; Crook, M A; Kottegoda, S R

2013-04-01

Severe hypertriglyceridaemia is a recognized complication of Type 2 diabetes mellitus (T2DM); however, there is no consensus on acute management despite the significant risk of developing associated complications such as acute pancreatitis and hyperviscosity syndrome. To identify the association between hyperglycaemia and severe hypertriglyceridaemia in patients with T2DM and assess the effect of continuous insulin infusion therapy on serum triglyceride (TG) concentrations and report any adverse events associated with this therapeutic approach. Retrospective review of case records. Patients with uncontrolled hyperglycaemia and severe hypertriglyceridaemia (serum TG > 15 mmol/l) treated with continuous intravenous insulin infusion between October 2008 and September 2009 were retrospectively evaluated (n = 15). Details recorded included demographics, admission details, lipid profiles, glycaemic control, serum amylase and adverse events. Patients receiving treatment-dose unfractionated heparin infusion were excluded. Severe hypertriglyceridaemia is associated with hyperglycaemia in our heterogeneous group of patients with T2DM presenting with new-onset diabetes or established disease on pre-existing insulin or oral hypoglycaemic agents. Administration of continuous exogenous insulin not only achieved normoglycaemia but also dramatically corrected severe hypertriglyceridaemia in all patients (P = 0.001). The administration of continuous insulin in patients with T2DM with severe hypertriglyceridaemia is a simple and safe method of significantly reducing the immediate risk associated with this metabolic complication and should be considered in any T2DM patient presenting with severe hypertriglyceridaemia and hyperglycaemia.

Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

PubMed

Nakayama, Hirokazu; Echizen, Hirotoshi; Ogawa, Ryuichi; Akabane, Atsuya; Kato, Toshiaki; Orii, Takao

2017-06-01

Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P < 0.05 was considered statistically significant. The induration group showed significantly reduced C/D ratio compared with the noninduration group [median (range): 0.131 (0.114-0.334) versus 0.219 (0.180-0.322) d/L, P < 0.05). Assuming that systemic clearance was constant in our patients, changes in the C/D ratio would have contributed to 40% (median) reduction in bioavailability of the drug from the injection or infusion site. Our data suggest that absolute bioavailability of phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Effect of tubing on loss of clonazepam administered by continuous subcutaneous infusion.

PubMed

Schneider, Jennifer J; Good, Phillip; Ravenscroft, Peter J

2006-06-01

Previous studies have reported loss of clonazepam from solutions administered intravenously from plastic infusion bags and administration sets. In palliative care, clonazepam is sometimes administered through syringe drivers using polyvinyl chloride (PVC) infusion tubing. No data currently exist to show whether use of PVC tubing affects the amount of clonazepam actually received by the patient. This study compared the use of two different types of PVC tubing with a non-PVC tubing. Solutions containing clonazepam or clonazepam and morphine were prepared with either normal saline or water for injection as diluent. Concentrations of morphine and clonazepam were determined using high-performance liquid chromatography. Significant loss of clonazepam (up to 50%) was observed in all solutions infused through PVC tubing. Solutions infused through non-PVC tubing retained greater than 90% of the initial concentration of clonazepam. It is recommended that when administering clonazepam using a syringe driver, non-PVC tubing be used.

Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study.

PubMed

Schulz, Craig A; Mehta, Minesh P; Badie, Benham; McGinn, Cornelius J; Robins, H Ian; Hayes, Lori; Chappell, Rick; Volkman, Jen; Binger, Kim; Arzoomanian, Rhoda; Simon, Kris; Alberti, Dona; Feierabend, Christine; Tutsch, Kendra D; Kunugi, Keith A; Wilding, George; Kinsella, Timothy J

2004-07-15

To investigate the maximal tolerated dose of a continuous 28-day iododeoxyuridine (IUdr) infusion combined with hyperfractionated accelerated radiotherapy (HART); to analyze the percentage of IUdr-thymidine replacement in peripheral granulocytes as a surrogate marker for IUdr incorporation into tumor cells; to measure the steady-state serum IUdr levels; and to assess the feasibility of continuous IUdr infusion and HART in the management of malignant glioma. Patients were required to have biopsy-proven malignant glioma. Patients received 100 (n = 4), 200 (n = 3), 300 (n = 3), 400 (n = 6), 500 (n = 4), 625 (n = 5), or 781 (n = 6) mg/m(2)/d of IUdr by continuous infusion for 28 days. HART was started 7 days after IUdr initiation. The total dose was 70 Gy (1.2 Gy b.i.d. for 25 days with a 10-Gy boost [2.0 Gy for 5 Saturdays]). Weekly assays were performed to determine the percentage of IUdr-DNA replacement in granulocytes and serum IUdr levels using standard high performance liquid chromatography methods. Standard Phase I toxicity methods were used. Between June 1994 and August 1999, 31 patients were enrolled. No patient had Grade 3 or worse HART toxicity. Grade 3 or greater IUdr toxicity predominantly included neutropenia (n = 3), thrombocytopenia (n = 3), and elevated liver function studies (n = 3). The maximal tolerated dose was 625 mg/m(2)/d. Thymidine replacement in the peripheral granulocytes peaked at 3 weeks and increased with the dose (maximal thymidine replacement 4.9%). The steady-state plasma IUdr level increased with the dose (maximum, 1.5 microM). In our study, continuous long-term IUdr i.v. infusion had a maximal tolerated dose of 625 mg/m(2)/d. Granulocyte incorporation data verified the concept that prolonged IUdr infusion results in IUdr-DNA replacement that corresponds to a high degree of cell labeling. IUdr steady-state plasma levels increased with increasing dose and attained levels needed for clinical radiosensitization. Continuous IUdr infusion and HART were both feasible and well tolerated.

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial

PubMed Central

2014-01-01

Introduction Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. Methods Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. Results A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04). Conclusions In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months. Trial registration ClinicalTrials.gov NCT01441245. Registered 23 September 2011. PMID:24974232

INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.

PubMed

Kemp, Brandon A; Howell, Nancy L; Padia, Shetal H

2018-06-20

The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA. In rats receiving intrarenal vehicle or intrarenal SCR siRNA, systemic Angiotensin II infusion increased sodium retention and BP on day 1, and BP remained elevated throughout the 5-day study. These rats also demonstrated increased CD GR expression after 5 days of infusion. However, intrarenal GR siRNA infusion prevented Angiotensin II-mediated sodium retention on day 1, induced a continuously negative cumulative sodium balance compared with Angiotensin II alone, and reduced BP chronically. Glomerular filtration rate and renal blood flow remained unchanged in GR siRNA-infused rats. Systemic Angiotensin II infusion also increased serum aldosterone levels, CD αENaC and pSGK1 expression in rats with intrarenal SCR siRNA; however these effects were not observed in the presence of intrarenal GR siRNA, despite exposure to the same systemic Angiotensin II. These data demonstrate that chronic inhibition of intrarenal GR activity significantly reduces αENaC -dependent sodium retention, resulting in a negative cumulative sodium balance, thereby ameliorating Angiotensin II-induced hypertension in rats. Renal GRs represent a novel therapeutic target for the treatment of hypertension and other sodium-retaining states.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

PubMed

Brown, Christine E; Alizadeh, Darya; Starr, Renate; Weng, Lihong; Wagner, Jamie R; Naranjo, Araceli; Ostberg, Julie R; Blanchard, M Suzette; Kilpatrick, Julie; Simpson, Jennifer; Kurien, Anita; Priceman, Saul J; Wang, Xiuli; Harshbarger, Todd L; D'Apuzzo, Massimo; Ressler, Julie A; Jensen, Michael C; Barish, Michael E; Chen, Mike; Portnow, Jana; Forman, Stephen J; Badie, Behnam

2016-12-29

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).

Advancing Novel Anesthetics: Pharmacodynamic and Pharmacokinetic Studies of Cyclopropyl-Methoxycarbonyl Metomidate in Dogs

PubMed Central

Campagna, Jason A.; Pojasek, Kevin; Grayzel, David; Randle, John; Raines, Douglas E.

2014-01-01

Background Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation “soft” (i.e., metabolically-labile) etomidate analogue. The purpose of these studies was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. Methods CPMM's and etomidate's hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs. Their pharmacokinetics were defined after single bolus administration and single bolus followed by 2-h infusion. Adrenocortical recovery times after single bolus followed by 2-h infusion of CPMM, propofol, etomidate, and vehicle were measured using an adrenocorticotropic hormone stimulation test. Results Compared to etomidate, CPMM was half as potent as a hypnotic (ED50 ~ 0.8 mg/kg), more rapidly metabolized, and had a shorter duration of sedative-hypnotic action. Recovery times after CPMM administration were also independent of infusion duration. After hypnotic infusion, adrenocorticotropic hormone-stimulated plasma cortisol concentrations were 4- to 27-fold higher in dogs that received CPMM versus etomidate. Adrenocortical recovery was faster in dogs after CPMM infusion versus etomidate infusion (half-time: 215 min vs. 1623 min, respectively). Adrenocortical responsiveness assessed 90 min after CPMM infusion was not significantly different from that after propofol infusion. Conclusion Our studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative-hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation. PMID:25170571

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus.

PubMed

Gaínza-Lein, Marina; Sánchez Fernández, Iván; Jackson, Michele; Abend, Nicholas S; Arya, Ravindra; Brenton, J Nicholas; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Tasker, Robert C; Tchapyjnikov, Dmitry; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

2018-04-01

Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11.0; 95% CI, 1.43 to ∞; P = .02), had greater odds of receiving continuous infusion (AOR, 1.8; 95% CI, 1.01-3.36; P = .047), had longer convulsive seizure duration (AOR, 2.6; 95% CI, 1.38-4.88; P = .003), and had more frequent hypotension (AOR 2.3; 95% CI, 1.16-4.63; P = .02). In addition, the timing of the first-line benzodiazepine treatment was correlated with the timing of the second-line (95% CI, 0.64-0.95; P < .001) and third-line antiseizure medications (95% CI, 0.25-0.78; P < .001). Among pediatric patients with RCSE, an untimely first-line benzodiazepine treatment is independently associated with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. Results of this study raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.

PP024. Effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures induced by electrical stimuli in a rat preeclampsia/eclampsia model.

PubMed

Liu, Lei; Liu, Huishu; Huang, Qian; Brennecke, Shaun; Hu, Bihui

2013-04-01

Eclampsia is a serious complication of pregnancy and remains a leading cause of maternal mortality worldwide. Magnesium sulfate is commonly used in the prophylaxis and treatment of eclampsia. However, uncertainty remain regarding its anticonvulsant mechanism(s) of action. This study examined the effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures in a rat preeclampsia/eclampsia model. All rats were implanted with stainless nickel-cadmium alloy bipolar electrodes one week before fertilization. Next, an experimental rat preeclampsia (PE) model was induced on gestational day 14 by anaesthetising rats and infusing over 1 hour into their tail veins lipopolysaccharide (LPS) (1.0μg/kg body weight) (with control rats receiving normal saline). The rats were then divided into three groups: a normal pregnancy (NP) group (n=6) which received a continuous infusion of saline; a control PE model group (n=7) (which had previously received the LPS treatment) which also received a continuous infusion of saline; and a treated PE model group (n=8) (which had previously received the LPS treatment) which received a continuous infusion of magnesium sulfate (60mg/kg/day). The continuous infusions in all three groups were delivered by implanted osmotic minipumps . Measurements were made of blood pressure, albuminuria, serum ALT, AST, and creatinine, BUN and serum magnesium concentrations. On gestational day 18, all experimental rats received a standardized electrical stimulus. Seizure activity was assessed using electroencephalogram (EEG) recordings. Terminations of pregnancy were performed on gestational day 21. Resorptions and pup birth weights were recorded. The pregnant LPS treated rats developed many features of human PE (e.g. hypertension, proteinuria, liver and kidney dysfunctions). The mean concentration of Mg(2+) in the magnesium sulfate therapy group (0.86±0.24mmol/L) was significantly higher (p<0.05) than in both the control PE model group (0.61±0.12mmol/L) and the NP group (0.62±0.09mmol/L). The magnesium sulfate therapy group had a significantly (p<0.05) increased latency period (21.7±8.9min) to evoke a full motor seizure compared to both the NP group (4.8±2.2min)and the control PE model group (3.3±1.4min), there being no significant difference (p>0.05) between the latency periods of the NP group and the control PE model group. Overall, the magnesium sulfate therapy regimen completely prevented seizure activity in 3/8 (37.5%) of the treated PE model rats compared to 6/6 (100%) of the NP rats and 7/7 (100%) of the control PE rats. The treated PE model group also had significantly (p<0.05) reduced seizure duration (26±4s) compared to both the NP (40±7s) and the control PE model (45±9s) groups. As well, there was a significantly (p<0.05) shorter EEG seizure amplitude change in the treated PE model group (58±6μv). In this rat preeclamsia/eclampsia model, the anticonvulsant characteristics of magnesium sulfate have been shown to include significantly increasing seizure latency period, reducing seizure duration and decreasing seizure EEG amplitude. Copyright © 2013. Published by Elsevier B.V.

Volume of hydration in terminal cancer patients.

PubMed

Bruera, E; Belzile, M; Watanabe, S; Fainsinger, R L

1996-03-01

In this retrospective study we reviewed the volume and modality of hydration of consecutive series of terminal cancer patients in two different settings. In a palliative care unit 203/290 admitted patients received subcutaneous hydration for 12 +/- 8 days at a daily volume of 1015 +/- 135 ml/day. At the cancer center, 30 consecutive similar patients received intravenous hydration for 11.5 +/- 5 days (P > 0.2) but at a daily volume of 2080 +/- 720 ml/day (P < 0.001). None of the palliative care unit patients required discontinuation of hydration because of complications. Hypodermoclysis was administered mainly as a continuous infusion, an overnight infusion, or in one to three 1-h boluses in 62 (31%), 98 (48%) and 43 (21%) patients, respectively. Our findings suggest that, in some settings, patients may be receiving excessive volumes of hydration by less comfortable routes such as the intravenous route. Increased education and research in this area are badly needed.

Comparison of intraoperative behavioral and hormonal responses to noxious stimuli between mares sedated with caudal epidural detomidine hydrochloride or a continuous intravenous infusion of detomidine hydrochloride for standing laparoscopic ovariectomy.

PubMed

Virgin, Joanna; Hendrickson, Dean; Wallis, Ty; Rao, Sangeeta

2010-08-01

To compare the presence or absence of pain, pain-related behavioral responses, and hormonal responses to noxious stimuli during standing laparoscopic ovariectomy in mares sedated with continuous intravenous (IV) detomidine infusion and caudal epidural detomidine. A double blind prospective study. Mares (n=12) Mares were divided into 2 treatment groups; 6 were sedated using continuous IV detomidine infusion and 6 were sedated with caudal epidural detomidine. All mares received IV xylazine (0.33 mg/kg) and butorphanol tartrate (5 mg) premedication before detomidine administration. Venous blood samples were taken to assess serum cortisol levels in each mare at 4 time points: a baseline cortisol measurement after the mares' arrival to the clinic, 10 minutes before surgery, at the removal of the 2nd ovary, and 10 minutes postsurgery. Two surgeons performed bilateral ovariectomy and at 8 time points involving surgical manipulations, noted the presence or absence of pain (yes/no) and scored the patient's response on a 10 cm visual analogue scale (VAS) for pain assessment with 0 indicating no pain responses and 10 cm indicating pain so severe that the mare required additional sedation or analgesia to complete the procedure. Each mare was also assigned a VAS score by each surgeon for the overall satisfaction of analgesia during the entire procedure. Serum cortisol levels between the 2 detomidine administration groups differed significantly at the baseline (precortisol) measurement but not at the 3 remaining time points. Seven of the procedures within the surgeries did not differ significantly in VAS scores between the 2 groups. The initial grasp of the left ovary (the 1st ovary) in the continuous infusion group had a significantly higher (P=.05) median VAS score compared with the caudal epidural group. Mares sedated with a continuous IV infusion of detomidine have similar hormonal and behavioral responses to painful stimuli during standing laparoscopic ovariectomy as mares sedated with caudal epidural detomidine. Sedation using a continuous IV infusion of detomidine can be used for laparoscopic ovariectomy in mares.

Continuous intra-arterial 5-FU chemotherapy in a patient with a repeated recurrence of rectal cancer: report of a case.

PubMed

Toh, U; Isomoto, H; Araki, Y; Matsumoto, A; Yasunaga, M; Ogoh, Y; Inuzuka, K; Ozaki, K; Shirouzu, K

2000-06-01

We report a patient with a recurrent pelvic tumor after abdominoperineal resection of a rectal carcinoma who was treated sufficiently by repeated intra-arterial infusions of 5-fluorouracil. A continuous, 24-hour 5-fluorouracil administration was made through the bilateral internal iliac artery at a dosage of 250 mg/m2/day by the subcutaneous reservoir located at both upper legs using a Baxter infusor. In this patient pain in the hip and pelvis was relieved. A complete regression in the infused field of pelvic tumor was observed not only with computed tomography and magnetic resonance imaging but also confirmed by operative findings at the seventh month after the intra-arterial infusion. The abnormal serum level of carcinoembryonic antigen and carbohydrate antigen 19-9 was decreased to within the normal range at the 19th and 3rd week respectively. When the repeated recurrence was suspected in follow-up, normalization of the re-elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels was also obtained by repeating the same treatment. The side effects and complications were tolerable, consisting of local skin erosion on the hips and lower extremity neuropathy caused by the 5-fluorouracil. Clinical local regression of a pelvic recurrence was observed in a patient with rectal recurrent tumor who received continuous intra-arterial chemotherapy. Local recurrence of rectal cancer may be controlled effectively and safely by repeating long-term, continuous, intra-arterial 5-fluorouracil infusion.

Subanesthetic, Subcutaneous Ketamine Infusion Therapy in the Treatment of Chronic Nonmalignant Pain.

PubMed

Zekry, Olfat; Gibson, Stephen B; Aggarwal, Arun

2016-06-01

This study was designed to describe the efficacy and toxicity of subcutaneous ketamine infusions and sublingual ketamine lozenges for the treatment of chronic nonmalignant pain. Data were collected prospectively on 70 subjects managed in an academic, tertiary care hospital between 2007 and 2012 who received between 3 and 7 days of subanesthetic, subcutaneous ketamine infusion. Data were analyzed for efficacy, adverse effects, and reduction in use of opioid medication. We also analyzed whether subsequent treatment with sublingual ketamine lozenges resulted in longer-term efficacy of the beneficial effects of the initial ketamine infusion. There was a significant reduction in pain intensity measured by numerical rating scale (NRS) from mean of 6.38 before ketamine to 4.60 after ketamine (P < .005) that was sustained for between 3 months and 6 years. In subjects on opioids, there was a significant reduction in opioid use at the end of the ketamine infusion from a mean morphine equivalent dose (MMED) of 216 mg/day before ketamine to 89 mg/day after ketamine (P < .005). The overall reduction in opioid use after ketamine infusion was 59%. No subjects increased their use of opioids during their hospitalization for the ketamine infusion. A small proportion of subjects who responded to the infusion were continued on ketamine lozenges. This group was followed for between 3 months and 2 years. The use of ketamine lozenges after the infusion resulted in 31% of these subjects being able to cease their use of opioids compared with only 6% who did not receive ketamine lozenges. Eleven percent of subjects who received lozenges subsequently increased their opioid usage. Adverse effects were fairly common, but only mild, with 46% of patients experiencing light-headedness and dizziness, 25% tiredness and sedation, 12% headaches, 12% hallucinations, and 8% vivid dreams. Adverse effects were easily managed by reducing the rate of the ketamine infusion. The administration of subanesthetic, subcutaneous ketamine infusion was well tolerated, with mostly mild adverse effects and no serious adverse effects. The infusion provided significant pain relief in subjects who had failed a wide range of pharmacological and cognitive behavioral therapies. In addition, the results indicate that sublingual ketamine lozenges offer a promising therapeutic option for longer-term relief of chronic nonmalignant pain. The ketamine lozenges have been shown to have acceptable storage stability, and the sublingual bioavailability is sufficiently high and reproducible to support its use in this context.

Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial.

PubMed

Nalos, Marek; Leverve, Xavier; Huang, Stephen; Weisbrodt, Leonie; Parkin, Ray; Seppelt, Ian; Ting, Iris; Mclean, Anthony

2014-03-25

Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality. The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality. Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function. Clinicaltrials.gov NCT01981655. Registered 13 August 2013.

Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules.

PubMed

Sankhala, Kamalesh; Takimoto, Chris H; Mita, Alain C; Xiong, Henry; Rodón, Jordi; Mehrvarz Sarshekeh, Amir; Burns, K; Iizuka, Kenzo; Kopetz, Scott

2018-04-18

Purpose DFP-10917 is a novel deoxycytidine analog with a unique mechanism of action. Brief exposure to high concentrations of DFP-10917 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to DFP-10917 at low concentration causes DNA fragmentation, G2/M-phase arrest, and apoptosis. DFP-10917 demonstrated activity in tumor xenografts resistant to other deoxycytidine analogs. Experimental design Two phase I studies assessed the safety, pharmacokinetic, pharmacodynamic and preliminary efficacy of DFP-10917. Patients with refractory solid tumors received DFP-10917 continuous infusion 14-day on/7-day off and 7-day on/7-day off. Enrollment required age > 18 years, ECOG Performance Status 0-2 and adequate organ function. Results 29 patients were dosed in both studies. In 14-day infusion, dose-limiting toxicities (DLT) consisting of febrile neutropenia and thrombocytopenia occurred at 4.0 mg/m 2 /day. At 3.0 mg/m 2 /day, 3 patients experienced neutropenia in cycle 2. The dose of 2.0 mg/m 2 /day was well tolerated in 6 patients. In 7-day infusion, grade 4 neutropenia was DLT at 4.0 mg/m 2 /day. The maximum tolerated dose was 3 mg/m 2 /day. Other toxicities included nausea, vomiting, diarrhea, neutropenia, and alopecia. Eight patients had stable disease for >12 weeks. Paired comet assays performed for 7 patients showed an increase in DNA strand breaks at day 8. Pharmacokinetic data showed dose-proportionality for steady-state concentration and AUC of DFP-10917 and its primary metabolite. Conclusion Continuous infusion of DFP-10917 is feasible and well tolerated with myelosuppression as main DLT. The recommended doses are 2.0 mg/m 2 /day and 3.0 mg/m 2 /day on the 14-day and 7-day continuous infusion schedules, respectively. Preliminary activity was suggested. Pharmacodynamic data demonstrate biological activity at the tested doses.

Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children.

PubMed

Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

2017-01-01

Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. A total of 124 children aged 1-8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. A statistically significant difference ( P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference ( P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in Group B. We recommend use of an infusion of tramadol in a dose of 0.25 mg/kg/h in the first 24 h after surgery, in combination with a regular per rectal paracetamol in a daily dose of 90 mg/kg/day in four divided doses for children after major abdominal surgery. However, a close nursing supervision is essential to increase the safety profile.

Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

PubMed

Gabriel, Janice

2014-11-01

Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set.

Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access.

PubMed

Perez, Claudia Andira; Figueroa, Stephen A

2017-06-01

Hyperosmolar therapy with hypertonic saline (HTS) is a cornerstone in the management of intracranial hypertension and hyponatremia in the neurological intensive care unit. Theoretical safety concerns remain for infiltration, thrombophlebitis, tissue ischemia, and venous thrombosis associated with continuous 3% HTS administered via peripheral intravenous (pIV) catheters. It is common practice at many institutions to allow only central venous catheter infusion of 3% HTS. Hospital policy was changed to allow the administration of 3% HTS via 16- to 20-gauge pIVs to a maximum infusion rate of 50 mL/h in patients without central venous access. We prospectively monitored patients who received peripheral 3% HTS as part of a quality improvement project. We documented gauge, location, maximum infusion rate, and total hours of administration. Patients were assessed for infiltration, erythema, swelling, phlebitis, thrombosis, and line infection. There were 28 subjects across 34 peripheral lines monitored. Overall, subjects received 3% HTS for a duration between 1 and 124 hours with infusion rates of 30 to 50 mL/h. The rate of complications observed was 10.7% among all subjects. Documented complications included infiltration (n = 2), with an incidence of 6%, and thrombophlebitis (n = 1), with an incidence of 3%. There has been a long concern among healthcare providers, including nursing staff, in regard to pIV administration of prolonged 3% HTS infusion therapy. Our study indicates that peripheral administration of 3% HTS carries a low risk of minor, nonlimb, or life-threatening complications. Although central venous infusion may reduce the risk of these minor complications, it may increase the risk of more serious complications such as large vessel thrombosis, bloodstream infection, pneumothorax, and arterial injury. The concern regarding the risks of pIV administration of 3% HTS may be overstated and unfounded.

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

PubMed

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Morphological changes in the sciatic nerve, skeletal muscle, heart and brain of rabbits receiving continuous sciatic nerve block with 0.2% ropivacaine.

PubMed

Zhou, Yangning; He, Miao; Zou, Tianxiao; Yu, Bin

2015-01-01

To investigate the morphological changes in various tissues of rabbits receiving sciatic nerve block with 0.2% ropivacaine for 48 h. Twenty healthy were randomly assigned to normal saline group (N group) and ropivacaine group (R group). The right sciatic nerve was exposed, and a nerve-blocking trocar cannula embedded. Animals received an injection of 0.5% ropivacaine hydrochloride at a dose of 0.75 ml/kg. Rabbit was then connected to an infusion pump containing 50 ml of normal saline in N group, or to a infusion pump containing 0.2% ropivacaine hydrochloride in R group at 0.25 ml/kg•h-1. In both R group and N group, a small number of nerve cells exhibited pyknotic degeneration. More nerve cells with pyknotic degeneration were found in R group than in N group (P<0.001). At 48 h after surgery, there was a significant correlation between the abnormality of right hind limb and the degree of edema in sciatic nerve (P<0.01). Pyknotic degeneration of sciatic nerve increased after an infusion of 0.2% ropivacaine hydrochloride for 48 h, suggesting the neurotoxicity of ropivacaine. An infusion of 0.2% ropivacaine hydrochloride for 48 h may cause necrosis of skeletal muscle cells. The sciatic nerve edema would greatly affect the hindlimb motor while both pyknotic degeneration of sciatic nerve and skeletal muscle have little influence on the hindlimb movement. After an infusion of 0.2% ropivacaine hydrochloride for 48 h, the morphology of right atrium and brain tissues around the ventriculus tertius and medulla oblongata remained unchanged.

The effect of meditation on regulation of internal body states

PubMed Central

Khalsa, Sahib S.; Rudrauf, David; Davidson, Richard J.; Tranel, Daniel

2015-01-01

Meditation is commonly thought to induce physiologically quiescent states, as evidenced by decreased autonomic parameters during the meditation practice including reduced heart rate, respiratory rate, blood pressure, skin conductance, and increased alpha activity in the electroencephalogram. Preliminary empirical support for this idea was provided in a case report by Dimsdale and Mills (2002), where it was found that meditation seemed to regulate increased levels of cardiovascular arousal induced by bolus isoproterenol infusions. In that study, while meditating, a self-taught meditator exhibited unexpected decreases in heart rate while receiving moderate intravenous doses of the beta adrenergic agonist isoproterenol. This effect was no longer observed when the individual received isoproterenol infusions while not meditating. The current study was designed to explore this phenomenon empirically in a group of formally trained meditators. A total of 15 meditators and 15 non-meditators individually matched on age, sex, and body mass index were recruited. Participants received four series of infusions in a pseudorandomized order: isoproterenol while meditating (or during a relaxation condition for the non-meditators), isoproterenol while resting, saline while meditating (or during a relaxation condition for the non-meditators), and saline while resting. Heart rate was continuously measured throughout all infusions, and several measures of heart rate were derived from the instantaneous cardiac waveform. There was no evidence at the group or individual level suggesting that meditation reduced the cardiovascular response to isoproterenol, across all measures. These results suggest that meditation is not associated with increased regulation of elevated cardiac adrenergic tone. PMID:26217263

Pharmacokinetic Analysis of Ziconotide (SNX-111), an Intrathecal N-type Calcium Channel Blocking Analgesic, Delivered by Bolus and Infusion in the Dog

PubMed Central

Yaksh, Tony L.; de Kater, Annelies; Dean, Robin; Best, Brookie M.; Miljanich, George P.

2012-01-01

SUMMARY Background and purpose Ziconotide is a peptide that blocks N-type calcium channels and is anti-hyperalgesic after intrathecal delivery. We here characterize the spinal kinetics of intrathecal bolus and infused ziconotide in dog. Experimental approach Male beagle dogs (N = 5) were prepared with chronic intrathecal (IT) lumbar injection and cerebrospinal fluid (LCSF) sampling catheters connected to vest-mounted pumps. Each dog received: i) IT bolus ziconotide (10 µg + 1 µCi 3H-inulin), ii) IT infusion for 48 hr of ziconotide (1 µg/100 µL/hr), iii) IT infusion for 48 hr of ziconotide (5 µg/100 µL/hr), and iv) intravenous injection of ziconotide (0.1 mg/kg). After IT bolus, LCSF ziconotide and inulin showed an initial peak and biphasic (distribtution/elimination) clearance (ziconotide T1/2 α / ß = 0.14 and 1.77 hr, and inulin T1/2 α / ß = 0.16 and 3.88 hr, respectively). The LCSF: plasma ziconotide concentration ratio was 20,000: 1 at 30 min, and 30: 1 at 8 hr. IT infusion of 1 and then 5 µg/hr resulted in LCSF concentrations that peaked by 8 hr and remained stable at 343 and 1380 ng/mL, respectively, to the end of the 48-hr infusions. Terminal elimination T1/2 after termination of continuous infusion was 2.47 hr. Ziconotide LCSF: cisternal CSF: plasma concentration ratios after infusion of 1 µg/hr and 5 µg/hr were 1: 0.017: 0.001 and 1: 0.015: 0.003, respectively. IT infusion of ziconotide at 1 µg/hr inhibited thermal skin twitch by 24 hr, and produced modest trembling, ataxia, and decreased arousal. Effects continued through the 48-hr infusion period, increased in magnitude during the subsequent 5 µg/hr infusion periods, and disappeared after drug clearance. Conclusions and Implications After intrathecal bolus or infusion, ziconotide displays linear kinetics that are consistent with a hydrophilic molecule of approximately 2500 Da that is cleared slightly more rapidly than inulin from the LCSF. Behavioral effects were dose dependent and reversible. PMID:22748108

Intramammary infusion of Escherichia coli lipopolysaccharide negatively affects feed intake, chewing, and clinical variables, but some effects are stronger in cows experiencing subacute rumen acidosis.

PubMed

Aditya, S; Humer, E; Pourazad, P; Khiaosa-Ard, R; Huber, J; Zebeli, Q

2017-02-01

Feeding high-grain diets increases the risk of subacute rumen acidosis (SARA) and adversely affects rumen health. This condition might impair the responsiveness of cows when they are exposed to external infectious stimuli such as lipopolysaccharide (LPS). The main objective of this study was to evaluate various responses to intramammary LPS infusion in healthy dairy cows and those experimentally subjected to SARA. Eighteen early-lactating Simmental cows were subjected to SARA (n = 12) or control (CON; n = 6) feeding conditions. Cows of the control group received a diet containing 40% concentrates (DM basis) throughout the experiment. The intermittent SARA feeding regimen consisted in feeding the cows a ration with 60% concentrate (DM basis) for 32 d, consisting of a first SARA induction for 8 d, switched to the CON diet for 7 d, and re-induction during the last 17 d. On d 30 of the experiment, 6 SARA (SARA-LPS) and 6 CON (CON-LPS) cows were intramammary challenged once with a single dose of 50 μg of LPS from Escherichia coli (O26:B6), whereas the other 6 SARA cows (SARA-PLA) received 10 mL of sterile saline solution as placebo. To confirm the induction of SARA, the reticular pH was continuously monitored via wireless pH probes. The DMI remained unchanged between SARA and CON cows during the feeding experiment, but was reduced in both treatment groups receiving the LPS infusion compared with SARA-PLA, whereby a significant decline was observed for cows of the SARA-LPS treatment (-38%) compared with CON-LPS (-19%). The LPS infusion did not affect the reticuloruminal pH dynamics, but significantly enhanced ruminal temperature and negatively affected chewing behavior. The ruminal temperature increased after the LPS infusion and peaked about 1 h earlier in SARA-LPS cows compared with the cows of the CON-LPS treatment. Moreover, a significant decline in milk yield was found in SARA-LPS compared with CON-LPS following the LPS infusion. Cows receiving LPS had elevated somatic cell counts, protein, and fat contents in milk as well as decreased lactose contents and pH following the LPS infusion, whereby the changes in milk constituents were more pronounced in SARA-LPS than CON-LPS cows. Rectal temperature and pulse rate were highest 6 h after LPS infusion, but rumen contractions were not affected by the LPS infusion. The data suggest that a single intramammary LPS infusion induced fever and negatively affected feed intake, chewing activity, rectal temperature, and milk yield and composition, whereby these effects were more pronounced in SARA cows. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

High-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients.

PubMed

Moriyama, Brad; Henning, Stacey A; Childs, Richard; Holland, Steven M; Anderson, Victoria L; Morris, John C; Wilson, Wyndham H; Drusano, George L; Walsh, Thomas J

2010-05-01

To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study

PubMed Central

Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-01-01

Introduction Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. Methods and analysis The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4–7 days, followed by the other for a further 4–7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. Ethics and dissemination This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. Trial registration number ACTRN12617000251325; Pre-results. PMID:28760798

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study.

PubMed

Hobbs, Jodie G; Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-07-31

Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days, followed by the other for a further 4-7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. ACTRN12617000251325; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Intraosseous infusion. An important technique also for paediatric anaesthesia].

PubMed

Weiss, M; Henze, G; Eich, C; Neuhaus, D

2009-09-01

Timely establishment of venous access in infants and toddlers can prove a particularly challenging task. Since the 1940s the technique of intraosseous infusion has established itself as a valuable alternative means for rapid, efficient and safe delivery of drugs and fluids to critically ill children. Whereas international guidelines for paediatric emergency medical care have assigned intraosseous infusion a high priority, most anaesthetists utilize this well-proven technique with great reluctance. This article describes the technique of intraosseous infusion, introduces two different cannulation systems, and discusses its potential indications in paediatric anaesthesia, based on current emergency medical care guidelines as well as some of our own case studies. In particular, children with acutely life-threatening conditions, such as circulatory arrest, laryngospasm, acute airway haemorrhage, hypovolaemic shock or hypothermia secondary to extensive burns, should receive an intraosseous cannula if intravenous access cannot be rapidly established. Future discussion may reveal whether a transiently inserted intraosseous infusion would also be indicated if the child with difficult or impossible venous access presents without acute life-threatening conditions for anaesthesia. Successful application of the intraosseous infusion technique requires immediate access to the necessary equipment, intensive education, continuous training and clear guidelines for its application in an anaesthesia department.

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

PubMed Central

Lamont, Leigh; Burton, Shelley; Caines, Deanne; Masaoud, Elmabrok; Troncy, Eric

2012-01-01

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin. PMID:23024457

High-Dose Continuous Infusion Beta-lactam Antibiotics for the Treatment of Resistant Pseudomonas aeruginosa Infections in Immunocompromised Patients

PubMed Central

Moriyama, Brad; Henning, Stacey A.; Childs, Richard; Holland, Steven M.; Anderson, Victoria L.; Morris, John C.; Wilson, Wyndham H.; Drusano, George L.; Walsh, Thomas J.

2011-01-01

OBJECTIVE To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. CASE SUMMARY Continuous infusion ceftazidime or aztreonam was administered to achieve target drug levels at or above the MIC when possible in three patients with P. aeruginosa infections. The maximal calculated target drug level was 100 mg/L. In the first patient with primary immunodeficiency, neutropenia, and aggressive cutaneous T cell lymphoma/leukemia, continuous infusion ceftazidime (6.5 to 9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient with severe aplastic anemia, continuous infusion ceftazidime (7 to 16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, the bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. DISCUSSION Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy when no other options are available is the administration of existing beta-lactam antibiotics by continuous infusion in order to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in three chronically immunocompromised patients. CONCLUSION Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients. PMID:20371747

Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role.

PubMed

Roberts, Jason A; Paratz, Jennifer; Paratz, Elizabeth; Krueger, Wolfgang A; Lipman, Jeffrey

2007-07-01

Continuous infusion of beta-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of beta-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is >or=4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of beta-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of beta-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (>or=4 days) may be the subgroup that will achieve better outcomes with continuous infusion.

Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

PubMed

Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

2017-01-01

This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

Comparison of Intravenous Infusion of Tramadol Alone with Combination of Tramadol and Paracetamol for Postoperative Pain after Major Abdominal Surgery in Children

PubMed Central

Ali, Shayesta; Sofi, Khalid; Dar, Abdul Qayoom

2017-01-01

Background: Pain is a common complaint after surgery and seems to be difficult to manage in children because of fear of complications of pain treatment or misconception that infants and small children do not feel pain at all or feel less pain. A survey reported that 40% of pediatric surgical patients experienced moderate or severe postoperative pain and that more than 75% had insufficient analgesia. Our study was carried to provide continuous infusion of intravenous (i.v.) tramadol alone using a dedicated infusion device Graseby 2100 syringe pump and compared it to a combination of i.v. tramadol infusion and per rectal paracetamol. Subjects and Methods: A total of 124 children aged 1–8 years selected for the study were randomized into two groups using a table of random numbers. Power calculation had suggested a sample size of 62 in each group with a power of 80% and significance level of 5%. Group A comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively. Group B comprising 62 children, received i.v. infusion of tramadol in a dose of 0.25 mg/kg/h for 24 h postoperatively in addition to per rectal suppository of paracetamol in a dose of 90 mg/kg in 24 h (30 mg/kg as first dose followed by 20 mg/kg every 6 hourly for the next 18 h). Postoperatively, patients were observed for 24 h. Results: A statistically significant difference (P ≤ 0.001) in Face, Legs, Activity, Cry, Consolability pain scores was seen between two groups at 4, 6, and 8 h. Pain scores being less in Group B patients who had received infusion of tramadol and per rectal suppositories of paracetamol compared to Group A patients who received only infusion of tramadol. A statistically significant difference (P < 0.05) was found in mean analgesic consumption during the first 24 h between the groups. Consumption was more in Group A as compared to Group B. In Group A, 13 patients (21%) required rescue analgesia as compared to only 4 patients (6.5%) in Group B. Conclusion: We recommend use of an infusion of tramadol in a dose of 0.25 mg/kg/h in the first 24 h after surgery, in combination with a regular per rectal paracetamol in a daily dose of 90 mg/kg/day in four divided doses for children after major abdominal surgery. However, a close nursing supervision is essential to increase the safety profile. PMID:28663644

Continuous-Infusion Antipseudomonal Beta-Lactam Therapy in Patients With Cystic Fibrosis

PubMed Central

Prescott, William A.; Gentile, Allison E.; Nagel, Jerod L.; Pettit, Rebecca S.

2011-01-01

Objective: We sought to evaluate the pharmacokinetics, efficacy, safety, stability, pharmacoeconomics, and quality-of-life effects of continuous-infusion antipseudomonal beta-lactam therapy in patients with cystic fibrosis (CF). Data Sources: Literature retrieval was accessed through Medline (from 1950 to December 2010) using the following terms: cystic fibrosis; beta-lactams or piperacillin or ticarcillin or cefepime or ceftazidime or doripenem or meropenem or imipenem/cilastin or aztreonam; continuous infusion or constant infusion; drug stability; economics, pharmaceutical; and quality of life. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: We evaluated all articles in English identified from the data sources. Data Synthesis: Patients with CF often harbor colonies of multidrug-resistant organisms, increasing the risk of suboptimal dosing and failure to meet the time above the minimum inhibitory concentration (T > MIC) pharmacodynamic targets. The pharmacokinetics of continuous-infusion antipseudomonal beta-lactam therapy in CF maintains serum concentrations above the MIC of susceptible strains and is more likely than intermittent infusion to achieve optimal T > MIC targets for some intermediate and resistant strains of Pseudomonas aeruginosa. Three noncomparative and four comparative studies have assessed the efficacy and safety of continuous-infusion antipseudomonal beta-lactam therapy during CF pulmonary exacerbations. Ceftazidime, the most extensively studied antibiotic for continuous infusion in CF, has been shown to improve forced expiratory volume in 1 second (FEV1), to improve forced vital capacity (FVC), and to extend the time between pulmonary exacerbations. Continuous-infusion cefepime has been studied in a small number of patients, and a trend toward improved pulmonary function has been observed. Continuous-infusion antipseudomonal beta-lactam therapy appears to be well tolerated, although most of the data pertain to ceftazidime. Because continuous infusion may necessitate that patients wear a portable pump in close proximity to the body, the stability of the antibiotic at body temperature must be considered. Several beta-lactams have good stability at body temperature (piperacillin/tazobactam, ticarcillin/clavulanate, and aztreonam) or acceptable if the medication cartridge is changed twice daily (cefepime and doripenem), whereas other beta-lactams have acceptable 24-hour stability only at lower temperatures (cefepime, ceftazidime, doripenem, and meropenem). Although no pharmacoeconomic studies have evaluated the cost–benefit of continuous infusion versus intermittent infusion in patients with CF, the potential medication cost reduction appears to be considerable. There is little information regarding the impact of continuous infusion on quality of life in patients with CF. Conclusion: Efficacy and safety studies suggest that ceftazidime, administered as a continuous infusion for the treatment of CF pulmonary exacerbations, is safe and effective; has the potential to reduce the costs of treatment; and is preferred to intermittent infusion among patients treated at home. Continuous-infusion ceftazidime may therefore be an alternative to traditional dosing on a case-by-case basis, such as for patients with multidrug-resistant isolates of P. aeruginosa. Treatment with continuous-infusion ceftazidime at home may be considered in such a case, assuming resources and support equivalent to the hospital setting can be ensured. Additional studies assessing the safety and efficacy of other antipseudomonal beta-lactams, when administered as a continuous infusion, during CF pulmonary exacerbations are needed. PMID:22346306

The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces pain: a randomized, double-blinded, placebo-controlled, prospective study.

PubMed

Goyal, Nitin; McKenzie, James; Sharkey, Peter F; Parvizi, Javad; Hozack, William J; Austin, Matthew S

2013-01-01

Postoperative pain after total knee arthroplasty remains one of the most important challenges facing patients undergoing this surgery. Providing a balance of adequate analgesia while limiting the functional impact of regional anesthesia and minimizing opioid side effects is critical to minimize adverse events and improve patient satisfaction. We asked whether bupivacaine delivered through an elastomeric device decreases the (1) patients' perception of pain after TKA; (2) narcotic consumption; and (3) narcotic-related side effects as compared with a placebo. In this prospective, double-blind, placebo-controlled study, all patients received standardized regional anesthesia, a preemptive and multimodal analgesic protocol, and a continuous intraarticular infusion at 5 mL/hour through an elastomeric infusion pump. The patients were randomized to receive either an infusion pump filled with (1) 300 mL of 0.5% bupivacaine, the experimental group (n = 75); or (2) 300 mL of 0.9% normal saline solution, the control group (n = 75). Data concerning postoperative pain levels through a visual analog scale, postoperative opioid consumption, opioid-related side effects, and complications were collected and analyzed. Patients in the experimental group receiving the bupivacaine reported a reduction in pain levels in highest, lowest, and current visual analog scale scores compared with the placebo group on the first postoperative day and highest visual analog scale score on postoperative Day 2 along with a 33% reduction in opioid consumption on postoperative Day 2 and a 54% reduction on postoperative Day 3. In patients undergoing TKA, continuous intraarticular analgesia provided an effective adjunct for pain relief in the immediate postoperative period without the disadvantages encountered with other analgesic methods.

Does growth hormone releasing factor desensitize the somatotroph? Interpretation of responses of growth hormone during and after 10-hour infusion of GRF 1-29 amide in man.

PubMed

Davis, J R; Sheppard, M C; Shakespear, R A; Lynch, S S; Clayton, R N

1986-02-01

It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10-h infusion of the equipotent 1-29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1-29). Four normal adult males received an intravenous infusion of 1-29 GRF (1 microgram/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 micrograms intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0.5 mU/l) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/l) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 micrograms GRF bolus increased mean (+/- SEM) GH from 0.82 +/- 0.21 mU/l to a peak of 59.0 +/- 44.8 mU/l (P less than 0.002). Following 10-GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6.4 and 7.2 rising to peak values of 11.2 and 23.0 mU/l respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak. The loss of GRF responsiveness after GRF infusion may be due to 'desensitization'.(ABSTRACT TRUNCATED AT 250 WORDS)

[Continuous subcutaneous infusion of opioids in cancer patients].

PubMed

Galamba, J M; Olsen, A K; Crawford, M E; Sjøgren, P

1995-07-17

This review article describes pharmacokinetics, pharmaco-dynamics, side effects and the practical use of continuous subcutaneous infusion of opioids in cancer patients with pain. Clinical studies have shown that the analgesic effects of continuous subcutaneous infusion of morphine are comparable to continuous intravenous morphine, and that the treatment modality is associated with a low frequency of side-effects and complications. Continuous subcutaneous infusions of morphine are therefore recommended as the treatment of choice for cancer patients with pain, when oral analgesic treatment is no longer possible.

Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus.

PubMed

Kwai, Natalie; Arnold, Ria; Poynten, Ann M; Lin, Cindy S-Y; Kiernan, Matthew C; Krishnan, Arun V

2015-02-01

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (P < 0.05). In contrast, axonal function in CSII-treated patients was within normal limits when compared with age-matched controls. The differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up. Axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performedmore » 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.« less

Chronic postthoracotomy pain and perioperative ketamine infusion.

PubMed

Hu, Jie; Liao, Qin; Zhang, Fan; Tong, Jianbin; Ouyang, Wen

2014-06-01

The objectives of this study were to investigate whether continuous intravenous ketamine during the first 72 hours after thoracotomy could reduce the incidence and intensity of chronic postthoracotomy pain (CPTP) and to define the incidence and risk factors of CPTP. Seventy-eight patients receiving thoracotomy for lung tumor (benign or malignant) were randomly divided into two groups: ketamine group (n = 31) and control groups (n = 47). Patients in the ketamine group received intravenous ketamine 1 mg/kg before incision, followed by 2 μg/kg/minute infusion for 72 hours plus sufentanil patient-controlled intravenous analgesia after thoracotomy. Patients in the control group received intravenous a 0.9% normal saline and infusion plus sufentanil patient-controlled intravenous analgesia. The solutions patients received were blinded. The numerical rating scale (NRS) pain scores and the incidence and risk factors of CPTP were recorded during the first 6 months after surgery. Compared with control group, the incidence of chronic pain in the ketamine group did not decrease at 2 months (χ(2) = 1.599, P = .206) and 6 months (χ(2) = 0.368, P = .544) after surgery. Postoperative pain scores in the ketamine group were not significantly different from those of the control group patients at 2 months (U = 677.5, P = .593) and 6 months (U = 690.5, P = .680). The incidence of CPTP was 78.2% (61/78) at 2 months and 53.8% (42/78) at 6 months after surgery. Retractor used time (OR = 5.811, P = .002), inadequate acute pain control (NRS ≥ 5) (OR = 5.425, P = .048), and chemotherapy (OR = 3.784, P = .056) were independent risk factors for chronic postthoracotomy pain. The authors conclude that continuous intravenous ketamine (2 μg/kg/min) during the first 72 hours after thoracotomy was not beneficial to prevent chronic postthoracotomy pain. The independent risk factors for chronic postthoracotomy pain were retractor used time, inadequate acute pain control, and chemotherapy.

The predictive ability of six pharmacokinetic models of rocuronium developed using a single bolus: evaluation with bolus and continuous infusion regimen.

PubMed

Sasakawa, Tomoki; Masui, Kenichi; Kazama, Tomiei; Iwasaki, Hiroshi

2016-08-01

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than -10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (-2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = -25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

Multiple Intravenous Infusions Phase 2b: Laboratory Study

PubMed Central

Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

2014-01-01

Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty

PubMed Central

2011-01-01

Background and purpose Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia. Patients and methods In this double-blind study, 36 rheumatic patients aged 51–78 years with physical status ASA 2–3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded. Results As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7–10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects. Interpretation Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty. PMID:22026413

The Effect of a Subcutaneous Infusion of GLP-1, OXM, and PYY on Energy Intake and Expenditure in Obese Volunteers

PubMed Central

Tan, Tricia; Behary, Preeshila; Tharakan, George; Minnion, James; Al-Najim, Werd; Albrechtsen, Nicolai J. Wewer; Holst, Jens J.

2017-01-01

Background: Roux-en-Y gastric bypass (RYGB) surgery is currently the most effective treatment of obesity, although limited by availability and operative risk. The gut hormones Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Oxyntomodulin (OXM) are elevated postprandially after RYGB, which has been postulated to contribute to its metabolic benefits. Objective: We hypothesized that infusion of the three gut hormones to achieve levels similar to those encountered postprandially in RYGB patients might be effective in suppressing appetite. The aim of this study was to investigate the effect of a continuous infusion of GLP-1, OXM, and PYY (GOP) on energy intake and expenditure in obese volunteers. Methods: Obese volunteers were randomized to receive an infusion of GOP or placebo in a single-blinded, randomized, placebo-controlled crossover study for 10.5 hours a day. This was delivered subcutaneously using a pump device, allowing volunteers to remain ambulatory. Ad libitum food intake studies were performed during the infusion, and energy expenditure was measured using a ventilated hood calorimeter. Results: Postprandial levels of GLP-1, OXM, and PYY seen post RYGB were successfully matched using 4 pmol/kg/min, 4 pmol/kg/min, and 0.4 pmol/kg/min, respectively. This dose led to a mean reduction of 32% in food intake. No significant effects on resting energy expenditure were observed. Conclusion: This is, to our knowledge, the first time that an acute continuous subcutaneous infusion of GOP, replicating the postprandial levels observed after RYGB, is shown to be safe and effective in reducing food intake. This data suggests that triple hormone therapy might be a useful tool against obesity. PMID:28379519

Plasma concentrations of fentanyl with subcutaneous infusion in palliative care patients.

PubMed

Miller, R S; Peterson, G M; Abbott, F; Maddocks, I; Parker, D; McLean, S

1995-12-01

1. Plasma concentrations of fentanyl were measured by g.c. in 20 patients (median age: 75 years and range: 54-86 years; eight females) in palliative care receiving the drug by continuous s.c. infusion (median rate: 1200 micrograms day-1 and range: 100-5000 micrograms day-1). 2. The infusion rate was significantly related to the duration of therapy (Spearman rho = 0.56, P < 0.05). The total steady-state plasma concentrations of fentanyl ranged between 0.1 and 9 ng ml-1, with a median of 1 ng ml-1. The unbound fraction of fentanyl in the plasma ranged from 17.8 to 44.4%, with a median value of 33.6%. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated (Spearman rho = 0.92, P < 0.05 in each case). Even with standardization for dosage, there was an eightfold variation in total plasma concentrations and 3.5-fold variation in unbound plasma concentrations of fentanyl. 3. There is considerable inter-patient variability in the pharmacokinetics of fentanyl with s.c. infusion in the palliative care setting, which necessitates careful titration of dosage according to individual clinical response.

Is continuous infusion of imipenem always the best choice?

PubMed

Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Propofol-Related Infusion Syndrome in Critically Ill Pediatric Patients: Coincidence, Association, or Causation?

PubMed Central

Timpe, Erin M.; Eichner, Samantha F.; Phelps, Stephanie J.

2006-01-01

Over the past two decades numerous reports have described the development of a propofol-related infusion syndrome (PRIS) in critically ill adult and pediatric patients who received continuous infusion propofol for anesthesia or sedation. The syndrome is generally characterized by progressive metabolic acidosis, hemodynamic instability and bradyarrhythmias that are refractory to aggressive pharmacological treatments. PRIS may occur with or without the presence of hepatomegaly, rhabdomyolysis or lipemia. To date, the medical literature contains accounts of 20 deaths in critically ill pediatric patients who developed features consistent with PRIS. These reports have generated considerable discussion and debate regarding the relationship, if any, between propofol and a constellation of clinical symptoms and features that have been attributed to its use in critically ill pediatric patients. This paper reviews the literature concerning PRIS, its clinical presentation, proposed mechanisms for the syndrome, and potential management should the syndrome occur. PMID:23118644

[Clinical study of recurrent stomach cancer].

PubMed

Taguchi, T

1983-11-01

There are various patterns of recurrence of gastric cancer after radical resection, such as hepatic metastasis, carcinomatous peritonitis, residual stomach recurrence, local lymph node metastasis and establishment of distant metastasis. In cases of residual stomach recurrence, resection is sometimes feasible. Kruckenberg's tumor resulting from metastasis to the ovary can frequently be removed. With such resectable metastasis, surgical procedure is actively employed, with subsequent chemotherapy. Chemotherapy in such a case consists of combined chemotherapy by arterial infusion for induction of remission and administration of oral preparation and/or suppositories for maintenance. In the treatment of recurrent gastric cancer by arterial infusion, we made it a rule to administer drugs through a catheter inserted subselectively into the aorta. In the treatment by arterial infusion, the daily administration of 5-FU serves as the basic regimen. Dissolve 250 mg 5-FU in about 20 cc physiologic saline or 5% dextrose solution, and infuse the solution over 2 hrs with the use of a continuous arterial infusion pump. Administer of 5-FU daily, and fortify this treatment by one-shot injection of MMC 10mg/body each time, MMC is usually given 3-4 times, with intervals between its administrations adjusted according to WBC and platelet counts. ADM is given at dosage of 40 mg/body each time. We found it advisable to continue the administrations of 5-FU until its total dose reached about 20 g, while giving sufficient doses of ADM or MMC for induction of remission. The results obtained from 108 cases of the recurrent gastric cancer were shown as follows. The median survival period was 5 months. The twenty-one cases out of 108 cases in recurrent gastric cancer survived more than one year, because they received the intensive chemotherapy such as arterial infusion chemotherapy and oral or rectal administration of FT. The most patients with liver metastasis were treated with selective arterial infusion chemotherapy consisting of 5-FU plus MMC or ACNU. And the efficacy of arterial infusion chemotherapy was remarkable. Our efforts must be made to continue any treatment as long as possible and change drugs as necessary. Also we must keep general condition of the patients as good as possible using support therapy such as IVH, prevention of infection, immunotherapy, drainage so on.

Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial.

PubMed

Roberts, G; Newsom, D; Gomez, K; Raffles, A; Saglani, S; Begent, J; Lachman, P; Sloper, K; Buchdahl, R; Habel, A

2003-04-01

The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study. Children aged 1-16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids. Subjects were randomised to receive either a short intravenous bolus of salbutamol (15 micro g/kg over 20 minutes) followed by a saline infusion or an aminophylline infusion (5 mg/kg over 20 minutes) followed by 0.9 mg/kg/h. Forty four subjects were enrolled, with 18 randomly allocated to receive salbutamol and 26 to receive aminophylline. The groups were well matched at baseline. An intention to treat analysis showed that there was no statistically significant difference in the asthma severity score (ASS) at 2 hours between the two groups (median (IQR) 6 (6, 8) and 6.5 (5, 8) for salbutamol and aminophylline respectively, p=0.93). A similar improvement in ASS to 2 hours was seen in the two groups (mean difference -0.08, 95% CI -0.97 to 0.80), there was a trend (p=0.07) towards a longer duration of oxygen therapy in the salbutamol group (17.8 hours (95% CI 8.5 to 37.5) v 7.0 hours (95% CI 3.4 to 14.2)), and a significantly (p=0.02) longer length of hospital stay in the salbutamol group (85.4 (95% CI 66.1 to 110.2) hours v 57.3 hours (95% CI 45.6 to 72.0)). There was no significant difference in adverse events between the two groups. This study suggests that, in severe childhood asthma, there is no significant difference in the effectiveness of a bolus of salbutamol and an aminophylline infusion in the first 2 hours of treatment. Overall, the aminophylline infusion was superior as it significantly reduced the length of stay in hospital.

Randomized trial of subfascial infusion of ropivacaine for early recovery in laparoscopic colorectal cancer surgery

PubMed Central

Lee, Sang Hyun; Kim, Go Eun; Kim, Hee Cheol; Jun, Joo Hyun; Lee, Jin Young; Shin, Byung-Seop; Yoo, Heejin; Jung, Sin-Ho; Kim, Joungyoun; Lee, Seung Hyeon; Yo, Deok Kyu; Na, Yu Ri

2016-01-01

Background There is a need for investigating the analgesic method as part of early recovery after surgery tailored for laparoscopic colorectal cancer (LCRC) surgery. In this randomized trial, we aimed to investigate the analgesic efficacy of an inverse ‘v’ shaped bilateral, subfascial ropivacaine continuous infusion in LCRC surgery. Methods Forty two patients undergoing elective LCRC surgery were randomly allocated to one of two groups to receive either 0.5% ropivacaine continuous infusion at the subfascial plane (n = 20, R group) or fentanyl intravenous patient controlled analgesia (IV PCA) (n = 22, F group) for postoperative 72 hours. The primary endpoint was the visual analogue scores (VAS) when coughing at postoperative 24 hours. Secondary end points were the VAS at 1, 6, 48, and 72 hours, time to first flatus, time to first rescue meperidine requirement, rescue meperidine consumption, length of hospital stay, postoperative nausea and vomiting, sedation, hypotension, dizziness, headache, and wound complications. Results The VAS at rest and when coughing were similar between the groups throughout the study. The time to first gas passage and time to first rescue meperidine at ward were significantly shorter in the R group compared to the F group (P = 0.010). Rescue meperidine was administered less in the R group; however, without statistical significance. Other study parameters were not different between the groups. Conclusions Ropivacaine continuous infusion with an inverse ‘v ’ shaped bilateral, subfascial catheter placement showed significantly enhanced bowel recovery and analgesic efficacy was not different from IV PCA in LCRC surgery. PMID:27924202

Knee strength retention and analgesia with continuous perineural fentanyl infusion after total knee replacement: randomized controlled trial.

PubMed

Mangar, Devanand; Karlnoski, Rachel A; Sprenker, Collin J; Downes, Katheryne L; Taffe, Narrene; Wainwright, Robert; Gustke, Kenneth; Bernasek, Thomas L; Camporesi, Enrico

2014-04-01

Despite providing adequate pain relief, a femoral nerve block can induce postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has been shown to have peripheral effects but has not been used as a perineural infusate alone after TKA. Sixty patients scheduled for TKA were randomized to one of three blinded groups: a continuous 24 h infusion of either fentanyl 3 μg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion), active range of motion of the operative knee, distance ambulated, incidence of knee buckling, supplemental morphine usage, postoperative side effects, and serum fentanyl levels. Quadriceps MVIC values were significantly greater in the fentanyl group compared to the group that received ropivacaine (median values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee buckling upon ambulation was higher in the ropivacaine group compared to the fentanyl group, although not statistically significant (40% vs. 15 %, respectively; p = 0.077). VAS scores while ambulating were not significantly different between the fentanyl group and the ropivacaine group (p = 0.270). Postoperative morphine consumption, nausea and vomiting, and resting VAS scores were similar among the three groups. A continuous perineural infusion of fentanyl produced greater strength retention than ropivacaine post-TKA.

Tocilizumab Injection

MedlinePlus

... of age or older after receiving certain immunotherapy infusions. Tocilizumab injection is in a class of medications ... you miss an appointment to receive a tocilizumab infusion, call your doctor.If you forget to inject ...

An unusual case of central diabetes insipidus & hyperglycemic hyperosmolar state following cardiorespiratory arrest

PubMed Central

2013-01-01

Background We are describing an unusual case of severe hyperglycemia and hypernatremia, resistant to treatment. Case presentation A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. Her initial serum glucose and sodium were normal, but after receiving dexamethasone and mannitol, the serum glucose progressively increased to 54.7 mmol/L and sodium to 175 mmol/L, despite receiving very high dose of intravenous (IV) insulin infusion. She was evaluated for diabetes insipidus because of continued polyuria even after correction of hyperglycemia. Her serum osmolality was 337 mmol/kg, and urine osmolality was 141 mmol/kg which rose to 382 mmol/kg, after receiving 4 mcg of IV Desmopressin. Conclusion Our patient developed central diabetes insipidus post cardiac arrest and severe dehydration because of diabetes insipidus. Stress of critical illness, dehydration, dexamethasone and IV dextrose infusion were likely responsible for this degree of severe and resistant to treatment hyperglycemia. PMID:23947429

Rice solution and World Health Organization solution by gastric infusion for high stool output diarrhea.

PubMed

Mota-Hernández, F; Bross-Soriano, D; Pérez-Ricardez, M L; Velásquez-Jones, L

1991-08-01

We sought to determine the efficacy of three different types of treatment in children with acute diarrhea who, during the oral rehydration period, had high stool output (greater than 10 mL/kg per hour). Sixty-six children, aged 1 to 18 months, with an average stool output of 22.6 mL/kg per hour were randomly distributed into three groups: group 1 received a rice flour solution, group 2 received the World Health Organization rehydration solution by gastric infusion, and group 3 continued to receive this solution orally. In all three groups, a decrease in stool output was observed, with the higher decrease observed in group 1 patients. Such a decrease facilitated rehydration of all 22 patients in group 1 (100%) in 3.3 +/- 1.5 hours, 16 (73%) in group 2 in 4.3 +/- 2.1 hours, and 15 (69%) in group 3 in 4.9 +/- 2.0 hours. No complications were observed. These data indicate that the rice flour solution is effective in children with high stool output diarrhea.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Effect of coefficient of viscosity and ambient temperature on the flow rate of drug solutions in infusion pumps.

PubMed

Kawabata, Yoshinori

2012-01-01

FOLFOX6 and FOLFIRI regimens are often selected as the first- or second-line treatment for advanced or recurrent colorectal cancer. Patients are now able to undergo at-home treatment by using a portable disposable infusion pump (SUREFUSER(®)A) for continuous intravenous infusion of 5-fluorouracil (5-FU). The duration of continuous 5-FU infusion is normally set at an average of 46 h, but large variations in the duration of infusion are observed. The relationship between the total volume of the drug solution in SUREFUSER(®)A and the duration of infusion was analyzed by regression analysis. In addition, multiple regression analysis of the total volume of the drug solution, dummy variables for temperature, and duration of infusion was carried out. The duration of infusion was affected by the coefficient of viscosity of the drug solution and the ambient temperature. The composition of the drug solutions and the ambient temperature must be considered to ensure correct duration of continuous infusion.

Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses.

PubMed

Ross, Julie; Dallap, Barbara L; Dolente, Brett A; Sweeney, Raymond W

2007-09-01

To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. 6 adult horses. Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program. Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 +/- 0.5 hours. Peak plasma EACA concentration was 462.9 +/- 70.1 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min). Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.

Comparison of rocuronium and succinylcholine on postintubation sedative and analgesic dosing in the emergency department.

PubMed

Korinek, Justin D; Thomas, Rachel M; Goddard, Luke A; St John, Alexander E; Sakles, John C; Patanwala, Asad E

2014-06-01

Rocuronium and succinylcholine are both commonly used neuromuscular blockers for rapid sequence intubation in the emergency department (ED). The objective of this study was to determine if patients who receive rocuronium are more likely to receive lower doses of postintubation sedatives and analgesics compared with patients who receive succinylcholine. This was a retrospective cohort study carried out in a tertiary, academic ED. Consecutive adult patients, who were intubated using etomidate for induction of sedation, were included. Patients were categorized on the basis of whether they received (a) rocuronium or (b) succinylcholine for paralysis. The dosing of postintubation sedative and analgesic infusions were compared 30 min after initiation between the two groups. A total of 254 patients were included in the final analysis (rocuronium=127 and succinylcholine=127). In the overall cohort, 90.2% (n=229) of patients were administered a sedative postintubation in the ED. Most of these patients were initiated on propofol infusions. The mean propofol infusion rate at 30 min was 30±23 mcg/kg/min in the rocuronium group and 42±24 mcg/kg/min in the succinylcholine group (P=0.002). A total of 42.5% of patients (n=108) received an analgesic infusion (all patients received fentanyl). The mean fentanyl infusion rate at 30 min was 0.65±0.55 and 0.86±0.49 mcg/kg/h in the rocuronium and succinylcholine groups, respectively (P=0.041). Patients who receive rocuronium are more likely to receive lower doses of sedative and analgesic infusions after intubation. This may place them at risk of being awake under paralysis.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

NASA Technical Reports Server (NTRS)

Dobnig, H.; Turner, R. T.

1997-01-01

PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

Intravenous colforsin daropate, a water-soluble forskolin derivative, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

PubMed

Wajima, Zen'ichiro; Yoshikawa, Tatsusuke; Ogura, Akira; Imanaga, Kazuyuki; Shiga, Toshiya; Inoue, Tetsuo; Ogawa, Ryo

2002-04-01

Forskolin, a direct activator of adenylate cyclase, can relax airway smooth muscle, similar to other agents that increase intracellular cyclic adenine monophosphate. However, the potential usefulness of forskolin in treating bronchospasm is limited by its poor water solubility. Colforsin daropate is a novel and potent water-soluble forskolin derivative. No clinical data have been published on the bronchorelaxant effects of this drug. The aim of this study was to investigate whether intravenous colforsin daropate prevents thiamylal-fentanyl-induced bronchoconstriction. Double-blind, prospective, placebo-controlled randomized study. University teaching hospital. Thirty-six patients were allocated randomly to two groups: the control group (n = 18) and colforsin daropate group (n = 18). Intravenous administration of colforsin daropate or placebo (normal saline). Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg. A 15 mg x kg(-1) x hr(-1) continuous infusion of thiamylal followed anesthetic induction. Controlled ventilation was maintained, delivering 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, the control group patients started to receive 7.5 mL/hr continuous infusion of normal saline, and the colforsin daropate group patients started to receive 0.75 microg x kg(-1) x min(-1) (7.5 mL/hr) continuous infusion of colforsin daropate for 60 min. After that, both groups received fentanyl 5 microg/kg. Systolic and diastolic arterial pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the administration of fentanyl (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48) and 30 min after fentanyl injection (T60). At baseline, both groups had comparable Rawm, Rawe, and Cdyn values. In the control group, Rawm increased significantly at T36-60 compared with the baseline, Rawe increased significantly at T36-48 compared with the baseline, and Cdyn decreased significantly at T36-60 compared with the baseline. In the colforsin daropate group, there were no changes in Rawm, Rawe or Cdyn at T36-60. These observations suggest that intravenous colforsin daropate has a bronchodilator effect in humans.

Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia.

PubMed

Eide, K; Stubhaug, A; Oye, I; Breivik, H

1995-05-01

The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

PubMed Central

Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

2015-01-01

Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health‐related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed‐loop ‘artificial pancreas’ systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. PMID:25865292

Convection Enhanced Delivery: A Comparison of infusion characteristics in ex vivo and in vivo non-human primate brain tissue.

PubMed

Miranpuri, Gurwattan; Hinchman, Angelica; Wang, Anyi; Schomberg, Dominic; Kubota, Ken; Brady, Martin; Raghavan, Raghu; Bruner, Kevin; Brodsky, Ethan; Block, Walter; Grabow, Ben; Raschke, Jim; Alexander, Andrew; Ross, Chris; Simmons, Heather; Sillay, Karl

2013-07-01

Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 μL/min and 2 μL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 μL/min for 30 minutes. The fourth brain received a total of 45 μL infused at a rate of 1 μL/min for 15 minutes followed by 2 μL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 μL. Subjects 1 and 2 received infusions at 1.0 μL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 μL/min. MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials.

Continuous subcutaneous use of levetiracetam: a retrospective review of tolerability and clinical effects.

PubMed

Rémi, Constanze; Lorenzl, Stefan; Vyhnalek, Birgit; Rastorfer, Karin; Feddersen, Berend

2014-12-01

To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.

Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety.

PubMed

Ley, David; Hansen-Pupp, Ingrid; Niklasson, Aimon; Domellöf, Magnus; Friberg, Lena E; Borg, Jan; Löfqvist, Chatarina; Hellgren, Gunnel; Smith, Lois E H; Hård, Anna-Lena; Hellström, Ann

2013-01-01

In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h. Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.

Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety

PubMed Central

Ley, David; Hansen-Pupp, Ingrid; Niklasson, Aimon; Domellöf, Magnus; Friberg, Lena E.; Borg, Jan; Löfqvist, Chatarina; Hellgren, Gunnel; Smith, Lois E.H.; Hård, Anna-Lena; Hellström, Ann

2014-01-01

BACKGROUND In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. METHODS In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900–1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47–168) h in dosages between 21 and 111 µg/kg/24 h. RESULTS Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75–100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. CONCLUSION In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe. PMID:23095978

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

PubMed

Valk, B I; Absalom, A R; Meyer, P; Meier, S; den Daas, I; van Amsterdam, K; Campagna, J A; Sweeney, S P; Struys, M M R F

2018-06-01

Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers. Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg -1  min -1 or placebo. Safety was evaluated through adverse event (AE) monitoring, safety laboratory tests, and arterial blood gasses. Haemodynamic and respiratory stability were assessed by continuous monitoring. Adrenocortical function was analysed by adrenocorticotropic hormone (ACTH) stimulation tests. Clinical effect was measured using the modified observer's assessment of alertness/sedation (MOAA/S) and continuous bispectral index monitoring. No serious AEs were reported. Haemodynamic and respiratory effects included mild dose-dependent tachycardia, slightly elevated blood pressure, and no centrally mediated apnoea. Upon stimulation with ACTH, no adrenocortical depression was observed in any subject. Involuntary muscle movements (IMM) were reported, which were more extensive with higher dosing regimens. Higher dosages of ABP-700 were associated with deeper sedation and increased likelihood of sedation. Time to onset of clinical effect was variable throughout the cohorts and recovery was swift. Infusions of ABP-700 showed a dose-dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression. The presentation and nature of IMM is a matter of concern. NTR4735. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Radiofrequency ablation during continuous saline infusion can extend ablation margins

PubMed Central

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats

PubMed Central

Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.

2012-01-01

Background Etomidate is a sedative–hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague–Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1–24 and measuring serum corticosterone concentrations every 30 min. Results The sedative–hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion terminationvaried(methoxycarbonyletomidate>carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable. PMID:21572317

Gemtuzumab Ozogamicin Injection

MedlinePlus

... cause serious or life-threatening reactions during an infusion and for up to a day afterwards. You ... watch you closely while you are receiving the infusion and shortly after the infusion to be sure ...

Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.

PubMed Central

Labenz, J; Peitz, U; Leusing, C; Tillenburg, B; Blum, A L; Börsch, G

1997-01-01

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance. PMID:9155573

[Successful management of neurosurgical procedures with continuous infusion of recombinant factor IX in a child with hemophilia B].

PubMed

Yamamoto, Mariko; Nakadate, Hisaya; Iguchi, Umefumi; Masuda, Hiroshi; Sakai, Hirokazu; Ishiguro, Akira

2013-03-01

This report describes the successful management of neurosurgical procedures with continuous infusion of recombinant factor IX (rFIX). A 1-year-old boy with severe hemophilia B was administered prophylactic therapy with rFIX after intracranial bleeding. We found the enlargement of an arachnoid cyst in a follow-up CT scan. He underwent marsupialization of the cyst under the continuous infusion of rFIX. FIX levels were examined in our hospital and the rFIX infusion rate was adjusted in an attempt to keep FIX levels above 90% intraoperatively, and 70% until his 7th post-operative day. We studied the pharmacokinetic profile of rFIX and found a half-time of 25 hours and mean in vivo recovery of 0.69 IU/dl/IU/kg. Reconstituted rFIX also retained at least 95% activity after 72 hours at room temperature. This is the first report of the perioperative management of a child undergoing a neurosurgical procedure under the continuous infusion of rFIX in Japan. Further studies are required before the routine use of this product for continuous infusion.

A Multicenter, Randomized, Triple-Masked, Placebo-Controlled Trial of The Effect of Ambulatory Continuous Femoral Nerve Blocks on Discharge-Readiness Following Total Knee Arthroplasty In Patients on General Orthopaedic Wards

PubMed Central

Ilfeld, Brian M.; Mariano, Edward R.; Girard, Paul J.; Loland, Vanessa J.; Meyer, R. Scott; Donovan, John F.; Pugh, George A.; Le, Linda T.; Sessler, Daniel I.; Shuster, Jonathan J.; Theriaque, Douglas W.; Ball, Scott T.

2010-01-01

A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a four-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation ≥ 30 meters) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day three. Patients given four days of perineural ropivacaine attained all three criteria in a median (25th–75th percentiles) of 47 (29–69) hours, compared with 62 (45–79) hours for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66–1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0–38) vs. 38 (15–64) hours (p=0.009), and intravenous opioid independence in 21 (0–37) vs. 33 (11–50) hours (p=0.061). We conclude that a four-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia. PMID:20573448

Accelerated infliximab infusions for inflammatory bowel disease improve effectiveness.

PubMed

McConnell, John; Parvulescu-Codrea, Simona; Behm, Brian; Hill, Beth; Dunkle, Elizabeth; Finke, Karen; Snyder, Kathryn; Tuskey, Anne; Cox, Debbie; Woodward, Beth

2012-10-06

To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease (IBD). Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min. Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions. To be eligible for the study, patients needed a minimum of four prior infusions. An initial infusion of 90-min was given to each patient; those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits. Any patient having significant infusion reactions would be reverted to the standard 120-min protocol. A change in a patient's dose mandated a single 120-min infusion before accelerated infusions could be administered again. The University of Virginia Medical Center's Institutional Review Board approved this study. Fifty IBD patients treated with infliximab 5 mg/kg, 7.5 mg/kg and 10 mg/kg were offered accelerated infusions. Forty-six patients consented to participate in the study. Nineteen (41.3%) were female, five (10.9%) were African American and nine (19.6%) had ulcerative colitis. The mean age was 42.6 years old. Patients under age 18 were excluded. Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine, three were taking 6-mercaptopurine and one was taking methotrexate. One of the 46 study patients used corticosteroid therapy for his IBD. Seventeen of the patients used prophylactic medications prior to receiving infusions; six patients received corticosteroids as pre-medication. Four patients had a history of distant transfusion reactions to infliximab. These reactions included shortness of breath, chest tightness, flushing, pruritus and urticaria. These patients all took prophylactic medications before receiving infusions. 46 patients (27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions. No infusion reactions were reported. There were no adverse events, including drug-related infections. None of the patients developed cancer of any type during the study timeframe. Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632 ($116 965 vs $63 333, P = 0.001). One hundred and eighteen hours were saved in the administration of the accelerated infusions (17 160 min vs 10 080 min, P = 0.001). In the study population, overweight females [body mass index (BMI) > 25.00 kg/m(2)] were found to have statistically higher BMIs than overweight males (mean BMI 35.07 ± 2.66 kg/m(2) vs 30.08 ± 0.99 kg/m(2), P = 0.05), finding which is of significance since obesity was described as being one of the risk factors for Crohn's disease. We are the first US group to report substantial cost savings, increased safety and patient satisfaction associated with accelerated infliximab infusion.

Effects of l-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia1234

PubMed Central

Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas EP

2011-01-01

Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of l-arginine pretreatment on arginine–nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. Design: In a randomized controlled trial, pigs (20–25 kg) received 3 μg ⋅ kg−1 ⋅ min−1 lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol ⋅ kg−1 ⋅ min−1) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [15N2]arginine and [13C-2H2]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Results: Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Conclusion: Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects. PMID:21508091

Elotuzumab Injection

MedlinePlus

... watch you closely while you are receiving the infusion and after the infusion to be sure you are not having a ... the following symptoms that may occur during the infusion or for up to 24 hours after you ...

Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation in a community teaching hospital adult intensive care unit.

PubMed

Schmees, Patrick M; Bergman, Scott J; Strader, Brandi D; Metzke, Megan E; Pointer, Sarah; Valenti, Kristine M

2016-06-01

The purpose of this study is to evaluate the outcome differences between patients receiving piperacillin-tazobactam pre- and post-implementation of an extended infusion dosing protocol in a community teaching hospital adult intensive care unit. On December 19th, 2011, extended infusion dosing of piperacillin-tazobactam was implemented at St. John's Hospital's intensive and cardiac care units (ICU/CCU) following IRB-approval. This is a historical case-control cohort study involving review of electronic medical charts of patients who received traditional or extended infusion therapy. Data was collected for patients that received piperacillin-tazobactam in the ICU/CCU from December 19th, 2010 through March 19th, 2011 for traditional infusion and from December 19th, 2011 through March 19th, 2012 for extended infusion. Primary endpoints were ICU/CCU mortality at discharge and length of stay. The study included 113 patients with 52 in the traditional-infusion group and 61 extended-infusion group. There was no statistically significant difference in the primary end-point of ICU/CCU mortality between the two groups (14.8% vs. 21.1%; p = 0.374). In the extended infusion group, there was a shorter length of ICU and CCU stay (8.32 vs. 12.06 days; p = 0.025) and shorter length of hospital stay (11.32 vs. 19.7 days; p = 0.006). The extended-infusion group showed a decrease in cost of therapy that was statistically significant ($120.21 vs. $155.17; p = 0.035). Adverse drug effects did not differ between the two study groups. This study showed that treatment with extended-infusion piperacillin-tazobactam therapy improved patient outcomes while maintaining patient safety and decreasing costs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

PubMed

Mullinax, John E; Hall, MacLean; Prabhakaran, Sangeetha; Weber, Jeffrey; Khushalani, Nikhil; Eroglu, Zeynep; Brohl, Andrew S; Markowitz, Joseph; Royster, Erica; Richards, Allison; Stark, Valerie; Zager, Jonathan S; Kelley, Linda; Cox, Cheryl; Sondak, Vernon K; Mulé, James J; Pilon-Thomas, Shari; Sarnaik, Amod A

2018-01-01

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 10 (2.3 × 10 10 to 1.0 × 10 11 ) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Continuous subcutaneous insulin infusion versus multiple daily injections in individuals with type 1 diabetes: a systematic review and meta-analysis.

PubMed

Benkhadra, Khalid; Alahdab, Fares; Tamhane, Shrikant U; McCoy, Rozalina G; Prokop, Larry J; Murad, Mohammad Hassan

2017-01-01

The relative efficacy of continuous subcutaneous insulin infusion and multiple daily injections in individuals with type 1 diabetes is unclear. We sought to synthesize the existing evidence about the effect of continuous subcutaneous insulin infusion on glycosylated hemoglobin, hypoglycemic events, and time spent in hypoglycemia compared to multiple daily injections. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus from January 2008 through November 2015 for randomized controlled trials that enrolled children or adults with type 1 diabetes. Trials identified in a previous systematic review and published prior to 2008 were also included. We included 25 randomized controlled trials at moderate risk of bias. Meta-analysis showed a significant reduction in glycosylated hemoglobin in patients treated with continuous subcutaneous insulin infusion compared to multiple daily injections (mean difference 0.37; 95 % confidence interval, 0.24-0.51). This effect was demonstrated in both children and adults. There was no significant difference in minor or severe hypoglycemic events. Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia. There was no significant difference in the time spent in hypoglycemia. In children and adults with type 1 diabetes and compared to multiple daily injections, continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin. There was no difference in severe or minor hypoglycemia, but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion.

Infusion dose requirement of rocuronium in patients on phenytoin therapy - A prospective comparative study.

PubMed

Sheshadri, Veena; Radhakrishnan, Arathi; Halemani, Kusuma; Keshavan, Venkatesh H

2017-10-01

Patients with intracranial tumour are usually on anticonvulsants. Patients on phenytoin therapy demonstrate rapid metabolism of nondepolarising muscle relaxants secondary to enzyme induction. Infusion dose requirement of rocuronium in such patients has been sparingly studied. We studied the continuous infusion dose requirement of rocuronium bromide in patients on phenytoin therapy and its correlation with serum levels of phenytoin. Seventy-five patients scheduled for supratentorial tumour surgery were included in the study. Patients not on phenytoin were taken as control. The primary outcome variable studied was the infusion dose requirement of rocuronium in patients on phenytoin. Based on pre-operative serum phenytoin levels, study group patients were divided into two groups: sub-therapeutic level group (phenytoin level <10 μg/mL) and therapeutic level group (phenytoin level >10 μg/mL). Following anaesthesia induction, rocuronium bromide 0.6 mg/kg was administered to achieve tracheal intubation. Rocuronium infusion was titrated to maintain zero response on the train-of-four response. Demographic data were comparable. Patients receiving phenytoin required higher infusion dose compared to the control group (0.429 ± 0.2 mg/kg/h vs. 0.265 ± 0.15 mg/kg/h, P < 0.001). The serum phenytoin level had no correlation to infusion dose requirement of rocuronium (0.429 ± 0.205 mg/kg/h vs. 0.429 ± 0.265 mg/kg/h ( P = 0.815). The recovery was faster in the phenytoin group compared to the control group. Haowever, it was not clinically significant. The infusion dose requirement of rocuronium bromide in patients on phenytoin is higher and the serum levels of phenytoin does not influence the dose required.

Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.

PubMed

Farrell, Richard J; Alsahli, Mazen; Jeen, Yoon-Tae; Falchuk, Kenneth R; Peppercorn, Mark A; Michetti, Pierre

2003-04-01

We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI. Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat. Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06. Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions.

[Usefulness of Bolus Administration Using the FLEX Mode(Bolus Infusion Mode)for Baclofen Tolerance].

PubMed

Tanaka, Kazunori

2017-02-01

Intrathecal baclofen(ITB)is used to treat intractable spasticity of various etiologies and can provide better control of spasticity through the adjustment of the dose administered through the pump. However, in patients who develop tolerance to baclofen with the standard simple continuous mode, a sharp increase in dose becomes necessary, and spasticity can become harder to control. We investigated whether switching from the simple continuous mode to the bolus infusion mode was effective in controlling spasticity in patients with baclofen tolerance. We reported four patients undergoing ITB therapy at our facility who were considered to have developed baclofen tolerance. We observed the number of bolus infusions and total dose suitable for maintaining spasticity control after switching from the simple continuous mode to the bolus infusion mode. After switching to the bolus infusion mode, the total dose could be reduced in the short term; however, in the long term, the frequency of bolus infusions had to be increased to maintain spasticity control. Two years after changing to bolus infusion six times a day, the total dose was higher than that in the simple continuous mode for two of the four patients, and was the same level in the other two patients. Our four cases suggest that bolus infusion is effective in patients with baclofen tolerance during ITB therapy. Therefore, the conditions of bolus infusion should be further investigated.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

PubMed

Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

2016-01-01

The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health-related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed-loop 'artificial pancreas' systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.

Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity.

PubMed

Luz, Matthias; Allen, Philip C; Bringas, John; Boiko, Chris; Stockinger, Diane E; Nikula, Kristen J; Lewis, Owen; Woolley, Max; Fibiger, H Christian; Bankiewicz, Krystof; Mohr, Erich

2018-05-22

Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions. Here we present the results of a 9-month toxicity study in which rhesus monkeys received intermittent intraputamenal infusions via convection-enhanced delivery. Animals were treated with GDNF (87.1 µg; N = 14) or vehicle (N = 6) once every 4 weeks for a total of 40 weeks (11 treatments). Four of the GDNF-treated animals were utilized in a satellite study assessing the impact of concomitant catheter repositioning prior to treatment. In the main study, eight animals (5 GDNF, 3 control) were euthanized at the end of the treatment period, along with the four satellite study animals, while the remaining eight animals (5 GDNF, 3 control) were euthanized at the end of a 12-week recovery period. There were no GDNF-related adverse effects and in particular, no GDNF-related microscopic findings in the brain, spinal cord, dorsal root ganglia, or trigeminal ganglia. Therefore, 87.1 µg/4 weeks is considered the no observed adverse effect level for GDNF in rhesus monkeys receiving intermittent, convection-enhanced delivery of GDNF for 9 months.

Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

PubMed Central

Brussee, Janneke M.; Yeo, Tsin W.; Lampah, Daniel A.; Anstey, Nicholas M.

2015-01-01

Impaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria. PMID:26482311

[Use of intravenous iron infusion in a gastroenterology day hospital: Indications, dosage and adverse effects].

PubMed

Dosal, Angelina; Calvet, Xavier; Moreno, Laura; López, María; Figuerola, Ariadna; Ruíz, Miquel Angel; Suárez, David; Gené, Emili; Miquel, Mireia; Villoria, Albert

2010-01-01

There are no data in the literature on the use of intravenous iron infusion in gastroenterology day hospitals. To determine the indications, dosage and tolerance of intravenous iron infusion in outpatients attending a gastroenterology day hospital. We retrospectively reviewed the medical records of patients who received intravenous iron infusion between August 2007 and July 2008. The indications, dosage, transfusion requirements, adverse effects and patients' clinical and laboratory data were recorded. During the study period, 111 patients (41% women, with a mean age of 63.8 ± 18 years) received intravenous iron infusions. The main causes of anemia indicating iron administration were portal hypertensive gastropathy (n=55), inflammatory bowel disease (n=22) and intestinal angiodysplasia (n=12). The patients received a total of 557 iron infusions with a mean dose of 1033 mg iron per patient. There were no adverse effects. Despite the treatment, 46 patients required transfusion. Iron and transfusion requirements and mortality were significantly higher in patients with liver cirrhosis than in the remainder of the study group. Intravenous iron therapy is frequently used in the gastroenterology day hospital. Most infusions were administered in patients with chronic iron loss. Patients with liver cirrhosis had the most severe anemia and underlying disease and the highest mortality.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

PubMed

Saccone, Gabriele; Ciardulli, Andrea; Baxter, Jason K; Quiñones, Joanne N; Diven, Liany C; Pinar, Bor; Maruotti, Giuseppe Maria; Martinelli, Pasquale; Berghella, Vincenzo

2017-11-01

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached. Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017. We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery. Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

Recombinant FVIIa (NovoSeven) continuous infusion and total hip replacement in patients with haemophilia and high titre of inhibitors to FVIII: experience of two cases.

PubMed

Tagariello, G; De Biasi, E; Gajo, G B; Risato, R; Radossi, P; Davoli, P G; Traldi, A

2000-09-01

In this report we describe our experience of total hip replacement in two patients with severe haemophilia A and high titres of inhibitors to FVIII. We used rFVIIa replacement therapy by continuous infusion to perform the surgery. The total amount of rFVIIa used in these two patients was very similar but the manner of administration was quite different. In our experience, it is an advantage to use a higher dose for shorter periods than a lower dose for a longer treatment period. Tranexamic acid by continuous infusion, and parallel saline infusion were useful for good haemostasis and avoided local thrombophlebitis in the side of rFVIIa infusion.

Pharmacokinetic properties and tolerability of single-dose terbutaline in patients with severe asthma treated in the pediatric intensive care unit

PubMed Central

Lebovitz, Daniel J; Smith, Paul G; O'Riordan, MaryAnn; Reed, Michael D

2004-01-01

Background: Asthmatic children requiring treatment in the pediatric intensive care unit (PICU) receive aggressive drug therapy that may include IV administration of β2-receptor agonists to prevent progression to life-threatening respiratory failure. The only pharmacologic agent in this class currently available for parenteral use in the United States is terbutaline. Study of IV dosing of terbutaline in the pediatric population has been limited. Objective: The aim of this study was to determine the pharmacokinetic (PK) properties and tolerability of single-dose terbutaline in pediatric patients across a broad age range who were admitted to the PICU and were receiving maximal conventional asthma drug therapy. Methods: This study was conducted at the PICU at Rainbow Babies and Children's Hospital (Cleveland, Ohio). Patients aged 6 months to 16 years with severe exacerbation of reactive airways disease and who were undergoing maximal conventional therapy and had an arterial catheter were enrolled. Patients were arbitrarily assigned to receive a single IV infusion of 1 of 3 doses of terbutaline (10, 20, or 30 μg/kg), infused over 5 minutes. Blood samples were obtained for the determination of plasma terbutaline concentrations just before terbutaline was administered (baseline), immediately on completion of the IV infusion, and at 10, 20, and 40 minutes and 1, 2, 4, 8, 16, 32, 48, and 72 hours after the 5-minute infusion. PK properties (elimination half-life [tl2], mean residence time [MRT], apparent steady-state volume of distribution [Vdss], and total body clearance [CI]) were determined and adverse effects were recorded. Results: The determination of terbutaline PK properties was possible in 50 of 56 enrolled patients (31 boys, 19 girls; mean [SD] age, 6.5 [4.5] years). The PK properties of terbutaline were linear over the dose range studied and, with the exception of the expected dose-dependent increases in peak terbutaline plasma concentration and area under the terbutaline plasma concentration-time curve, no statistically significant differences were observed in PK relative to dose. Therefore, we pooled the data for all subsequent analyses. Statistically significant correlations with patient age were observed with tl2 (r = 0.4, P < 0.006), MRT (r = 0.4, P < 0.002), and Vdss (r = 0.33, P < 0.02), but not C1 (r = −0.03, P = NS). Single-dose terbutaline administration was generally well tolerated. Conclusions: Single-dose IV terbutaline was well tolerated in this study. In maximally treated asthmatic patients in the PICU, terbutaline elimination may be more rapid than in nonacutely ill children. These PK data suggest that if the drug is to be administered intravenously, the continuous IV infusion method, including loading doses for any subsequent dose escalations, may be the most appropriate. The influence of age and safety of long-term, continuous terbutaline IV infusion requires further study. PMID:24936108

Freezing and thawing effects on fat, protein, and lactose levels of human natural milk administered by gavage and continuous infusion.

PubMed

Abranches, Andrea D; Soares, Fernanda V M; Junior, Saint-Clair G; Moreira, Maria Elisabeth L

2014-01-01

to analyze the changes in human milk macronutrients: fat, protein, and lactose in natural human milk (raw), frozen and thawed, after administration simulation by gavage and continuous infusion. an experimental study was performed with 34 human milk samples. The infrared spectrophotometry using the infrared analysis equipment MilkoScan Minor® (Foss, Denmark) equipment was used to analyze the macronutrients in human milk during the study phases. The analyses were performed in natural (raw) samples and after freezing and fast thawing following two steps: gavage and continuous infusion. The non-parametric Wilcoxon test for paired samples was used for the statistical analysis. the fat content was significantly reduced after administration by continuous infusion (p<0.001) during administration of both raw and thawed samples. No changes in protein and lactose content were observed between the two forms of infusion. However, the thawing process significantly increased the levels of lactose and milk protein. the route of administration by continuous infusion showed the greatest influence on fat loss among all the processes required for human milk administration. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A randomized trial of misoprostol versus extra-amniotic sodium chloride infusion with oxytocin for induction of labor.

PubMed

Buccellato, C A; Stika, C S; Frederiksen, M C

2000-05-01

Our purpose was to compare the efficacy and safety of misoprostol and extra-amniotic sodium chloride infusion with oxytocin for induction of labor. This randomized trial compared two methods of labor induction in women requiring cervical ripening. One hundred twenty-three women undergoing labor induction with a Bishop score < or =5 were randomly selected to receive either misoprostol, 50 microg intravaginally every 4 hours, or extra-amniotic sodium chloride infusion. The primary outcome variable was the time interval from induction to vaginal delivery. Sixty-one women received extra-amniotic sodium chloride infusion and 62 women received misoprostol. The mean time interval from the start of induction to vaginal delivery was 15.0 +/- 5.0 hours and 16.5 +/- 7.2 hours for the extra-amniotic infusion and misoprostol groups, respectively (P, not significant). The cesarean delivery rate was not significantly different between the 2 groups (32.8% for the extra-amniotic infusion group; 19.4% for the misoprostol group). Maternal and neonatal outcomes were similar between the 2 groups. Both methods of induction are equally efficacious and result in similar maternal and neonatal outcomes.

Prevention of dimethylsulfoxide-related nausea and vomiting by prophylactic administration of ondansetron for patients receiving autologous cryopreserved peripheral blood stem cells.

PubMed

Eisenberg, Seth; Wickline, Mihkaila; Linenberger, Michael; Gooley, Ted; Holmberg, Leona

2013-05-01

To evaluate the effectiveness of ondansetron for the prevention of nausea and vomiting from dimethylsulfoxide (DMSO) during autologous stem cell transplantation (ASCT) infusion. Nonrandomized cohort using historical control. Comprehensive cancer center outpatient infusion department. 50 patients receiving ASCT in the outpatient setting. Patients were assessed for nausea and vomiting on their infusion day using the Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) at arrival, pre-ASCT infusion, pre-ondansetron administration, prior to the first bag, and after each bag of stem cells. A standard script was used to ensure consistency. Ondansetron, 16 mg IV, was administered 30-90 minutes prior to each ASCT infusion. Number and volume of stem cells bags, as well as infusion rate and emesis episodes, were recorded. Nausea scores and vomiting episodes were compared to historical data. Subjectivity of nausea, potential Hawthorne Effect. Forty-five percent of patients had an MAT score greater than 2 on arrival, decreasing to 18% after receiving ondansetron before the first bag. Twenty-four percent had MAT increases of more than two points by infusion end compared to 58% in the historic control group. Eighteen percent of patients vomited compared to 28% of historic controls. The administration of 16 mg of IV ondansetron significantly reduced DMSO-related nausea and episodes of vomiting in patients receiving ASCT. Prophylactic administration of ondansetron had a positive effect on reducing nausea symptoms and episodes of vomiting during ASCT infusions. These results prompted a change in clinical practice. More research is required to determine whether the inclusion of other antiemetic agents would provide even greater benefit. To date, no other published studies have explored the benefits of premedicating patients with ondansetron prior to ASCT infusions. This study is the first to establish efficacy of ondansetron for an unlabeled indication. These results may pave the way for future research in decreasing nausea and vomiting in this setting.

A remote drip infusion monitoring system employing Bluetooth.

PubMed

Amano, Hikaru; Ogawa, Hidekuni; Maki, Hiromichi; Tsukamoto, Sosuke; Yonezawa, Yoshiharu; Caldwell, W Morton

2012-01-01

We have developed a remote drip infusion monitoring system for use in hospitals. The system consists of several infusion monitoring devices and a central monitor. The infusion monitoring device employing a Bluetooth module can detect the drip infusion rate and an empty infusion solution bag, and then these data are sent to the central monitor placed at the nurses' station via the Bluetooth. The central monitor receives the data from several infusion monitoring devices and then displays graphically them. Therefore, the developed system can monitor intensively the drip infusion situation of the several patients at the nurses' station.

Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

PubMed Central

Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

2013-01-01

OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

Nitric oxide released by Lactobacillus farciminis improves TNBS-induced colitis in rats.

PubMed

Lamine, F; Fioramonti, J; Bueno, L; Nepveu, F; Cauquil, E; Lobysheva, I; Eutamène, H; Théodorou, V

2004-01-01

Beneficial effects of lactobacilli have been reported in experimental colitis. On the other hand, despite the controversial role of nitric oxide (NO) in the inflammatory gut process, a protective action of exogenous NO in inflammation has been suggested. Consequently, this study aimed to determine the effect of (i) sodium nitroprusside (SNP), a NO donor and (ii) treatment with Lactobacillus farciminis, which produces NO in vitro, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and to evaluate the role of exogenous NO in this effect. Rats were divided into three groups receiving one of the following: (i) a continuous intracolonic (IC) infusion of SNP for 4 days, (ii) L. farciminis orally for 19 days, or (iii) saline. On day 1 and day 15, respectively, TNBS and saline were administrated IC, followed by a continuous IC infusion of saline or haemoglobin, a NO scavenger. At the end of treatments, the following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase and nitric oxide synthase activities and colonic luminal NO production. In colitic rats, SNP and L. farciminis treatment significantly (P < 0.05) reduced macroscopic damage scores, myeloperoxidase and nitric oxide synthase activities compared to controls. Haemoglobin infusion abolished the anti-inflammatory effect of both NO donor treatments, but had no effect per se on colitis. NO released intraluminally by SNP infusion or by L. farciminis given orally improves TNBS-induced colitis in rats. These results indicate a protective role of NO donation in colonic inflammation and show for the first time a mechanism involving NO delivery by a bacterial strain reducing an experimental colitis.

Jejunal Infusion of Glucose Decreases Energy Intake to a Greater Extent than Fructose in Adult Male Rats12

PubMed Central

Moghadam, Alexander A; Moran, Timothy H; Dailey, Megan J

2016-01-01

Background: Intestinal nutrient infusions result in variable decreases in energy intake and body weight based on nutrient type and specific intestinal infusion site. Objective: The objective was to test whether an intrajejunal fructose infusion (FRU) would lower energy intake and body weight and induce similar increases in gut hormones as those found after intrajejunal glucose infusions (GLU). Methods: Male Sprague-Dawley rats received an intrajejunal infusion of either an equal kilocalorie load of glucose or fructose (11.4 kcal) or saline (SAL) for 5 d while intake of a standard rodent diet was continuously recorded; body weight was measured daily. Immediately after the infusion on the final day, rats were killed and plasma was collected to measure hormones. Results: Daily energy intake was significantly lower in the GLU group than in the SAL group, but the FRU group did not differ from the GLU or SAL groups when the 11.4 kcal of the infusate was included as energy intake. Lower energy intake was due to smaller meal sizes during the infusion period in the GLU group than in the FRU and SAL groups; the FRU and SAL groups did not differ. The percentage of change in body weight was lower in the GLU group than in the FRU and SAL groups. Plasma glucagon-like-peptide 1 (GLP-1) concentrations were greater in the GLU group than in the SAL group; the FRU group did not differ from the GLU or SAL groups. The plasma insulin concentration was greater in the FRU group than in both the GLU and SAL groups. Conclusion: These results demonstrate that glucose induces a greater decrease in energy intake and increase in GLP-1 at distal intestinal sites than fructose in rats, which may explain differential effects of these monosaccharides between studies when delivered orally or along the proximal to distal axis of the intestine. PMID:27581579

A gravimetric technique for evaluating flow continuity from two infusion devices.

PubMed

Leff, R D; True, W R; Roberts, R J

1987-06-01

A computerized gravimetric technique for examining the flow continuity from infusion devices was developed, and two infusion devices with different mechanisms of pump operation were evaluated to illustrate this technique. A BASIC program that records serial weight measurements and calculates weight change from previous determinations was written for and interfaced with a gravimetric balance and IBM PC. A plot of effused weight (normalized weight change that reflects the difference between desired timed-sample interval and actual time) versus time (desired timed-sample interval) was constructed. The gravimetric technique was evaluated using both a peristaltic-type and a piston-type infusion pump. Intravenous solution (5% dextrose and 0.9% sodium chloride) was effused at 10 mL/hr and collected in a beaker. Weights were measured at 10-second intervals over a two-hour infusion period, and the weights of the effused solution were plotted versus time. Flow continuity differed between the two infusion devices. Actual effused weight decreased to 0.007 g/10 sec during the refill cycle of the piston-type pump; the mean (+/- S.D.) effused weight was 0.029 +/- 0.002 g/10 sec. The desired effusion rate was 0.028 g/10 sec. The peristaltic pump had greater flow continuity, with a mean effusion weight of 0.028 +/- 0.003 g/10 sec. The gravimetric technique described in this report can be used to quantitatively depict the effusion profiles of infusion devices. Further studies are needed to identify the degree of flow continuity that is clinically acceptable for infusion devices.

Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

PubMed

Altier, N; Stewart, J

1993-11-19

Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

Combined enteral infusion of glutamine, carbohydrates, and antioxidants modulates gut protein metabolism in humans.

PubMed

Coëffier, Moïse; Claeyssens, Sophie; Lecleire, Stéphane; Leblond, Jonathan; Coquard, Aude; Bôle-Feysot, Christine; Lavoinne, Alain; Ducrotté, Philippe; Déchelotte, Pierre

2008-11-01

Available data suggest that nutrients can affect intestinal protein metabolism, which contributes to the regulation of gut barrier function. We aimed to assess whether an oral nutritional supplement (ONS) containing glutamine (as the dipeptide Ala-Gln), carbohydrates, and antioxidants would modulate duodenal protein metabolism in healthy humans. Thirty healthy control subjects were included and, over a period of 5 h, received by nasogastric tube either saline or ONS providing 11.7 kcal/kg as 0.877 g Ala-Gln/kg, 3.9 g carbohydrates/kg, and antioxidants (29.25 mg vitamin C/kg, 9.75 mg vitamin E/kg, 195 microg beta-carotene/kg, 5.85 mg Se/kg, and 390 microg Zn/kg) or glutamine (0.585 g/kg, 2.34 kcal/kg). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]-leucine was done until endoscopy. Leucine enrichment was assessed by using gas chromatography-mass spectrometric analysis, and mucosal fractional synthesis rate was calculated by using intracellular amino acid enrichment as precursor. Mucosal proteolytic pathways were also evaluated. ONS infusion resulted in a doubling increase (P < 0.01) of duodenal fractional synthesis rate and a significant (P < 0.05) decrease in cathepsin D-mediated proteolysis compared with saline, whereas proteasome and Ca(2+)-dependent activities were unaffected. ONS infusion significantly (P < 0.01) decreased duodenal glutathione but not glutathione disulfide concentrations or the ratio of glutathione to glutathione disulfide. Insulinemia increased after ONS infusion, whereas plasma essential amino acids decreased. Infusion of glutamine alone did not reproduce ONS effects. ONS infusion improves duodenal protein balance in healthy humans. Further investigations are needed to study the origin of these effects and to evaluate ONS supply in stressed persons.

Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.

PubMed

Albertini, M; Clement, M G; Lafortuna, C L; Caniatti, M; Magder, S; Abdulmalek, K; Hussain, S N

2000-06-01

To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.

A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels

PubMed Central

Huang, Vivian Wai-Mei; Dhami, Neil; Fedorak, Darryl; Prosser, Connie; Shalapay, Carol; Kroeker, Karen Ivy; Halloran, Brendan Phillip; Dieleman, Levinus Albert; Fedorak, Richard Neil

2015-01-01

BACKGROUND: Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists. OBJECTIVES: To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab. METHODS: Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab. RESULTS: One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; P<0.001). CONCLUSION: One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events. PMID:25706572

Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: A randomized control study.

PubMed

Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Hong, Chen-Jee; Tu, Pei-Chi; Bai, Ya-Mei; Cheng, Chih-Ming; Su, Tung-Ping

2018-01-01

A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18 F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer.

PubMed

Javid, Gul; Zargar, Showkat Ali; U-Saif, Riyaz-; Khan, Bashir Ahmad; Yatoo, Ghulam Nabi; Shah, Altaf Hussain; Gulzar, Ghulam Mohammad; Sodhi, Jaswinder Singh; Khan, Mushtaq Ahmad

2009-07-01

After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer. Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72-h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72-h pH study. Mean 72-h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion (P = 0.48). Mean 72-h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion (P = 0.62). Mean 72-h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. (P = 0.55). Mean 72-h pH for the no proton pump inhibitor group was 2.04. There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.

Computerized Orders with Standardized Concentrations Decrease Dispensing Errors of Continuous Infusion Medications for Pediatrics

PubMed Central

Sowan, Azizeh K.; Vaidya, Vinay U.; Soeken, Karen L.; Hilmas, Elora

2010-01-01

OBJECTIVES The use of continuous infusion medications with individualized concentrations may increase the risk for errors in pediatric patients. The objective of this study was to evaluate the effect of computerized prescriber order entry (CPOE) for continuous infusions with standardized concentrations on frequency of pharmacy processing errors. In addition, time to process handwritten versus computerized infusion orders was evaluated and user satisfaction with CPOE as compared to handwritten orders was measured. METHODS Using a crossover design, 10 pharmacists in the pediatric satellite within a university teaching hospital were given test scenarios of handwritten and CPOE order sheets and asked to process infusion orders using the pharmacy system in order to generate infusion labels. Participants were given three groups of orders: five correct handwritten orders, four handwritten orders written with deliberate errors, and five correct CPOE orders. Label errors were analyzed and time to complete the task was recorded. RESULTS Using CPOE orders, participants required less processing time per infusion order (2 min, 5 sec ± 58 sec) compared with time per infusion order in the first handwritten order sheet group (3 min, 7 sec ± 1 min, 20 sec) and the second handwritten order sheet group (3 min, 26 sec ± 1 min, 8 sec), (p<0.01). CPOE eliminated all error types except wrong concentration. With CPOE, 4% of infusions processed contained errors, compared with 26% of the first group of handwritten orders and 45% of the second group of handwritten orders (p<0.03). Pharmacists were more satisfied with CPOE orders when compared with the handwritten method (p=0.0001). CONCLUSIONS CPOE orders saved pharmacists' time and greatly improved the safety of processing continuous infusions, although not all errors were eliminated. pharmacists were overwhelmingly satisfied with the CPOE orders PMID:22477811

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

PubMed

Haldar, Rudrashish; Samanta, Sukhen; Singla, Ankush

2016-01-01

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.

PubMed

Cappellini, Maria Domenica; Bejaoui, Mohamed; Agaoglu, Leyla; Porter, John; Coates, Thomas; Jeng, Michael; Lai, Maria Eliana; Mangiagli, Antonio; Strauss, Gabriele; Girot, Robert; Watman, Nora; Ferster, Alina; Loggetto, Sandra; Abish, Sharon; Cario, Holger; Zoumbos, Nicolaos; Vichinsky, Elliott; Opitz, Herbert; Ressayre-Djaffer, Catherine; Abetz, Linda; Rofail, Diana; Baladi, Jean-Francois

2007-05-01

Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries. This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670). PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication. Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001). In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives.

The role of magnesium as an adjuvant during general anaesthesia.

PubMed

Gupta, K; Vohra, V; Sood, J

2006-11-01

Magnesium sulphate is used extensively in the treatment of eclampsia, and is also used to treat refractory arrhythmias, asthma, myocardial ischaemia and acute respiratory failure. We studied the interaction between magnesium sulphate and the anaesthetic agents propofol, rocuronium bromide and fentanyl citrate. This randomised, double blind study was conducted in 50 patients. The magnesium group A (n = 25) received 30 mg x kg(-1) magnesium sulphate before induction of anaesthesia and 10 mg x kg(-1) continuously intra-operatively until the end of surgery. Group B (n = 25) received the same volume of isotonic saline. Propofol, rocuronium and fentanyl infusions were started and the patients lungs' were ventilated with 33% oxygen in nitrous oxide. Anaesthetic depth was maintained at a bispectral index value of between 40 and 60. Muscle relaxation was maintained at a train-of-four count of 1 throughout surgery using neuromuscular monitoring. The fentanyl infusion was titrated to haemodynamic variables: heart rate and blood pressure. We concluded that magnesium sulphate has anaesthetic, analgesic and muscle relaxation effects and significantly reduces the drug requirements of propofol, rocuronium and fentanyl during anaesthesia.

Effects of magnesium sulphate on postoperative coagulation, measured by rotational thromboelastometry (ROTEM(®)).

PubMed

Na, H S; Chung, Y H; Hwang, J W; Do, S H

2012-08-01

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in gynaecological patients undergoing pelviscopic surgery. Patients were randomly allocated to the magnesium group (n = 20) or control group (n = 20). The magnesium group received magnesium sulphate (50 mg.kg(-1) followed by continuous infusion of 15 mg.kg(-1).h(-1)), whereas the control group received the same volume of isotonic saline according to the same methods. Mean (SD) postoperative serum magnesium levels were 1.58 (0.17) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). Postoperative clotting time, clot formation time, α-angle and maximum clot firmness of INTEM, and clot formation time, α-angle, and maximum clot firmness of EXTEM were significantly different between the two groups (p < 0.05). Intra-operative infusion of magnesium sulphate seems to attenuate postoperative hypercoagulability by maintaining magnesium levels at the upper limit of the normal range. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

Incidence and severity of phlebitis in patients receiving peripherally infused amiodarone.

PubMed

Boyce, Brenda A Brady; Yee, Barbara Homer

2012-08-01

Nurses noted that the rate of phlebitis was high when intravenous amiodarone was infused via a peripheral site. Hospital policy recommends a central vascular catheter, but this method is often not feasible because the drug is administered in emergent situations for short periods. To determine the rate and severity of phlebitis in patients given peripherally infused amiodarone. The literature, policy, and procedures for administration of amiodarone were reviewed; the pharmacy was consulted; and a data collection tool was developed. The tool was pilot tested and revised, and face validation was established. Data were collected during a 6-month period. A convenience sample was used. The study included a total of 12 patients. Each new infusion of intravenous amiodarone was considered a separate occurrence, for a total of 24 infusions. Various grades of phlebitis developed in 8 patients (67%). Phlebitis developed at 12 of the 24 infusion sites (50%). Patients receiving peripherally infused amiodarone are at high risk for phlebitis. This complication may lead to infection, additional medical intervention, delay in treatment, and prolonged hospitalization.

Brexanolone as adjunctive therapy in super‐refractory status epilepticus

PubMed Central

Claassen, Jan; Wainwright, Mark S.; Husain, Aatif M.; Vaitkevicius, Henrikas; Raines, Shane; Hoffmann, Ethan; Colquhoun, Helen; Doherty, James J.; Kanes, Stephen J.

2017-01-01

Objective Super‐refractory status epilepticus (SRSE) is a life‐threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE‐547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open‐label evaluation of brexanolone response during and after anesthetic third‐line agent (TLA) weaning. Methods Patients receiving TLAs for SRSE control were eligible for open‐label, 1‐hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow‐up. Results Twenty‐five patients received open‐label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty‐two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. Interpretation In an open‐label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342–352 PMID:28779545

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

PubMed Central

Armstrong, Peter; Wilkinson, Pauline; McCorry, Noleen K

2018-01-01

Objectives To characterise the use of the parenteral non-steroidal anti-inflammatory drug parecoxib when given by continuous subcutaneous infusion (CSCI) in a hospice population. Clinical experience suggests parecoxib CSCI may be of benefit in this population, but empirical evidence in relation to its safety and efficacy is lacking. Methods Retrospective chart review of patients with a cancer diagnosis receiving parecoxib CSCI from 2008 to 2013 at the Marie Curie Hospice, Belfast. Data were collected on treatment regime, tolerability and, in patients receiving at least 7 days treatment, baseline opioid dose and changes in pain scores or opioid rescue medication requirements. Results Parecoxib CSCI was initiated in 80 patients with a mean administration of 17.9 days (median 11, range 1–94). When used for a period of 7 days, there was a statistically significant reduction in pain scores (p=0.002) and in the number of rescue opioid doses required (p=0.001), but no statistically significant opioid-sparing effect (p=0.222). It was generally well tolerated, although gastrointestinal, renal adverse effects and local site irritation were reported. Conclusions Parecoxib may have a valuable place in the management of cancer pain, especially towards the end of life when oral administration is no longer possible and CSCI administration is relied on. Further studies into the efficacy and tolerability of parecoxib CSCI are merited. PMID:28864447

A Randomized, Placebo-Controlled Trial of Human Umbilical Cord Blood Mesenchymal Stem Cell Infusion for Children With Cerebral Palsy

PubMed Central

Huang, Li; Zhang, Che; Gu, Jiaowei; Wu, Wei; Shen, Zhujun; Zhou, Xihui; Lu, Haixia

2018-01-01

Cerebral palsy (CP) is a common disability which results in permanent chronic motor disability appearing in early childhood. Recently human umbilical cord blood mesenchymal stem cell (hUCB-MSC) infusion has emerged as a promising therapeutic strategy for CP, and the treatment efficacy remains to be confirmed by clinical trials. All 54 patients received basic rehabilitation as a background treatment. The infusion group comprising 27 patients received 4 infusions of hUCB-MSCs (intravenous infusions at a fixed dose of 5 × 107) and basic rehabilitation treatment, whereas 27 patients in the control group received 0.9% normal saline and basic rehabilitation treatment. Several indices were tested from baseline up to 24 months posttreatment regarding efficacy and safety evaluations, including the gross motor function measurement 88 (GMFM-88) scores, the comprehensive function assessment (CFA), lab tests, electroencephalogram (EEG), routine magnetic resonance imaging (MRI), and adverse events. The changes in the total proportion of GMFM-88 and total scores of CFA in the hUCB-MSC infusion group were significantly higher than that in control group at 3, 6, 12, 24 months posttreatment. Less diffuse slow waves were noticed after hUCB-MSC infusion in patients with slowing of EEG background rhythms at baseline. Based on the routine MRI exams, improvements in cerebral structures were rare after treatment. Serious adverse events were not observed during the whole study period. The results of the study indicated that hUCB-MSC infusion with basic rehabilitation was safe and effective in improving gross motor and comprehensive functions in children with CP. PMID:29637820

Increasing the use of 'smart' pump drug libraries by nurses: a continuous quality improvement project.

PubMed

Harding, Andrew D

2012-01-01

The use of infusion pumps that incorporate "smart" technology (smart pumps) can reduce the risks associated with receiving IV therapies. Smart pump technology incorporates safeguards such as a list of high-alert medications, soft and hard dosage limits, and a drug library that can be tailored to specific patient care areas. Its use can help to improve patient safety and to avoid potentially catastrophic harm associated with medication errors. But when one independent community hospital in Massachusetts switched from older mechanical pumps to smart pumps, it neglected to assign an "owner" to oversee the implementation process. One result was that nurses were using the smart pump library for only 37% of all infusions.To increase pump library usage percentage-thereby reducing the risks associated with infusion and improving patient safety-the hospital undertook a continuous quality improvement project over a four-month period in 2009. With the involvement of direct care nurses, and using quantitative data available from the smart pump software, the nursing quality and pharmacy quality teams identified ways to improve pump and pump library use. A secondary goal was to calculate the hospital's return on investment for the purchase of the smart pumps. Several interventions were developed and, on the first of each month, implemented. By the end of the project, pump library usage had nearly doubled; and the hospital had completely recouped its initial investment.

Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

PubMed

Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

2014-05-01

To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

Effects of peptide YY on gallbladder motility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conter, R.L.; Roslyn, J.J.; Taylor, I.L.

1987-06-01

The effects of peptide YY (PYY) on cholecystokinin-stimulated gallbladder contraction were investigated in the prairie dog model. Twelve animals underwent laparotomy with catheter placement into the gallbladder and common bile duct (vent). The gallbladder was continuously perfused with (/sup 14/C)polyethylene glycol-labeled lactated Ringer at 0.03 ml/min, and vent effluent was collected at 2.5-min intervals. All animals received 20 min of intravenous infusion of cholecystokinin octapeptide (CCK-OP), 2.5 ng x kg/sup -1/ x min/sup -1/, immediately followed by 60-min infusions of either lactated Ringer (LR) or synthetic PYY, 10 or 50 ng x kg/sup -1/ x min/sup -1/. When LR wasmore » infused after CCK-OP, gallbladder filling increased by 15.4 +/- 10.5% with minimal changes in gallbladder pressure. Infusion of PYY/sub 10/ resulted in a significant increase in gallbladder volume and filling with a significant decrease in intragallbladder pressure. Similar findings were noted with PYY/sub 50/. These data indicate that synthetic PYY significantly augments gallbladder filling after CCK-OP-stimulated gallbladder contraction. These finding, coupled with the observation that PYY inhibits pancreatic secretion, suggest that this peptide may be the anti-CCK hormone and may have an important role in regulating biliary activity postprandially.« less

Comparison between a disposable and an electronic PCA device for labor epidural analgesia.

PubMed

Sumikura, Hiroyuki; van de Velde, Marc; Tateda, Takeshi

2004-01-01

The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients. Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3 mg ropivacaine and 1.5 microg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75 microg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4 ml/h, 3 ml, 15 min, and 16 ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4 ml/h, 3 ml, and 16 ml, respectively, but lockout function was not available. No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 +/- 4.7 ml/h; electronic, 8.2 +/- 4.0 ml/h) and VAS score during the delivery (disposable, 26 +/- 25; electronic, 21 +/- 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one. The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.

Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia.

PubMed

Cies, Jeffrey J; Jain, Jaimi; Kuti, Joseph L

2015-03-01

To describe the population pharmacokinetics of the piperacillin component of piperacillin/tazobactam. This pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia. Each patient contributed 1-3 blood samples for piperacillin concentration determination. Population pharmacokinetic analyses were conducted using Pmetrics software. A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold. Mean ± SD body weight was 28.5 ± 9.7 kg. Piperacillin concentration data best fit a two-compartment model with linear clearance, using total body weight as a covariate for clearance (CLθ ) and volume of the central compartment (Vcθ ). Population estimates for CLθ , Vcθ , and intercompartment transfer constants were 0.204 ± 0.076 L/h/kg, 0.199 ± 0.107 L/kg, 0.897 ± 1.050 h(-1) , and 1.427 ± 1.609 h(-1) , respectively. R(2) , bias, and precision for the Bayesian fit were 0.998, -0.032, and 2.2 µg/ml, respectively. At the MIC breakpoint of 16 µg/ml for Pseudomonas aeruginosa, PTAs for 50 mg/kg q4h as a 0.5 hr infusion was 93.9%; for 100 mg/kg q8h as 0.5 and 4 hr infusion: 64.6% and 100%; for 100 mg/kg q6h as 0.5 and 3 hr infusion: 86.5% and 100%; and for 400 mg/kg continuous infusion: 100%, respectively. In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure. © 2014 Wiley Periodicals, Inc.

Comparison of analgesic efficacy and safety of continuous epidural infusion versus local infiltration and systemic opioids in video-assisted thoracoscopic surgery decortication in pediatric empyema patients.

PubMed

Karnik, Priyanka Pradeep; Dave, Nandini Malay; Garasia, Madhu

2018-01-01

The stripping of the densely innervated and inflamed parietal pleura in empyema during video-assisted thoracoscopic surgery (VATS) decortication can lead to significant pain and major postoperative respiratory compromise. Hence, we compared the analgesic efficacy of continuous epidural infusion versus local infiltration and systemic opioids in children undergoing VATS decortications. Following ethics approval and informed consent, forty patients from 1 to 12 years of age were randomized into two groups, Group E (epidural) and Group L (local infiltration) after induction of anesthesia. In Group E, a thoracic epidural catheter was inserted between T4 and T8. A bolus dose of 0.5 ml/kg of 0.25% injection bupivacaine was given epidurally before incision. Postoperatively, the patients received epidural infusion with bupivacaine and fentanyl up to 48 h using an elastomeric balloon pump. In Group L, patients received local infiltration of bupivacaine (2 mg/kg) and lignocaine (5 mg/kg) at the port sites before incision and at the end of surgery. They also received injection tramadol 1 mg/kg intravenously TDS with thrice daily postoperatively. The pain scores (Face, Legs, Activity, Cry, Consolability/ Wong-Baker FACES scale) were assessed every 4 h on the 1 st day and 6 h on the 2 nd day. Injection diclofenac 1 mg/kg intravenous was used as a rescue analgesic for pain scores more than 4. Side effects such as nausea, vomiting, constipation, and motor blockade were noted. Quantitative and categorical data were assessed using t -test and Chi-square test, respectively. The pain scores were lower in the epidural group than in the local infiltration group at 0, 4, and 20 h postoperatively ( P = 0.001, 0.01, and 0.038, respectively). Seventeen out of nineteen patients required rescue analgesia in the local infiltration group in the postoperative period as compared to five patients in the epidural group with a P value of 0.000081. Epidural analgesia can be considered as an effective modality of reducing pain in patients undergoing VATS decortication for empyema in pediatric patients.

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

PubMed

Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

2018-04-30

Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation < 95% was 49% in the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is always required. EUDRACT number 2013-003040-23.

The effectiveness and adverse effects profile of "burst" ketamine in refractory cancer pain: The VCOG PM 1-00 study.

PubMed

Jackson, Kate; Ashby, Michael; Howell, Deb; Petersen, Jennifer; Brumley, David; Good, Phillip; Pisasale, Maria; Wein, Simon; Woodruff, Roger

2010-01-01

This multi-centre study of adjuvant "burst" ketamine in palliative care in-patients documents its effectiveness, duration of pain relief, and adverse effects (AE) profile. Patients received a three-to-five day continuous subcutaneous infusion (CSCI) of ketamine escalated from 100 to 300 to 500 mg/24 hours if required. When the effective or maximum tolerated dose was attained, the infusion was continued for three days and each patient assessed as a responder or non-responder using strict criteria. The response rate was 22/44 (50 percent), with 4 (9 percent) becoming pain-free. Pain relief lasting two or more weeks was documented in 50 percent of responders. AEs were documented daily using the National Cancer Institute (NCI) Common Toxicity Criteria 0-4 scales. There were 11 grade 3 and 4 neurological AEs. However, no responders elected to cease treatment early due to neurological AEs. We concluded that this protocol in the controlled environment of an in-patient PC unit is relatively safe and simple with reasonable effectiveness.

[Portable elastomeric infusion system applied to patients with knee prosthesis].

PubMed

Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

2007-03-01

An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion.

Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols.

PubMed

Schomberg, Dominic; Wang, Anyi; Marshall, Hope; Miranpuri, Gurwattan; Sillay, Karl

2013-04-01

Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin.

PubMed

Winnick, Jason J; An, Zhibo; Moore, Mary Courtney; Ramnanan, Christopher J; Farmer, Ben; Shiota, Masakazu; Cherrington, Alan D

2009-08-01

To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline (n = 7) or fructose (n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 +/- 0.27 and 5.55 +/- 0.53 mg x kg(-1) x min(-1) and glycogen synthesis averaged 0.72 +/- 0.24 and 3.98 +/- 0.57 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively (P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 +/- 0.4 and 0.9 +/- 0.2 to 3.1 +/- 0.6 and 2.5 +/- 0.5 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively, a change of 1.6 mg x kg(-1) x min(-1) in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

Interrupted intracarotid artery cold saline infusion as an alternative method for neuroprotection after ischemic stroke.

PubMed

Ji, Ya-Bin; Wu, Yong-Ming; Ji, Zhong; Song, Wei; Xu, Sui-Yi; Wang, Yao; Pan, Su-Yue

2012-07-01

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI). Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated. Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method. Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

PubMed

Okuhara, Yoshitaka; Hirotani, Shinichi; Ando, Tomotaka; Nishimura, Koichi; Orihara, Yoshiyuki; Komamura, Kazuo; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru

2017-04-01

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

PubMed Central

Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

2014-01-01

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use.

PubMed

Moulin, D E; Johnson, N G; Murray-Parsons, N; Geoghegan, M F; Goodwin, V A; Chester, M A

1992-03-15

To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems. Retrospective study. Tertiary care facilities and patients' homes. Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home). Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible. Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness. The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months. Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.

A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

PubMed Central

Liu, Zhenwen; Wang, Ying; Xu, Rounan; Sun, Yanling; Zhang, Min; Yu, Xi; Wang, Hongbo; Meng, Lingzhan; Su, Haibin; Jin, Lei

2017-01-01

Abstract Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned into the UC‐MSC infusion group or the control group. Thirteen patients received one infusion of UC‐MSCs (1 × 106/kg body weight); one patient received multiple UC‐MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow‐up for 12 weeks after UC‐MSC infusions. No side effects occurred in treated patients. Four weeks after UC‐MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12‐week follow‐up period. Importantly, allograft histology was improved after administration of UC‐MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC‐MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC‐MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053–2061 PMID:29178564

Severe lactic acidosis after an iatrogenic propylene glycol overdose.

PubMed

Zosel, Amy; Egelhoff, Elizabeth; Heard, Kennon

2010-02-01

Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his lactic acidosis was treated successfully with fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of lorazepam may result in severe propylene glycol toxicity, which may be treated with fomepizole and CVVH.

[Management of patients with bronchial asthma received general anesthesia and surgical intervention].

PubMed

To, Masako; Tajima, Makoto; Ogawa, Cyuhei; Otomo, Mamoru; Suzuki, Naohito; Sano, Yasuyuki

2002-01-01

Stimulation to bronchial mucosa is one of the major risk factor of asthma attack. When patients receive surgical intervention and general anesthesia, they are always exposed to stimulation to bronchial mucosa. Prevention method of bronchial asthma attack during surgical intervention is not established yet. We investigated that clinical course of patients with bronchial asthma who received general anesthesia and surgical intervention. Seventy-six patients with bronchial asthma were received general anesthesia and surgical intervention from 1993 to 1998. Twenty-four patients were mild asthmatic patients, 39 were moderate asthmatic patients and 13 were severe asthmatic patients. Preoperative treatment for preventing asthma attack was as follows; Eight patients were given intravenous infusion of aminophylline before operation. Fifty-two patients were given intravenous infusion of aminophylline and hydrocortisone before operation. Three patients were given intravenous infusion of hydrocortisone for consecutive 3 days before operation. Thirteen patients were given no treatment for preventing asthma attack. One patient was suffered from asthma attack during operation. She was given no preventing treatment for asthma attack before operation. Three patients were suffered from asthma attack after operation. No wound dehiscence was observed in all patients. To prevent asthma attack during operation, intravenous infusion of steroid before operation is recommended, when patients with asthma receive general anesthesia and surgical intervention.

Isoflurane minimum alveolar concentration reduction by fentanyl.

PubMed

McEwan, A I; Smith, C; Dyar, O; Goodman, D; Smith, L R; Glass, P S

1993-05-01

Isoflurane is commonly combined with fentanyl during anesthesia. Because of hysteresis between plasma and effect site, bolus administration of fentanyl does not accurately describe the interaction between these drugs. The purpose of this study was to determine the MAC reduction of isoflurane by fentanyl when both drugs had reached steady biophase concentrations. Seventy-seven patients were randomly allocated to receive either no fentanyl or fentanyl at several predetermined plasma concentrations. Fentanyl was administered using a computer-assisted continuous infusion device. Patients were also randomly allocated to receive a predetermined steady state end-tidal concentration of isoflurane. Blood samples for fentanyl concentration were taken at 10 min after initiation of the infusion and before and immediately after skin incision. A minimum of 20 min was allowed between the start of the fentanyl infusion and skin incision. The reduction in the MAC of isoflurane by the measured fentanyl concentration was calculated using a maximum likelihood solution to a logistic regression model. There was an initial steep reduction in the MAC of isoflurane by fentanyl, with 3 ng/ml resulting in a 63% MAC reduction. A ceiling effect was observed with 10 ng/ml providing only a further 19% reduction in MAC. A 50% decrease in MAC was produced by a fentanyl concentration of 1.67 ng/ml. Defining the MAC reduction of isoflurane by all the opioids allows their more rational administration with inhalational anesthetics and provides a comparison of their relative anesthetic potencies.

Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis.

PubMed

Rhodes, Nathaniel J; Liu, Jiajun; O'Donnell, J Nicholas; Dulhunty, Joel M; Abdul-Aziz, Mohd H; Berko, Patsy Y; Nadler, Barbara; Lipman, Jeffery; Roberts, Jason A

2018-02-01

Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients. We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies. Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities. Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20-1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24-2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84-1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results. Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.

Influence of infusion pump operation and flow rate on hemodynamic stability during epinephrine infusion.

PubMed

Klem, S A; Farrington, J M; Leff, R D

1993-08-01

To determine whether variations in the flow rate of epinephrine solutions administered via commonly available infusion pumps lead to significant variations in blood pressure (BP) in vivo. Prospective, randomized, crossover study with factorial design, using infusion pumps with four different operating mechanisms (pulsatile diaphragm, linear piston/syringe, cyclic piston-valve, and linear peristaltic) and three drug delivery rates (1, 5, and 10 mL/hr). Two healthy, mixed-breed dogs (12 to 16 kg). Dogs were made hypotensive with methohexital bolus and continuous infusion. BP was restored to normal with constant-dose epinephrine infusion via two pumps at each rate. Femoral mean arterial pressure (MAP) was recorded every 10 secs. Pump-flow continuity was quantitated in vitro using a digital gravimetric technique. Variations in MAP and flow continuity were expressed by the coefficient of variation; analysis of variance was used for comparisons. The mean coefficients of variations for MAP varied from 3.8 +/- 3.1% (linear piston/syringe) to 6.1 +/- 6.6% (linear peristaltic), and from 3.4 +/- 2.2% (10 mL/hr) to 7.9 +/- 6.6% (1 mL/hr). The coefficients of variation for in vitro flow continuity ranged from 9 +/- 8% (linear piston-syringe) to 250 +/- 162% (pulsatile diaphragm), and from 35 +/- 44% (10 mL/hr) to 138 +/- 196% (1 mL/hr). Both the type of pump and infusion rate significantly (p < .001) influenced variation in drug delivery rate. The 1 mL/hr infusion rate significantly (p < .01) influenced MAP variation. Cyclic fluctuations in MAP of < or = 30 mm Hg were observed using the pulsatile diaphragm pump at 1 mL/hr. Factors inherent in the operating mechanisms of infusion pumps may result in clinically important hemodynamic fluctuations when administering a concentrated short-acting vasoactive medication at slow infusion rates.

Suppression of GH secretion in pituitary gigantism by continuous subcutaneous octreotide infusion in a pubertal boy.

PubMed

Näntö-Salonen, K; Koskinen, P; Sonninen, P; Toppari, J

1999-01-01

We describe a 12-y-old boy with excessive growth hormone and prolactin secretion presumably due to diffuse somatotroph hyperplasia. Until mid-puberty, his growth rate was under reasonable control, with high-dose octreotide injections every 8 h combined with a dopamine agonist. As his growth velocity started to increase, the efficacy of continuous s.c. octreotide infusion on GH secretion was tested. Similar total daily doses (600 microg) of octreotide were administered either by incremental s.c. injections at 8 h intervals, or by continuous s.c. infusion, two-thirds of the amount during night-time to control the presumed high nocturnal growth hormone (GH) peaks of the pubertal growth spurt. An overnight GH profile showed inadequate suppression of GH levels by incremental injections, while continuous s.c. infusion efficiently brought down the GH secretion. Another somatostatin analogue, lanreotide as a single depot injection was not effective. A 6-mo trial on the s.c. infusion regimen significantly reduced growth hormone secretion (as judged by IGF-I and IGFBP3 concentrations), and normalized growth velocity overcoming the pubertal growth spurt. It also caused a decrease in the pituitary size in magnetic resonance images. We conclude that the efficacy of octreotide infusion in suppressing GH secretion is superior to incremental injections with the same dose.

Dreaming in sedation during spinal anesthesia: a comparison of propofol and midazolam infusion.

PubMed

Kim, Duk-Kyung; Joo, Young; Sung, Tae-Yun; Kim, Sung-Yun; Shin, Hwa-Yong

2011-05-01

Although sedation is often performed during spinal anesthesia, the details of intraoperative dreaming have not been reported. We designed this prospective study to compare 2 different IV sedation protocols (propofol and midazolam infusion) with respect to dreaming during sedation. Two hundred twenty adult patients were randomly assigned to 2 groups and received IV infusion of propofol or midazolam for deep sedation during spinal anesthesia. Patients were interviewed on emergence and 30 minutes later to determine the incidence, content, and nature of their dreams. Postoperatively, patient satisfaction with the sedation was also evaluated. Two hundred fifteen patients (108 and 107 in the propofol and midazolam groups, respectively) were included in the final analysis. The proportion of dreamers was 39.8% (43/108) in the propofol group and 12.1% (13/107) in the midazolam group (odds ratio=4.78; 95% confidence interval: 2.38 to 9.60). Dreams of the patients receiving propofol were more memorable and visually vivid than were those of the patients receiving midazolam infusion. The majority of dreams (36 of 56 dreamers, 64.3%) were simple, pleasant ruminations about everyday life. A similarly high level of satisfaction with the sedation was observed in both groups. In cases of spinal anesthesia with deep sedation, dreaming was almost 5 times more common in patients receiving propofol infusion than in those receiving midazolam, although this did not influence satisfaction with the sedation. Thus, one does not need to consider intraoperative dreaming when choosing propofol or midazolam as a sedative drug in patients undergoing spinal anesthesia. © 2011 International Anesthesia Research Society

Daratumumab Injection

MedlinePlus

... watch you closely while you are receiving the infusion and afterwards to be sure you are not ... and treat reactions to daratumumab prior to your infusion and for the first and second days after ...

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

PubMed

Hurlbut, B J; Lubar, J F; Switzer, R; Dougherty, J; Eisenstadt, M L

1987-01-01

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

Total intravenous anaesthesia by boluses or by continuous rate infusion of propofol in mute swans (Cygnus olor).

PubMed

Müller, Kerstin; Holzapfel, Judith; Brunnberg, Leo

2011-07-01

To investigate intravenous (IV) propofol given by intermittent boluses or by continuous rate infusion (CRI) for anaesthesia in swans. Prospective randomized clinical study. Twenty mute swans (Cygnus olor) (eight immature and 12 adults) of unknown sex undergoing painless diagnostic or therapeutic procedures. Induction of anaesthesia was with 8 mg kg(-1) propofol IV. To maintain anaesthesia, ten birds (group BOLI) received propofol as boluses, whilst 10 (group CRI) received propofol as a CRI. Some physiological parameters were measured. Anaesthetic duration was 35 minutes. Groups were compared using Mann-Whitney U-test. Results are median (range). Anaesthetic induction was smooth and tracheal intubation was achieved easily in all birds. Bolus dose in group BOLI was 2.9 (1.3-4.3) mg kg(-1); interval between and number of boluses required were 4 (1-8) minutes and 6 (4-11) boluses respectively. Total dose of propofol was 19 (12.3-37.1) mg kg(-1). Awakening between boluses was very abrupt. In group CRI, propofol infusion rate was 0.85 (0.8-0.9) mg kg(-1) minute(-1), and anaesthesia was stable. Body temperature, heart and respiratory rates, oxygen saturation (by pulse oximeter) and reflexes did not differ between groups. Oxygen saturations (from pulse oximeter readings) were low in some birds. Following anaesthesia, all birds recovered within 40 minutes. In 55% of all, transient signs of central nervous system excitement occurred during recovery. 8 mg kg(-1) propofol appears an adequate induction dose for mute swans. For maintenance, a CRI of 0.85 mg kg(-1) minute(-1) produced stable anaesthesia suitable for painless clinical procedures. In contrast bolus administration, was unsatisfactory as birds awoke very suddenly, and the short intervals between bolus requirements hampered clinical procedures. Administration of additional oxygen throughout anaesthesia might reduce the incidence of low arterial haemoglobin saturation. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).

PubMed

Charles, Pierre; Terrier, Benjamin; Perrodeau, Élodie; Cohen, Pascal; Faguer, Stanislas; Huart, Antoine; Hamidou, Mohamed; Agard, Christian; Bonnotte, Bernard; Samson, Maxime; Karras, Alexandre; Jourde-Chiche, Noémie; Lifermann, François; Gobert, Pierre; Hanrotel-Saliou, Catherine; Godmer, Pascal; Martin-Silva, Nicolas; Pugnet, Grégory; Matignon, Marie; Aumaitre, Olivier; Viallard, Jean-François; Maurier, François; Meaux-Ruault, Nadine; Rivière, Sophie; Sibilia, Jean; Puéchal, Xavier; Ravaud, Philippe; Mouthon, Luc; Guillevin, Loïc

2018-04-25

To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group. Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations. AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions. NCT01731561; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

PubMed

Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Maintenance of plasma branched-chain amino acid concentrations during glucose infusion directs essential amino acids to extra-mammary tissues in lactating dairy cows.

PubMed

Curtis, Richelle V; Kim, Julie J M; Doelman, John; Cant, John P

2018-05-01

The objectives of this study were to investigate the effects of branched-chain AA (BCAA) supplementation when glucose is infused postruminally into lactating dairy cows consuming a diet low in crude protein (CP) and to test the hypothesis that low BCAA concentrations are responsible for the poor stimulation of milk protein yield by glucose. Twelve early-lactation Holstein cows were randomly assigned to 15% and 12% CP diets in a switchback design of 6-wk periods. Cows consuming the 12% CP diet received 96-h continuous jugular infusions of saline and 1 kg/d of glucose with 0, 75, or 150 g/d of BCAA in a Latin square sequence of treatments. Compared with saline, glucose infusion did not affect dry matter intake but increased milk yield by 2.2 kg/d and milk protein and lactose yields by 63 and 151 g/d, respectively. Mammary plasma flow increased 36% during glucose infusion compared with saline infusion, possibly because of a 31% decrease in total acetate plus β-hydroxybutyrate concentrations. Circulating concentrations of total essential AA and BCAA decreased 19 and 31%, respectively, during infusion of glucose, yet net mammary uptakes of AA remained unchanged compared with saline infusion. The addition of 75 and 150 g/d of BCAA to glucose infusions increased arterial concentrations of BCAA to 106 and 149%, respectively, of the concentrations in saline-infused cows, but caused a decrease in concentrations of non-branched-chain essential AA in plasma, as well as their mammary uptakes and milk protein yields. Plasma urea concentration was not affected by BCAA infusion, indicating no change in catabolism of AA. The lack of mammary and catabolic effects leads us to suggest that BCAA exerted their effects on plasma concentrations of the other essential AA by stimulating utilization in skeletal muscle for protein accretion. Results indicate that the glucose effect on milk protein yield was not limited by low BCAA concentrations, and that a stimulation of extra-mammary use of non-branched-chain essential amino acids by BCAA led to a decrease in milk protein yield. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Improving compliance with iron infusion therapy in the treatment of chronic anemia in haemodialysis patients with chronic kidney disease.

PubMed

Nuti, Amith

2015-01-01

This quality improvement project was conducted at the haemodialysis unit in the paediatric nephrology department at Noah's Ark Children's Hospital, Cardiff. Stakeholders involved were the medical and nursing staff at the haemodialysis unit, responsible for the care of children with chronic kidney disease CKD. Anaemia is prevalent among children with CKD. Iron infusion is administered to such children with chronic anaemia. Children on haemodialysis attending the Children's Kidney Center receive iron infusion if they satisfy the criteria based on haemoglobin and serum ferritin values according to departmental guidelines. This involves measurement of c-reactive protein and serum ferritin prior to iron administration. High iron exposure is detrimental to end organ function and hence warrants regular monitoring in conjunction with CRP, another inflammatory marker. We suspect that some children may be receiving iron infusions despite being iron replete. Also, we may be over-investigating these children with anaemia. We identified all children receiving iron infusion in the haemodialysis unit over a four week period. We retrospectively enquired blood investigations done, prior to and after iron infusion. Blood investigations lagged on pre and post infusion times. We devised a checklist for nursing staff to follow, primarily looking at set times for measuring haemoglobin, serum ferritin, and CRP during the month (at the start of the first and third week of the month) and also tabulating the ferritin values that would trigger frequency of iron infusions. These were aimed to: 1. Prevent iron overloading in patients with chronic anemia 2. Regularise the checking of bloods in those receiving iron infusions 3. Empower the nursing staff to independently take decisions on iron infusion delivery. The strategy for change encompassed multiple PDSA cycles. Plan: empower decision making on iron infusion by haemodialysis nursing staff Do: formulate a checklist for iron infusion based on the recommended set values of ferritin, CRP and haemoglobin Study: analyse adherence to checklist in three months time Act: make appropriate changes to workplace behaviour based on findings of the PDSA cycle We analysed 13 patient episodes prior to the intervention and a total of 19 patient episodes after the improvement cycles. The checklist was improved based on feedback obtained after the first PDSA cycle. A second cycle showed that investigations done were optimised. The third cycle showed improved adherence and compliance with prevention of over-treatment with iron infusion. There was 100% adherence to the investigations done prior to infusion and complied well with the department guidelines. This meant that the required number of blood tests were done on a more regular basis and it did not exceed from those done previously. Nursing behaviour with regard to initiation and maintenance of iron infusion became more independent. This empowered nursing decision making skills and consequently freed doctor-time. It also resulted in improving team morale and ultimately patient safety by mitigating human errors. For any QI project, interventions should be carefully designed. Stakeholder buy-in and easy accessibility of the intervention improves sustainability. Multiple PDSA cycles and incorporating stakeholder feedback into the cycle are key to success.

Improving compliance with iron infusion therapy in the treatment of chronic anemia in haemodialysis patients with chronic kidney disease

PubMed Central

Nuti, Amith

2015-01-01

This quality improvement project was conducted at the haemodialysis unit in the paediatric nephrology department at Noah's Ark Children's Hospital, Cardiff. Stakeholders involved were the medical and nursing staff at the haemodialysis unit, responsible for the care of children with chronic kidney disease CKD. Anaemia is prevalent among children with CKD. Iron infusion is administered to such children with chronic anaemia. Children on haemodialysis attending the Children's Kidney Center receive iron infusion if they satisfy the criteria based on haemoglobin and serum ferritin values according to departmental guidelines. This involves measurement of c-reactive protein and serum ferritin prior to iron administration. High iron exposure is detrimental to end organ function and hence warrants regular monitoring in conjunction with CRP, another inflammatory marker. We suspect that some children may be receiving iron infusions despite being iron replete. Also, we may be over-investigating these children with anaemia. We identified all children receiving iron infusion in the haemodialysis unit over a four week period. We retrospectively enquired blood investigations done, prior to and after iron infusion. Blood investigations lagged on pre and post infusion times. We devised a checklist for nursing staff to follow, primarily looking at set times for measuring haemoglobin, serum ferritin, and CRP during the month (at the start of the first and third week of the month) and also tabulating the ferritin values that would trigger frequency of iron infusions. These were aimed to: 1. Prevent iron overloading in patients with chronic anemia 2. Regularise the checking of bloods in those receiving iron infusions 3. Empower the nursing staff to independently take decisions on iron infusion delivery. The strategy for change encompassed multiple PDSA cycles. Plan: empower decision making on iron infusion by haemodialysis nursing staff Do: formulate a checklist for iron infusion based on the recommended set values of ferritin, CRP and haemoglobin Study: analyse adherence to checklist in three months time Act: make appropriate changes to workplace behaviour based on findings of the PDSA cycle We analysed 13 patient episodes prior to the intervention and a total of 19 patient episodes after the improvement cycles. The checklist was improved based on feedback obtained after the first PDSA cycle. A second cycle showed that investigations done were optimised. The third cycle showed improved adherence and compliance with prevention of over-treatment with iron infusion. There was 100% adherence to the investigations done prior to infusion and complied well with the department guidelines. This meant that the required number of blood tests were done on a more regular basis and it did not exceed from those done previously. Nursing behaviour with regard to initiation and maintenance of iron infusion became more independent. This empowered nursing decision making skills and consequently freed doctor-time. It also resulted in improving team morale and ultimately patient safety by mitigating human errors. For any QI project, interventions should be carefully designed. Stakeholder buy-in and easy accessibility of the intervention improves sustainability. Multiple PDSA cycles and incorporating stakeholder feedback into the cycle are key to success. PMID:26734315

The Pringle maneuver reduces the infusion rate of rocuronium required to maintain surgical muscle relaxation during hepatectomy.

PubMed

Kajiura, Akira; Nagata, Osamu; Sanui, Masamitsu

2018-04-27

We investigated the continuous infusion rates of rocuronium necessary to obtain the surgical muscle relaxation before, during, and after the Pringle maneuver on patients who underwent hepatectomy. Fifteen patients were induced by total intravenous anesthesia with propofol. After obtaining the calibration of acceleromyography, the patient was intubated with rocuronium 0.6 mg/kg. Fifteen minutes after initial rocuronium injection, the continuous infusion was started at 7.5 µg/kg/min. The infusion rate was adjusted every 15 min so that the first twitch height (% T1) might become from 3 to 10% of control. The infusion rates at the time when the state of surgical muscle relaxation was achieved for more than 15 min were recorded before, during and after the Pringle maneuver. The 25% recovery time was measured after discontinuing the continuous infusion. The infusion rate of rocuronium before, during, and after the Pringle maneuver was 7.2 ± 1.8, 4.2 ± 1.4, and 4.7 ± 1.5 µg/kg/min (mean ± SD), respectively. The rocuronium infusion rate during the Pringle maneuver was decreased about 40% compared to that before this maneuver, and that after completion of the Pringle maneuver was not recovered to that before the Pringle maneuver. The 25% recovery time was 20 ± 7 min. In case of continuous administration of rocuronium during surgery performing the Pringle maneuver, it was considered necessary to regulate the administration of rocuronium using muscle relaxant monitoring in order to deal with the decrease in muscle relaxant requirement by the Pringle maneuver.

Radiofrequency Thermal Ablation: Increase in Lesion Diameter with Continuous Acetic Acid Infusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lubienski, Andreas; Duex, Markus; Lubienski, Katrin

Purpose. To evaluate the influence of continuous infusion of acetic acid 50% during radiofrequency ablation (RFA) on the size of the thermal lesion produced. Methods. Radiofrequency (RF) was applied to excised bovine liver by using an expandable needle electrode with 10 retractable tines (LeVeen Needle Electrode, RadioTherapeutics, Sunnyvale, CA) connected to a commercially available RF generator (RF 2000, RadioTherapeutics, Sunnyvale, CA). Experiments were performed using three different treatment modalities: RF only (n = 15), RF with continuous saline 0.9% infusion (n = 15), and RF with continuous acetic acid 50% infusion (n = 15). RF duration, power output, tissue impedance,more » and time to a rapid rise in impedance were recorded. The ablated lesions were evaluated both macroscopically and histologically. Results. The ablated lesions appeared as spherical or ellipsoid, well-demarcated pale areas with a surrounding brown rim with both RF only and RF plus saline 0.9% infusion. In contrast, thermolesions generated with RF in combination with acetic acid 50% infusion were irregular in shape and the central portion was jelly-like. Mean diameter of the coagulation necrosis was 22.3 {+-} 2.1 mm (RF only), 29.2 {+-} 4.8 mm (RF + saline 0.9%) and 30.7 {+-} 5.7 mm (RF + acetic acid 50%), with a significant increase in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Time to a rapid rise in impedance was significantly prolonged in the RF plus saline 0.9% and RF plus acetic acid 50% groups compared with RF alone. Conclusions. A combination of RF plus acetic acid 50% infusion is able to generate larger thermolesions than RF only or RF combined with saline 0.9% infusion.« less

Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis.

PubMed

Trent Magruder, J; Grimm, Joshua C; Dungan, Samuel P; Shah, Ashish S; Crow, Jessica R; Shoulders, Bethany R; Lester, Laeben; Barodka, Viachaslau

2015-12-01

The authors sought to determine whether an institutional transition from intermittent to continuous dosing of intraoperative antibiotics in cardiac surgery affected surgical site infection (SSI) outcomes. A retrospective chart review utilizing propensity matching. A single academic, tertiary care hospital. One thousand one hundred seventy-nine patients undergoing coronary artery bypass grafting (CABG) and/or cardiac valvular surgery between April 2013 and November 2014 who received perioperative cefazolin. By method of cefazolin administration, patients were divided into an "intermittent-dosing" (ID) group and a "continuous-infusion" (CI) group. Of the 1,179 patients who underwent cardiac surgery during the study period, 1:1 propensity score matching yielded 399 patients in each group. Rates of diabetes (33.6% ID v 33.8% CI, p = 0.94), coronary artery bypass (62.3% v 61.4%, p = 0.66), and bilateral internal mammary artery harvesting (6.0% v 8.3%, p = 0.22) were similar between groups. SSIs occurred in more ID patients than CI patients (2.3% v 0.5%, p = 0.03). This difference was driven by decreases in extremity and conduit harvest site SSIs (1.8% v 0.3%, p = 0.03), as there were no episodes of mediastinitis, and superficial sternal SSI rates did not differ (0.5% v 0.3%, p = 0.56). There also were significantly fewer episodes of pneumonia in the CI group (6.0% v 2.3%, p = 0.008). Intensive care unit and total lengths of stay did not differ. Thirty-day mortality was 2.8% in both groups (p = 1.00). As compared to ID regimens, CI cefazolin infusion may reduce post-cardiac surgery infectious complications. Further study in larger patient populations is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Continuous Triiodothyronine Infusion on Citric Acid Cycle in the Normal Immature Swine Heart under Extracorporeal Membrane Oxygenation in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Ledee, Dolena R.

Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T 3) levels and modifies myocardial metabolism. We assessed the hypothesis that T 3 supplementation reverses ECMO induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age 25-38 days) with ECMO were received [2- 13C]lactate, [2,4,6,8- 13C]octanoate (medium chain fatty acid) and [U- 13C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 minutes of each protocol. Nuclear magnetic resonance (NMR) analysis of left ventricularmore » tissue determined the fractional contribution (Fc) of these substrates to the citric acid cycle (CAC). Fifty percent of the pigs in each group received intravenous T 3 supplement (bolus at 0.6 μg/kg and then continuous infusion at 0.2 μg/kg/hour) during ECMO. Under both substrate loading conditions T 3 significantly increased lactate-Fc with a marginal increase in octanoate-Fc. Both T 3 and high substrate provision increased myocardial energy status indexed by [Phosphocreatine]/[ATP]. In conclusion, T 3 supplementation promoted lactate metabolism to the CAC during ECMO suggesting that T 3 releases inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T 3 may be used therapeutically during ECMO to improve resting energy state and facilitate weaning.« less

Six years of continuous intrathecal infusion of opioid and bupivacaine in the treatment of refractory pain due to intrapelvic extrusion of bone cement after total hip arthroplasty.

PubMed

Dahm, P O; Nitescu, P V; Appelgren, L K; Curelaru, I D

1998-01-01

There is at present no reliable method for long-term treatment of severe pain following complications of total hip arthroplasty. We explored the long-term use of continuous intrathecal opioid/bupivacaine analgesia in a case not amendable to corrective surgery. A 77-year-old woman, having a total hip arthroplasty, developed refractory nociceptive-neuropathic pain located at the ventral and dorsal aspects of the left hip. Radiographs showed a mandarine-sized intrapelvic mass of bone cement adhering to the roof of the acetabular cup. Further surgery had been declined by the surgeon and by the patient. An 18-gauge Portex intrathecal catheter was inserted, and an intrathecal infusion of 4.75 mg/mL bupivacaine and 0.015 mg/mL buprenorphine was started from a portable Pharmacia-Deltec (St. Paul, Minnesota) pump. The mean daily doses during the treatment period (more than 6 years up to now) were 37 mg for bupivacaine and 0.114 mg for buprenorphine. The intrathecal treatment gave the patient 85-100% pain relief. The patient could transport herself in a wheelchair, was able to perform her own hygiene, receive visits, read, watch television, and also shop and visit restaurants. There has been no need to replace the intrathecal catheter. Intrathecal infusion of opioid/bupivacaine can provide satisfactory long-term analgesia in patients with refractory pain from the hip joint.

Development of effective prophylaxis against intraoperative carcinoid crisis.

PubMed

Woltering, Eugene A; Wright, Anne E; Stevens, Melissa A; Wang, Yi-Zarn; Boudreaux, John P; Mamikunian, Gregg; Riopelle, James M; Kaye, Alan D

2016-08-01

The prophylactic use of a preoperative, intraoperative, and postoperative high-dose continuous octreotide acetate infusion was evaluated for its ability to minimize the incidence of carcinoid crises during neuroendocrine tumor (NET) cytoreductive surgeries. A retrospective study was approved by the institutional review boards at Ochsner Medical Center-Kenner and Louisiana State University Health Sciences Center. Ochsner Medical Center-Kenner operating room and multispecialty NET clinic. One hundred fifty consecutive patients who underwent a total of 179 cytoreductive surgeries for stage IV, small bowel NETs. All patients received a 500-μg/h infusion of octreotide acetate preoperatively, intraoperatively, and postoperatively. Anesthesia and surgical records were reviewed. Carcinoid crisis was defined as a systolic blood pressure of less than 80mm Hg for greater than 10minutes. Patients who experienced intraoperative hypertension or hypotension, profound tachycardia, or a "crisis" according to the operative note were also reviewed. One hundred sixty-nine (169/179; 94%) patients had normal anesthesia courses. The medical records of 10 patients were further investigated for a potential intraoperative crisis using the aforementioned criteria. Upon review, 6 patients were determined to have had a crisis. The final incidence of intraoperative crisis was 3.4% (6/179). A continuous high-dose infusion of octreotide acetate intraoperatively minimizes the incidence of carcinoid crisis. We believe that the low cost and excellent safety profile of octreotide warrant the use of this therapy during extensive surgical procedures for midgut and foregut NETs. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of infusion-site reactions in renal transplant recipients receiving peripherally administered rabbit antithymocyte globulin as compared with basiliximab.

PubMed

Erickson, Abbie L; Roberts, Keri; Malek, Sayeed K; Chandraker, Anil K; Tullius, Stefan G; Gabardi, Steven

2010-06-01

Antithymocyte globulin rabbit (r-ATG) has been used for the treatment and prevention of acute rejection in renal transplant recipients (RTR). Current manufacturer recommendations for r-ATG dictate the need for administration through a high-flow vein (central line). Previous studies have shown peripheral administration of r-ATG to be safe; however, these studies suggest the co-administration of heparin and hydrocortisone and did not compare the infusion-site reaction rates to a control group. A retrospective analysis was conducted of adult RTR receiving r-ATG or basiliximab between January 2004 and October 2006. Each agent was administered through a dedicated peripheral line. The primary endpoint was the incidence of infusion-site reactions. Other endpoints included the need to replace the intravenous catheter and the incidence of systemic thrombosis within 1 month of transplantation. During the study period, 152 peripheral infusions of r-ATG and 92 peripheral infusions of basiliximab were administered. No difference in infusion-site reactions was noted between the groups. There was also no difference either in the need for peripheral line replacement or the rates of systemic thrombosis. Peripheral administration of r-ATG is safe and can be infused without concomitant heparin and hydrocortisone. This method of r-ATG infusion was shown to be as safe as peripherally administered basiliximab.

Extended Infusion of Piperacillin/Tazobactam in Children.

PubMed

Knoderer, Chad A; Karmire, Lauren C; Andricopulos, Katie L; Nichols, Kristen R

2017-01-01

Extended-infusion piperacillin/tazobactam (TZP) has been associated with positive clinical outcomes in adults, but similar data in children are lacking. The objective of this study was to describe efficacy outcomes with pediatric patients receiving extended-infusion TZP. This was a retrospective case series of children aged 1 month to 17 years who had documented Gram-negative infection and received extended-infusion TZP between April 2011 and March 2012. The primary outcome was 21-day clinical cure defined as negative follow-up cultures, where available, and infection resolution. Fifty children with a median (interquartile range [IQR]) age of 5 (2-9) years were included in the study. Patients received a median (IQR) TZP dose of 111.4 (100-112.5) mg/kg administered every 8 hours over 4 hours. Clinical and microbiologic cure were observed in 74% and 100% of patients, respectively. Patients not meeting criterial for 21-day clinical cure were younger (1 vs 7 years, p = 0.087) and had a longer length of hospital stay (23 vs 11 days, p = 0.037). The majority of children in this cohort achieved 21-day clinical cure with extended-interval TZP. Those without clinical cure tended to be younger and critically ill. Additional comparative studies evaluating traditional and extended-infusion TZP in children are needed.

Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients

PubMed Central

Arvia, Caterina; Siciliano, Valeria; Chatzianagnostou, Kyriazoula; Laws, Gillian; Quinones Galvan, Alfredo; Mammini, Chiara; Berti, Sergio; Molinaro, Sabrina; Iervasi, Giorgio

2014-01-01

AIM: To evaluate the impact on glucose variability (GLUCV) of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity. METHODS: We enrolled 44 type 2 diabetic patients (n = 32 males; n = 12 females) with acute coronary syndrome (ACS) and randomy assigned to standard a subcutaneous insulin treatment (n = 23) or a nurse-implemented continuous intravenous insulin infusion protocol (n = 21). We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis, i.e., glucose standard deviation (SD), the mean daily δ glucose (mean of daily difference between maximum and minimum glucose), and the coefficient of variation (CV) of glucose, expressed as percent glucose (SD)/glucose (mean). RESULTS: At the admission, first fasting blood glucose, pharmacological treatments (insulin and/or anti-diabetic drugs) prior to entering the study and basal glycated hemoglobin (HbA1c) were observed in the two groups treated with subcutaneous or intravenous insulin infusion, respectively. When compared with patients submitted to standard therapy, insulin-infused patients showed both increased first 24-h (median 6.9 mmol/L vs 5.7 mmol/L P < 0.045) and overall hospitalization δ glucose (median 10.9 mmol/L vs 9.3 mmol/L, P < 0.028), with a tendency to a significant increase in first 24-h glycaemic CV (23.1% vs 19.6%, P < 0.053). Severe hypoglycaemia was rare (14.3%), and it was observed only in 3 patients receiving insulin infusion therapy. HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment. CONCLUSION: Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment PMID:25126402

Contribution of propionate to glucose synthesis in sheep

PubMed Central

Leng, R. A.; Steel, J. W.; Luick, J. R.

1967-01-01

1. The production rate of propionate in the rumen and the entry rate of glucose into the body pool of glucose in sheep were measured by isotope-dilution methods. Propionate production rates were measured by using a continuous infusion of specifically labelled [14C]propionate. Glucose entry rates were estimated by using either a primed infusion or a continuous infusion of [U-14C]glucose. 2. The specific radioactivity of plasma glucose was constant between 4 and 9hr. after the commencement of intravenous infusion of [U-14C]glucose and between 1 and 3hr. when a primed infusion was used. 3. Infusion of [14C]propionate intraruminally resulted in a fairly constant specific radioactivity of rumen propionate between about 4 and 9hr. and of plasma glucose between 6 and 9hr. after the commencement of the infusion. Comparison of the mean specific radioactivities of glucose and propionate during these periods allowed estimates to be made of the contribution of propionate to glucose synthesis. 4. Comparisons of the specific radioactivities of plasma glucose and rumen propionate during intraruminal infusions of one of [1-14C]-, [2-14C]-, [3-14C]- and [U-14C]-propionate indicated considerable exchange of C-1 of propionate on conversion into glucose. The incorporation of C-2 and C-3 of propionate into glucose and lactate indicated that 54% of both the glucose and lactate synthesized arose from propionate carbon. 5. No differences were found for glucose entry rates measured either by a primed infusion or by a continuous infusion. The mean entry rate (±s.e.m.) of glucose estimated by using a continuous infusion into sheep was 0·33±0·03 (4) m-mole/min. and by using a primed infusion was 0·32±0·01 (4) m-mole/min. The mean propionate production rate was 1·24±0·03 (8) m-moles/min. The conversion of propionate into glucose was 0·36 m-mole/min., indicating that 32% of the propionate produced in the rumen is used for glucose synthesis. 6. It was indicated that a considerable amount of the propionate converted into glucose was first converted into lactate. PMID:4860545

Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

PubMed

Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

2015-01-01

There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

A continuous [15O]H2O production and infusion system for PET imaging

NASA Astrophysics Data System (ADS)

Sajjad, Munawwar; Liow, Jeih-San

1999-06-01

A system for continuous production and infusion of [15O]H2O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [15O]H2O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakagawa, Motoo, E-mail: lmloltlolol@gmail.com; Ogino, Hiroyuki; Shimohira, Masashi

2009-05-15

A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

A case report of dexmedetomidine used to treat intractable pain and delirium in a tertiary palliative care unit.

PubMed

Hilliard, Neil; Brown, Stuart; Mitchinson, Steve

2015-03-01

This case report describes an end-stage cancer patient with intractable neuropathic pain and delirium who was successfully managed during the last 3 weeks of her life with a continuous subcutaneous infusion of dexmedetomidine. A 55-year-old woman with locally advanced cervical cancer and uncontrolled pelvic pain was admitted to a tertiary palliative care unit for pain management. As her disease progressed, the patient's pelvic pain intensified despite treatment with methadone, gabapentin, ketamine, and hydromorphone administered by continuous subcutaneous infusion plus frequent breakthrough doses of hydromorphone and sufentanil. A continuous subcutaneous infusion of dexmedetomidine was started and titrated to achieve pain relief. The patient's pain and delirium cleared. The treatment was successful in fulfilling the patient's goal of care: not to be deeply and continuously sedated, but to be rousable and of clear mind while still having good pain control. Dexmedetomidine is a potentially useful medication for the targeted treatment of intractable pain and delirium in the tertiary palliative care environment. Future research is required to compare dexmedetomidine infusion to standard treatment with midazolam infusion for treatment of intractable symptoms in the palliative care environment. © The Author(s) 2014.

Dose-response studies of intracerebroventricular infusion of aldosterone in sensitized and non-sensitized rats.

PubMed

Gomez Sanchez, E P

1988-06-01

We have shown previously that the intracerebroventricular (icvt) infusion of 5 ng/h aldosterone (ALD) in the sensitized rat (one kidney removed, 1% NaCl plus 0.15% KCl solution to drink) produced hypertension similar in amplitude and time of onset to a 100-fold dose administered subcutaneously (s.c.), while a 5-ng/h subcutaneous infusion had no effect on blood pressure (BP). Dose-response studies on the icvt infusion of ALD were carried out in sensitized and non-sensitized (intact, with tap water to drink) male Sprague-Dawley rats (SDR). In both studies, a control group received the diluent, artificial cerebrospinal fluid (CSF), icvt. In sensitized rats, the pressures became significantly (P less than 0.05) elevated at day 7 in those receiving 15 ng/h icvt, day 11 in those receiving 5 ng/h icvt and 500 ng/h s.c. and day 18 in those receiving 1.5 ng/h icvt. The indirect systolic BPs at day 20 of infusion were 119 +/- 0.8 (s.e.) mmHg for controls, 182 +/- 5 for 15 ng/h icvt, 140 +/- 2 mmHg for 5 ng/h icvt, 131 +/- 1 mmHg for 1.5 ng/h icvt, 125 +/- 1 mmHg for 0.5 ng/h, and 159 +/- 5 mmHg for 500 ng/h s.c. Recovery (removal of pumps and return to water to drink) for 18 days resulted in the return of normal pressures in all groups except the 15 ng/h, icvt group in which pressures remained slightly, but significantly elevated at 127 +/- 3 mmHg. In non-sensitized rats, the pressures became significantly elevated in animals receiving 45 ng/h icvt and 1 microgram/h s.c. by day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh.

PubMed

Abedin, Mohammed Joynal; Sayeed, Abdullah Abu; Basher, Ariful; Maude, Richard J; Hoque, Gofranul; Faiz, M A

2012-06-01

Severe organophosphate compound (OPC) poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine the best therapy. A study was therefore undertaken to determine the optimal dosing regimen for atropine in the treatment of OPC poisoning. An open-label randomized clinical trial was conducted in Chittagong Medical College Hospital, Chittagong, Bangladesh, on 156 hospitalized individuals with OPC poisoning from June to September 2006. The aim was to compare the efficacy and safety of conventional bolus doses with individualized incremental doses of atropine for atropinization followed by continuous atropine infusion for management of OPC poisoning. Inclusion criteria were patients with a clear history of OPC poisoning with clear clinical signs of toxicity, i.e. features of cholinergic crisis. The patients were observed for at least 96 h. Immediate outcome and complications were recorded. Out of 156 patients, 81 patients received conventional bolus dose atropine (group A) and 75 patients received rapidly incremental doses of atropine followed by infusion (group B). The mortality in group 'A' was 22.5% (18/80) and in group 'B' 8% (6/75) (p < 0.05). The mean duration of atropinization in group 'A' was 151.74 min compared to 23.90 min for group 'B' (p < 0.001). More patients in group A experienced atropine toxicity than in group 'B' (28.4% versus 12.0%, p < 0.05); intermediate syndrome was more common in group 'A' than in group 'B' (13.6% versus 4%, p < 0.05), and respiratory support was required more often for patients in group 'A' than in group 'B' (24.7% versus 8%, p < 0.05). Rapid incremental dose atropinization followed by atropine infusion reduces mortality and morbidity from OPC poisoning and shortens the length of hospital stay and recovery. Incremental atropine and infusion should become the treatment of choice for OPC poisoning. Given the paucity of existing evidence, further clinical studies should be performed to determine the optimal dosing regimen of atropine that most rapidly and safely achieves atropinization in these patients.

Prostacyclin production in rabbit arteries in situ: inhibition by arachidonic acid-induced endothelial cell damage or by low-dose aspirin.

PubMed

Ingerman-Wojenski, C; Silver, M J; Smith, J B; Nissenbaum, M; Sedar, A W

1981-04-01

The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1 alpha and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that had previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicylic acid (ASA) inhibited 6-K-PGF1 alpha production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA.

Rotator cuff healing after continuous subacromial bupivacaine infusion: an in vivo rabbit study

PubMed Central

FRIEL, NICOLE A.; WANG, VINCENT M.; SLABAUGH, MARK A.; WANG, FANCHIA; CHUBINSKAYA, SUSAN; COLE, BRIAN J.

2013-01-01

Background The objective of this study was to evaluate the effects of continuous subacromial bupivacaine infusion on supraspinatus muscle and rotator cuff tendon healing via gross, biomechanical, and histologic analyses. Methods Thirty-three New Zealand White rabbits underwent unilateral supraspinatus transection and rotator cuff repair (RCR). Rabbits were assigned to 1 of 3 groups: (1)RCR only, (2)RCR with continuous saline infusion for 48 hours, or (3)RCR with continuous 0.25% bupivacaine with epinephrine (1:200,000) infusion for 48 hours. Rabbits were sacrificed at either 2 (for histologic assessment) or 8 weeks post-operatively (for biomechanical and histologic assessment). Results Tensile testing showed significantly higher load to failure in intact tendons compared to repaired tendons (p<0.01); however, no statistical differences were detected among RCR only, RCR Saline, and RCR Bupivacaine groups. Histologically, the enthesis of repaired tendons showed increased cellularity and disorganized collagen fibers compared to intact tendons, with no differences between treatment groups. Muscle histology demonstrated scattered degenerative muscle fibers at 2 weeks in both RCR Saline and RCR Bupivacaine, but no degeneration was noted at 8 weeks. Conclusions The healing supraspinatus tendons exposed to bupivacaine infusion showed similar histologic and biomechanical characteristics compared to untreated and saline infused RCR groups. Muscle histology showed fiber damage at 2 weeks for both the saline and bupivacaine treated groups, with no apparent disruption at 8 weeks, suggesting a recovery process. Therefore, subacromial bupivacaine infusion in this rabbit rotator cuff model does not appear to impair muscle or tendon following acute injury and repair. Level Of Evidence Basic science study PMID:22818894

Intravenous parecoxib and continuous femoral block for postoperative analgesia after total knee arthroplasty. A randomized, double-blind, prospective trial.

PubMed

Sarridou, Despoina G; Chalmouki, Georgia; Braoudaki, Maria; Koutsoupaki, Anna; Mela, Argiro; Vadalouka, Athina

2015-01-01

Up until now, the optimal strategy for postoperative pain management after total knee arthroplasty (TKA) remains to be elucidated. The current investigation aimed to examine the analgesic efficacy and the opioid sparing effects of intravenous parecoxib in combination with continuous femoral blockade. Randomized, double-blind, prospective trial. University hospital in the United Kingdom. In total, 90 patients underwent TKA under subarachnoid anesthesia and received continuous femoral block initially as a bolus with 20 mL of ropivacaine 0.75%. Infusion of 0.2% on 10 mL/h followed. Patients were randomized into 2 groups. Group D and Group P received parecoxib and placebo, respectively at 12 hour time intervals. Visual analog scale (VAS) pain scores were obtained at different time intervals including 4, 8, 12, 24 and 36 hours. The pain scores were measured with patients in a resting position. Morphine could also be administered with a patient controlled analgesia (PCA) pump if the specified analgesia was deemed inadequate (VAS > 5). None of the patients were withdrawn from the study. Parecoxib provided greater relief than placebo following TKA. The VAS pain scores measured at rest were statistically significantly lower in parecoxib-treated patients compared to the placebo group (P = 0.007) at 4 (P = 0.044), 12 (P = 0.001), and 24 hours (P = 0.012), postoperatively. Patients receiving parecoxib consumed less morphine at all time intervals than patients receiving placebo, with borderline statistical significance (P = 0.054). In each time period, all patients receiving continuous femoral block irrespectively of the treatment group, required low morphine doses. Current protocol did not answer question as to functional recovery. According to our findings intravenous parecoxib in combination with continuous femoral block provided superior analgesic efficacy and opioid sparing effects in patients undergoing TKA.

77 FR 40073 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... exposed T cells. Methods for generating better T cells to utilize for infusion into patients in adoptive... treated with total body radiation and then receives an infusion of the treated cell culture bone marrow...

Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo

PubMed Central

Bates, Darcy J P; Lewis, Lionel D; Eastman, Alan; Danilov, Alexey V

2015-01-01

Aims The authors’ aim was to conduct a proof-of-principle study to test whether c-Jun N-terminal kinase (JNK) phosphorylation and Noxa induction occur in peripheral blood chronic lymphocytic leukaemia (CLL) cells in patients receiving a vincristine infusion. Methods Patients with CLL received 2 mg vincristine by a 5-min intravenous infusion. Blood samples were collected at baseline and up to 6 h after the vincristine infusion, and assayed for JNK activation, Noxa induction and vincristine plasma concentrations. Results Ex vivo treated peripheral CLL cells activated JNK in response to 10–100 nM vincristine in 6 h. Noxa protein expression, while variable, was also observed over this time frame. In CLL patients, vincristine infusion led to rapid (<1 h) JNK phosphorylation in peripheral blood CLL cells which was sustained for at least 4–6 h after the vincristine infusion. Noxa protein expression was not observed in response to vincristine infusion. Conclusions This study confirmed that vincristine can activate JNK but not induce Noxa in CLL cells in vivo. The results suggest that novel JNK-dependent drug combinations with vincristine warrant further investigation. PMID:25753324

Effect of Intravenous Infusion Solutions on Bioelectrical Impedance Spectroscopy.

PubMed

Yap, Jason; Rafii, Mahroukh; Azcue, Maria; Pencharz, Paul

2017-05-01

Bioelectrical impedance (BIA) is often used to measure body fluid spaces and thereby body composition. However, in acute animal studies, we found that impedance was driven by the saline content of intravenous (IV) fluids and not by the volume. The aim of the study was to investigate the effect of 3 different fluids acutely administered on the change in impedance, specifically resistance (R). Nine healthy adults participated in 3 treatment (0.9% saline, 5% dextrose, and a mixture of 0.3% saline + 3.3% dextrose) experiments on nonconsecutive days. They all received 1 L of one of the treatments intravenously over a 1-hour period. Repeated BIA measurements were performed prior to IV infusion and then every 5 minutes for the 1-hour infusion period, plus 3 more measurements up to 15 minutes after the completion of the infusion. The change in R in the 0.9% saline infusion experiment was significantly lower than that of the glucose and mixture treatment ( P < .001). Bioelectrical impedance spectroscopy and BIA measure salt rather than the volume changes over the infusion period. Hence, in patients receiving IV fluids, BIA of any kind (single frequency or multifrequency) cannot be used to measure body fluid spaces or body composition.

Efficacy and safety of an insulin infusion protocol in a surgical ICU.

PubMed

Taylor, Beth E; Schallom, Marilyn E; Sona, Carrie S; Buchman, Timothy G; Boyle, Walter A; Mazuski, John E; Schuerer, Douglas E; Thomas, James M; Kaiser, Christy; Huey, Way Y; Ward, Myrna R; Zack, Jeanne E; Coopersmith, Craig M

2006-01-01

Hyperglycemia is associated with complications in the surgical intensive care unit. The purpose of this study was to determine the efficacy and safety of nurse-driven insulin infusion protocols in lowering blood glucose (BG) in critical illness. All patients in a 24-bed surgical intensive care unit who required i.v. insulin infusions during 3 noncontiguous 6-month periods from 2002 to 2004 were evaluated. In the preintervention phase, 71 patients received a physician-initiated insulin infusion without a developed protocol. They were compared with 95 patients who received a nurse-driven insulin infusion protocol with a target BG of 120 to 150 mg/dL and to 119 patients who received a more stringent protocol with a target BG of 80 to 110 mg/dL. There was a stepwise decrease in average daily BG levels, from 190 to 163 to 132 mg/dL (p < 0.001). The less stringent protocol decreased the time to achieve a BG level < 150 mg/dL from 14.1 to 7.4 hours compared with physician-driven management (p < 0.05) resulting in similar time on an insulin infusion (53 versus 48 hours). The more intensive protocol brought BG levels < 150 mg/dL in 7.2 hours and < 111 mg/dL in 13.6 hours, but increased the length of time a patient was on an insulin infusion to 77 hours. The incidence of severe hypoglycemia (BG < 40 mg/dL) was statistically similar between the groups, ranging between 1.1% and 3.4%. Implementation of a nurse-driven protocol led to more rapid and more effective BG control in critically ill surgical patients compared with physician management. Tighter BG control can be obtained without a significant increase in hypoglycemia, although this is associated with increased time on an insulin infusion.

Comparison of the effect of bone marrow cells infusion through the portal vein and inferior vena cava combined with short-term rapamycin on allogeneic islet grafts in diabetic rats.

PubMed

Gao, Qingzhen; Wang, Xiaoping; Zhang, Ruibin; Wang, Pu; Jing, Yongsheng; Ren, Wanjun; Zhu, Bin

2016-07-01

The study aimed to compare the impact of allogeneic bone marrow cells (BMCs) infusion through the inferior vena cava (IVC) and portal vein (PV) combined with rapamycin on allogeneic islet grafts in diabetic rats. Recipient diabetic Wistar rats were infused with islets from Sprague-Dawley rats through the PV. PKH26-labeled BMCs of Sprague-Dawley rats were infused to recipients through the PV or IVC, followed by administration of rapamycin for 4 days. Blood glucose level was measured to evaluate the survival time of the islets. Lymphocytes separated from blood, BMCs, thymus, liver, spleen and lymph node were analyzed by flow cytometry. The peripheral blood smear, BMCs smear and frozen sections of tissues were observed by a fluorescence microscope. The survival time of the islets was significantly prolonged by the BMCs infusion combined with rapamycin. The rats receiving BMCs infusion through the PV induced a significantly longer survival time of the islets, and increased mixed chimeras of allogeneic BMCs in the thymus, liver, spleen and lymph node compared with the rats receiving BMCs infusion through the IVC. The amount of the mixed chimeras on day 14 was lower than that on day 7 after islet transplantation. Furthermore, PV transplantation had significantly more mixed chimera than IVC transplantation in all analyzed organs or tissues. BMCs infusion combined with rapamycin prolongs the islets survival and induces mixed chimeras of BMCs. PV infusion of BMCs might be a more effective strategy than IVC infusion of BMCs. © 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss: a double-blinded clinical study.

PubMed

Ogawa, Kaoru; Takei, Satoshi; Inoue, Yasuhiro; Kanzaki, Jin

2002-09-01

The authors conducted a prospective, randomized, double-blinded clinical trial for the purpose of elucidating the effects of prostaglandin E1 (PGE1) on idiopathic sudden sensorineural hearing loss. With the approval of the institute ethics committee, a total of 57 consecutive patients with diagnoses of idiopathic sudden sensorineural hearing loss were included in the study. The patients in the PGE1 group received continuous infusion containing 60 microg PGE1 and 100 mg hydrocortisone for 7 days, and the patients in the placebo group were treated with continuous infusion containing an inactive placebo and 100 mg hydrocortisone. No significant differences were observed in the improvements of pure-tone average and subjective symptoms between the PGE1 and the placebo groups. However, the hearing improvement at high frequencies (4 kHz and 8 kHz) was significantly higher in the PGE1 group than in the placebo group, especially in the patients with severe tinnitus. These results failed to prove a beneficial effect of PGE1 in the treatment of idiopathic sudden sensorineural hearing loss. Further studies will be needed to clarify the pharmacologic actions of PGE1 in the cochlea.

Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses.

PubMed

Wilson, D V; Bohart, G V; Evans, A T; Robertson, S; Rondenay, Y

2002-01-01

To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. Retrospective study. Fifty-one adult horses aged 9.5 ± 6.9 years (range 1-23 years) and weighing 575 ± 290.3 kg. Records of horses presented to our clinic over a 3-year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. Detomidine was administered as an initial bolus loading dose (mean ± SD) of 7.5 ± 1.87 μg kg -1 . The initial infusion rate was 0.6 μg kg -1 minute -1 , and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

The impact of iron overload and its treatment on quality of life: results from a literature review.

PubMed

Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana

2006-09-28

To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL.

Preliminary findings on the interactive effects of IV ethanol and IV nicotine on human behavior and cognition: a laboratory study.

PubMed

Ralevski, Elizabeth; Perry, Edward B; D'Souza, D Cyril; Bufis, Vanessa; Elander, Jacqueline; Limoncelli, Diana; Vendetti, Michael; Dean, Erica; Cooper, Thomas B; McKee, Sherry; Petrakis, Ismene

2012-05-01

There are mixed reports on nicotine's effects on alcohol-induced impairment in cognitive performance and behavior in humans. The main objective of this study was to characterize the interactive effects of acute intravenous (IV) alcohol and nicotine administration on behavior and cognition in healthy nonsmokers. Healthy subjects aged 21-44 years participated in 3 test days. On each test day, they received in a double-blind randomized manner one of three IV alcohol infusion conditions using a "clamp": placebo, targeted breathalyzer of 40 mg%, or targeted breathalyzer of 80 mg%. Alcohol infusion was delivered over 20 min and lasted for 120 min. They also received both placebo and active nicotine in a fixed order delivered intravenously. Placebo nicotine was delivered first over 10 min at the timepoint when the breath alcohol was "clamped"; active nicotine (1.0 mcg/kg/min) was delivered for 10 min, 70 min after the alcohol infusion was clamped. Subjective effects of alcohol were measured using the Biphasic Alcohol Effects Scale and the Number of Drinks Scale. Cognitive inhibition and attention were measured by the Continuous Performance Task-Identical Pairs and working memory by the Rey Auditory Verbal Learning Task (RAVLT). Nicotine significantly reversed subjective intoxication and sedation of alcohol at the low dose. Alcohol impaired performance on the RAVLT, and nicotine further impaired verbal learning and recall at both doses of alcohol. The data showed that nicotine had an effect on subjective alcohol effects but did not reverse and actually worsened alcohol-induced deficits in memory.

I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.

PubMed

Hwang, J-Y; Na, H-S; Jeon, Y-T; Ro, Y-J; Kim, C-S; Do, S-H

2010-01-01

In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

Regular intermittent bolus provides similar incidence of maternal fever compared with continuous infusion during epidural labor analgesia.

PubMed

Feng, Shan-Wu; Xu, Shi-Qin; Ma, Li; Li, Cai-Juan; Wang, Xian; Yuan, Hong-Mei; Wang, Fu-Zhou; Shen, Xiao-Feng; Ding, Zheng-Nian

2014-10-01

To compare the effects of regular intermittent bolus versus continuous infusion for epidural labor analgesia on maternal temperature and serum interleukin-6 (IL-6) level. This randomized trial was performed in Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, China between October 2012 and February 2014. Either regular intermittent bolus (RIB, n=66) or continuous infusion (CI, n=66) was used for epidural labor analgesia. A bolus dose (10 ml of 0.08% ropivacaine + 0.4 ug·ml-1 sufentanil) was manually administrated once an hour in the RIB group, whereas the same solution was continuously infused at a constant rate of 10 ml·h-1 in the CI group. Maternal tympanic temperature and serum IL-6 level were measured hourly from baseline to one hour post partum. The incidences of fever (>/=38 degree celsius ) were calculated. The incidence of maternal fever was similar between the 2 groups. There was a rising trend in mean temperature over time in both groups, but no statistical difference was detected between the groups at respective time points; maternal serum IL-6 showed similar changes. Compared with continuous infusion, regular intermittent bolus presents with the same incidence of maternal fever for epidural labor analgesia. Interleukin-6 elevation could be involved in mean maternal temperature increase. 

Failure of intrathecal ketorolac to reduce remifentanil-induced postinfusion hyperalgesia in humans.

PubMed

Eisenach, James C; Tong, Chuanyao; Curry, Regina S

2015-01-01

In rodents, acute exposure to opioids results in transient antinociception followed by longer lasting hypersensitivity to tactile or thermal stimuli, a phenomenon termed opioid-induced hyperalgesia. This hypersensitivity can be blocked or reversed by intrathecally administered cyclooxygenase inhibitors, including ketorolac, suggesting a role for spinal prostaglandins. In surgical patients, the dose of intraoperative opioid, particularly the short-acting drug, remifentanil, is directly related to increased pain and opioid requirements for many hours postoperatively. In addition, experimentally induced tactile hypersensitivity in humans is exaggerated after cessation of remifentanil infusions. The degree of this experimental opioid-induced hyperalgesia is reduced by systemic treatment with cyclooxygenase inhibitors, and investigators have speculated that this reduction reflects the actions in the central nervous system, most likely in the spinal cord. To test this hypothesis, we measured cerebrospinal fluid prostaglandin E2 concentrations during and after remifentanil infusion in 30 volunteers. These volunteers received intrathecal ketorolac or saline in a random, blinded manner during intravenous remifentanil infusion after generation of hypersensitivity by topical capsaicin. Remifentanil reduced pain to noxious heat stimuli and reduced areas of capsaicin-induced hypersensitivity similarly in those receiving intrathecal ketorolac or saline. The primary outcome measure, area of capsaicin-induced hypersensitivity after stopping remifentanil, showed a similar increase in those receiving ketorolac as in those receiving saline. Cerebrospinal fluid prostaglandin E2 concentrations did not increase during postinfusion hyperalgesia compared with those during infusion, and they were not increased during infusion compared with those in historical controls. These data fail to support the hypothesis that acute opioid-induced hyperalgesia reflects spinal cyclooxygenase activation causing central sensitization.

21 CFR 870.1800 - Withdrawal-infusion pump.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1800 Withdrawal-infusion...

The use of an "unnatural" prostaglandin in the termination of pregnancy.

PubMed

Gillespie, A; Beazley, J M; van Dorp, D A

1971-04-01

An unnatural prostaglandin (PG) (prepared by biosynthesis using the method described by Vonkerman et al.) was used to terminate midtrimester pregnancy in 3 primiparous patients aged 21-24. The PG was administered intravenously using a Palmer slow infusion pump. The patients were monitored continuously with particular attention given to pulse, respiration, blood pressure, uterine contractions and cervical dilatation. All 3 cases successfully aborted. Effective infusion rate was similar to that of PGE1 and PGE2 (5-6 mcg/minute) and side effects were trivial (minimal skin flushing, vomiting, mild urticarial reaction). 2 of the patients aborted 8 and 22 hours after infusion stopped without being conscious of continuing uterine activity; the 3rd patient necessitated infusion on the 2nd day and exhibited increased response to the infusion; however, the PG supply was exhausted and syntocinon infusion facilitated the complete abortion. This study shows that this synthetic prostaglandin containing an uneven number of carbon atoms is pharmacologically active and can induce contractions in the intact human pregnant uterus.

The effect of on-demand vs deep neuromuscular relaxation on rating of surgical and anaesthesiologic conditions in patients undergoing thoracolaparoscopic esophagectomy (DEPTH trial): study protocol for a randomized controlled trial.

PubMed

Veelo, Denise P; Gisbertz, Suzanne S; Hannivoort, Rebekka A; van Dieren, Susan; Geerts, Bart F; van Berge Henegouwen, Mark I; Hollmann, Markus W

2015-08-05

Deep muscle relaxation has been shown to facilitate operating conditions during laparoscopic surgery. Minimally invasive esophageal surgery is a high-risk procedure in which the use of deep neuromuscular block (NMB) may improve conditions in the thoracic phase as well. Neuromuscular antagonists can be given on demand or by continuous infusion (deep NMB). However, the positioning of the patient often hampers train-of-four (TOF) monitoring. A continuous infusion thus may result in a deep NMB at the end of surgery. The use of neostigmine not only is insufficient for reversing deep NMB but also may be contraindicated for this procedure because of its cholinergic effects. Sugammadex is an effective alternative but is rather expensive. This study aims to evaluate the use of deep versus on-demand NMB on operating, anaesthesiologic conditions, and costs in patients undergoing a two- or three-phase thoracolaparoscopic esophageal resection. We will conduct a single-center randomized controlled double-blinded intervention study. Sixty-six patients undergoing a thoracolaparoscopic esophageal resection will be included. Patients will receive either continuous infusion of rocuronium 0.6 mg/kg per hour (group 1) or continuous infusion of NaCl 0.9 % 0.06 ml/kg per hour (group 2). In both groups, on-demand boluses of rocuronium can be given (open-label design). The primary aim of this study is to compare the surgical rating scale (SRS) during the abdominal phase. Main secondary aims are to evaluate SRS during the thoracic phase, to evaluate anesthesiologic conditions, and to compare costs (in euros) associated with use of rocuronium, sugammadex, and duration of surgery. This study is the first to evaluate the benefits of deep neuromuscular relaxation on surgical and anaesthesiologic conditions during thoracolaparoscopic esophageal surgery. This surgical procedure is unique because it consists of both an abdominal phase and a thoracic phase taking place in different order depending on the subtype of surgery (a two- or three-stage transthoracic esophagectomy). In addition, possible benefits associated with deep NMB, such as decrease in operating time, will be weighed against costs. European Clinical Trials Database (EudraCT) number: 2014-002147-18 (obtained 19 May 2014) ClinicalTrials.gov: NCT02320734 (obtained 18 Dec. 2014).

Comparison of the Effects of Intermittent Boluses to Simple Continuous Infusion on Patients' Global Perceived Effect in Intrathecal Therapy for Pain: A Randomized Double-Blind Crossover Study.

PubMed

Eldabe, Sam; Duarte, Rui V; Madzinga, Grace; Batterham, Alan M; Brookes, Morag E; Gulve, Ashish P; Perruchoud, Christophe; Raphael, Jon H; Lorenzana, David; Buchser, Eric

2017-05-01

Intrathecal drug delivery (ITDD) is commonly used for intractable pain management. A paucity of good-quality studies in chronic noncancer patients and concerns over increased dosages have focused interest on different modes of administration. The aim of this international multicenter randomized double-blind crossover trial was to compare the efficacy of the same daily dose of drugs administered by intermittent boluses vs simple continuous infusion. Eligible patients implanted with a programmable ITDD device were randomized to receive two weeks of either intermittent boluses or a simple continuous flow in period 1, followed by a crossover to the alternative mode of administration. The primary outcome measure was the Patients' Global Impression of Change (PGIC) scale. The mean proportion of positive responders (at least "minimally improved") was 38.4% in the continuous condition vs 37.3% in the bolus (difference in proportions = 1.1%, 95% confidence interval [CI] = -21.8-24.0%, P  = 0.93). The mean PGIC in the continuous condition was 3.8 vs 3.9 in the bolus (mean difference = -0.1, -0.6-0.4, P  = 0.72). Exploratory analyses revealed a tendency for the mean proportion of positive responders to be higher at low vs high flow rates for both bolus and continuous administrations. Two patients were withdrawn from the study due to adverse events during the bolus phase, both with symptoms of increased pain, and one patient with additional symptoms of numbness and urinary retention. The mean PGIC and proportion of positive responders was not substantially different after intermittent bolus vs continuous administration. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Apparent lack of cross-reactivity for infusion-related reactions between two forms of lipid-based amphotericin B.

PubMed

Buckley, Mitchell S; Anderson, Clint S; Patel, Shardool A; Yerondopoulos, Melanie J; Wicks, Laura M; Martin, Mary T

2013-06-15

The case of a patient who experienced probable infusion-related reactions to amphotericin B lipid complex (ABLC) but tolerated continued amphotericin B therapy after a switch to an alternative lipid-based formulation is reported. A 28-year-old immunocompromised man with pneumonia, respiratory failure, and neutropenic fever was initiated on ABLC and other antibiotics for suspected invasive aspergillosis. Due to the patient's deteriorating renal function, the use of amphotericin B was deemed preferable to the standard therapy for invasive aspergillosis (voriconazole) even though he had experienced likely infusion-related reactions to ABLC on two prior occasions. During the infusion of ABLC, significant increases in the man's temperature, respiratory rate, systolic blood pressure, and heart rate were observed. Although those symptoms were suspected to be infusion related, it was decided that continuing amphotericin B therapy with an alternative lipid-based form of the drug was the best course of action. After the patient was switched to liposomal amphotericin B one day later, no further infusion-related adverse reactions were noted for the duration of therapy. While this case suggests that adverse reactions to one type of amphotericin B might not occur with the use of an alternative formulation, further research is needed to better define the potential for cross-reactivity among various forms of amphotericin B and related safe-infusion practices. A patient with invasive aspergillosis who experienced likely infusion- related reactions to ABLC was able to tolerate continued amphotericin B therapy after a switch to the liposomal formulation.

Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses.

PubMed

Yamashita, Kazuto; Muir, William W; Tsubakishita, Sae; Abrahamsen, Eric; Lerch, Phillip; Izumisawa, Yasuharu; Kotani, Tadao

2002-10-15

To evaluate effects of infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. Randomized clinical trial. 40 horses. Horses were premedicated with xylazine and anesthetized with diazepam and ketamine. Anesthesia was maintained by infusion of guaifenesin, ketamine, and medetomidine and inhalation of sevoflurane (20 horses) or by inhalation of sevoflurane (20 horses). A surgical plane of anesthesia was maintained by controlling the inhaled concentration of sevoflurane. Sodium pentothal was administered as necessary to prevent movement in response to surgical stimulation. Hypotension was treated with dobutamine; hypoxemia and hypercarbia were treated with intermittent positive-pressure ventilation. The quality of anesthetic induction, maintenance, and recovery and the quality of the transition to inhalation anesthesia were scored. The delivered concentration of sevoflurane (ie, the vaporizer dial setting) was significantly lower and the quality of transition to inhalation anesthesia and of anesthetic maintenance were significantly better in horses that received the guaifenesin-ketamine-medetomidine infusion than in horses that did not. Five horses, all of which received sevoflurane alone, required administration of pentothal. Recovery time and quality of recovery were not significantly different between groups, but horses that received the guaifenesin-ketamine-medetomidine infusion required fewer attempts to stand. Results suggest that in horses, the combination of a guaifenesin-ketamine-medetomidine infusion and inhalation of sevoflurane resulted in better transition and maintenance phases while improving cardiovascular function and reducing the number of attempts needed to stand after the completion of anesthesia, compared with inhalation of sevoflurane.

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

PubMed

Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

2010-06-29

Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

Infusion fluids contain harmful glucose degradation products

PubMed Central

Bryland, Anna; Broman, Marcus; Erixon, Martin; Klarin, Bengt; Lindén, Torbjörn; Friberg, Hans; Wieslander, Anders; Kjellstrand, Per; Ronco, Claudio; Carlsson, Ola

2010-01-01

Purpose Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients’ blood. Methods The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. Results All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. Conclusions These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-1873-x) contains supplementary material, which is available to authorized users. PMID:20397009

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

PubMed

Avsar, M; Jansson, K; Sommer, W; Kruse, B; Thissen, S; Dreckmann, K; Knoefel, A-K; Salman, J; Hafer, C; Hecker, J; Buechler, G; Karstens, J H; Jonigk, D; Länger, F; Kaever, V; Falk, C S; Hewicker-Trautwein, M; Ungefroren, H; Haverich, A; Strüber, M; Warnecke, G

2016-05-01

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Phase II study of DFP-10917, a deoxycytidine analog, given by 14-day continuous intravenous infusion for chemotherapy-refractory advanced colorectal cancer.

PubMed

Mehrvarz Sarshekeh, Amir; Xiong, Henry Q; Iizuka, Kenzo; Hochster, Howard S; Kopetz, Scott

2018-06-13

Background DFP-10917 is a cytotoxic deoxycytidine analogue that causes DNA fragmentation, G 2 /M-phase arrest, and apoptosis. This agent has been shown to have antitumor activity against colorectal cancer (CRC) in preclinical studies and to be tolerable in patients. The purpose of our phase II trial was to evaluate the safety, efficacy and pharmacogenomics of DFP-10917 as well as DNA damage studies in patients with advanced CRC refractory to cytotoxic chemotherapy. Methods In this single-arm, Simon two-stage, phase II trial, patients with chemotherapy-refractory advanced CRC received 2.0 mg/m 2 /day DFP-10917 via 14-day continuous infusion. Enrollment criteria included age ≥ 18 years, Eastern Cooperative Oncology Group status of 0 or 1, and adequate organ function. The primary endpoint was 3-month progression-free survival, defined as the proportion of patients who did not have progressive disease or death within 3 months of starting therapy. All patients who received any amount of DFP-10917 were included in the safety analysis. DNA damage study was assessed by comet assay. Results Of 28 patients initially enrolled, 26 received DFP-10917. Three patients (12%) were progression free at 3 months. The median progression-free survival was 1.3 months (95% confidence interval, 1.3-1.6 months). There were no complete or partial responses. Most patients (n = 20, 77%) had progressive disease, and only six (23%) had stable disease at any time. The trial was terminated according to the pre-planned stopping rule. The most frequent (≥5%) medication-related grade 3 or higher adverse events were neutropenia (n = 10, 38%), fatigue (n = 4, 15%), anemia (n = 3, 12%), and leukopenia (n = 3, 12%). DNA strand-breaks were detected after infusion (medians of % tail intensity were 2.89 and 12.64 on day 1 and day 15, respectively, p < 0.001, sign test). Conclusion Overall, single-agent DFP-10917 did not show meaningful antitumor activity in chemotherapy-refractory advanced CRC. The safety profile of DFP-10917 was tolerable and similar to that observed in earlier clinical studies.

A Novel Approach to Improving Fat Delivery in Neonatal Enteral Feeding

PubMed Central

Jarjour, Jane; Juarez, Alexa M.; Kocak, Denizen K.; Liu, Nathan J.; Tabata, Mika M.; Hawthorne, Keli M.; Ramos, Renata F.; Abrams, Steven A.

2015-01-01

Continuous infusion systems used for enteral nutrition support in the neonatal intensive care unit deliver as little as 60% of the fat in human milk to the neonate. This study determined the effect of mixing common feedings for preterm infants in the feeding bag and tubing on fat losses during enteral feeding. Laboratory models were developed to assess the contribution of various mixing techniques to delivered fat content. Fat content was measured periodically during feeding and compared to baseline measurements. A multistage approach incorporating a feeding bag inverter and a tubing circulation loop delivered >90% of milk fat when used in conjunction with a commercial continuous infusion system. With unfortified human milk, this approach delivered 91.9% ± 1.5% of fat content over a one hour feed, significantly greater (p < 0.01) than 77.5% ± 2.2% delivered by continuous infusion controls (Mean ± SEM). With fortified human milk, this approach delivered 92.1% ± 2.4% of fat content, significantly greater (p < 0.01) than 79.4% ± 1.0% delivered by a non-adapted infusion system (Mean ± SEM). Mixing human milk during continuous infusion improves fat delivery, which may improve nutrition and growth outcomes in low birth weight neonates. PMID:26110253

Short communication: Acute but transient increase in serum insulin reduces messenger RNA expression of hepatic enzymes associated with progesterone catabolism in dairy cows.

PubMed

Vieira, F V R; Cooke, R F; Aboin, A C; Lima, P; Vasconcelos, J L M

2013-02-01

The objective of this experiment was to evaluate the effects of glucose infusion on serum concentrations of glucose, insulin, and progesterone (P4), as well as mRNA expression of hepatic CYP2C19 and CYP3A4 in nonlactating, ovariectomized cows in adequate nutritional status. Eight Gir × Holstein cows were maintained on a low-quality Brachiaria brizantha pasture with reduced forage availability, but they individually received, on average, 3 kg/cow daily (as fed) of a corn-based concentrate from d -28 to 0 of the experiment. All cows had an intravaginal P4-releasing device inserted on d -14, which remained in cows until the end of the experiment (d 1). On d 0, cows were randomly assigned to receive, in a crossover design containing 2 periods of 24h each (d 0 and 1), (1) an intravenous glucose infusion (GLUC; 0.5 g of glucose/kg of BW, over a 3-h period) or (2) an intravenous saline infusion (SAL; 0.9%, over a 3-h period). Cows were fasted for 12h before infusions, and they remained fasted during infusion and sample collections. Blood samples were collected at 0, 3, and 6h relative to the beginning of infusions. Liver biopsies were performed concurrently with blood collections at 0 and 3h. After the last blood collection of period 1, cows received concentrate and returned to pasture. Cows gained BW (16.5 ± 3.6 kg) and BCS (0.08 ± 0.06) from d -28 to 0. Cows receiving GLUC had greater serum glucose and insulin concentrations at 3h compared with SAL cohorts. No treatment effects were detected for serum P4 concentrations, although mRNA expression of CYP2C19 and CYP3A4 after the infusion period was reduced for cows in the GLUC treatment compared with their cohorts in the SAL treatment. In conclusion, hepatic CYP3A4 and CYP2C19 mRNA expression can be promptly modulated by glucose infusion followed by acute increases in circulating insulin, which provides novel insight into the physiological mechanisms associating nutrition and reproductive function in dairy cows. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Adequacy of Fixed-Dose Heparin Infusions for Venous Thromboembolism Prevention after Microsurgical Procedures.

PubMed

Bertolaccini, Corinne M; Prazak, Ann Marie B; Agarwal, Jayant; Goodwin, Isak A; Rockwell, W Bradford; Pannucci, Christopher J

2018-05-22

 In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments.  This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of-range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE.  Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p  = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%.  Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12 units/kg/h deserve future study in patients undergoing microsurgical procedures to increase the proportion of patients receiving adequate VTE prophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Episodic Dural Stimulation in Awake Rats: A Model for Recurrent Headache

PubMed Central

Oshinsky, Michael L.; Gomonchareonsiri, Sumittra

2014-01-01

Objectives To model, in rats, the development of chronic trigeminal nociceptive hypersensitivity seen in patients with recurrent headache. Background Pathophysiology studies suggest that patients with recurrent migraine headache experience repeated bouts of dural nociceptor activation. In some patients, the severity and frequency of headache attacks increase over time. Patients with recurrent headache are hypersensitive to nitric oxide donors, such as glyceryl trinitrate (GTN). Current trigeminal pain models do not reflect the repeated episodic nature of dural nociceptor activation in patients with recurrent headache. Repeated nociceptor activation creates long-lasting changes in the periphery and brain due to activity-dependent neuronal plasticity. An animal model of repeated activation of dural nociceptors will facilitate the study of the physiological changes caused by repeated, episodic pain and the factors important for the transition of episodic to chronic migraine. Methods We induced dural inflammation by infusing an inflammatory soup (IS) through a cannula on the dura in awake behaving rats. This was repeated 3 times per week for up to 4 weeks. Periorbital pressure sensory testing was used to monitor the change in trigeminal sensitivity. Rats were challenged with GTN to test the hypothesis that many dural stimulations are required to model the hypersensitivity of migraine patients. Quantitative trigeminal sensory testing and microdialysis in the trigeminal nucleus caudalis (TNC) were used to measure GTN hypersensitivity. Results Multiple infusions of IS (>8), over weeks, induced a long-lasting decrease in periorbital pressure thresholds that lasted >3 weeks after the last infusion. In contrast, IS infusion in IS-naive rats and those that received 3 IS infusions produced only short-lasting decreases in periorbital pressure thresholds. Rats that received more than 8 IS infusions showed a marked increase in their neurochemical and behavioral responses to GTN. In these rats, GTN induced a decrease in periorbital von Frey thresholds that lasted >5 hours. In contrast, in rats that received only 3 IS infusions, GTN caused a threshold decrease for 1.5 hour. In vivo microdialysis in the TNC showed that GTN increased extracellular glutamate levels in rats with more than 8 IS infusions to 7.7 times the basal levels. In IS-naive rats and those that received only 3 IS infusions, the extracellular glutamate levels rose to only 1.7 and 1.9 times the basal level, respectively. Conclusions Repeated IS stimulation of the dura produces a chronic state of trigeminal hypersensitivity and potentiates the response to GTN. This hyperresponsiveness outlasts the last IS infusion and is the basis of our rat model of recurrent headache. This model can be used to study the changes in the brain and periphery induced by repeated trigeminovascular nociceptor activation and has the potential to elucidate the mechanisms for the transition of episodic to chronic headache. PMID:17635594

Ad hoc versus standardized admixtures for continuous infusion drugs in neonatal intensive care: cognitive task analysis of safety at the bedside.

PubMed

Brannon, Timothy S

2006-01-01

Continuous infusion intravenous (IV) drugs in neonatal intensive care are usually prepared based on patient weight so that the dose is readable as a simple multiple of the infusion pump rate. New safety guidelines propose that hospitals switch to using standardized admixtures of these drugs to prevent calculation errors during ad hoc preparation. Extended hierarchical task analysis suggests that switching to standardized admixtures may lead to more errors in programming the pump at the bedside.

Ad Hoc versus Standardized Admixtures for Continuous Infusion Drugs in Neonatal Intensive Care: Cognitive Task Analysis of Safety at the Bedside

PubMed Central

Brannon, Timothy S.

2006-01-01

Continuous infusion intravenous (IV) drugs in neonatal intensive care are usually prepared based on patient weight so that the dose is readable as a simple multiple of the infusion pump rate. New safety guidelines propose that hospitals switch to using standardized admixtures of these drugs to prevent calculation errors during ad hoc preparation. Extended hierarchical task analysis suggests that switching to standardized admixtures may lead to more errors in programming the pump at the bedside. PMID:17238482

Tolerability of ketorolac administered via continuous subcutaneous infusion for cancer pain: a preliminary report.

PubMed

De Conno, F; Zecca, E; Martini, C; Ripamonti, C; Caraceni, A; Saita, L

1994-02-01

We evaluated the local and systemic tolerability of ketorolac administered through continuous subcutaneous infusion in ten cancer patients. The patients were monitored daily for the severity and duration of pain, and the development of other symptoms. The duration of injection site varied from 1 to more than 7 days. No patients complained of local discomfort or pain. Mild local bleeding at the site of drug injection was observed in seven cases. No increase in the intensity of symptoms was observed during the infusion of ketorolac.

Population Pharmacokinetics of Ceftizoxime Administered by Continuous Infusion in Clinically Ill Adult Patients

PubMed Central

Facca, Bryan; Frame, Bill; Triesenberg, Steve

1998-01-01

Ceftizoxime is a widely used beta-lactam antimicrobial agent, but pharmacokinetic data for use with clinically ill patients are lacking. We studied the population pharmacokinetics of ceftizoxime in 72 clinically ill patients at a community-based, university-affiliated hospital. A population pharmacokinetic model for ceftizoxime was created by using a prospective observational design. Ceftizoxime was administered by continuous infusion to treat patients with proven or suspected bacterial infections. While the patients were receiving infusions of ceftizoxime, serum samples were collected for pharmacokinetic analysis with the nonlinear mixed-effect modeling program NONMEM. In addition to clearance and volume of distribution, various comorbidities were examined for their influence on the kinetics. All 72 subjects completed the study, and 114 serum samples were collected. Several demographic and comorbidity variables, namely, age, weight, serum creatinine levels, congestive heart failure, and long-term ventilator dependency, had a significant impact on the estimate for ceftizoxime clearance. A mixture model, or two populations for estimation of ceftizoxime clearance, was discovered. One population presented with an additive clearance component of 1.6 liters per h. In addition, a maximizer function for serum creatinine levels was found. In summary, two models for ceftizoxime clearance, mixture and nonmixture, were found and are presented. Clearance for ceftizoxime can be estimated with commonly available clinical information and the models presented. From the clearance estimates, the dose of ceftizoxime to maintain the desired concentration in serum can be determined. Work is needed to validate the model for drug clearance and to evaluate its predictive performance. PMID:9661021

The use of subcutaneous infusion in medication administration.

PubMed

Gabriel, Janice

The subcutaneous administration of medications is an area that receives little attention compared with other types of parenteral therapy. Parenteral administration is used by many thousands of patients who self-administer their medication on a daily basis-for example, those using insulin to manage diabetes, recipients of some types of hormone therapy and so on. It is also an effective route for the continuous administration of medication(s) in individuals who are terminally ill. Patients approaching the end of their life may be unable to tolerate the administration of oral medication to control their symptoms and make them more comfortable. This paper will discuss how subcutaneous infusion can be used to deliver these medications, but at the same time how important the selection of the most appropriate subcutaneous infusion device is to the overall comfort of the patient, and to reduce the potential for sharps-related injuries to healthcare workers. Appropriate device selection, together with its management, is an important contributing factor to patient safety and comfort. It will diminish the potential for premature device loss, which can lead to repeated insertion procedures for the patient, as well as delaying their medication. There is also a resource implication for the NHS, as the replacement of any device involves the use of additional equipment and staff time. Additionally, the use of any infusion device poses a risk to healthcare workers of acquiring a bloodborne infection should they experience a percutaneous injury. Knowledge of what equipment is available will reduce the potential risk to these staff.

Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation.

PubMed

Sezai, Akira; Iida, Mitsuru; Yoshitake, Isamu; Wakui, Shinji; Osaka, Shunji; Kimura, Haruka; Yaoita, Hiroko; Hata, Hiroaki; Shiono, Motomi; Nakai, Toshiko; Takayama, Tadateru; Kunimoto, Satoshi; Kasamaki, Yuji; Hirayama, Atsushi

2015-06-01

Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid-binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of β-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. -Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. -URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958. © 2015 American Heart Association, Inc.

Fentanyl-induced respiratory depression is attenuated in pregnant patients

PubMed Central

Sun, Jie; Yu, Min; Fang, Yin; Ding, Zhengnian

2017-01-01

Background Respiratory depression is a complication of intravenous fentanyl administration. The effect of pregnancy on respiratory depression following opioid administration is unclear. This study investigated the effect of pregnancy on fentanyl-induced respiratory depression. Patients and methods Female patients were divided into three groups (n=20 per group): control group (non-pregnant and scheduled for laparoscopic surgery), early pregnancy group (pregnant for 45–60 days and scheduled for abortion), and postpartum group (5–7 days postpartum scheduled for complete curettage of uterine cavity). All patients received an intravenous infusion of fentanyl 2 μg/kg. Respiratory rate (RR), end-tidal pressure of carbon dioxide (PETCO2), and pulse oxygen saturation (SpO2) were recorded continuously from just before fentanyl infusion to 15 min after commencing infusion. Plasma levels of progesterone were measured. Results SpO2 levels in the early pregnancy and postpartum groups were significantly higher and the levels of RR and PETCO2 were significantly lower than the control group. RR and SpO2 levels were significantly decreased in all groups, whereas PETCO2 was significantly increased after fentanyl infusion. The rates of RR increase and SpO2 decrease were significantly faster in the control group than in the other groups. The lowest SpO2 after intravenous fentanyl administration was significantly positively correlated with plasma progesterone levels. Conclusion Pregnancy improves fentanyl-induced respiratory depression, which may be associated with the increased levels of plasma progesterone. PMID:29200828

40 CFR 721.10706 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic). 721.10706 Section 721.10706 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10706 Infused...

40 CFR 721.10287 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Infused carbon nanostructures (generic). 721.10287 Section 721.10287 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10287 Infused...

40 CFR 721.10287 - Infused carbon nanostructures (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic). 721.10287 Section 721.10287 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10287 Infused...

Sedative and cardiorespiratory effects of detomidine constant rate infusion in sheep.

PubMed

de Moura, Rauane Sousa; Bittar, Isabela Plazza; da Silva, Luiz Henrique; Villela, Ana Carolina Vasquez; Dos Santos Júnior, Marcelo Borges; Borges, Naida Cristina; Franco, Leandro Guimarães

2018-02-01

The use of sheep in experiments is widespread and is increasing worldwide, and so is the need to develop species-specific anaesthetic techniques to ensure animal safety. Previous studies have mentioned several protocols involving the administration of alpha-2 adrenergic agonists in sheep; however, assessment of the efficacy and safety of these infusion techniques is still relatively new. Thus, the aim of the present study is to assess the effectiveness of detomidine constant rate infusion (CRI) in sheep by measuring the cardiovascular and respiratory parameters, blood gas variables and sedation scores. Eight adult female Santa Inês sheep received 20 µg/kg of detomidine hydrochloride intravenously as a bolus loading dose, followed by an infusion rate of 60 µg/kg/h. The heart rates and respiratory rates changed continuously during the CRI period. No arrhythmias were observed. The reduction in arterial partial pressure of oxygen (PaO 2 ) was not significant, but one animal showed signs of hypoxaemia (minimum PaO 2 of 66.9 mmHg). The arterial partial pressure of carbon dioxide (PaCO 2 ) increased, but the animals did not become hypercapnic. The bicarbonate (HCO 3- ), pH and base excess (BE) tended towards metabolic alkalosis. The cardiac output (CO), stroke volume (SV), cardiac index (CI) and ejection fraction (EF%) showed no significant changes. The fractional shortening (FS%) decreased slightly, starting at T 45min . Sedation scores varied between 3 (0/10) after sedation and during recovery and 7 (0/10) during CRI. We concluded that administering detomidine at an infusion rate of 60 µg/kg/h in Santa Inês sheep is a simple technique that produces satisfactory sedation for minimally invasive procedures.

Long-Term Antihyperalgesic and Opioid-Sparing Effects of 5-Day Ketamine and Morphine Infusion ("Burst Ketamine") in Diabetic Neuropathic Rats.

PubMed

Mak, Plato; Broadbear, Jillian H; Kolosov, Anton; Goodchild, Colin S

2015-09-01

"Burst ketamine" (BK) is the long-term infusion of subanesthetic ketamine in combination with an opioid. It is used clinically with mixed success to provide long-term pain relief and improve opioid response in patients. BK has not been simulated preclinically, therefore, its effectiveness was investigated in an animal model of neuropathic pain--streptozotocin-induced diabetic neuropathy. Diabetic neuropathic rats were randomized to receive a subcutaneous infusion of ketamine 20 mg/kg/day plus morphine 20 mg/kg/day (BK), either drug alone at the same dose, or sham treatment. Drugs were administered continuously over 5 days via osmotic minipump. Antihyperalgesic effects and antinociceptive responsiveness to morphine (0.625-10 mg/kg, i.p.) were assessed at 2, 4, 6, and 12 weeks post-treatment using paw withdrawal latency (PWL) from noxious heat (thermal hyperalgesia) and mechanical touch (tactile allodynia). Antihyperalgesic effects with significant increases in PWL from noxious heat occurred following BK and ketamine-only infusion, persisting 12 and 4 weeks, respectively. Opioid-sparing effects from noxious heat with increased sensitivity to morphine analgesia also occurred for 6 weeks after BK and 2 weeks after ketamine treatment; acute treatment with the maximum nonsedating dose of morphine (5 mg/kg) produced an antinociceptive effect in these two groups, but not in sham-treated rats. In morphine-only infusion rats, hyperalgesia and opioid insensitivity were both increased. This is the first preclinical study to use a model of neuropathic pain to demonstrate the utility of the BK procedure for delivering a long-lasting reduction in hyperalgesia and improved antinociceptive responsiveness to opioids. Wiley Periodicals, Inc.

Blood glucose regulation during living-donor liver transplant surgery.

PubMed

Gedik, Ender; İlksen Toprak, Hüseyin; Koca, Erdinç; Şahin, Taylan; Özgül, Ülkü; Ersoy, Mehmet Özcan

2015-04-01

The goal of this study was to compare the effects of 2 different regimens on blood glucose levels of living-donor liver transplant. The study participants were randomly allocated to the dextrose in water plus insulin infusion group (group 1, n = 60) or the dextrose in water infusion group (group 2, n = 60) using a sealed envelope technique. Blood glucose levels were measured 3 times during each phase. When the blood glucose level of a patient exceeded the target level, extra insulin was administered via a different intravenous route. The following patient and procedural characteristics were recorded: age, sex, height, weight, body mass index, end-stage liver disease, Model for End-Stage Liver Disease score, total anesthesia time, total surgical time, and number of patients who received an extra bolus of insulin. The following laboratory data were measured pre- and postoperatively: hemoglobin, hematocrit, platelet count, prothrombin time, international normalized ratio, potassium, creatinine, total bilirubin, and albumin. No hypoglycemia was noted. The recipients exhibited statistically significant differences in blood glucose levels during the dissection and neohepatic phases. Blood glucose levels at every time point were significantly different compared with the first dissection time point in group 1. Excluding the first and second anhepatic time points, blood glucose levels were significantly different as compared with the first dissection time point in group 2 (P < .05). We concluded that dextrose with water infusion alone may be more effective and result in safer blood glucose levels as compared with dextrose with water plus insulin infusion for living-donor liver transplant recipients. Exogenous continuous insulin administration may induce hyperglycemic attacks, especially during the neohepatic phase of living-donor liver transplant surgery. Further prospective studies that include homogeneous patient subgroups and diabetic recipients are needed to support the use of dextrose plus water infusion without insulin.

Colloid vs. crystalloid infusions in gastrointestinal surgery and their different impact on the healing of intestinal anastomoses.

PubMed

Marjanovic, Goran; Villain, Christian; Timme, Sylvia; zur Hausen, Axel; Hoeppner, Jens; Makowiec, Frank; Holzner, Philipp; Hopt, Ulrich Theodor; Obermaier, Robert

2010-04-01

The aim of this study was to investigate if colloid infusions have different effects on intestinal anastomotic healing when compared to crystalloid infusions depending on the amount of the administered volume. Twenty-eight Wistar rats were randomly assigned to four groups receiving different amounts of either a crystalloid (Cry) or a colloid (Col) infusion solution. Animals with volume restriction (Cry (-) or Col (-)) were treated with a low and animals with volume overcharge (Cry (+) or Col (+)) with a high flow rate. All animals received an infusion for a 60-min period, while an end-to-end small bowel anastomosis was performed. At reoperation, the anastomotic bursting pressure (millimeters of mercury) was measured, as well as anastomotic hydroxyproline concentration. The presence of bowel wall edema was assessed histologically. Median bursting pressures were comparable in the Col (-) [118 mm Hg (range 113-170)], the Cry (-) [118 mm Hg (78-139)], and the Col (+) [97 mm Hg (65-152)] group. A significantly lower median bursting pressure was found in animals with crystalloid volume overload Cry (+) [73 mm Hg (60-101)]. Corresponding results were found for hydroxyproline concentration. Histology revealed submucosal edema in Cry (+) animals. In case of a fixed, high-volume load, colloids seem to have benefits on intestinal anastomotic healing when compared to crystalloid infusions.

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population.

PubMed

Armstrong, Peter; Wilkinson, Pauline; McCorry, Noleen K

2018-03-01

To characterise the use of the parenteral non-steroidal anti-inflammatory drug parecoxib when given by continuous subcutaneous infusion (CSCI) in a hospice population. Clinical experience suggests parecoxib CSCI may be of benefit in this population, but empirical evidence in relation to its safety and efficacy is lacking. Retrospective chart review of patients with a cancer diagnosis receiving parecoxib CSCI from 2008 to 2013 at the Marie Curie Hospice, Belfast. Data were collected on treatment regime, tolerability and, in patients receiving at least 7 days treatment, baseline opioid dose and changes in pain scores or opioid rescue medication requirements. Parecoxib CSCI was initiated in 80 patients with a mean administration of 17.9 days (median 11, range 1-94). When used for a period of 7 days, there was a statistically significant reduction in pain scores (p=0.002) and in the number of rescue opioid doses required (p=0.001), but no statistically significant opioid-sparing effect (p=0.222). It was generally well tolerated, although gastrointestinal, renal adverse effects and local site irritation were reported. Parecoxib may have a valuable place in the management of cancer pain, especially towards the end of life when oral administration is no longer possible and CSCI administration is relied on. Further studies into the efficacy and tolerability of parecoxib CSCI are merited. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of continuous triiodothyronine infusion on the tricarboxylic acid cycle in the normal immature swine heart under extracorporeal membrane oxygenation in vivo

PubMed Central

Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy; Olson, Aaron K.

2014-01-01

Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T3) levels and modifies myocardial metabolism. We assessed the hypothesis that T3 supplementation reverses ECMO-induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age: 25–38 days) with ECMO received [2-13C]lactate, [2,4,6,8-13C4]octanoate (medium-chain fatty acid), and [U-13C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 min of each protocol. NMR analysis of left ventricular tissue determined the fractional contribution of these substrates to the tricarboxylic acid cycle. Fifty percent of the pigs in each group received intravenous T3 supplement (bolus at 0.6 μg/kg and then continuous infusion at 0.2 μg·kg−1·h−1) during ECMO. Under both substrate loading conditions, T3 significantly increased the fractional contribution of lactate with a marginal increase in the fractional contribution of octanoate. Both T3 and high substrate provision increased the myocardial energy status, as indexed by phosphocreatine concentration/ATP concentration. In conclusion, T3 supplementation promoted lactate metabolism to the tricarboxylic acid cycle during ECMO, suggesting that T3 releases the inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve the resting energy state and facilitate weaning. PMID:24531815

Effects of continuous triiodothyronine infusion on the tricarboxylic acid cycle in the normal immature swine heart under extracorporeal membrane oxygenation in vivo.

PubMed

Kajimoto, Masaki; Priddy, Colleen M O'Kelly; Ledee, Dolena R; Xu, Chun; Isern, Nancy; Olson, Aaron K; Portman, Michael A

2014-04-15

Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T3) levels and modifies myocardial metabolism. We assessed the hypothesis that T3 supplementation reverses ECMO-induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age: 25-38 days) with ECMO received [2-(13)C]lactate, [2,4,6,8-(13)C4]octanoate (medium-chain fatty acid), and [U-(13)C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 min of each protocol. NMR analysis of left ventricular tissue determined the fractional contribution of these substrates to the tricarboxylic acid cycle. Fifty percent of the pigs in each group received intravenous T3 supplement (bolus at 0.6 μg/kg and then continuous infusion at 0.2 μg·kg(-1)·h(-1)) during ECMO. Under both substrate loading conditions, T3 significantly increased the fractional contribution of lactate with a marginal increase in the fractional contribution of octanoate. Both T3 and high substrate provision increased the myocardial energy status, as indexed by phosphocreatine concentration/ATP concentration. In conclusion, T3 supplementation promoted lactate metabolism to the tricarboxylic acid cycle during ECMO, suggesting that T3 releases the inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve the resting energy state and facilitate weaning.

Minimum infusion rate and adrenocortical function after continuous infusion of the novel etomidate analog ET-26-HCl in rats.

PubMed

Jiang, Junli; Wang, Bin; Zhu, Zhaoqiong; Yang, Jun; Liu, Jin; Zhang, Wensheng

2017-01-01

Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats ( n  = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26-HCl as an infused anesthetic.

[Perioperative managements of the patients with cancer-pain receiving morphine].

PubMed

Matsuda, M; Murakawa, K; Noma, K; Uemura, Y; Maeda, S; Tashiro, C

1998-09-01

In the patients receiving morphine preoperatively, it is preoperatively important to avoid withdrawal symptoms postoperatively and to suppress postoperative pain and to maintain an appropriate anesthetic depth during the operation. We experienced six patients who had been under preoperative pain control with oral and/or epidural morphine and undergone palliative operation for their cancer pain. Four of the patients were preoperatively administered with oral morphine ranging from 30 to 270 mg.day-1. One patient was given epidural morphine 10 mg.day-1. Another was with morphine 1800 mg.day-1 orally and 50 mg.day-1 epiduraly. In all cases, general anesthesia was maintained with inhalation anesthetics. Anesthetic supplementation and postoperative pain management were performed with continuous i.v. infusion of morphine (half dosage of daily oral dosage), or subcutaneous injection (one sixth dosage of daily oral morphine) while preoperative epidural morphine was continued throughout the perioperative period. We were able to manage these patients well and none of them developed withdrawal symptom or increased postoperative pain.

Basic and clinical research on the therapeutic effect of intervention in primary liver cancer by targeted intra-arterial verapamil infusion.

PubMed

Pingsheng, Fan; Tengyue, Zhang; Qiang, Huang; Qiang, Wei; Xin, Sun; Liting, Qian

2012-01-01

The aim of this study was assess the therapeutic effect of targeted intra-arterial verapamil infusion in liver cancer patients and its side-effects in a dog model. The blood verapamil levels in dogs were determined after one-off intra-arterial infusion (0.7 mg/kg). Blood pressure, breathing state, and II-lead electrocardiogram were measured. Primary liver cancer patients (100) were randomly assigned into two groups. Controls (50) were treated with targeted intra-arterial infusion, and every patient received once-a-month interventional therapy, twice. Treatment group (50) received chemotherapeutics plus verapamil. Therapeutic and toxic side effects were evaluated. Control (41) and treatment group (45) patients were further treated with a second round of targeted intra-arterial infusion of chemotherapeutics plus verapamil, in 30 days after the 2-time interventional therapy. Every patient accepted interventional therapy 4-5 times during the 6 months after the first confirmed diagnosis. Following verapamil infusion, verapamil in dog liver was tenfold higher than in blood and was 4- to 20-fold higher than that needed for reversing carcinoma drug resistance. After interventional therapy, there were no significant changes in iconographic evaluation indices between the groups. Average activities of aminotransferases were 332 and 178 U/l in the treatment and control groups (P < 0.05). The imaging parameters of the treatment group were significantly better than those of control group. No side effects were found among the 91 patients who accepted verapamil infusion. After verapamil infusion, verapamil levels in dog hepatic tissue exceeded the effective concentration that reverses carcinoma multidrug resistance without any visible changes in the vital signs. Targeted intra-arterial verapamil infusion could improve the chemotherapy for the primary liver cancer patients without any side effects.

Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

PubMed

Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

2012-01-01

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

PubMed

Phillips, Michelle A; Acquisto, Nicole M; Gorodetsky, Rachel M; Wiegand, Timothy J

2014-06-01

Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

PubMed

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

A systematic review on clinical benefits of continuous administration of beta-lactam antibiotics.

PubMed

Roberts, Jason A; Webb, Steven; Paterson, David; Ho, Kwok M; Lipman, Jeffrey

2009-06-01

The clinical benefits of extended infusion or continuous infusion of beta-lactam antibiotics remain controversial. We systematically reviewed the literature to determine whether any clinical benefits exist for administration of beta-lactam antibiotics by extended or continuous infusion. PubMed (January 1950 to November 2007), EMBASE (1966 to November 2007), and the Cochrane Controlled Trial Register were searched (updated November 2007). Randomized controlled trials (RCTs) were meta-analyzed, and observational studies were described by two unblinded reviewers. A total of 846 patients from eligible prospective randomized controlled studies were included in the meta-analysis. Two observational studies were deemed appropriate for description. A meta-analysis of prospective RCTs was undertaken using Review Manager. Among a total of 59 potentially relevant studies, 14 RCTs involving a total of 846 patients from nine countries were deemed appropriate for meta-analysis. The use of continuous infusion of a beta-lactam antibiotic was not associated with an improvement in clinical cure (n = 755 patients; odds ratio: 1.04, 95% confidence interval: 0.74-1.46, p = 0.83, I = 0%) or mortality (n = 541 patients; odds ratio: 1.00, 95% confidence interval: 0.48-2.06, p = 1.00, I = 14.8%). All RCTs except one used a higher antibiotic dose in the bolus administration group. Two observational studies, not pooled because they did not meet the a priori criteria for meta-analysis, showed that beta-lactam administration by extended or continuous infusion was associated with an improvement in clinical cure. The difference in the results between the meta-analysis results and the observational studies could be explained by the bias created by a higher dose of antibiotic in the bolus group in the RCTs and because many of the RCTs only recruited patients with a low acuity of illness. The limited data available suggest that continuous infusion of beta-lactam antibiotics leads to the same clinical results as higher dosed bolus administration in hospitalized patients.

Attenuation of acute lung injury with propofol in endotoxemia.

PubMed

Takao, Yumiko; Mikawa, Katsuya; Nishina, Kahoru; Obara, Hidefumi

2005-03-01

Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.

Priming Effect of a Morning Meal on Hepatic Glucose Disposition Later in the Day

PubMed Central

Smith, Marta S.; Farmer, Ben; Kraft, Guillaume; Shiota, Masakazu; Williams, Phillip E.; Cherrington, Alan D.

2017-01-01

We used hepatic balance and tracer ([3H]glucose) techniques to examine the impact of “breakfast” on hepatic glucose metabolism later in the same day. From 0–240 min, 2 groups of conscious dogs (n = 9 dogs/group) received a duodenal infusion of glucose (GLC) or saline (SAL), then were fasted from 240–360 min. Three dogs from each group were euthanized and tissue collected at 360 min. From 360–600 min, the remaining dogs underwent a hyperinsulinemic (4× basal) hyperglycemic clamp (arterial blood glucose 146 ± 2 mg/dL) with portal GLC infusion. The total GLC infusion rate was 14% greater in dogs infused with GLC than in those receiving SAL (AUC360–600min 2,979 ± 296 vs. 2,597 ± 277 mg/kg, respectively). The rates of hepatic glucose uptake (5.8 ± 0.8 vs. 3.2 ± 0.3 mg ⋅ kg−1 ⋅ min−1) and glycogen storage (4.7 ± 0.6 vs. 2.9 ± 0.3 mg ⋅ kg−1 ⋅ min−1) during the clamp were markedly greater in dogs receiving GLC compared with those receiving SAL. Hepatic glycogen content was ∼50% greater, glycogen synthase activity was ∼50% greater, glycogen phosphorylase activity was ∼50% lower, and the amount of phosphorylated glycogen synthase was 34% lower, indicating activation of the enzyme, in dogs receiving GLC compared with those receiving SAL. Thus, morning GLC primed the liver to extract and store more glucose in the presence of hyperinsulinemic hyperglycemia later in the same day, indicating that breakfast enhances the liver’s role in glucose disposal in subsequent same-day meals. PMID:28174290

Bispectral index monitoring during infant cardiac surgery: relationship of BIS to the stress response and plasma fentanyl levels.

PubMed

Kussman, B D; Gruber, E M; Zurakowski, D; Hansen, D D; Sullivan, L J; Laussen, P C

2001-11-01

We evaluated the relationship of the bispectral index (BIS) to commonly used indices of depth of anaesthesia in 19 infants enrolled in a prospective study of the stress response to hypothermic cardiopulmonary bypass. Group 1 (n=8) received high-dose fentanyl by bolus technique; group 2 (n=6) received high-dose fentanyl by continuous infusion; and group 3 (n=5) received a fentanyl-midazolam infusion. Blood pressure (BP), heart rate (HR) and plasma epinephrine, norepinephrine, cortisol, ACTH, glucose, lactate and fentanyl were analysed 15 min postinduction, 15 min poststernotomy, 15 min on CPB during cooling and during skin closure. Mean BIS (SD) values for all 19 patients were 45.3 (12.3), 40.4 (14.5), 24.4 (12.4) and 47.9 (13.9), at the successive time points. No significant differences were observed in changes in BIS over time between the groups. A significant correlation was found 15 min postinduction between BIS and BP (systolic r=0.51, mean r=0.56) in all groups, but not between BIS and HR. BIS did not correlate with BP or HR at any other time point. There was no significant correlation between BIS and hormonal, biochemical or plasma fentanyl levels for any group at any time point. We were unable to demonstrate a relationship between the BIS and haemodynamic, metabolic or hormonal indices of anaesthetic depth. Further evaluation of the BIS algorithm is required in neonates and infants.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

PubMed

Valgimigli, Marco; Frigoli, Enrico; Leonardi, Sergio; Rothenbühler, Martina; Gagnor, Andrea; Calabrò, Paolo; Garducci, Stefano; Rubartelli, Paolo; Briguori, Carlo; Andò, Giuseppe; Repetto, Alessandra; Limbruno, Ugo; Garbo, Roberto; Sganzerla, Paolo; Russo, Filippo; Lupi, Alessandro; Cortese, Bernardo; Ausiello, Arturo; Ierna, Salvatore; Esposito, Giovanni; Presbitero, Patrizia; Santarelli, Andrea; Sardella, Gennaro; Varbella, Ferdinando; Tresoldi, Simone; de Cesare, Nicoletta; Rigattieri, Stefano; Zingarelli, Antonio; Tosi, Paolo; van 't Hof, Arnoud; Boccuzzi, Giacomo; Omerovic, Elmir; Sabaté, Manel; Heg, Dik; Jüni, Peter; Vranckx, Pascal

2015-09-10

Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Transient central diabetes insipidus induced by ketamine infusion.

PubMed

Hatab, Sarah Z; Singh, Arun; Felner, Eric I; Kamat, Pradip

2014-12-01

Report a case of central diabetes insipidus (DI) associated with ketamine infusion. A 2-year-old girl with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and stable hypertrophic cardiomyopathy was admitted to the pediatric intensive care with pneumonia. She subsequently developed respiratory failure and required intubation. Continuous ketamine infusion was used for the sedation and facilitation of mechanical ventilation. Shortly after infusion of ketamine, the patient developed DI and responded appropriately to vasopressin. The Naranjo adverse drug reaction probability scale indicated a probable relationship between the development of central DI and ketamine. The most likely mechanism involves ketamine's antagonist action on N-methyl-d-aspartate receptors, resulting in inhibition of glutamate-stimulated arginine vasopressin release from the neurohypophysis. This is the second case report of ketamine-induced central DI and the only report in children. Clinicians who sedate children with continuous ketamine infusions should monitor patients for developing signs and symptoms of DI by measuring serum sodium and urine output prior to, during, and after ketamine infusion in order to make a timely diagnosis of this potentially serious complication. © The Author(s) 2014.

Propylene Glycol-Related Delirium After Esmolol Infusion.

PubMed

Kapitein, Berber S; Biesmans, Renee S C G; van der Sijs, Heleen S I; de Wildt, Saskia S N

2014-07-01

Excipients used in oral or intravenous preparations may cause serious adverse events. We present the case of a 15-year-old boy with hypertrophic cardiomyopathy. In the pediatric intensive care unit, he received high doses of continuous intravenous esmolol (range = 20-400 µg/kg/min) for cardiac rhythm control. After a few days he developed a delirium not responding to high doses of antipsychotics or discontinuation of benzodiazepines. We eventually realized that the IV esmolol formulation contained high doses of propylene glycol and ethanol, which may accumulate after prolonged infusion and cause intoxication. Intoxication with propylene glycolcan cause neuropsychiatric symptoms. The boy's propylene glycol plasma concentration was approximately 4 g/L, whereas clinical symptoms arise at concentrations above 1 to 1.44 g/L. Application of the Naranjo adverse drug reaction probability scale suggested a probable relationship (score 6) between the propylene glycol infusion and the delirium. After discontinuation of esmolol, the delirium disappeared spontaneously. This is the first case describing excipient toxicity of esmolol, with an objective causality assessment revealing a probable relationship for the adverse event-namely, delirium-and esmolol. Although excipient toxicity is a well-known adverse drug reaction, this case stresses the importance for easily available information for and education of physicians. © The Author(s) 2014.

Does intravenous ketamine enhance analgesia after arthroscopic shoulder surgery with ultrasound guided single-injection interscalene block?: a randomized, prospective, double-blind trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Baik, Hee Jung; Han, Jong In; Chung, Rack Kyung

2014-07-01

Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and prevents pain associated with wind-up. We investigated whether low doses of ketamine infusion during general anesthesia combined with single-shot interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB. Forty adult patients scheduled for elective arthroscopic shoulder surgery were enrolled and randomized to either the control group or the ketamine group. All patients underwent SSISB and followed by general anesthesia. During an operation, intravenous ketamine was infused to the patients of ketamine group continuously. In control group, patients received normal saline in volumes equivalent to ketamine infusions. Pain score by numeric rating scale was similar between groups at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than 3 in both groups. The time to first analgesic request after admission on post-anesthesia care unit was also not significantly different between groups. Intraoperative low dose ketamine did not decrease acute postoperative pain after arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The preventive analgesic effect of ketamine could be mitigated by SSISB, which remains one of the most effective methods of pain relief after arthroscopic shoulder surgery.

Comparison of the effects of enteral feeding with continuous and intermittent parenteral nutrition on hepatic triglyceride secretion in human beings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isabel-Martinez, L.; Skinner, C.; Parkin, A.

Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained bymore » deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion.« less

Continuous subcutaneous delivery of medications for home care palliative patients-using an infusion set or a pump?

PubMed

Menahem, Sasson; Shvartzman, Pesach

2010-09-01

The purpose of this study was to evaluate safety, feasibility, and efficacy of continuous drug delivery by the subcutaneous route through a solution bag connected to an infusion set compared with an infusion pump in a home palliative care setting. Patients in need of continuous subcutaneous medication delivery for pain control, nausea, and/or vomiting were recruited. The study was designed as a double-blind, crossover study. The patient was connected to two parallel subcutaneous lines running simultaneously, connected together to a line entering the subcutaneous tissue. One line is connected to an infusion set and the other to a pump. The infusion set included a 500-cc solution bag connected to a 1.5-m plastic tube containing a drip chamber controlled by a roller clamp that is gravity driven without hyaluronidase. Active medications were randomly assigned to start in either administration method and switched after 24 h. An independent research assistant evaluated symptom control and side effects at baseline and every 24 h for 2 days using a structured questionnaire. Another independent research assistant connected the lines after adding medications and evaluated technical and clinical failures. Twenty-seven patients were recruited, and of them, 18 completed the study. Incidents in fluid administration were more common through the infusion set (18 times) compared to the pump (only twice). On the other hand, no clinical significant change was noted in the average symptom levels and side effects when medications were given through the infusion set versus the pump. No local edema or irritation was observed in either way of administration. In a home palliative care setting with a medical staff on call for 24 h, using medications for symptom control can be considered to be infused to a fluid solution bag through an infusion set instead of using a syringe driver or a pump when there is a responsible caregiver to follow up on the fluid. Subcutaneous constant drug delivery through a pump is more accurate.

The impact of iron overload and its treatment on quality of life: results from a literature review

PubMed Central

Abetz, Linda; Baladi, Jean-Francois; Jones, Paula; Rofail, Diana

2006-01-01

Background To assess the literature for the impact of iron overload and infusion Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the availability of QoL instruments for patients undergoing infusion ICT. Also, to obtain patients' experiences of having iron overload and receiving infusion ICT, and experts' clinical opinions about the impact of treatment on patients' lives. Methods A search of studies published between 1966 and 2004 was conducted using Medline and the Health Economic Evaluation Database (HEED). Qualitative results from patient and expert interviews were analysed. Hand searching of relevant conference abstracts completed the search. Results Few studies measuring the impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL domains affected included: depression; fatigue; dyspnoea; physical functioning; psychological distress; decrease in QoL during hospitalization. One theme in all articles was that oral ICT should improve QoL. No iron overload or ICT-specific QoL instruments were located in the articles. Interviews revealed that the impact of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic syndromes is high. Conclusion A limited number of studies assessed the impact of ICT or iron overload on QoL. All literature suggested a need for easily administered, efficacious and well tolerated oral iron overload treatments, given the impact of current ICT on adherence. Poor adherence to ICT was documented to negatively impact survival. Further research is warranted to continue the qualitative and quantitative study of QoL using validated instruments in patients receiving ICT to further understanding the issues and improve patients QoL. PMID:17007645

A Phase I and pharmacodynamic study of AT9283, a small molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis

PubMed Central

Foran, James; Ravandi, Farhad; Wierda, William; Garcia-Manero, Guillermo; Verstovsek, Srdan; Kadia, Tapan; Burger, Jan; Yule, Murray; Langford, Gillian; Lyons, John; Ayrton, John; Lock, Victoria; Borthakur, Gautham; Cortes, Jorge; Kantarjian, Hagop

2014-01-01

Purpose To identify the MTD of AT9283, an inhibitor of Aurora kinases A and B, in patients with relapsed or refractory leukemias. Other endpoints included pharmacokinetics, safety and tolerability, pharmacodynamics and preliminary evidence of efficacy. Patients and Methods AT9283 was administered as a continuous 72h infusion every 21 days. Doses were escalated by a standard 3+3 design. After the MTD for the 72h infusion was identified, infusion duration was increased incrementally to 96h and 120h. In total, 48 patients received ≥1 cycle of AT9283. Median age was 61 years (range 22–86 years), with 56% men, 75% diagnosed with AML, and 89% having received ≥3 (up to 16) prior lines of therapy. Results 324 mg/m2/72h AT9283 was determined to be the MTD. DLTs were myocardial infarction, hypertension, cardiomyopathy, tumor lysis syndrome, pneumonia and multiorgan failure. Other AT9283-related toxicities (non-DLT) included myelosuppression, predominantly leucopenia and mucositis. Bone marrow blasts decreased ≥38% after AT9283 treatment in approximately one-third of patients with relapsed/refractory AML; however, this effect was transient and no objective responses were achieved, despite evidence of aurora kinase B inhibition. Two patients with accelerated phase CML showed evidence of benefit, manifest as a cytogenetic response in one case; one patient completed 6 cycles of treatment. Exposure to AT9283 was generally dose proportional. Conclusion AT9283 tolerability was strongly dose dependent with reversible myelosuppression predominating at lower doses and events such as cardiovascular toxicities manifesting at higher doses. Clinical trials with AT9283 are ongoing in alternative patient populations. PMID:24355079

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

PubMed

Costello, John M; Dunbar-Masterson, Carolyn; Allan, Catherine K; Gauvreau, Kimberlee; Newburger, Jane W; McGowan, Francis X; Wessel, David L; Mayer, John E; Salvin, Joshua W; Dionne, Roger E; Laussen, Peter C

2014-07-01

We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. http://www.clinicaltrials.gov. Unique identifier: NCT00543309. © 2014 American Heart Association, Inc.

Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

PubMed

Kunwar, Sandeep; Chang, Susan M; Prados, Michael D; Berger, Mitchel S; Sampson, John H; Croteau, David; Sherman, Jeffrey W; Grahn, Amy Y; Shu, Vince S; Dul, Jeanne L; Husain, Syed R; Joshi, Bharat H; Pedain, Christoph; Puri, Raj K

2006-04-15

Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with administration of the infusate over a few days. Cintredekin besudotox (also known as IL13- PE38QQR) is a recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium, which targets malignant glioma cells. Cintredekin besudotox was administered via intraparenchymal CED after resection of supratentorial recurrent malignant glioma. The safety and toxicity profile was reviewed for 53 patients in whom infusion catheters had been placed; 51 of them received CED of the study drug. Adverse events were categorized based on time of onset in relation to CED, and the causal relationship with catheter placement or delivery of cintredekin besudotox. Catheters were placed in 53 patients, although only 51 of them received cintredekin besudotox. Most adverse events related to catheter placement or the study drug originated from the central nervous system. Three symptomatic windows were defined: the first one was between surgical procedure and CED; the second was during CED and up to 1 week after its completion; and the third window was 2 to 10 weeks after treatment. Those windows generally reflected adverse events related to surgical procedures, mass effect from infusate, and drug effect on tumor-infiltrated and normal brain parenchyma, respectively. The symptomatic windows identified in this study apply to any CED clinical trials, particularly those in which chimeric cytotoxins are used, and will help to determine the most likely underlying pathophysiological process causing symptoms. This information, in turn, will help to prevent adverse events or minimize their severity. Those events also have implications for dose escalation and outcome measures.

Intravenous Lidocaine for Effective Pain Relief After a Laparoscopic Colectomy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Ahn, EunJin; Kang, Hyun; Choi, Geun Joo; Park, Yong Hee; Yang, So Young; Kim, Beom Gyu; Choi, Seung Won

2015-01-01

A perioperative intravenous lidocaine infusion has been reported to decrease postoperative pain. The goal of this study was to evaluate the effectiveness of intravenous lidocaine in reducing postoperative pain for laparoscopic colectomy patients. Fifty-five patients scheduled for an elective laparoscopic colectomy were randomly assigned to 2 groups. Group L received an intravenous bolus injection of lidocaine 1.5 mg/kg before intubation, followed by 2 mg/kg/h continuous infusion during the operation. Group C received the same dosage of saline at the same time. Postoperative pain was assessed at 2, 4, 8, 12, 24, and 48 hours after surgery by using the visual analog scale (VAS). Fentanyl consumption by patient-controlled plus investigator-controlled rescue administration and the total number of button pushes were measured at 2, 4, 8, 12, 24, and 48 hours after surgery. In addition, C-reactive protein (CRP) levels were checked on the operation day and postoperative days 1, 2, 3, and 5. VAS scores were significantly lower in group L than group C until 24 hours after surgery. Fentanyl consumption was lower in group L than group C until 12 hours after surgery. Moreover, additional fentanyl injections and the total number of button pushes appeared to be lower in group L than group C (P < 0.05). The CRP level tended to be lower in group L than group C, especially on postoperative day1 and 2 and appeared to be statistically significant. The satisfaction score was higher in group L than group C (P = 0.024). Intravenous lidocaine infusion during an operation reduces pain after a laparoscopic colectomy. PMID:25785316

Patient-controlled Intermittent Epidural Bolus Versus Epidural Infusion for Posterior Spinal Fusion After Adolescent Idiopathic Scoliosis: Prospective, Randomized, Double-blinded Study.

PubMed

Erdogan, Mehmet Ali; Ozgul, Ulku; Ucar, Muharrem; Korkmaz, Mehmet Fatih; Aydogan, Mustafa Said; Ozkan, Ahmet Selim; Colak, Cemil; Durmus, Mahmut

2017-06-15

A prospective, randomized, double-blinded study. The aim of this study was to compare the efficacy and side effects of patient-controlled intermittent bolus epidural analgesia (PCIEA) and patient-controlled continuous epidural analgesia (PCCEA) for postoperative pain control in adolescent idiopathic scoliosis. Epidural analgesia is an accepted efficacious and safe procedure for postoperative pain management in scoliosis surgery. However, the PCIEA has not been adequately investigated for postoperative pain control in adolescent idiopathic scoliosis. Forty-seven patients, 8 to 18 years of age, who were undergoing posterior spinal fusion for idiopathic scoliosis were randomized to either the PCIEA or PCCEA group. An epidural catheter was inserted by a surgeon under direct visualization. The PCIEA group received 0.2 mg/mL of morphine, 0.25 mL/kg of morphine bolus, additional doses of 0.25 mL/kg morphine with a 1-hour lockout given by patient-controlled demand, and no infusion. The PCCEA group received the following: 0.2 mg/mL morphine, an initial morphine loading set at 0.1 mL/kg, followed by a 0.05 mL/kg/h continuous infusion of morphine, and a 0.025 mL/kg bolus dose of morphine. There was a 30-minute lockout interval. The primary outcome was morphine usage. The secondary outcomes were pain score, postoperative nausea and vomiting, and pruritus. Cumulative morphine consumption was lower in the PCIEA group than in the PCCEA group. Both methods provided effective pain control. There were no differences in pain scores between the groups. Postoperative nausea, vomiting, and pruritus were lower in the PCIEA group. The two epidural analgesia techniques studied are both safe and effective methods for postoperative pain control after posterior spinal fusion in idiopathic scoliosis. Nausea, vomiting and pruritus were considerably higher in the PCCEA group. Concerns regarding side effects associated with epidural opioids can be avoided by an intermittent bolus with a relatively lower amount of opioid. 2.

Titrated propofol induction vs. continuous infusion in children undergoing magnetic resonance imaging.

PubMed

Cho, J E; Kim, W O; Chang, D J; Choi, E M; Oh, S Y; Kil, H K

2010-04-01

Propofol is the popular intravenous (i.v.) anaesthetic for paediatric sedation because of its rapid onset and recovery. We compared the efficacy and safety of a single dose and conventional infusion of propofol for sedation in children who underwent magnetic resonance imaging (MRI). This was a double-blind, randomized-controlled study. One hundred and sixty children were assigned to group I (single dose) or II (infusion). Sedation was induced with i.v. propofol 2 mg/kg, and supplemental doses of propofol 0.5 mg/kg were administered until adequate sedation was achieved. After the induction of sedation, we treated patients with a continuous infusion of normal saline at a rate of 0.3 ml/kg/h in group I and the same volume of propofol in group II. In case of inadequate sedation, additional propofol 0.5 mg/kg was administered and the infusion rate was increased by 0.05 ml/kg/h. Induction time, sedation time, recovery time, additional sedation and adverse events were recorded. Recovery time was significantly shorter in group I compared with group II [0 (0-3) vs. 1 (0-3), respectively, P<0.001]. Group I (single dose) had significantly more patients with recovery time 0 compared with group II (infusion) (65/80 vs. 36/80, respectively, P<0.001). Induction and sedation times were not significantly different between groups. There was no significant difference in the frequency of additional sedation and adverse events between groups. A single dose of propofol without a continuous infusion can provide appropriate sedation in children undergoing MRI for <30 min.

Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya

1999-09-15

We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

Multiple Intravenous Infusions Phase 2a: Ontario Survey

PubMed Central

Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

2014-01-01

Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID:26257837

Blood magnesium concentration and dopamine or dobutamine infusion demand in patients during CABG (coronary artery bypass grafting) with normovolemic haemodilution.

PubMed

Pasternak, K; Wrońska, J; Dabrowski, W; Sztanke, M

2006-12-01

It is well known that magnesium (Mg) plays an essential role in cardiac protection. Mg has many beneficial effects on the myocardium and cardiac function, e.g. it improves contractility and reduces the number of cardiac arrhythmia episodes. The inotropically positive effects of Mg are interesting and worth stressing. High blood Mg concentration may result in an increase in cardiac contraction strength, which may be important for haemodynamic stabilization, and thus it is likely to decrease the demand for dopamine and dobutamine infusions. However, the exact determination of correlation between blood Mg concentrations and dopamine or dobutamine infusion demand is still unknown. The aim of the study was to assess the demand for dopamine or dobutamine infusion in relation to changes in blood magnesium concentrations in patients undergoing CABG (Coronary artery bypass graft) with extracorporeal circulation and normovolemic haemodilution. The study included 20 male patients, aged 53-70 (61.1 +/- 6.9) who underwent general anaesthesia and coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) and normovolemic haemodilution (NH) due to stable angina pectoris. The patients were retrospectively divided into three groups: A--patients who did not receive dopamine or dobutamine infusion, B--those receiving only D infusion in the doses dependent on their clinical state and C--those receiving DB infusion in the doses dependent on their clinical state. Mg was measured in 7 stages: 1) just before anaesthesia after the radial artery cannulation, 2) during normovolemic haemodilution and ECC, 3) immediately after surgery, 4) in the evening of the surgery day, 5) in the morning of the lst postoperative day, 6) in the evening of 1st postoperative day, 7) in the morning of the 2nd postoperative day. The spectrophotometric methods were used to determine Mg. The CABG procedure resulted in a decrease in Mg. Its level returned to normal in the evening of surgery day. The NH caused a similar Mg decrease in groups A, B and C, but these significantly low values of Mg were observed only in stage 2. There was no correlation between blood Mg concentrations and dopamine or dobutamine infusion demand. 1) The CABG procedure resulted in decreased blood magnesium concentrations. 2) The Mg changes do not correlate with dopamine or dobutamine infusion demand.

Effects of intravenous glucose infusion and nutritional balance on serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows.

PubMed

Vieira, F V R; Lopes, C N; Cappellozza, B I; Scarpa, A B; Cooke, R F; Vasconcelos, J L M

2010-07-01

The objective of this study was to evaluate serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows according to nutritional balance and glucose infusion. Ten nonlactating, ovariectomized Gir x Holstein cows were stratified by body weight (BW) and body condition score (BCS) on d -28 of the study, and randomly assigned to 1) negative nutrient balance (NB) or 2) positive nutrient balance (PB). From d -28 to d 0, cows were allocated according to nutritional treatment (5 cows/treatment) into 2 low-quality pastures with reduced forage availability. However, PB cows individually received, on average, 3 kg/cow per day (as-fed) of a concentrate during the study. All cows had an intravaginal progesterone releasing device inserted on d -14, which remained in cows until the end of the study. Cow BW and BCS were assessed again on d 0. On d 0, cows within nutritional treatment were randomly assigned to receive, in a crossover design containing 2 periods of 24h each, 1) intravenous glucose infusion (GLU; 0.5 g of glucose/kg of BW, as a 5% glucose solution administered, on average, at 32 mL/min over a 3-h period), or 2) intravenous saline infusion (SAL; 0.9% solution infused on average at 32 mL/min over a 3-h period). Prior to the beginning of each period, all cows were fasted for 12h. Blood samples were collected, relative to the beginning of the infusion, at -12 and -11.5h (beginning of fasting), and at -0.5, 0, 0.5, 1, 2, 3, 4, 5, and 6h. Following the last blood collection of period 1, cows received (PB) or not (NB) concentrate and were returned to their respective pastures. Changes in BCS and BW were greater in NB cows compared with PB cows (-0.60 and -0.25+/-0.090 for BCS, respectively; -22.4 and 1.2+/-6.58 kg for BW, respectively). Cows receiving GLUC had greater glucose concentrations from 0.5 to 3h relative to infusion compared with SAL cows. Insulin concentrations were greater in PB cows assigned to GLUC compared with SAL cohorts at 0.5 and 3h following infusion, whereas NB cows assigned to GLUC had greater insulin concentrations compared with SAL cohorts at 0.5, 1, 2, and 3h. Progesterone concentrations were greater in PB cows assigned to GLUC at 2, 3, and 4h following infusion compared with SAL cohorts. In conclusion, the effects of glucose infusion on serum concentrations of insulin and progesterone in nonlactating dairy cows were dependent on cow nutritional status. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Stimulation of skeletal muscle protein synthesis in neonatal pigs by long-term infusion of leucine is amino acid dependent

USDA-ARS?s Scientific Manuscript database

Infusing leucine for 1 hr increases skeletal muscle protein synthesis in neonatal pigs, but this is not sustained for 2 h unless the leucine-induced fall in amino acids is prevented. We aimed to determine whether continuous leucine infusion can stimulate protein synthesis for a prolonged period whe...

Hypophosphatemia, Hypomagnesemia, and Hypokalemia in Pediatric Patients Before and During Exclusive Individualized Parenteral Nutrition.

PubMed

Hortencio, Taís Daiene Russo; Nogueira, Roberto José Negrao; de Lima Marson, Fernando Augusto; Ribeiro, Antonio Fernando

2016-04-01

Hypophosphatemia, hypomagnesemia, and hypokalemia occur in patients receiving parenteral nutrition (PN), mainly when the body's stores are depleted due to fasting or inflammation. Although these disorders are potentially fatal, few studies have reported the incidence in the pediatric population. This study evaluated, in a historical cohort of pediatric patients, the prevalence of hypophosphatemia, hypokalemia, and hypomagnesaemia until 48 hours before initiation of PN infusion (P1) and from days 1-4 (P2) and days 5-7 (P3) of PN infusion and investigated if malnutrition, calories, and protein infusion were correlated to these disorders. Malnutrition was present in 32.8% (n = 119) of the subjects; 66.4% of the patients were in the pediatric intensive care unit. Survival rate was 86.6%. P1 had the highest prevalence of mineral disorders, with 54 events (58.1%; P2, n = 35, 37.6%; P3, n = 4, 4.3%). Hypokalemia events were related to malnutrition (odds ratio, 2.79; 95% confidence interval, 1.09-7.14; P = .045). In the first 7 days, infused calories were below the amount recommended by current guidelines in up to 84.9% of patients, and protein infused was adequate in up to 75.7%. Protein infused above the recommendation in the first 4 days was related to hypomagnesaemia (odds ratio, 5.66; 95% confidence interval, 1.24-25.79; P = .033). Hypophosphatemia, hypokalemia, and hypomagnesemia were frequent in hospitalized pediatric patients before and during the first 4 days of PN infusion. Patients with malnutrition had more chances of having hypokalemia, and those who received high protein infusion had an increased chance of developing hypomagnesemia. © 2016 American Society for Parenteral and Enteral Nutrition.

Short-Term Safety of Zoledronic Acid in Young Patients With Bone Disorders: An Extensive Institutional Experience.

PubMed

George, Sobenna; Weber, David R; Kaplan, Paige; Hummel, Kelly; Monk, Heather M; Levine, Michael A

2015-11-01

Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited. The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients. This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia. Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025-0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation. Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population.

Circulating free fatty acids inhibit food intake in an oleate-specific manner in rats.

PubMed

Oh, Young Taek; Oh, Hyun Hee; Nguyen, Anh-Khoi; Choi, Cheol Soo; Youn, Jang H

2016-12-01

Previous rodent studies showed that when injected into the brain, free fatty acids (FFAs) reduced food intake in an oleate-specific manner. The present study was performed to test whether food intake is regulated by circulating FFAs in an oleate-specific manner. Male Wistar rats received an intravenous infusion of olive, safflower, or coconut oil (100mg/h), together with heparin, to raise circulating oleate, linoleate, or palmitate, respectively, and their effects on overnight food intake were evaluated. Compared to other oils, olive oil infusion showed a significantly greater effect to reduce food intake (P<0.01). Total caloric intake, the sum of the calories from the diet and infused oil, was significantly reduced with olive oil (P<0.01) but not with coconut or safflower oil infusion, suggesting an oleate-specific effect on caloric intake. To further test this idea, different groups of rats received an intravenous infusion of oleate, linoleate, or octanoate (0.5mg/h). Oleate infusion decreased overnight food intake by 26% (P<0.001), but no significant effect was seen with linoleate, octanoate, or vehicle infusion (P>0.05). The effects of olive oil or oleate infusion could not be explained by changes in plasma glucose, insulin, leptin, or total FFA levels. The olive oil effect on food intake was not reduced in vagotomized rats, suggesting that oleate sensing may not involve peripheral sensors. In contrast, olive oil's effect was attenuated in high-fat-fed rats, suggesting that this effect is regulated (or impaired) under physiological (or pathological) conditions. Taken together, the present study provides evidence that circulating oleate is sensed by the brain differentially from other FFAs to control feeding in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1: Vector Trafficking and Immune Response

PubMed Central

Forsayeth, John; Mirek, Hanna; Munson, Keith; Bringas, John; Pivirotto, Phil; McBride, Jodi L; Davidson, Beverly L.; Bankiewicz, Krystof S.

2009-01-01

Abstract We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohisto-chemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm3 coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4+ lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2. PMID:19292604

Hepatic and peripheral glucose metabolism in intensive care patients receiving continuous high- or low-carbohydrate enteral nutrition.

PubMed

Tappy, L; Berger, M; Schwarz, J M; McCamish, M; Revelly, J P; Schneiter, P; Jéquier, E; Chioléro, R

1999-01-01

The suppression of endogenous glucose production during parenteral nutrition is impaired in critically ill patients. It is, however, unknown whether enteral administration of carbohydrates, which normally promote hepatic glucose uptake, improves hepatic glucose metabolism in such patients. We studied two groups of 7 patients during a 3-day continuous isocaloric enteral nutrition. A high-carbohydrate, low-lipid (EN-C) or a high-lipid, low-carbohydrate (EN-L) nutrient mixture was administered. Endogenous glucose production assessed with [2H7]glucose was similarly increased in both groups, indicating absence of its suppression by carbohydrate feeding. Gluconeogenesis estimated from [13C]glucose synthesis during [13C]bicarbonate infusion also was not suppressed by EN-C compared with EN-L. Systemic appearance of exogenous glucose was monitored by enteral infusion of [6,6-2H]glucose and was not different from the rate of glucose equivalent administered enterally, indicating no significant hepatic uptake of glucose in both groups. Plasma glucose and insulin concentrations were slightly higher with EN-C, although not significantly, and plasma triglycerides were similar in both groups. Both nutrition formulas were well tolerated clinically. These results indicate that enteral carbohydrate administration, whatever its quantity, fails to suppress endogenous glucose production and to promote net splanchnic glucose uptake in critically ill patients.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

PubMed

Indelicato, L; Mariano, V; Galasso, S; Boscari, F; Cipponeri, E; Negri, C; Frigo, A; Avogaro, A; Bonora, E; Trombetta, M; Bruttomesso, D

2017-05-01

To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA 1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA 1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA 1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control. © 2017 Diabetes UK.

Investigation of standard care versus sham Reiki placebo versus actual Reiki therapy to enhance comfort and well-being in a chemotherapy infusion center.

PubMed

Catlin, Anita; Taylor-Ford, Rebecca L

2011-05-01

To determine whether provision of Reiki therapy during outpatient chemotherapy is associated with increased comfort and well-being. Double-blind, randomized clinical controlled trial. Outpatient chemotherapy center. 189 participants were randomized to actual Reiki, sham Reiki placebo, or standard care. Patients receiving chemotherapy were randomly placed into one of three groups. Patients received either standard care, a placebo, or an actual Reiki therapy treatment. A demographic tool and pre- and post-tests were given before and after chemotherapy infusion. Reiki therapy, sham Reiki placebo therapy, standard care, and self-reported levels of comfort and well-being pre- and postintervention. Although Reiki therapy was statistically significant in raising the comfort and well-being of patients post-therapy, the sham Reiki placebo also was statistically significant. Patients in the standard care group did not experience changes in comfort and well-being during their infusion session. The findings indicate that the presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels, with or without an attempted healing energy field. An attempt by clinic nurses to provide more designated one-to-one presence and support for patients while receiving their chemotherapy infusions could increase patient comfort and well-being.

Duodenal supply of glutamate and casein both improve intestinal starch digestion in cattle but by apparently different mechanisms.

PubMed

Brake, D W; Titgemeyer, E C; Anderson, D E

2014-09-01

Greater postruminal flows of protein increase small intestinal starch digestion in cattle. Our objective was to determine if small intestinal starch digestion is increased by duodenal supplementation of AA. We fed 5 duodenally and ileally cannulated steers a low-starch soybean hull-based diet in 5 × 5 Latin square designs and provided continuous duodenal infusion of raw cornstarch in combination with AA or casein and measured small intestinal starch digestion. In Exp. 1 treatments were continuous duodenal infusion of 1) no supplement (control), 2) casein (400 g/d), 3) crystalline AA similar in amount and AA composition to the casein (CASAA), 4) crystalline nonessential AA similar to those provided by casein, or 5) crystalline essential AA similar to those provided by casein. In Exp. 2 treatments were continuous duodenal infusion of 1) no supplement (control), 2) casein (400 g/d), 3) Glu (133 g/d), 4) Phe and Trp plus Met (30.4, 6.5, and 17.5 g/d, respectively; PTM), or 5) a combination of Glu and PTM. Duodenal infusion of casein increased (P ≤ 0.05) small intestinal starch digestion. When CASAA was infused, small intestinal starch digestion was similar (P = 0.30) to casein infusion. Infusion of only nonessential AA tended to increase (P = 0.14) small intestinal starch digestion relative to the control, but infusion of essential AA alone did not affect (P = 0.84) small intestinal starch digestion. In addition, infusion of casein or CASAA increased ileal flows of ethanol-soluble starch (small-chain α-glycosides), but nonessential AA alone were not different than the control. Duodenal infusion of Glu increased (P ≤ 0.05) small intestinal starch digestion, whereas PTM did not. Neither Glu nor PTM increased ileal flow of ethanol-soluble starch, but Glu and PTM provided together tended (P = 0.07) to increase ileal flows of small chain α-glycosides. Our data suggest that Glu alone can increase small intestinal starch digestion in cattle similar to casein, but increases in small intestinal starch digestion in response to Glu are not associated with an increase in ileal flows of small chain α-glycosides.

A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover.

PubMed

Horwitz, Mara J; Tedesco, Mary Beth; Sereika, Susan M; Prebehala, Linda; Gundberg, Caren M; Hollis, Bruce W; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Carneiro, Raquel M; Stewart, Andrew F

2011-09-01

Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM), or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed 7-day continuous-infusion models using human parathyroid hormone(1-34) [hPTH(1-34)] and human parathyroid hormone-related protein(1-36) [hPTHrP(1-36)] in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dL), with marked suppression of endogenous PTH(1-84). The maximal tolerated infused doses over a 7-day period (2 and 4 pmol/kg/h for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8 to 28 pmol/kg/h). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] and tubular maximum for phosphorus (TmP/GFR) remained unaltered with these low doses despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30% to 40% for the 7 days of the infusions. With cessation of PTH and PTHrP infusion, bone-formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone-resorption program but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions are reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. Copyright © 2011 American Society for Bone and Mineral Research.

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

PubMed Central

2013-01-01

Introduction Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. Methods Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 106 aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. Results Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. Conclusions Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters. PMID:23632128

Controlled Study of the Effects of Continuous Intrathecal Baclofen Infusion in Non-Ambulant Children with Cerebral Palsy

ERIC Educational Resources Information Center

Morton, Richard E.; Gray, Natalie; Vloeberghs, Michael

2011-01-01

Aim: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. Method: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before…

Pembrolizumab-induced acute thrombosis: A case report.

PubMed

Kunimasa, Kei; Nishino, Kazumi; Kimura, Madoka; Inoue, Takako; Tamiya, Motohiro; Kumagai, Toru; Imamura, Fumio

2018-05-01

Acute thrombosis has not been reported in the literature so far in lung cancer patients as an immune-related adverse event (irAE) associated with PD-1 pathway inhibitors. Here, we for the first time present two NSCLC (non-small cell lung cancer) patients suffering from acute thrombosis as a pembrolizumab-induced irAE. Immediate treatment with continuous heparin infusion improved their symptoms and enabled them to continue pembrolizumab administration. Ethical approval was given by the ethics committee of Osaka International Cancer Institute and the informed consents were given by the patients. Serum D-dimer level testing, venous ultrasonography, enhanced computed tomography (CT). Continuous heparin infusion, direct oral anticoagulants (DOAC). Immediate continuous heparin infusion improved their symptoms and continuing pembrolizumab with direct oral anticoagulant successfully induced tumor shrinkage. Reinvigoration of exhausted T cells by pembrolizumab induced systemic inflammation possibly resulting in development of thrombosis. Although acute thrombosis is a rare irAE, it may lead to cessation of treatment and can be lethal.

Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology.

PubMed

Early, P J; Crook, K I; Williams, L M; Davis, E G; Muñana, K R; Papich, M G; Messenger, K M

2017-08-01

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m 2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (C MAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma. © 2016 John Wiley & Sons Ltd.

EFFECTS OF NGF AND FETAL CELL TRANSPLANTS ON SPATIAL LEARNING AFTER INTRADENTATE ADMINISTRATION OF COLCHICINE

EPA Science Inventory

This study was performed to assess the effects of NGF infusion alone or in combination with fetal hippocampal transplants on recovery of function after damage to hippocampal dentate granule cells. Two groups of male Fischer-344 rats received bilateral infusions of colchicine (COL...

Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com; Kennedy, Derek; Reed, Randall P.

CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mildmore » increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered rhTPP1 to treat CLN2.« less

Intravenous magnesium sulphate infusion in the management of very severe tetanus in a child: a descriptive case report.

PubMed

Puliyel, Mammen M; Pillai, Rajappan; Korula, Sophy

2009-02-01

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.

Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.

PubMed

Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L

2014-05-01

The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Fosaprepitant-induced Phlebitis: A Focus on Patients receiving Doxorubicin/Cyclophosphamide therapy

PubMed Central

Leal, A. D.; Kadakia, K. C.; Looker, S.; Hilger, C.; Sorgatz, K.; Anderson, K.; Jacobson, A.; Grendahl, D.; Seisler, D.; Hobday, T.; Loprinzi, C. L.

2014-01-01

Purpose The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. Methods A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Results Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7% (n=34), while the incidence of aprepitant-associated ISAEs was 2.3% (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were: infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5) and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. Conclusions The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy is significant and appreciably higher than what has been previously reported. PMID:24402411

Assessment of sustained effects of levosimendan and dobutamine on left ventricular systolic functions by using novel tissue Doppler derived indices in patients with advanced heart failure.

PubMed

Oner, Ender; Erturk, Mehmet; Birant, Ali; Kurtar Mansıroglu, Aslı; Akturk, Ibrahim Faruk; Karakurt, Huseyin; Yalcin, Ahmet Arif; Uzun, Fatih; Somuncu, Mustafa Umut; Yildirim, Aydin

2015-01-01

Previous studies comparing levosimendan vs. dobutamine have revealed that levosimendan is better in relieving symptoms. Echocardiographic studies have been done using second measurements immediately following a dobutamine infusion or while it was still being administered. The aim of our study was assessment of sustained effects of 24 h levosimendan and dobutamine infusions on left ventricular systolic functions. A total of 61 patients with acutely decompensated heart failure with New York Heart Association (NYHA) class III or IV symptoms were randomized to receive either levosimendan or dobutamine 2:1 in an open label fashion. Before and 5 days after the initiation of infusions, functional class was assessed, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fraction (LVEF), mitral inflow peak E and A wave velocity, and E/A ratios were measured; using tissue Doppler imaging, isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), early (E') and late (A') diastolic velocities, and E'/A' and E/E' ratios were measured. The NYHA class improved in both groups, but improvements were prominent in the levosimendan group. NT-proBNP levels were significantly reduced in the levosimendan group. Improvements in LVEF and diastolic indices were significant in the levosimendan group. Tissue Doppler-derived systolic indices of IVV and IVA increased significantly in the levosimendan group. Improvements in left ventricular systolic and diastolic functions continue after a levosimendan infusion.

Hyponatremia induced by hyperinsulinemia-euglycemia therapy.

PubMed

Beavers, Jennifer R; Stollings, Joanna L; Rice, Todd W

2017-07-15

A case of symptomatic hyponatremia induced by hyperinsulinemia-euglycemia (HIE) therapy is reported. A 59-year-old, 81.65-kg woman with hypertension, major depressive disorder, and anxiety arrived at a tertiary medical center 1.5 hours after an intentional overdose of oral amlodipine 200 mg, metoprolol tartrate 2,000 mg, and isosorbide mononitrate 1,200 mg. Upon arrival, her pulse was 63 beats/min and blood pressure was 106/56 mm Hg. The patient's blood pressure was refractory to fluids, calcium gluconate, and norepinephrine, resulting in initiation of HIE therapy. She had recurrent episodes of hypoglycemia, which required increases of the dextrose infusion and resulted in the patient receiving a total of 6.9 L of dextrose with free water. Seventeen hours into the hospitalization, the patient became obtunded due to hyponatremia (serum sodium concentration, 121 mmol/L). HIE therapy was discontinued, an infusion of 5% dextrose injection with sodium bicarbonate added was started, and a bolus of 3% sodium chloride was administered. Nine hours after the presentation of hyponatremia, the patient's serum sodium concentration normalized (137 mmol/L), and her symptoms resolved. The patient's blood pressure, pulse, and mental status continued to improve, and the patient was transferred out of the medical intensive care unit 41 hours after her arrival at the hospital. A woman who overdosed on amlodipine, metoprolol tartrate, and isosorbide mononitrate was treated with HIE therapy and developed symptomatic hyponatremia. Hyponatremia resolved after administration of dextrose with sodium bicarbonate infusion and 3% sodium chloride infusion and cessation of HIE therapy. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

An observational 7-year study of continuous subcutaneous insulin infusion for the treatment of type 1 diabetes mellitus.

PubMed

Papargyri, Panagiota; Ojeda Rodríguez, Sylvie; Corrales Hernández, Juan José; Mories Álvarez, María Teresa; Recio Córdova, José María; Delgado Gómez, Manuel; Sánchez Marcos, Ana Isabel; Iglesias López, Rosa Ana; Herrero Ruiz, Ana; Beaulieu Oriol, Myriam; Miralles García, José Manuel

2014-03-01

This work reports the experience with use of continuous subcutaneous insulin infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and previously treated with multiple daily insulin injections (MDII). A retrospective, observational study in 112 patients with diabetes mellitus treated with CSII from 2005 to 2012, previously treated with MDII and receiving individualized diabetic education with a specific protocol. Variables analyzed included: prevalence of the different indications of pump treatment; mean annual HbA1c and fructosamine values before and after CSII treatment; and hypoglycemia frequency and symptoms. The most common reason for pump treatment was brittle diabetes (74.1%), followed by frequent or severe hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were irregular food intake times for professional reasons (20.2%), dawn phenomenon (15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia unawareness was found in 21%. Hypoglycemia was more common at treatment start, and its frequency rapidly decreased thereafter. CSII therapy provides a better glycemic control than MDII treatment. Specific patient training and fine adjustment of insulin infusion doses are required to prevent hypoglycemic episodes, which are the most common complications, mainly at the start of treatment. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure.

PubMed

Ruggero, M A; Argento, A C; Heavner, M S; Topal, J E

2013-04-01

The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS(®)). The patient was a 32-year-old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin-enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein-bound toxins. In addition to protein-bound waste, MARS removes water-soluble, low molecular-weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k(e)) for the removal of piperacillin in this patent was 0.453 h(-1) and the half-life (λ) was 1.53 h. The k(e) was 2.9-fold higher than with CVVHD alone and the λ was 3.7-fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations. © 2012 John Wiley & Sons A/S.

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

PubMed Central

Pak, Linda Ma; Haroutounian, Simon; Hawkins, William G; Worley, Lori; Kurtz, Monika; Frey, Karen; Karanikolas, Menelaos; Swarm, Robert A; Bottros, Michael M

2018-01-01

Introduction Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. Methods The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1β, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. Ethics and dissemination The E-PRO trial has been approved by the institutional review board. Recruitment began in May 2016 and will continue until the end of May 2018. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02681796. PMID:29374667

Incidence of infusion reactions to anti-neoplastic agents in early phase clinical trials: The MD Anderson Cancer Center experience.

PubMed

Bupathi, Manojkumar; Hajjar, Joud; Bean, Stacie; Fu, Siqing; Hong, David; Karp, Daniel; Stephen, Bettzy; Hess, Kenneth; Meric-Bernstam, Funda; Naing, Aung

2017-02-01

Infusion reactions (IRs) to anti-neoplastic agents require prompt recognition and immediate treatment to avert significant complications. We conducted a retrospective review of the medical records of consecutive patients who received anti-neoplastic therapy in the outpatient treatment center of the Department of Investigational Cancer Therapeutics from January 1, 2013 to November 30, 2013. Of the 597 patients who received treatment, 9 (1.5 %) had IRs (all ≤ grade 2). The most common IRs observed on first occurrence were chills (n = 5), itching, rash, and facial flushing (n = 3 each). There were no IR-related deaths. All the IRs were reversible with appropriate symptomatic treatment and the therapy was completed after temporary cessation of infusion in 7 of the 9 patients. The infusion was stopped in 2 patients due to symptoms suggestive of IgE-mediated allergic reaction and cytokine storm. Five of the 8 patients who were re-challenged with the same therapy developed a similar reaction. However, the infusion was completed in 4 of the 5 patients after administration of intravenous diphenhydramine and/or hydrocortisone, or slowing the rate of infusion. And, subsequent cycles with the same agents were uneventful. IRs to anti-neoplastic agents are rare. Though the clinical presentations are overlapping, most IRs are not IgE-mediated allergic reactions. Appropriate premedication and slow rate of infusion facilitates uneventful administration of the anti-neoplastic agents in subsequent cycles. Further study in a larger cohort of patients to identify biomarkers of hypersensitivity is warranted.

Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure

PubMed Central

Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

2016-01-01

Abstract The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863–2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (−7.74 ± 5.95 vs −1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34–4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.) PMID:26945407

Ethical validity of palliative sedation therapy: a multicenter, prospective, observational study conducted on specialized palliative care units in Japan.

PubMed

Morita, Tatsuya; Chinone, Yoshikazu; Ikenaga, Masayuki; Miyoshi, Makoto; Nakaho, Toshimichi; Nishitateno, Kenji; Sakonji, Mitsuaki; Shima, Yasuo; Suenaga, Kazuyuki; Takigawa, Chizuko; Kohara, Hiroyuki; Tani, Kazuhiko; Kawamura, Yasuo; Matsubara, Tatsuhiro; Watanabe, Akihiko; Yagi, Yasuo; Sasaki, Toru; Higuchi, Akiko; Kimura, Hideyuki; Abo, Hirofumi; Ozawa, Taketoshi; Kizawa, Yoshiyuki; Uchitomi, Yosuke

2005-10-01

Although palliative sedation therapy is often required in terminally ill cancer patients to achieve acceptable symptom relief, empirical data supporting the ethical validity of this approach are lacking. The primary aim of this study was to systematically investigate whether empirical evidence supports the ethical validity of sedation. This was a multicenter, prospective, observational study, which was conducted by 21 specialized palliative care units in Japan. One-hundred two consecutive adult cancer patients who received continuous deep sedation were enrolled. Continuous deep sedation was defined as the continuous use of sedative medications to relieve intolerable and refractory distress by achieving almost or complete unconsciousness until death. Prior to the study, we conceptualized the ethical validity of sedation from the viewpoints of physicians' intent, proportionality, and autonomy. Sedation was performed mainly with midazolam and phenobarbital. The initial doses of midazolam and phenobarbital were 1.5 mg/hour and 20 mg/hour, respectively. Main administration routes were continuous subcutaneous infusion and continuous intravenous infusion, and no rapid intravenous injection was reported. Of 59 patients who received artificial hydration or could intake adequate fluids/foods orally before sedation, 63% received artificial hydration therapy after sedation, and in the remaining patients, artificial hydration was withheld or withdrawn due to fluid retention symptoms and/or patient wishes. Of 66 patients who were able to verbally express themselves, 95% explicitly stated that symptoms were intolerable. The etiologies of the symptoms requiring sedation were primarily related to the progression of the underlying malignancy, such as cancer cachexia and organ failure, and standard palliative treatments had failed: steroids in 68% of patients with fatigue, opioids in 95% of patients with dyspnea, antisecretion medications in 75% of patients with bronchial secretion, antipsychotic medications in 74% of patients with delirium, and opioids in all patients with pain. On the basis of the Palliative Prognostic Index, 94% of the patients were predicted to die within 3 weeks. Before sedation, 67% of the patients expressed explicit wishes for sedation. In the remaining 34 patients, previous wishes for sedation were noted in 4 patients, and in the other 30 patients, the families were involved in the decision-making process. The chief reason for patient non-involvement in the decision making was cognitive impairment. These data indicate that palliative sedation therapy performed in specialized palliative care units in Japan generally followed the principles of double effect, proportionality, and autonomy.

Nonmetabolic Complications of Continuous Subcutaneous Insulin Infusion: A Patient Survey

PubMed Central

Yemane, Nardos; Brackenridge, Anna; Pender, Siobhan

2014-01-01

Abstract Background: Little is known about the frequencies and types of nonmetabolic complications occurring in type 1 diabetes patients being treated by modern insulin pump therapy (continuous subcutaneous insulin infusion [CSII]), when recorded by standardized questionnaire rather than clinical experience. Subjects and Methods: A self-report questionnaire was completed by successive subjects with type 1 diabetes attending an insulin pump clinic, and those with a duration of CSII of ≥6 months were selected for analysis (n=92). Questions included pump manufacturer, insulin, infusion set type and duration of use, frequency of infusion set and site problems, pump malfunctions, and patient-related problems such as weight change since starting CSII. Results: Median (range) duration of CSII was 3.3 (0.5–32.0) years, and mean±SD duration of infusion set use was 3.2±0.7 (range 2–6) days. The commonest infusion set problems were kinking (64.1% of subjects) and blockage (54.3%). Blockage was associated with >3 days of use of infusion sets plus lispro insulin in the pump (relative risk [95% confidence interval], 1.71 [1.03–2.85]; P=0.07). The commonest infusion site problem was lipohypertrophy (26.1%), which occurred more often in those with long duration of CSII (4.8 [2.38–9.45] vs. 3.0 [1.50–4.25] years; P=0.01). Pump malfunction had occurred in 48% of subjects (43% in the first year of CSII), with “no delivery,” keypad, and battery problems commonly occurring. Although some patients reported weight gain (34%) and some weight loss (15%) on CSII, most patients (51%) reported no change in weight. Conclusions: Pump, infusion set, and infusion site problems remain common with CSII, even with contemporary technology. PMID:24180294

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review.

PubMed

Baker, James; Dickman, Andrew; Mason, Stephen; Ellershaw, John

2018-01-01

A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. A systematically-structured review following PRISMA guidelines. Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice.

Wasabi nose: an underreported complication of cyclophosphamide infusions.

PubMed

Janow, Ginger L; Ilowite, Norman T; Wahezi, Dawn M

2011-07-01

Wasabi nose, a term used to describe the nasopharyngeal discomfort experienced during cyclophosphamide infusions, is a rare phenomenon, previously described in case reports of adult oncology patients typically receiving high-dose chemotherapy regimens. The underlying mechanism by which this phenomenon occurs is unknown. We report four cases of children with rheumatic diseases afflicted by profound nasopharyngeal discomfort secondary to low-dose cyclophosphamide infusions. We additionally review the literature regarding potential medical management of these complications and describe our experience using these interventions.

Propofol sedation in children: sleep trumps amnesia.

PubMed

Veselis, Robert; Kelhoffer, Eric; Mehta, Meghana; Root, James C; Robinson, Fay; Mason, Keira P

Detailed assessments of the effects of propofol on memory in children are lacking. We assessed the feasibility of measuring memory during propofol infusion, as commonly performed in sedation for MRI scanning. In addition, we determined the onset of memory loss in relation to the onset of sedation measured by verbal responsiveness. Children scheduled for sedation for MRI received a 10-min infusion of propofol (3 mg/kg) as they viewed and named 100 simple line drawings, one shown every five seconds, until they were no longer responsive (encoding). A control group receiving no sedation for MRI underwent similar tasks. Sedation was measured as any verbal response, regardless of correctness. After recovery from sedation, recognition memory was tested, with correct yes/no recognitions matched to sedation responses during encoding (subsequent memory paradigm). Of the 48 children who received propofol, 30 could complete all study tasks (6.2 ± 1.6 years, 16 males). Individual responses could be modeled in all 30 children. On average, there was a 50% probability of no verbal response 3.1 min after the start of infusion, with 50% memory loss at 2.7 min. Children receiving propofol recognized 65 ± 16% of the pictures seen, whereas the control group recognized 93 ± 5%. Measurement of memory and sedation is possible in verbal children receiving propofol by infusion in a clinical setting. Despite propofol being an amnestic agent, there was little or no amnestic effect of propofol while the child was verbally responsive. It is important for sedation providers to realize that propofol sedation does not always produce amnesia while the child is responsive. CLINICALTRIALS. NCT02278003. Copyright © 2016. Published by Elsevier B.V.

Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction.

PubMed

De Conno, F; Caraceni, A; Zecca, E; Spoldi, E; Ventafridda, V

1991-11-01

We describe the use of hyoscine butylbromide as a subcutaneous infusion in 3 patients with inoperable malignant bowel obstruction. An objective reduction of drainage from the gastrointestinal tract was observed with the hyoscine butylbromide infusion (60-120 mg/day). We suggest that this effect can be useful in the palliative treatment of vomiting in inoperable bowel obstruction.

Continuous spinal labor analgesia for two deliveries in a parturient with severe subvalvular aortic stenosis.

PubMed

Hyuga, Shunsuke; Okutomi, Toshiyuki; Kato, Rie; Hosokawa, Yuki

2016-12-01

Various degrees of left ventricular outflow tract (LVOT) obstruction have been seen in patients with subvalvular aortic stenosis (SAS). Regional analgesia during labor for parturients with SAS is relatively contraindicated because it has a potential risk for hemodynamic instability due to sympathetic blockade as a result of vasodilation by local anesthetics. We thought continuous spinal analgesia (CSA) using an opioid and minimal doses of local anesthetic could provide more stable hemodynamic status. We demonstrate the management of a 28-year-old pregnant patient with SAS who received CSA for her two deliveries. For her first delivery (peak pressure gradient (∆P) between LV and aorta was approximately 55 mmHg), intrathecal fentanyl was used as a basal infusion, but we needed a small amount of bupivacaine to provide supplemental intrathecal analgesia as labor progressed. Although there were mild fluctuations in hemodynamics, she was asymptomatic. For her second delivery (∆P between LV and aorta was approximately 90 mmHg), minimal doses of continuous bupivacaine were used as a basal infusion. For her additional analgesic requests, bolus co-administration of fentanyl was effective. There were no fluctuations in her hemodynamics. Although her SAS in her second pregnancy was more severe than in the first, her hemodynamics exhibited less fluctuation during the second delivery with this method. In conclusion, CSA using fentanyl combined with minimal doses of bupivacaine provided satisfactory analgesia and stable hemodynamics in parturient with severe SAS.

Continuous Transversus Abdominis Plane Nerve Blocks: Does Varying Local Anesthetic Delivery Method-Automatic Repeated Bolus Versus Continuous Basal Infusion-Influence the Extent of Sensation to Cold?: A Randomized, Triple-Masked, Crossover Study in Volunteers.

PubMed

Khatibi, Bahareh; Said, Engy T; Sztain, Jacklynn F; Monahan, Amanda M; Gabriel, Rodney A; Furnish, Timothy J; Tran, Johnathan T; Donohue, Michael C; Ilfeld, Brian M

2017-04-01

It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion. Bilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6. Although there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval -2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval -1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6. No evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.

Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

PubMed

Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

2011-01-01

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

Bolus and continuous infusion mitoxantrone in newly diagnosed adult acute lymphoblastic leukemia: results of two consecutive phase II clinical studies.

PubMed

Koc, Y; Akpek, G; Kansu, E; Kars, A; Tekuzman, G; Baltali, E; Güler, N; Barista, I; Güllü, I; Ozisik, Y; Firat, D

1998-01-01

Two consecutive phase II clinical studies were designed to evaluate the efficacy and safety of bolus and continuous infusion (CI) mitoxantrone (MTZ) in 39 patients with newly diagnosed acute lymphocytic leukemia (ALL). MTZ was used as part of the classical ALL induction regimen. Twenty patients were treated with bolus MTZ (10 mg/m2 for 3 days) combined with vincristine and prednisone. The same regimen was given to a second set of 19 patients, except that MTZ was administered as a 24-hr CI. Both groups received bimonthly intensifications with vincristine and prednisone for 3 years, along with oral maintenance therapy. Patients in the CI-MTZ study arm received additional MTZ on the first day of intensification cycles. Seventeen patients (85%) in the bolus arm and 15 patients (79%) in the CI arm achieved complete remission (CR). Median disease-free survivals (DFS) in the bolus and CI groups were 11 and 15 months after median follow-ups of 16 (3.5-96) and 13 (2.3-32) months, respectively. At 2.5 years, DFS rates were 29.4% and 34.4% in the bolus and CI groups (p > 0.05). There were no significant differences between two groups in rates of early death, degree of organ toxicity, or duration of neutropenia and thrombocytopenia. Significant cardiac toxicity was not observed in either group. Bolus or CI administration of MTZ was equally effective and was well tolerated. Neither the mode of administration nor increasing the dose intensity of MTZ by incorporating intensification cycles reduced relapse rates. Development of new antileukemia agents and novel treatment approaches are still needed to improve the high relapse rates in adult ALL once a complete response is achieved.

[Effect of nonsteroidal antiinflammatory drugs on colonic lipoxygenase and cyclooxygenase activities from patients with colonic neoplasia].

PubMed

Di Girolamo, G; Franchi, A; De Los Santos, A R; Martí, M L; Farina, M; Fernández de Gimeno, M A

2001-01-01

Lysine clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with good gastrointestinal tolerance. Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosatetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 (COX-1) in in vitro studies carried out on human tissues. This study deals with the in vivo effect of the drug on human colon segments. Experiment 1: Five patients about to undergo hemicholectomy due to colon neoplasia were treated preoperatively with a continuous infusion of LC, to achieve a steady-state concentration between 4 and 6 mg/ml. Human colon segments from the five patients and from another five control patients receiving no treatment with [14C]-arachidonic acid were incubated. Human colon segments treated with LC showed significant inhibition of PGE2, the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen patients received an i.v. bolus of LC 100 mg (n1 = 5); LC 200 mg (n2 = 5) or indomethacin (INDO) 50 mg (n3 = 5). Both doses of LC showed greater inhibition of PGE2 synthesis than the INDO bolus. Both NSAIDs studied proved to have different effects on the production of 5-HETE; while treatment with LC elicited significant inhibition, levels with INDO remained unchanged. Western blotting analysis showed expression of both COX isoforms in colon segments, COX-2 levels being 20% higher. Both types of in vivo studies conducted continuous infusion and i.v. bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE.

Continuous Infusion Ketorolac for Postoperative Analgesia Following Unilateral Total Knee Arthroplasty.

PubMed

Schwinghammer, Amy J; Isaacs, Alex N; Benner, Rodney W; Freeman, Heather; O'Sullivan, Jacob A; Nisly, Sarah A

2017-06-01

Previous clinical trials have demonstrated benefit with the addition of continuous infusion (CI) ketorolac to a multimodal pain regimen in surgical patients. Data following major orthopedic surgery are minimal and conflicting. To evaluate CI ketorolac use following unilateral total knee arthroplasty (TKA) through assessment of patient-reported pain scores, opioid consumption, and safety outcomes. This was a retrospective, open-label cohort study that included patients undergoing unilateral TKA at a single-center teaching hospital. Participants were categorized into 2 study groups based on postoperative management: CI ketorolac or opioid protocol (OP). The first group received a ketorolac 30-mg bolus followed by CI 3.6 mg/h plus as-needed (PRN) opioids. The OP group received PRN narcotics in a tiered protocol. The primary end point was comparison of median pain scores. Secondary end points included opioid consumption (morphine equivalent units [MEUs]) in the first 48 hours postoperatively, length of stay, and adverse effects. Of 447 patients screened, 191 were analyzed (CI ketorolac, n = 116; OP, n = 75). Median pain scores were significantly lower in the CI ketorolac group at 48 hours postoperatively (3 [2-4] vs 3.5 [2.5-5], P = 0.033). Cumulative MEUs at 48 hours were significantly lower in the CI ketorolac group (33.9 ± 38.5 mg vs 301.6 ± 36.6 mg, P < 0.001). Patients in the CI ketorolac group experienced less respiratory depression (5.2% vs 25.3%, P < 0.001) and less naloxone administration (0% vs 8%, P = 0.002) compared with the OP group. Other adverse effects were similar among groups. Postoperative CI ketorolac improved pain control while reducing opioid consumption and adverse effects.

The effects of specified chemical meals on food intake.

PubMed

Koopmans, H S; Maggio, C A

1978-10-01

Rats received intragastric infusions of various specified chemical meals and were subsequently tested for a reduction in food intake. A second experiment, using a novel technique, tested for conditioned aversion to the meal infusions. The nonnutritive substances, kaolin clay and emulsified fluorocarbon, had no significant effect on food intake. Infusions of 1 M glucose and 1 M sorbitol reduced feeding behavior, but the 1 M sorbitol infusion also produced a conditioned aversion to flavored pellets paired with the sorbitol infusion, showing that the reduced feeding could have been caused by discomfort. Infusion of a high-fat meal consisting of emulsified triolein mixed with small amounts of sugar and protein or the rat's normal liquid diet, Nutrament, also reduced food intake, and both infusions failed to produce a conditioned aversion. The use of specified meals to understand the chemical basis of satiety requires a sensitive behavioral test to establish that the meal does not cause discomfort or other nonspecific effects.

Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

PubMed

Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

2016-08-01

We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications.

Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and sedation

PubMed Central

Tarıkçı Kılıç, Ebru; Aydın, Gaye

2018-01-01

ABSTRACT Background: We evaluated the effects of intravenous dexmedetomidine during spinal anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and compared them with those of saline infusion. Sixty American Society of Anesthesiologists physical status I and II cases were randomly divided into two groups. Patients were connected to the monitor after premedication, and spinal anesthesia was administered. Sensory and motor blockades were assessed using pinprick test and Bromage scale, respectively. Group I received dexmedetomidine infusion and Group II received saline infusion. Throughout the infusion process, hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage score, amnesia, bispectral index, and side effects were recorded. Postoperative hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained. Sedation and pain were evaluated using the Ramsay and visual analog scales, respectively. Analgesics were administered in cases with high scores on the visual analog scale. Postoperative analgesic consumption, side effects, treatments were recorded. No significant differences were found between the groups with respect to oxygen saturation, respiratory rate, pain, and side effects in the intraoperative period. Time to onset of sensorial block, maximum sensorial block, onset of motor block, and maximum motor block; bispectral index values; and apex heartbeat until 80 min of infusion, systolic arterial blood pressure until 90 min, and diastolic arterial blood pressure until 50 min were lower, whereas amnesia and sedation levels were higher in dexmedetomidine group. Postoperative pain and analgesic requirement were not different. Apex heartbeat at 15 min and systolic arterial blood pressure at 30 min were lower and sedation scores were higher in the dexmedetomidine infusion group. We demonstrated dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively whereas it had no significant effect on peripheral oxygen saturation, respiratory rate, visual analog scale scores, and side effects. Dexmedetomidine infusion enhanced motor and sensory blockade quality and induced amnesia and sedation. PMID:29457538

Safety and Efficacy of the Off-Label Use of Milrinone in Pediatric Patients with Heart Diseases

PubMed Central

Lee, Joowon; Kwon, Hye Won; Kwon, Bo Sang; Bae, Eun Jung; Noh, Chung Il; Lim, Hong Gook; Kim, Woong Han; Lee, Jeong Ryul; Kim, Yong Jin

2014-01-01

Background and Objectives Milrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for ≥3 days in infants and children with heart diseases. Subjects and Methods We retrospectively reviewed the medical records of patients aged <13 years who received milrinone for ≥3 days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia. Results We assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (≥7 days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use. Conclusion Milrinone was generally administered for ≥3 days in children with heart diseases. The use of milrinone for ≥3 days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases. PMID:25278985

The U.K. service level audit of insulin pump therapy in adults.

PubMed

White, H D; Goenka, N; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Paul, P; Ghatak, A; Weston, P J

2014-04-01

The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first U.K.-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the U.K. were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the U.K., of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. The prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the U.S.A. (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

UK service level audit of insulin pump therapy in paediatrics.

PubMed

Ghatak, A; Paul, P; Hawcutt, D B; White, H D; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Weston, P J

2015-12-01

To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Continuous infusion or bolus injection of loop diuretics for patients admitted for severe acute heart failure: is one strategy better than the other?

PubMed

Caetano, Francisca; Mota, Paula; Almeida, Inês; Fernandes, Andreia; Botelho, Ana; Leitão Marques, António

2015-02-01

Intravenous loop diuretics are an essential part of acute heart failure management; however, data to guide their use is sparse. Our aim was to compare continuous intravenous infusion of loop diuretics with intravenous bolus administration in terms of efficacy and adverse events in patients admitted with severe acute heart failure. Over a period of three years, 110 patients were admitted to our cardiac intensive care unit with acute heart failure. Clinical, laboratory and prognostic parameters were compared according to the diuretic strategy used and mortality and readmission for acute heart failure during follow-up were analyzed. Previous medical history was similar in the two groups. At admission, the continuous infusion group met criteria for worse prognosis: lower systolic blood pressure (p=0.011), more severe renal injury (p=0.008), lower left ventricular ejection fraction (p=0.016) and higher incidence of restrictive pattern of diastolic dysfunction (p=0.032). They were more often treated with vasopressors (p=0.003), inotropes (p=0.010), renal support therapy (p=0.003) and non-invasive ventilation (p<0.001). They had longer hospitalizations (p=0.014) and a higher incidence of cardiorenal syndrome (p=0.009); however, at discharge, there were no differences in renal function between the groups. In-hospital mortality was similar, and during follow-up there were no differences in mortality or readmission for acute heart failure. Continuous infusion was preferred in patients presenting with worse clinical status, in whom renal dysfunction was transiently worse. However, in-hospital mortality and creatinine at discharge were similar. Continuous infusion thus appears to counteract the initial dire prognosis of more unstable patients. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Medication and volume delivery by gravity-driven micro-drip intravenous infusion: potential variations during "wide-open" flow.

PubMed

Pierce, Eric T; Kumar, Vikram; Zheng, Hui; Peterfreund, Robert A

2013-03-01

Gravity-driven micro-drip infusion sets allow control of medication dose delivery by adjusting drops per minute. When the roller clamp is fully open, flow in the drip chamber can be a continuous fluid column rather than discrete, countable, drops. We hypothesized that during this "wide-open" state, drug delivery becomes dependent on factors extrinsic to the micro-drip set and is therefore difficult to predict. We conducted laboratory experiments to characterize volume delivery under various clinically relevant conditions of wide-open flow in an in vitro laboratory model. A micro-drip infusion set, plugged into a bag of normal saline, was connected to a high-flow stopcock at the distal end. Vertically oriented IV catheters (gauges 14-22) were connected to the stopcock. The fluid meniscus height in the bag was fixed (60-120 cm) above the outflow point. The roller clamp on the infusion set was in fully open position for all experiments resulting in a continuous column of fluid in the drip chamber. Fluid volume delivered in 1 minute was measured 4 times with each condition. To model resistive effects of carrier flow, volumetric infusion pumps were used to deliver various flow rates of normal saline through a carrier IV set into which a micro-drip infusion was "piggybacked." We also compared delivery by micro-drip infusion sets from 3 manufacturers. The volume of fluid delivered by gravity-driven infusion under wide-open conditions (continuous fluid column in drip chamber) varied 2.9-fold (95% confidence interval, 2.84-2.96) depending on catheter size and fluid column height. Total model resistance of the micro-drip with stopcock and catheter varied with flow rate. Volume delivered by the piggybacked micro-drip decreased up to 29.7% ± 0.8% (mean ± SE) as the carrier flow increased from 0 to 1998 mL/min. Delivery characteristics of the micro-drip infusion sets from 3 different manufacturers were similar. Laboratory simulation of clinical situations with gravity-driven micro-drip infusion sets under wide-open flow conditions revealed that infusion rate (drug and/or volume delivery) can vary widely depending on extrinsic factors including catheter size, fluid column height, and carrier flow. The variable resistance implies nonlaminar flow in the micro-drip model that cannot be easily predicted mathematically. These findings support the use of mechanical pumps instead of gravity-driven micro-drips to enhance the precision and safety of IV infusions, especially for vasoactive drugs.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

PubMed

Murray, Michael J; DeBlock, Heidi; Erstad, Brian; Gray, Anthony; Jacobi, Judi; Jordan, Che; McGee, William; McManus, Claire; Meade, Maureen; Nix, Sean; Patterson, Andrew; Sands, M Karen; Pino, Richard; Tescher, Ann; Arbour, Richard; Rochwerg, Bram; Murray, Catherine Friederich; Mehta, Sangeeta

2016-11-01

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Generic Critical Thinking Infusion and Course Content Learning in Introductory Psychology

ERIC Educational Resources Information Center

Solon, Tom

2007-01-01

One group of introductory psychology students received a moderate infusion of generic critical thinking material. The other group did not. Otherwise both groups had the same course content, and took the same pretests and posttests of their critical thinking ability and their knowledge of psychology. The experimental group improved its critical…

REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure.

PubMed

Patel, Amit N; Mittal, Sanjay; Turan, Goekmen; Winters, Amalia A; Henry, Timothy D; Ince, Hueseyin; Trehan, Naresh

2015-09-01

Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients. This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery. ©AlphaMed Press.

Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

PubMed

Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-05-01

Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

PubMed

Kaneishi, Keisuke; Kawabata, Masahiro

2013-03-01

Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.

The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia.

PubMed

Abdulatif, M; Ahmed, A; Mukhtar, A; Badawy, S

2013-10-01

This randomised, controlled, double-blind study investigated the effects of intra-operative magnesium sulphate administration on the incidence of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Seventy children were randomly allocated to receive a 30 mg.kg(-1) bolus of intravenous magnesium sulphate after induction of anaesthesia followed by a continuous infusion of 10 mg.kg(-1).h(-1) or an equal volume of saline 0.9%. All children received titrated sevoflurane anaesthesia adjusted to maintain haemodynamic stability. The Pediatric Anesthesia Emergence Delirium scale and the Children's Hospital of Eastern Ontario Score were used for the assessment of postoperative emergence agitation and pain, respectively. Emergence agitation was more common in the control group than in the magnesium group (23 (72%) and 12 (36%), respectively (p = 0.004)), with a relative risk of 0.51 (95% CI 0.31-0.84), an absolute risk reduction of 0.35 (95% CI 0.10-0.54), and number needed to treat of 3 (95% CI 2-9). Postoperative pain scores were comparable in the two groups. Magnesium sulphate reduces the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia and is not associated with increased postoperative side-effects or delayed recovery. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Acid sensitization of esophageal mucosal afferents: implication for symptom perception in patients across the gastroesophageal reflux disease spectrum.

PubMed

Szczesniak, Michal Marcin; Fuentealba, Sergio Enrique; Cook, Ian J

2013-01-01

Sensitization of esophageal chemoreceptors, either directly by intermittent acid exposure or indirectly through esophagitis-associated inflammatory mediators, is likely to be the mechanism underlying the perception of heartburn. To compare basal esophageal sensitivity with electrical stimulation and acid, and to compare the degree of acid-induced sensitization in controls and in patient groups across the entire spectrum of gastroesophageal reflux disease: erosive oesophagitis (EO), nonerosive reflux disease (NERD), and functional heartburn (FH). Esophageal sensory and pain thresholds to electrical stimulation were measured before, 30, and 60 minutes after an intraesophageal infusion of saline or HCl. Patients received a 30-minute infusion of 0.15 M HCl and controls were randomized to receive either HCl (n = 11) or saline (n = 10). After electrical sensory threshold testing, participants received another 30-minute infusion of HCl to determine whether sensitivity to acid is increased by prior acid exposure All patient groups had higher basal sensory thresholds than healthy controls (controls, 13 ± 1.4 mA; FH, 20 ± 5.1 mA; NERD, 21 ± 5.1 mA; EO, 23 ± 5.4 mA; P < 0.05). Acute esophageal acid exposure reduced sensory thresholds to electrical stimulation in FH and NERD patients (P < 0.05). The level of acid sensitivity during the first HCl infusion was comparable between all patient groups and controls. The secondary infusion caused increased discomfort in all participants (P < 0.01). This acid-induced sensitization to HCl was significantly elevated in the patient groups ( P < 0.05). (1) Esophageal acid infusion sensitizes it to subsequent electrical and chemical stimulation. (2) The acid-related sensitization is greater in gastroesophageal reflux disease than in controls and may influence in part symptom perception in this population. (3) Acid-related sensitization within the gastroesophageal reflux disease population is not dependant on mucosal inflammation.

Intravenous labetolol in treating hypertensive crisis following dexmedetomidine infusion for procedural sedation.

PubMed

Muthiah, Thilaka; Moni, Amarnath; Mathews, Lailu; Balaji, Sudarshan

2016-03-01

Dexmedetomidine is widely used for procedural sedation because of its unique combination of sedation, analgesia, and anxiolysis with minimal respiratory depression. Transient hypertension has been reported during the use of dexmedetomidine which is usually benign and is taken over by the hypotensive response on continuing the infusion. We report a case of hypertensive crisis following dexmedetomidine infusion used for procedural sedation, necessitating discontinuation of the infusion and treatment of hypertension. The dilemmas involved in treating hypertension caused by dexmedetomidine are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

PubMed Central

Heinemann, Lutz; Krinelke, Lars

2012-01-01

Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep.

PubMed

Wassink, Guido; Davidson, Joanne O; Dhillon, Simerdeep K; Fraser, Mhoyra; Galinsky, Robert; Bennet, Laura; Gunn, Alistair J

2017-03-01

Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus ( P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes ( P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes ( P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation.

Partial white and grey matter protection with prolonged infusion of recombinant human erythropoietin after asphyxia in preterm fetal sheep

PubMed Central

Wassink, Guido; Davidson, Joanne O; Dhillon, Simerdeep K; Fraser, Mhoyra; Galinsky, Robert; Bennet, Laura

2016-01-01

Perinatal asphyxia in preterm infants remains a significant contributor to abnormal long-term neurodevelopmental outcomes. Recombinant human erythropoietin has potent non-haematopoietic neuroprotective properties, but there is limited evidence for protection in the preterm brain. Preterm (0.7 gestation) fetal sheep received sham asphyxia (sham occlusion) or asphyxia induced by umbilical cord occlusion for 25 min, followed by an intravenous infusion of vehicle (occlusion-vehicle) or recombinant human erythropoietin (occlusion-Epo, 5000 international units by slow push, then 832.5 IU/h), starting 30 min after asphyxia and continued until 72 h. Recombinant human erythropoietin reduced neuronal loss and numbers of caspase-3-positive cells in the striatal caudate nucleus, CA3 and dentate gyrus of the hippocampus, and thalamic medial nucleus (P < 0.05 vs. occlusion-vehicle). In the white matter tracts, recombinant human erythropoietin increased total, but not immature/mature oligodendrocytes (P < 0.05 vs. occlusion-vehicle), with increased cell proliferation and reduced induction of activated caspase-3, microglia and astrocytes (P < 0.05). Finally, occlusion-Epo reduced seizure burden, with more rapid recovery of electroencephalogram power, spectral edge frequency, and carotid blood flow. In summary, prolonged infusion of recombinant human erythropoietin after severe asphyxia in preterm fetal sheep was partially neuroprotective and improved electrophysiological and cerebrovascular recovery, in association with reduced apoptosis and inflammation. PMID:27207167

Randomised controlled trial of effect of terbutaline before elective caesarean section on postnatal respiration and glucose homeostasis

PubMed Central

Eisler, G.; Hjertberg, R.; Lagercrantz, H.

1999-01-01

AIM—To determine if terbutaline given to mothers before elective caesarean section facilitates neonatal respiration and metabolism.
METHODS—A randomised controlled trial of 25 full term infants delivered by elective caesarean section was conducted. The mothers received a continuous infusion of terbutaline or saline 120-0 minutes before birth. Umbilical artery blood was collected at birth and analysed for blood gases and catecholamines. The lung function of each infant was assessed two hours after birth, and blood pressure, heart rate, blood glucose and body temperature were monitored until 24 hours of age.
RESULTS—The infants of the treated mothers (n=13) had significantly higher dynamic lung compliance (p<0.001), lower airway resistance (p<0.001), and respiratory frequency than control infants (n=12). Blood glucose and adrenaline concentrations were significantly higher in the treated group (p=0.0014 and p<0.01). None of these infants had any clinical respiratory difficulties; there were two cases of transient tachypnoea in the control group. No negative side effects due to the terbutaline treatment were seen among the infants. The mothers felt no discomfort caused by the terbutaline infusion, although they bled more during surgery (p=0.03).
CONCLUSION—Stimulation of the β adrenoceptors in utero with terbutaline infusion to the mothers promotes neonatal respiratory and metabolic adaptation after elective caesarean section.

 PMID:10325782

Delivered volumes of enteral nutrition exceed prescribed volumes.

PubMed

Walker, Renee Nichole; Utech, Anne; Velez, Maria Eugenia; Schwartz, Katie

2014-10-01

Enteral nutrition (EN) provisions are typically calculated based on a 24-hour infusion period. However, feedings are often interrupted for daily activities, procedures, or gastrointestinal intolerance. The study's objective was to determine the delivered EN quantities provided to stable hospitalized patients, using cellular time and measured volumes to verify our EN calculation adjustment. A supply of consecutively numbered ready-to-hang (RTH) EN product was delivered to the bedside of 26 inpatients with established EN tolerance at goal rates on various types of nursing units. The dietitian weighed the volume remaining in the infusing product and recorded the measurement time. On the following days, the dietitian continued to weigh the infusing RTH product and the empty RTH bottles saved by nursing. The primary outcome was the difference between the prescribed and delivered EN provisions, which was calculated with a paired t test. Patients received significantly more calories in the delivered enteral feeding (mean [SD], 1678 [385] kcal) than prescribed calories in the EN order (1489 [246 kcal]; t = 3.736, P = .001), adjusting for observed time. No significant differences were found between nursing units, product, and rate. EN delivered may actually exceed ordered amounts by 5%–21% (mean, 12%) with feeding pump inaccuracy as the primary contributing factor. This differs from what others have found. Our findings support using a volume-based ordering system vs a rate-based ordering system for more accurate EN delivery.

Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis.

PubMed

Ranganathan, Usha; Kaunzner, Ulrike; Foster, Stacyann; Vartanian, Timothy; Perumal, Jai S

2018-04-01

Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). Although Immune thrombocytopenia (ITP) has been reported as a secondary autoimmune phenomenon following alemtuzumab infusion, immediate thrombocytopenia during the infusion has not been reported. We report transient, reversible, self-limiting acute-onset thrombocytopenia during the first course with alemtuzumab. In total, 3 of 22 paitents developed mild self-limited bruising associated with a drop in platelet count from their baseline during the intial 5-day course of alemtuzumab. Upon chart review, all 22 patients who received alemtuzumab developed an immediate mostly asymptomatic drop in platelet count which returned to normal within 2 months post-infusion.

Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia.

PubMed

Calenda, Emile; Baste, Jean Marc; Hajjej, Ridha; Danielou, Eric; Peillon, Christophe

2014-03-01

A case of systemic ropivacaine toxicity from a continuous thoracic paravertebral block in an adult patient who received a lobectomy is presented. The catheter was placed by the surgeon. Eleven hours after the start of the infusion, the patient experienced an arrhythmia leading to death. The total venous plasma concentration of ropivacaine was high (3.2 μg/mL). Furthermore, the patient had severe hypoalbuminemia (albumin 24 g/L), which resulted in the increase of the unbound ropivacaine plasma concentration that was responsible for the toxic side effects. Copyright © 2014 Elsevier Inc. All rights reserved.

[Anaphylactoid reactions inducing effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata injection on beagle].

PubMed

Sun, Wei-wei; Li, Yi-kui; Zhang, Jin-yan

2011-01-01

To evaluate the sensitization effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata Injection in different concentrations on Beagle. Beagles, a kind of animal highly sensitive to sensitizing agents, were randomly divided into 18 groups, 3 in each group. They received respectively the intravenous infusion of polysorbate 80 made by different factories in different concentrations (0.25%, 0.10%, 0.05%), and Houttuynia cordata Injection containing polysorbate 80 in concentration of 0.25% or 0.30%, with the constant infusing speed of 5 mL/min and volume of 10 mL/kg. Changes of animals' condition were observed before infusion and in the 24 h after infusion, time of symptom appearance and disappearance was recorded, and the grade of response was determined. Moreover, blood samples of animals were collected before infusion and 10 min after ending infusion for measuring histamine content in plasma using ELISA. Then the sensitization effect was comprehensively estimated by combined consideration of the responding grade and histamine level. No typical symptom of anaphylactoid reaction and over 1-fold increase of histamine level was found in all groups that received intravenous infusion of polysorbate 80 or polysorbate 80 contained Houttuynia cordata Injection in different concentrations. Estimation showed that all test solutions didn't induce typical anaphylactoid reaction on Beagle. Considering both the appearance of symptoms and the elevation of blood content of histamine could be taken as the criteria for comprehensive diagnosis of anaphylactoid reactions. The solubilization effect and safety (for foreclose anaphylactoid reaction) of polysorbate 80 could be ensured by controlling its quality and concentration below 0.25% or 0.30%.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Wansheng; Dong Yonghua, E-mail: dongyhua@yahoo.com; Liu Bin

The objective of this study was to evaluate the feasibility and safety of lung volume reduction by transbronchial alcohol and lipiodol suspension infusion with the aid of balloon-tipped catheter occlusion. Twenty-six healthy adult rabbits were divided into four treatment groups: alcohol and lipiodol suspension infusion (n = 8), lipiodol infusion (n = 8), alcohol infusion (n = 5), or bronchial lumen occlusion (n = 5). After selective lobar or segmental bronchial catheterization using a balloon-tipped occlusion catheter, the corresponding drug infusion was performed. Bone cement was used to occlude the bronchial lumen in the occlusion group. The animals were followedmore » up for 10 weeks by chest X-ray and computed tomography (CT), and then the whole lungs were harvested for histological examination. Alcohol and lipiodol suspension or lipiodol could be stably retained in alveoli in the first two groups based on chest X-ray and CT, but obvious collapse only occurred in the group receiving alcohol and lipiodol suspension or the bronchial lumen occlusion group. Histological examination revealed damage and disruption of the alveolar epithelium and fibrosis in related lung tissue in the group receiving alcohol and lipiodol suspension. Similar changes were seen in the bronchial lumen occlusion group, apart from obvious marginal emphysema of the target areas in two animals. Interstitial pneumonia and dilated alveoli existed in some tissue in target areas in the lipiodol group, in which pulmonary fibrosis obliterating alveoli also occurred. Chronic alveolitis and pleural adhesion in target areas occurred in the group infused with alcohol alone, whereas visceral pleura of the other three groups was regular and no pleural effusion or adhesion was found. Alcohol and lipiodol suspension that is stably retained in alveoli can result in significant lung volume reduction. Through alcohol and lipiodol suspension infusion, obstructive emphysema or pneumonia arising from bronchial lumen occlusion could be avoided.« less

Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial.

PubMed

Tarui, Suguru; Ishigami, Shuta; Ousaka, Daiki; Kasahara, Shingo; Ohtsuki, Shinichi; Sano, Shunji; Oh, Hidemasa

2015-11-01

Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS). In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up. No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion. Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of Intradermal and Subcutaneous Infusion Set Performance Under 24-Hour Basal and Bolus Conditions

PubMed Central

McVey, Elaine; Keith, Steven; Herr, Joshua K.; Sutter, Diane; Pettis, Ronald J.

2015-01-01

Background: This study sought to assess the function and delivery reliability of intradermal (ID) infusion sets used with commercial insulin pumps. Method: Healthy subjects (n = 43) were randomized to either ID or subcutaneous (SC) arms, and received basal/bolus placebo delivery for 24 hours. Subjects received 4 of 8 infusion set combinations (ID: microneedle design A or B, with 2 pump brands [Animas or MiniMed]; SC: Teflon Quickset or steel Rapid-D, Animas pump only, with or without overtaping) and were evaluated for pump occlusion alarms, fluid leakage, pain, and tissue tolerability. A novel algorithm was developed to determine flow consistency based on fluid pressure, and the duration and occurrence rate for periods of unalarmed but interrupted flow (“silent occlusions’”) were compared. Results: ID delivery was successfully maintained over the 24-hour infusion period. The number of silent occlusions was lower for ID microneedle cannula design B than A (P < .01) and lower for Rapid-D SC device compared to Quick-set (P = .03). There was no significant difference in the number of occlusion alarms between the ID and SC devices with the Animas pump. However, the pumps tested with ID devices had significantly different alarm rates (MiniMed 29.5%, Animas 0%, P < .001). Leakage and tissue tolerability were comparable across devices. Conclusion: The ID infusion set reliably delivered diluent for an extended 24-hour period in healthy subjects and was well tolerated. Silent occlusion flow interruptions could be detected in both ID and SC infusion sets using a proprietary algorithm. This algorithm is a promising method for quantitatively evaluating infusion set flow performance. PMID:26319228

Industrial hemp decreases intestinal motility stronger than indian hemp in mice.

PubMed

Sabo, A; Horvat, O; Stilinovic, N; Berenji, J; Vukmirovic, S

2013-02-01

Indian hemp has shown beneficial effects in various gastrointestinal conditions but it is not widely accepted due to high content of tetrahydrocannabinol resulting in unwanted psychotropic effects. Since industrial hemp rich in cannabidiol lacks psychotropic effects the aim of research was to study the effects of industrial hemp on intestinal motility. Animals were randomly divided in six groups (each group consisting of 6 animals): Control group, Cind group - receiving indian hemp infuse for 20 days, Cids group-receiving industrial hemp infuse for 20 days, M group - treated with single dose of morphine (5 mg/kg i.m.) Cind+M group - treated with indian hemp infuse and single dose of morphine (5 mg/kg i.m.), Cids+M - treated with industrial hemp infuse and single dose of morphine (5 mg/kg i.m.). On the 20th day of the study animals were administered charcoal meal, and were sacrificed 35 minutes after administration. Intestinal motility was estimated according to distance between carbo medicinalis and cecum in centimeters. Decrease of intestinal motility in animals treated with indian hemp infuse was not significant compared to controls and it was smaller compared to animals treated with morphine (Indian hemp =15.43±10.5 cm, morphine = 20.14±5.87 cm). Strongest decrease of intestinal motility was recorded in animals treated with industrial hemp infuse, and it was significant compared to controls and morphine (industrial hemp = 26.5±9.90 cm, morphine = 20.14±5.87 cm; p < 0.005). Although not completely without psychotropic activity cannabidiol could be a potential replacement for tetrahydrocannabinol. Since industrial hemp infuse rich in cannabidiol reduces intestinal motility in healthy mice cannabidiol should be further evaluated for the treatment of intestinal hypermotility.

Small intestinal digestion of raw cornstarch in cattle consuming a soybean hull-based diet is improved by duodenal casein infusion.

PubMed

Brake, D W; Titgemeyer, E C; Bailey, E A; Anderson, D E

2014-09-01

Six duodenally and ileally cannulated steers were used in 3 sequential studies to measure 1) basal nutrient flows from a soybean hull-based diet, 2) small intestinal digestibility of raw cornstarch continuously infused into the duodenum, and 3) responses of small intestinal starch digestion to duodenal infusion of 200 or 400 g/d casein. Our objective was to evaluate responses in small intestinal starch digestion in cattle over time and to measure responses in small intestinal starch digestion to increasing amounts of MP. On average, cattle consumed 3.7 kg/d DM, 68 g/d dietary N, and 70 g/d dietary starch. Starch flow to the duodenum was small (38 g/d), and N flow was 91 g/d. Small intestinal digestibility of duodenal N was 57%, and small intestinal digestion of duodenal starch flow was extensive (92%). Small intestinal starch digestibility was 34% when 1.5 kg/d raw cornstarch was continuously infused into the duodenum. Subsequently, cattle were placed in 1 of 2 replicated Latin squares that were balanced for carryover effects to determine response to casein infusions and time required for adaptation. Duodenal infusion of casein linearly increased (P ≤ 0.05) small intestinal starch digestibility, and small intestinal starch digestion adapted to infusion of casein in 6 d. Ethanol-soluble starch and unpolymerized glucose flowing to the ileum increased linearly (P ≤ 0.05) with increasing infusion of casein. Plasma cholecystokinin was not affected by casein infusion, but circulating levels of glucose were increased by casein supplementation (P ≤ 0.05). Responses in small intestinal starch digestion in cattle adapted to casein within 6 d, and increases in duodenal supply of casein up to 400 g/d increased small intestinal starch digestion in cattle.

Continuous infusion or bolus injection of loop diuretics for congestive heart failure?

PubMed

Zepeda, Patricio; Rain, Carmen; Sepúlveda, Paola

2016-04-22

Loop diuretics are widely used in acute heart failure. However, there is controversy about the superiority of continuous infusion over bolus administration. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 pertinent randomized controlled trials overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded continuous administration of loop diuretics probably reduces mortality and length of stay compared to intermittent administration in patients with acute heart failure.

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review

PubMed Central

Dickman, Andrew; Mason, Stephen; Ellershaw, John

2018-01-01

Background A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. Aim To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. Design A systematically-structured review following PRISMA guidelines. Data sources Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. Results Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. Conclusions There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice. PMID:29538455

Type of homogenization and fat loss during continuous infusion of human milk.

PubMed

García-Lara, Nadia Raquel; Escuder-Vieco, Diana; Alonso Díaz, Clara; Vázquez Román, Sara; De la Cruz-Bértolo, Javier; Pallás-Alonso, Carmen Rosa

2014-11-01

Substantial fat loss may occur during continuous feeding of human milk (HM). A decrease of fat loss has been described following homogenization. Well-established methods of homogenization of HM for routine use in the neonatal intensive care unit (NICU) would be desirable. We compared the loss of fat based on the use of 3 different methods for homogenizing thawed HM during continuous feeding. Sixteen frozen donor HM samples were thawed, homogenized with ultrasound and separated into 3 aliquots ("baseline agitation," "hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots were thawed again and a baseline agitation was applied. Subsequently, aliquots baseline agitation and hourly agitation were drawn into a syringe, while ultrasound was applied to aliquot ultrasound before it was drawn into a syringe. The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the hourly agitation infusion was stopped, the syringe was disconnected and gently shaken. During infusion, samples from the 3 groups were collected hourly for analysis of fat and caloric content. The 3 groups of homogenization showed similar fat content at the beginning of the infusion. For fat, mean (SD) hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed for the hourly agitation, baseline agitation, and ultrasound groups, respectively. The decrease was smaller for the hourly agitation group (P < .001). When thawed HM is continuously infused, a smaller fat loss is observed when syringes are agitated hourly versus when ultrasound or a baseline homogenization is used. © The Author(s) 2014.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

PubMed Central

Spiller, R C; Trotman, I F; Adrian, T E; Bloom, S R; Misiewicz, J J; Silk, D B

1988-01-01

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions. PMID:3410330

Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs)

PubMed Central

Howsmon, Daniel P.; Cameron, Faye; Baysal, Nihat; Ly, Trang T.; Forlenza, Gregory P.; Maahs, David M.; Buckingham, Bruce A.; Hahn, Juergen; Bequette, B. Wayne

2017-01-01

Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis—a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios. PMID:28098839

Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs).

PubMed

Howsmon, Daniel P; Cameron, Faye; Baysal, Nihat; Ly, Trang T; Forlenza, Gregory P; Maahs, David M; Buckingham, Bruce A; Hahn, Juergen; Bequette, B Wayne

2017-01-15

Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

PubMed Central

Lei, Bai; Nakano, Daisuke; Fan, Yu-Yan; Kitada, Kento; Hitomi, Hirofumi; Kobori, Hiroyuki; Mori, Hirohito; Masaki, Tsutomu; Nishiyama, Akira

2012-01-01

We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren. PMID:22673148

Absorption of subcutaneously infused insulin: influence of the basal rate pulse interval.

PubMed

Hildebrandt, P; Birch, K; Jensen, B M; Kühl, C; Brange, J

1985-01-01

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

Comparison between the synthetic cholecystokinin analogues caerulein and Thr28NlE31CCK25-33(CCK9) with regards to plasma bioactivity, degradation rate and stimulation of pancreatic exocrine function.

PubMed

Mössner, J; Sprenger, C; Secknus, R; Kestel, W; Fischbach, W

1991-02-01

A new synthetic analogue of cholecystokinin, Thr28Nle31CCK25-33(CCK9) is compared with caerulein with regards to plasma bioactivity, degradation rate, side effects, and stimulation of pancreatic secretion. 24 healthy male volunteers were intubated with a double lumen Lagerlöf-tube. 30 min after correct positioning of the tube subjects received a continuous intravenous infusion of synthetic secretin (1 U/kg) together with either ceruletide (61.5 pM/kg) or CCK9 (30 pM/kg) both for 45 min. 30 pM/kg of CCK9 have been shown by others to cause maximal enzyme secretion (1). 61.5 pM/kg (= 100 ng) of caerulein are probably supramaximal but used by many centers for direct pancreatic function tests. Plasma CCK was measured by bioassay which compares amylase release of isolated rat pancreatic acini stimulated by plasma extracts with known standards of CCK8. Lipase, amylase, trypsin, chymotrypsin, and bicarbonate were measured in 15 min fractions after the onset of CCK infusion. Both drugs caused a similar stimulation of pancreatic enzyme secretion during infusion of the respective analogue which declined after termination. After the onset of CCK9 infusion plasma bioactivity reached a plateau around 20 pM at 15 min. Values declined after 30 min. After termination of infusion bioactivity rapidly declined within 3 min but still remained slightly elevated after further 15 min as compared to basal values (3.9 vs 0.6 pM). Plasma kinetics of caerulein were quite similar. However, despite a dose which was only twice as high as compared to CCK9, plasma bioactivity was six times higher with plateau values of about 120 pM.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcutaneous Immunoglobulin Replacement Therapy with Hizentra® is Safe and Effective in Children Less Than 5 Years of Age.

PubMed

Patel, Niraj C; Gallagher, Joel L; Ochs, Hans D; Prescott Atkinson, Thomas; Wahlstrom, Justin; Dorsey, Morna; Bonilla, Francisco A; Heimall, Jennifer; Kobrynski, Lisa; Morris, David; Haddad, Elie

2015-08-01

Hizentra® (IGSC 20%) is a 20% liquid IgG product approved for subcutaneous administration in adults and children 2 years of age and older who have primary immunodeficiency disease (PIDD). There is limited information about the use of IGSC 20 % in very young children including those less than 5 years of age. A retrospective chart review involved 88 PIDD infants and children less than 5 years of age who received Hizentra®. The mean age at the start of Hizentra® was 34 months (range 2 to 59 months). IGSC 20 % was administered weekly to 86 infants (two additional infants received twice weekly and three times weekly infusions, respectively) and included an average of 63 infusions (range 6-182) for an observation period up to 45.5 months. Infusion by manual delivery occurred in 15 patients. The mean dose was 674 mg/kg/4 weeks. The mean IgG level was 942 mg/dL while on IGSC 20 %, compared to a mean trough IgG level of 794 mg/dL (p < 0.0001) during intravenous or subcutaneous IgG administration prior to IGSC 20 %. Average infusion time was 47 (range 5-120) minutes, and the median number of infusion sites was 2 (range 1-4). Local reactions were mostly mild and observed in 36/88 (41%) children. No serious adverse events were reported. A significant increase in weight percentile (7 % ± 19.2, p = 0.0012) among subjects was observed during IGSC 20% administration. The rate of serious bacterial infections was 0.067 per patient-year while receiving IGSC 20%, similar to previously reported efficacy studies. Hizentra® is effective in preventing infections, and is well tolerated in children less than age 5 years.

Excretory, secretory, and tissue residues after label and extra-label administration of flunixin meglumine to saline or lipopolysaccharide-exposed dairy cows

USDA-ARS?s Scientific Manuscript database

Twenty lactating dairy cattle were intravenously infused with either lipopolysaccharide (n = 10) or sterile saline (n = 10). Five cattle in each group received 3 doses of flunixin meglumine administered by either IV infusion or IM injection at 24 h intervals. Milk, urine, and tissues were collected....

High-dose ifosfamide by infusion with Mesna in advanced refractory sarcomas.

PubMed

Güllü, I; Yalçin, S; Tekuzman, G; Barişta, I; Alkiş, N; Celik, I; Zengin, N; Güler, N; Kars, A; Baltali, E

1996-01-01

Twenty patients with advanced sarcomas entered a pilot study with ifosfamide (IF) and mercaptoethane sulfonate sodium (Mesna) as a second-line treatment for six planned cycles. All patients had received prior doxorubicin- and cyclophosphamide-based chemotherapies. IF was administered at a dose of 3 g/m2 given as continuous intravenous infusion for 24 hr on day 1-5 with Mesna. In the absence of disease progression, chemotherapy was planned to be repeated every 4 weeks for six consecutive cycles. Following chemotherapy, only 2 patients (11%) achieved partial response with response durations of 6 and 9 months. There was no complete response. When considered for only high-grade tumors, the response rate reached up to 22%. Toxicity was reported for 48 cycles and the dose-limiting toxicities were myelosuppression (22%) and encephalopathy (17%). Chemotherapy protocol was changed after two or three courses in 16 patients with stable or progressive disease. IF/Mesna chemotherapy at this dose and schedule was not found to be very promising in refractory sarcomas as a second-line chemotherapy.

Single-injection or continuous femoral nerve block for total knee arthroplasty?

PubMed

Albrecht, Eric; Morfey, Dorothea; Chan, Vincent; Gandhi, Rajiv; Koshkin, Arkadiy; Chin, Ki Jinn; Robinson, Sylvie; Frascarolo, Philippe; Brull, Richard

2014-05-01

The ideal local anesthetic regime for femoral nerve block that balances analgesia with mobility after total knee arthroplasty (TKA) remains undefined. We compared two volumes and concentrations of a fixed dose of ropivacaine for continuous femoral nerve block after TKA to a single injection femoral nerve block with ropivacaine to determine (1) time to discharge readiness; (2) early pain scores and analgesic consumption; and (3) functional outcomes, including range of motion and WOMAC scores at the time of recovery. Ninety-nine patients were allocated to one of three continuous femoral nerve block groups for this randomized, placebo-controlled, double-blind trial: a high concentration group (ropivacaine 0.2% infusion), a low concentration group (ropivacaine 0.1% infusion), or a placebo infusion group (saline 0.9% infusion). Infusions were discontinued on postoperative Day (POD) 2. The primary outcome was time to discharge readiness. Secondary outcomes included opioid consumption, pain, and functional outcomes. Ninety-three patients completed the study protocol; the study was halted early because of unanticipated changes to pain protocols at the host institution, by which time only 61% of the required number of patients had been enrolled. With the numbers available, the mean time to discharge readiness was not different between groups (high concentration group, 62 hours [95% confidence interval [CI], 51-72 hours]; low concentration group, 73 hours [95% CI, 63-83 hours]; placebo infusion group 65 hours [95% CI, 56-75 hours]; p = 0.27). Patients in the low concentration group consumed significantly less morphine during the period of infusion (POD 1, high concentration group, 56 mg [95% CI, 42-70 mg]; low concentration group, 35 mg [95% CI, 27-43 mg]; placebo infusion group, 48 mg [95% CI, 38-59 mg], p = 0.02; POD 2, high concentration group, 50 mg [95% CI, 41-60 mg]; low concentration group, 33 mg [95% CI, 24-42 mg]; placebo infusion group, 39 mg [95% CI, 30-48 mg], p = 0.04); however, there were no important differences in pain scores or opioid-related side effects with the numbers available. Likewise, there were no important differences in functional outcomes between groups. Based on this study, which was terminated prematurely before the desired sample size could be achieved, we were unable to demonstrate that varying the concentration and volume of a fixed-dose ropivacaine infusion for continuous femoral nerve block influences time to discharge readiness when compared with a conventional single-injection femoral nerve block after TKA. A low concentration of ropivacaine infusion can reduce postoperative opioid consumption but without any important differences in pain scores, side effects, or functional outcomes. These pilot data may be used to inform the statistical power of future randomized trials. Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients

PubMed Central

Malone, Rebecca S.; Fish, Douglas N.; Abraham, Edward; Teitelbaum, Isaac

2001-01-01

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m2 polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 ± 13.0 years [standard deviation]; mean weight, 96.7 ± 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CLS) and elimination half-life (t1/2) of cefepime were 35.9 ± 6.0 ml/min and 12.9 ± 2.6 h during CVVH versus 46.8 ± 12.4 ml/min and 8.6 ± 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CLS, respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CLS of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC ≤ 8 μg/ml) during CVVH or CVVHDF. PMID:11600370

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid].

PubMed

Arranz Martín, Alfonso; Calle Pascual, Alfonso; Del Cañizo Gómez, Francisco Javier; González Albarrán, Olga; Lisbona Gil, Arturo; Botella Serrano, Marta; Pallardo Sánchez, Luis Felipe

2015-04-01

To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Short-Term Safety of Zoledronic Acid in Young Patients With Bone Disorders: An Extensive Institutional Experience

PubMed Central

George, Sobenna; Weber, David R.; Kaplan, Paige; Hummel, Kelly; Monk, Heather M.

2015-01-01

Context: Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited. Objective: The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients. Design, Setting, and Participants: This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia. Results: Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025–0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation. Conclusion: Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population. PMID:26308295

Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ognibene, F.P.; Parker, M.M.; Natanson, C.

Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was amore » strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.« less

Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

PubMed

Gay, V L; Mikuma, N; Plant, T M

1993-03-01

One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

The importance of the form of nitrogen on microbial protein synthesis in the rumen of cattle receiving grass silage and continuous intrarumen infusions of sucrose.

PubMed

Rooke, J A; Armstrong, D G

1989-01-01

1. In a 4 x 4 Latin square design experiment, four cattle were given grass silage in two meals per d to satisfy maintenance energy requirements. In addition, sucrose (170 g/kg silage dry matter (DM] was infused intraruminally at a constant rate with no nitrogen supplementation; with the infusion intraruminally of either casein (23 g/kg silage DM) or urea (8 g/kg silage DM); or with soya-bean meal (64 g/kg silage DM) fed in two equal portions. 2. Samples of duodenal digesta representative of a 24 h period were obtained using chromium-EDTA and ytterbium acetate for flow estimation and 35S as a marker of microbial N entering the small intestine. Samples of rumen fluid were also taken for estimation of rumen pH and concentrations of ammonia-N and volatile fatty acids. Estimates of apparent organic matter (OM) and N digestibility and of the rates of silage DM and N disappearance from porous synthetic-fibre bags incubated in the rumen were also made. 3. The N supplements had no significant effects on rumen pH, concentrations of volatile fatty acids, their molar proportions or the disappearance of DM or N from porous synthetic-fibre bags. N supplementation increased rumen ammonia-N concentrations (urea, P less than 0.05; casein, soya-bean meal, not significant). 4. N supplementation had no significant effects on the digestion of OM, acid-detergent fibre or soluble carbohydrate. 5. Infusion of casein increased the quantities of total non-ammonia-N (not significant) and microbial N (P less than 0.05) entering the small intestine daily and the efficiency of rumen microbial N synthesis (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of apixaban on antifactor Xa levels in a patient with acute kidney injury.

PubMed

Wendte, Jodi; Voss, Glenn; VanOverschelde, Beau

2016-04-15

The case of a patient requiring conversion from apixaban to heparin in the setting of acute kidney injury is reported. A 70-year-old man was initiated on apixaban 5 mg twice daily for new-onset, nonvalvular atrial fibrillation with a CHA2DS2-VASc score of 4, indicating a high risk of stroke. Soon after starting apixaban, he experienced pulmonary edema with pneumonia requiring hospitalization. During the course of hospitalization, the patient developed acute kidney injury requiring hemodialysis, and apixaban was stopped due to concerns about altered pharmacokinetics and impaired drug elimination in this setting. A heparin infusion was started 36 hours after the last dose of apixaban was administered. Antifactor Xa levels were monitored consistent with the hospital's standard practice protocols. The initial and repeat antifactor Xa concentrations were elevated (1.8-4.4 IU/mL) for up 72 hours after stopping the heparin infusion. Given the suspected interference of apixaban with standard antifactor Xa level monitoring, the heparin protocol was modified to reflect drip-rate adjustments based on activated partial thromboplastin times (aPTTs). The hospital protocol for heparin infusions was reinstituted on hospital day 7, with dosage adjustments based on antifactor Xa levels. The patient remained on a continuous heparin infusion for atrial fibrillation for the remainder of his hospitalization without complications or bleeding events. A 70-year-old man with new-onset nonvalvular atrial fibrillation and receiving apixaban discontinued this therapy and was given heparin instead due to acute kidney injury. His heparin dosage was successfully adjusted based on antifactor Xa levels and aPPTs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT.

PubMed

Allen, A P; Naughton, M; Dowling, J; Walsh, A; Ismail, F; Shorten, G; Scott, L; McLoughlin, D M; Cryan, J F; Dinan, T G; Clarke, G

2015-11-01

Ketamine is associated with rapid antidepressant efficacy but the biological mechanisms underpinning this effect are unclear. Serum brain-derived neurotrophic factor (sBDNF) is a potential circulating biomarker of treatment-resistant depression (TRD) and ketamine response but it is unclear if this is a common target of both ketamine and electroconvulsive therapy (ECT), the current gold standard for TRD. Moreover, the impact of multiple ketamine infusions on sBDNF has not yet been established. Thirty five TRD patients with a current DSM-IV diagnosis of recurrent depressive disorder received up to 12 ECT sessions (N=17) or up to three intravenous infusions of low-dose (0.5mg/kg) ketamine (N=18). Blood samples were taken over the course of the study for assessment of sBDNF. Symptom severity and response were monitored using the 17-item Hamilton Depression Rating Scale (HDRS). sBDNF was assessed in 20 healthy controls to allow comparison with TRD patients. As expected, sBDNF was lower in TRD patients at baseline compared to healthy controls. Ketamine and ECT treatment were both associated with significant reductions in depressive symptoms. However, sBDNF was significantly elevated only at one week following the first ketamine infusion in those classified as responders one week later. sBDNF was not elevated following subsequent infusions. ECT reduced depressive symptoms, as expected, but was not associated with an enhancement in BDNF. Patients continued with their psychotropic medications throughout this trial. SBDNF normalisation does not appear to be a prerequisite for symptomatic improvement in TRD following ketamine or ECT treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

[Comparison of metaraminol, phenylephrine and ephedrine in prophylaxis and treatment of hypotension in cesarean section under spinal anesthesia].

PubMed

Aragão, Fábio Farias de; Aragão, Pedro Wanderley de; Martins, Carlos Alberto de Souza; Salgado Filho, Natalino; Barroqueiro, Elizabeth de Souza Barcelos

2014-01-01

Maternal hypotension is a common complication after spinal anesthesia for cesarean section, with deleterious effects on the fetus and mother. Among the strategies aimed at minimizing the effects of hypotension, vasopressor administration is the most efficient. The aim of this study was to compare the efficacy of phenylephrine, metaraminol, and ephedrine in the prevention and treatment of hypotension after spinal anesthesia for cesarean section. Ninety pregnant women, not in labor, undergoing cesarean section were randomized into three groups to receive a bolus followed by continuous infusion of vasopressor as follows: phenylephrine group (50μg+50μg/min); metaraminol group (0.25mg+0.25mg/min); ephedrine group (4mg+4mg/min). Infusion dose was doubled when systolic blood pressure decreased to 80% of baseline and a bolus was given when systolic blood pressure decreased below 80%. The infusion dose was divided in half when systolic blood pressure increased to 120% and was stopped when it became higher. The incidence of hypotension, nausea and vomiting, reactive hypertension, bradycardia, tachycardia, Apgar scores, and arterial cord blood gases were assessed at the 1st and 5th minutes. There was no difference in the incidence of hypotension, bradycardia, reactive hypertension, infusion discontinuation, atropine administration or Apgar scores. Rescue boluses were higher only in the ephedrine group compared to metaraminol group. The incidence of nausea and vomiting and fetal acidosis were greater in the ephedrine group. The three drugs were effective in preventing hypotension; however, fetal effects were more frequent in the ephedrine group, although transient. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Recombinant human hyaluronidase-enabled subcutaneous pediatric rehydration.

PubMed

Allen, Coburn H; Etzwiler, Lisa S; Miller, Melissa K; Maher, George; Mace, Sharon; Hostetler, Mark A; Smith, Sharon R; Reinhardt, Neil; Hahn, Barry; Harb, George

2009-11-01

The Increased Flow Utilizing Subcutaneously-Enabled (INFUSE)-Pediatric Rehydration Study was designed to assess efficacy, safety, and clinical utility of recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration in children 2 months to 10 years of age. Patients with mild/moderate dehydration requiring parenteral treatment in US emergency departments were eligible for this phase IV, multicenter, single-arm study. They received subcutaneous injection of 1 mL rHuPH20 (150 U), followed by subcutaneous infusion of 20 mL/kg isotonic fluid over the first hour. Subcutaneous rehydration was continued as needed for up to 72 hours. Rehydration was deemed successful if it was attributed by the investigator primarily to subcutaneous fluid infusion and the child was discharged without requiring an alternative method of rehydration. Efficacy was evaluated in 51 patients (mean age: 1.9 years; mean weight: 11.2 kg). Initial subcutaneous catheter placement was achieved with 1 attempt for 46/51 (90.2%) of patients. Rehydration was successful for 43/51 (84.3%) of patients. Five patients (9.8%) were hospitalized but deemed to be rehydrated primarily through subcutaneous therapy, for a total of 48/51 (94.1%) of patients. No treatment-related systemic adverse events were reported, but 1 serious adverse event occurred (cellulitis at infusion site). Investigators found the procedure easy to perform for 96% of patients (49/51 patients), and 90% of parents (43/48 parents) were satisfied or very satisfied. rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.

Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.

PubMed

Zufferey, Paul J; Lanoiselée, Julien; Chapelle, Céline; Borisov, Dmitry B; Bien, Jean-Yves; Lambert, Pierre; Philippot, Rémi; Molliex, Serge; Delavenne, Xavier

2017-09-01

Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss. This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy. The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid. A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss.

Long-term subcutaneous pulsatile low dose LH-RH administration for treatment of infertile men with secondary hypogonadotrophic hypogonadism.

PubMed

Skarin, G; Nillius, S J; Wide, L

1984-01-01

Chronic pulsatile subcutaneous low dose LH-RH treatment was given to three infertile men with longstanding (2-4 years) secondary hypothalamic pituitary failure. Before the therapy they had very low serum concentrations of gonadotrophins and testosterone. They were impotent and could not produce any ejaculate for sperm analysis. The pulsatile LH-RH treatment, which was continued up to 250 days, was given by means of a small portable automatically-timed infusion pump. Fifty microliter of the LH-RH solution was infused during one min every 90 min. The LH-RH doses were 1, 5 and 20 micrograms. The serum concentrations of the gonadotrophins and testosterone were normalized in the three patients within 10 days of pulsatile low dose LH-RH therapy. Libido and potency returned. The first ejaculates contained no sperms. With continued LH-RH treatment spermatogenesis was induced and normalized. Two of the men fertilized their wives. The pregnancy tests were positive after 181 and 230 days of treatment, respectively. Two healthy girls have been born. Paternity tests were positive. The third man is still receiving pulsatile LH-RH therapy. He has up till now been treated for four months. Chronic pulsatile s.c. low dose LH-RH administration is a very promising new therapy for those hypogonadal men who previously have required human gonadotrophin treatment to restore fertility.

Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

PubMed Central

Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-01-01

Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Effect of heroin-conditioned auditory stimuli on cerebral functional activity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trusk, T.C.; Stein, E.A.

1988-08-01

Cerebral functional activity was measured as changes in distribution of the free fatty acid (1-14C)octanoate in autoradiograms obtained from rats during brief presentation of a tone previously paired to infusions of heroin or saline. Rats were trained in groups of three consisting of one heroin self-administering animal and two animals receiving yoked infusions of heroin or saline. Behavioral experiments in separate groups of rats demonstrated that these training parameters imparts secondary reinforcing properties to the tone for animals self-administering heroin while the tone remains behaviorally neutral in yoked-infusion animals. The optical densities of thirty-seven brain regions were normalized to amore » relative index for comparisons between groups. Previous pairing of the tone to heroin infusions irrespective of behavior (yoked-heroin vs. yoked-saline groups) produced functional activity changes in fifteen brain areas. In addition, nineteen regional differences in octanoate labeling density were evident when comparison was made between animals previously trained to self-administer heroin to those receiving yoked-heroin infusions, while twelve differences were noted when comparisons were made between the yoked vehicle and self administration group. These functional activity changes are presumed related to the secondary reinforcing capacity of the tone acquired by association with heroin, and may identify neural substrates involved in auditory signalled conditioning of positive reinforcement to opiates.« less

[Incorrect programming of a target controlled infusion pump. Case SENSAR of the trimester].

PubMed

2014-10-01

We report the case of a patient who underwent surgical aortic valve replacement. During general anaesthesia maintenance, the patient received a remifentanyl infusion via a target controlled infusion (TCI) system. The infusion pump that was prepared to deliver the infusion showed malfunction at the beginning of the surgery, so it was quickly replaced with a second pump. After a few minutes into the surgery, the patient presented with hypotension refractory to treatment. The remifentanyl syringe also emptied faster than expected. On reviewing the TCI pump, it was found that it was erroneously programmed for propofol instead of remifentanyl, thus the patient had received a very high dose of remifentanyl that was probably the cause of the haemodynamic disturbances. The incident was an error in equipment use, facilitated by hurry, lack of checking of the equipment prior to its use, and the complex and unclear design of the devices' screens. After analysis of this incident, all TCI pumps were reviewed, and all the programs for infrequently used drugs were deleted. Furthermore, 2 pumps were selected for exclusive use in the cardiac surgery theatre, one with propofol-only programming, and the other with remifentanyl-only programming, both clearly marked and situated in fixed places in that theatre. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

PubMed

Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

2013-09-13

Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development of cutaneous gangrene during continuous peripheral infusion of vasopressin.

PubMed Central

Anderson, J R; Johnston, G W

1983-01-01

Five patients given vasopressin by infusion to reduce portal hypertension developed signs of cutaneous gangrene 18-24 hours after the start of the infusion. Four patients were treated by application of local dressings; in three cases the lesions healed, but the fourth patient died from variceal haemorrhage. The remaining patient required split skin grafting but died 48 hours after operation. The mechanism of this effect of vasopressin is not clear, but if local blanching of the skin is noted during infusion the catheter should be flushed immediately with a vasodilator in an effort to counteract the drug's vasoconstrictor effect. PMID:6416538

An unusual cutaneous manifestation of Crohn's disease.

PubMed

Weiser, Jessica A; Markowitz, David M; Husain, Sameera; Grossman, Marc E

2011-01-01

A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without organisms. Tissue cultures were negative for bacterial, fungal, and mycobacterial infection. Skin biopsy taken from the central upper back demonstrated subcorneal pustules with areas of eroded epidermis and collections of neutrophils in the superficial dermis (Figure 3). Special stains were negative for organisms. He received infliximab infusion 5 mg/kg for a total dose of 420 mg over 2 hours. Within 48 hours of infusion, there was notable decrease in size of lesions, in addition to reduction of purulent drainage from both eyes. The patient was discharged home following infliximab infusion. His skin lesions resolved during a period of 2 weeks, leaving small pink atrophic scars. He received his second infusion of infliximab 2 weeks after discharge with continued improvement in his gastrointestinal symptoms.

Could pharmacogenetic data explain part of the interindividual sensitivity to methadone-induced respiratory depression?

PubMed Central

Crettol, Séverine; Monnat, Martine; Eap, Chin B

2007-01-01

In this issue of Critical Care, Megarbane and colleagues present a case report of methadone-induced respiratory depression and conduct a toxicokinetic/toxicodynamic evaluation. An opioid-dependent patient receiving methadone maintenance treatment (daily dose 70 mg) was found unconscious after ingesting 240 mg methadone and 2 mg flunitrazepam. Significant improvement in consciousness was achieved after an intravenous bolus of 0.3 mg naloxone followed by a continuous infusion of naloxone at 0.3 mg/hour. In patients receiving methadone maintenance treatment, an occasional intake of two to four times the usual daily dose of methadone is not an exceptional occurrence. However, few such patients experience episodes of life-threatening respiratory depression. Here, we discuss whether recent pharmacogenetic data could help us to understand interindividual variability in sensitivity to respiratory depression and, ultimately, to predict which patients are most likely to be affected. PMID:17338832

Management of Hyperglycemia During Enteral and Parenteral Nutrition Therapy

PubMed Central

Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia is a frequent complication of enteral and parenteral nutrition in hospitalized patients. Extensive evidence from observational studies indicates that the development of hyperglycemia during parenteral and enteral nutrition is associated with an increased risk of death and infectious complications. There are no specific guidelines recommending glycemic targets and effective strategies for the management of hyperglycemia during specialized nutritional support. Managing hyperglycemia in these patients should include optimization of carbohydrate content and administration of intravenous or subcutaneous insulin therapy. The administration of continuous insulin infusion and insulin addition to nutrition bag are efficient approaches to control hyperglycemia during parenteral nutrition. Subcutaneous administration of long-acting insulin with scheduled or corrective doses of short-acting insulin is superior to the sliding scale insulin strategy in patients receiving enteral feedings. Randomized controlled studies are needed to evaluate safe and effective therapeutic strategies for the management of hyperglycemia in patients receiving nutritional support. PMID:23065369

Magnesium flux during continuous venovenous haemodiafiltration with heparin and citrate anticoagulation.

PubMed

Brain, Matthew; Anderson, Mike; Parkes, Scott; Fowler, Peter

2012-12-01

To describe magnesium flux and serum concentrations in ICU patients receiving continuous venovenous haemodiafiltration (CVVHDF). Samples were collected from 22 CVVHDF circuits using citrate anticoagulation solutions (Prismocitrate 10/2 and Prism0cal) and from 26 circuits using Hemosol B0 and heparin anticoagulation. CVVHDF prescription, magnesium supplementation and anticoagulation choice was by the treating intensivist. We analysed 334 sample sets consisting of arterial, prefilter and postfilter blood and effluent. Magnesium loss was calculated from an equation for conservation of mass, and arterial magnesium concentration was described by an equation for exponential decay. Using flow rates typical of adults receiving CVVHDF, we determined a median half-life for arterial magnesium concentration to decay to a new steady state of 4.73 hours (interquartile range [IQR], 3.73-7.32 hours). Median arterial magnesium concentration was 0.88mmol/L (IQR, 0.83-0.97mmol/L) in the heparin group and 0.79mmol/L (IQR, 0.69-0.91mmol/L) in the citrate group. Arterial magnesium concentrations fell below the reference range regularly in the citrate group and, when low, there was magnesium flux from dialysate to patient. Magnesium loss was greater in patients receiving citrate. Exponential decline in magnesium concentrations was sufficiently rapid that subtherapeutic serum magnesium concentrations may occur well before detection when once-daily sampling was used. Measurements should be interpreted with regard to timing of magnesium infusions. We suggest that continuous renal replacement therapy fluids with higher magnesium concentrations be introduced in the critical care setting.

Necessity of heparin for maintaining peripheral venous catheters: A systematic review and meta-analysis

PubMed Central

You, Tao; Jiang, Jianliang; Chen, Jianchang; Xu, Weiting; Xiang, Li; Jiao, Yang

2017-01-01

Heparin has typically been used as a flushing or infusion solution for vascular lines in daily practice. However, several clinical trials have yielded controversial results about the benefits of heparin in maintaining peripheral venous catheters. The present meta-analysis was conducted to evaluate the efficacy of heparin on the patency profiles and complications in peripheral intravenous catheters. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched up to February 2016 for randomized controlled trials comparing heparin with placebo in maintaining peripheral intravenous catheters. Additional studies were retrieved from the reference lists of identified articles. In total 32 eligible studies were included, from which the pooled standard mean difference (SMD), relative risk (RR) and corresponding 95% confidence interval (CI) were calculated. The use of heparin as a continuous infusion significantly prolonged the duration of patency (SMD, 0.90; 95% CI, 0.48–1.32; P<0.001), reduced rates of infusion failure (RR, 0.83; 95% CI, 0.76–0.92; P<0.001) and occlusion (RR, 0.82; 95% CI, 0.69–0.98; P<0.05) in a peripheral intravenous catheter. However, there were no significant changes in the duration of patency and infusion failure when heparin was used intermittently as a flushing solution, although a significantly decreased risk of occlusion was observed in this setting (RR, 0.80; 95% CI, 0.66–0.98; P<0.05). Furthermore, the risk of phlebitis was significantly decreased by both continuous infusion (RR, 0.66; 95% CI, 0.58–0.75; P<0.01) and intermittent flushing (RR, 0.70; 95% CI, 0.56–0.86; P<0.01) of heparin in peripheral venous catheters. In conclusion, the use of heparin as continuous infusion in peripheral intravenous catheters improved the duration of patency, reduced infusion failure and phlebitis, whereas heparin as intermittent flushing showed more benefits in ameliorating phlebitis rather than in patency profiles. PMID:28810636

DORSAL HIPPOCAMPAL PROGESTERONE INFUSIONS ENHANCE OBJECT RECOGNITION IN YOUNG FEMALE MICE

PubMed Central

Orr, Patrick T.; Lewis, Michael C.; Frick, Karyn M.

2009-01-01

The effects of progesterone on memory are not nearly as well studied as the effects of estrogens. Although progesterone can reportedly enhance spatial and/or object recognition in female rodents when given immediately after training, previous studies have injected progesterone systemically, and therefore, the brain regions mediating this enhancement are not clear. As such, this study was designed to determine the role of the dorsal hippocampus in mediating the beneficial effect of progesterone on object recognition. Young ovariectomized C57BL/6 mice were trained in a hippocampal-dependent object recognition task utilizing two identical objects, and then immediately or 2 hrs afterwards, received bilateral dorsal hippocampal infusions of vehicle or 0.01, 0.1, or 1.0 μg/μl water-soluble progesterone. Forty-eight hours later, object recognition memory was tested using a previously explored object and a novel object. Relative to the vehicle group, memory for the familiar object was enhanced in all groups receiving immediate infusions of progesterone. Progesterone infusion delayed 2 hrs after training did not affect object recognition. These data suggest that the dorsal hippocampus may play a critical role in progesterone-induced enhancement of object recognition. PMID:19477194

Effects of injection-site splinting on the incidence of phlebitis in patients taking peripherally infused amiodarone: A randomized clinical trial.

PubMed

Ayat-Isfahani, Farah; Pashang, Mina; Davoudi, Bita; Sadeghian, Saeed; Jalali, Arash

2017-03-01

Intravenous amiodarone is considered an effective treatment option for cardiac ventricular and atrial arrhythmias. Peripheral infusion of amiodarone may cause blood vessels irritation and phlebitis that is the most common complication of this drug by this route even when it is administered within recommended dosing limits. The effect of injection-site splinting on the occurrence of phlebitis among a group of cardiac arrhythmia patients receiving peripherally infused amiodarone. This research is a clinical trial on patients of Tehran Heart Center who were hospitalized due to cardiac arrhythmias. A sample of 60 patients with mean age 65 ± 14 years were randomly divided into control and test groups. In the experimental group with close splint and restrict the movement of the injection site until the end of the infusion and control groups without closing brace, at the same time received amiodarone. Injection protocol was similar for both groups. The results were analyzed with Spss18. The results of this research still significantly reduced the incidence of amiodarone injection-site phlebitis in the injection time (P = .005). Copyright © 2016 Society for Vascular Nursing, Inc. Published by Elsevier Inc. All rights reserved.

Fluoropyrimidine-associated cardiotoxicity: revisited.

PubMed

Saif, M Wasif; Shah, Manasi M; Shah, Anuj R

2009-03-01

The syndrome of 5-fluorouracil (5-FU)-associated cardiotoxicity remains poorly defined. We performed a literature review (1969 - 2007) and compiled data derived from 377 evaluable cases out of 448 reported cases. Patient age ranged from 14 to 86 years. Of the patients 65% were 55 years old and the male:female ratio was 1.5:1. The most commonly treated tumors were gastrointestinal (60%), head and neck (22%) and breast (4%). Of the patients 14% had a history of heart disease whereas cardiac risk factors were found in 37%. Mode of administration included: continuous infusion (72%); bolus (22.5%); intermediate infusion (3%); oral (2%); and intraperitoneal (1 patient). The dosages of 5-FU used were < 750 mg/m(2)/day (36%), 751 - 999 (16%), 1,000 (26%), 1,001 - 1,499 (4%) and 1,500 (16%). Of the patients 54% received 5-FU in combination with other chemotherapeutic agents (cisplatin 44%) whereas 51% received 5-FU alone or with leucovorin. Only 4% patients had undergone previous or concomitant radiation therapy to the mediastinum. Of cardiac incidents that happened 69% were seen during or within 72 h of the first cycle of 5-FU. Angina occurred in 45% of patients whereas myocardial infarction was seen in 22%, arrhythmias in 23, acute pulmonary edema in 5, cardiac arrest and pericarditis in 1.4 and heart failure in 2. Electro-cardiographic evidence of ischemia or ST-T changes were recorded in 69% of patients, but abnormal cardiac enzymes were found in only 12%. The cardiac symptoms were reproducible in 47%, including in one patient subsequently treated with 5-FU p.o. Symptoms were also elicited when the same patients were treated with lower doses or different schedules. Of the patients 68% responded to conservative anti-anginal therapy, although prophylactic coronary vasodilators had limited efficacy. Overall, 8% of patients showing cardiotoxicity on 5-FU administration died. Furthermore, 13% reexposed to 5-FU died. Our review suggests that 5-FU cardiotoxicity is an infrequent but real phenomenon that is independent of dose and may be related to a continuous infusion schedule. The presence of cardiac risk factors is not predictive. Patients should be observed closely and 5-FU administration discontinued if cardiac symptoms develop. A rechallenge with 5-FU should be reserved only for those patients in whom there is no reasonable alternative therapy and should be performed in the setting of aggressive prophylaxis and close monitoring.

Continuous Intravenous Milrinone Therapy in Pediatric Outpatients.

PubMed

Curley, Michelle; Liebers, Jill; Maynard, Roy

Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy.

Continuous Intravenous Milrinone Therapy in Pediatric Outpatients

PubMed Central

Curley, Michelle; Liebers, Jill

2017-01-01

Milrinone is a phosphodiesterase 3 inhibitor with both positive inotropic and vasodilator properties. Administered as a continuous infusion, milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure. Despite limited data supporting long-term milrinone therapy in adults with congestive heart failure, children managed as outpatients may benefit from continuous milrinone as a treatment for cardiac dysfunction, as a destination therapy for cardiac transplant, or as palliative therapy for cardiomyopathy. The aim of this article is to review the medical literature and describe a home infusion company's experience with pediatric outpatient milrinone therapy. PMID:28248808

[Optimization of ventricular function during anesthesia induction by administering crystalloids and colloids to heart surgery patients].

PubMed

Ballesteros, M; Boldt, J; Zickmann, B; Knothe, C; Hempelmann, G

1995-01-01

To describe the changes in cardiac function after administration of three different solutions infused after anesthetic induction. Thirty-six patients scheduled for elective aortocoronary bypass surgery were randomly distributed into three groups. Over a period of 25 min after anesthetic induction, 12 received 10 ml/kg of Ringer solution (low dose crystalloid group), 12 received 20 ml/kg of Ringer solution (high dose crystalloid group), and 12 received 10 ml/kg of Ringer solution with 10 ml/kg of hydroxi-ethyl-almidon solution 450,000 D, 0.7 substitution grade (group C-HEA). Minute volume, systemic and pulmonary pressures, osmolality of blood and urine, and plasma and urine sodium concentrations were measured before and after infusion of the assigned liquid. In spite of the volume infused, low dose crystalloid group showed a high incidence of oliguria, increased urinary osmolality and decreased sodium in urine. Cardiac and systolic indices and left ventricular work load remained stable after infusion of the assigned liquid in low and high dose crystalloid groups, whereas they increased significantly ion group C-HEA (+23%, +16% and +20%). Administration of restricted doses of crystalloids after anesthetic induction favors the retention of water and sodium. Higher doses of crystalloids weaken this effect. However, neither of these two regimens leads to a more effective cardiac work load. A combination of crystalloids and colloids administered immediately after anesthetic induction temporarily improves cardiac performance during surgery.

Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.

PubMed

Duncan, Michael A; McNicholas, Walter; O'Keeffe, Declan; O'Reilly, Maeve

2002-01-01

Sternal fracture pain is severe and is difficult to alleviate due to the forces acting on the chest wall during respiration. We describe a continuous infusion regional analgesic technique for pain due to sternal fracture. A 47-year-old woman presented with a spontaneous sternal fracture, precluding effective coughing. Diclofenac and increasing doses of opioids did not give adequate pain relief and led to opioid toxicity. Two brief periods of analgesia were achieved with deep subcutaneous infiltration of bupivacaine. An epidural catheter was positioned periosteally, and an infusion of bupivacaine was commenced at 5 mL/h, achieving long-lasting analgesia. The bupivacaine concentration was reduced in a stepwise fashion from 0.5% to 0.25% and was changed to levobupivacaine after 3 days. Adding morphine (5 mg/60 mL levobupivicaine) permitted a reduction in infusion rate. The catheter was removed after 14 days because a local infection developed that resolved uneventfully with antibiotic therapy. Continuous infusion of local anesthetic and opioid to a sternal fracture site using a periosteally positioned catheter led to successful analgesia and hence improved respiratory function. Clinicians should consider placing a periosteal catheter when pain associated with sternal fracture cannot be adequately controlled with conventional methods.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

PubMed

Wang, Chen-Yu; Lai, Yu-Ju; Hwang, Kwei-Shuai; Chen, Chi-Huang; Yu, Mu-Hsien; Chen, Huei-Tsung; Su, Her-Young

2016-10-01

Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment. Copyright © 2016. Published by Elsevier B.V.

Effect of microbubble contrast on intracranial blood flow velocity assessed by transcranial Doppler.

PubMed

Logallo, Nicola; Fromm, Annette; Waje-Andreassen, Ulrike; Thomassen, Lars; Matre, Knut

2014-03-01

Ultrasound contrast agents (UCA) salvage a considerable number of transcranial Doppler (TCD) exams which would have failed because of poor bone window. UCA bolus injection causes an undesirable increase in measured blood flow velocity (BFV). The effect of UCA continuous infusion on measured BFV has not been investigated, and some in vitro experiments suggest that gain reduction during UCA administration may also influence measured BFV. This study aimed to investigate the effect of UCA continuous infusion on BFV measured by TCD and the influence of gain reduction on these measurements in a clinical setting. The right middle cerebral artery of ten patients with optimal bone window was insonated using a 2 MHz probe. UCA were administered using an infusion pump. BFV was measured (1) at baseline, (2) during UCA infusion, (3) during UCA infusion with gain reduction, and (4) after UCA wash-out phase. Gain reduction was based on the agreement between two neurosonographers on the degree of gain reduction necessary to restore baseline Doppler signal intensity (DSI). Actual DSI was estimated offline by analysis of raw data. BFV measured during UCA infusion with no gain adjustment was significantly higher than baseline BFV [peak systolic velocity (PSV): 85.1 ± 19.7 vs. 74.4 ± 19.7 cm/s, p < 0.0001; Mean velocity (MV): 56.5 ± 11.8 vs. 50.2 ± 12.3 cm/s, p < 0.0001]. BFV measured during UCA infusion with gain reduction was not significantly higher than baseline BFV (PSV: 74.3 ± 18.9 vs. 74.4 ± 19.4 cm/s, p = 0.8; MV: 49.4 ± 11.0 vs. 50.2 ± 12.3 cm/s, p = 0.8). Actual DSI during UCA infusion with gain reduction was not significantly higher than baseline DSI (13 ± 1 vs. 13 ± 1 dB). This study shows that UCA continuous infusion leads to an increase in measured BFV which may be counteracted by reducing Doppler gain thus restoring pre-contrast DSI.

Intravenous Sedation with Low-Dose Dexmedetomidine: Its Potential for Use in Dentistry

PubMed Central

Ogawa, Sachie; Seino, Hiroaki; Ito, Hiroshi; Yamazaki, Shinya; Ganzberg, Steven; Kawaai, Hiroyoshi

2008-01-01

This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures. PMID:18788843

Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.

PubMed

Dubuc, I; Pain, C; Suaudeau, C; Costentin, J

1994-01-01

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.

Long-Term Outcomes and Toxicity of Concurrent Paclitaxel and Radiotherapy for Locally Advanced Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Citrin, Deborah; Mansueti, John; Likhacheva, Anna

2009-07-15

Purpose: To report the long-term outcomes and toxicity of a regimen of infusion paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. Patients and Methods: Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous cell carcinoma of the head and neck were treated with three cycles of paclitaxel as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with radiotherapy. The initial 16 patients received 105 mg/m{sup 2}/cycle, and the subsequent 19 patients received 120 mg/m{sup 2}/cycle. External beam radiotherapy was delivered to amore » dose of 70.2-72 Gy at five fractions weekly. Patients were followed to evaluate the disease outcomes and late toxicity of this regimen. Results: The median follow-up for all patients was 56.5 months. The median survival was 56.5 months, and the median time to local recurrence was not reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33 patients who underwent percutaneous endoscopic gastrostomy tube placement, 11 were percutaneous endoscopic gastrostomy tube dependent until death or their last follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and 3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). Conclusion: The results of our study have shown that concurrent chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local control and survival in patients with squamous cell carcinoma of the head and neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.« less

Simultaneous measurement and integrated analysis of analgesia and respiration after an intravenous morphine infusion.

PubMed

Dahan, Albert; Romberg, Raymonda; Teppema, Luc; Sarton, Elise; Bijl, Hans; Olofsen, Erik

2004-11-01

To study the influence of morphine on chemical control of breathing relative to the analgesic properties of morphine, the authors quantified morphine-induced analgesia and respiratory depression in a single group of healthy volunteers. Both respiratory and pain measurements were performed over single 24-h time spans. Eight subjects (four men, four women) received a 90-s intravenous morphine infusion; eight others (four men, four women) received a 90-s placebo infusion. At regular time intervals, respiratory variables (breathing at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)-pharmacodynamic models were applied to the respiratory and pain data. The models are characterized by potency parameters, shape parameters (gamma), and blood-effect site equilibration half-lives. All collected data were analyzed simultaneously using the statistical program NONMEM. Placebo had no systematic effect on analgesic or respiratory variables. Morphine potency parameter and blood-effect site equilibration half-life did not differ significantly among the three measured effect parameters (P > 0.01). The integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h. Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for analgesia (P < 0.01). Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack of good pain relief, moderate to severe respiratory depression remains possible.

[Autocontrol of muscle relaxation with vecuronium].

PubMed

Sibilla, C; Zatelli, R; Marchi, M; Zago, M

1990-01-01

The optimal conditions for maintaining desired levels of muscle relaxation with vecuronium are obtained by means of the continuous infusion (I.V.) technique. A frequent correction of the infusion flow is required, since it is impossible to predict the exact amount for the muscle relaxant in single case. In order to overcome such limits the authors propose a very feasible infusion system for the self-control of muscle relaxation; furthermore they positively consider its possible daily clinical application.

Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

PubMed

Zhang, YanPing; Kawedia, Jitesh D; Myers, Alan L; McIntyre, Chelsey M; Anderson, Peter M; Kramer, Mark A; Culotta, Kirk S

2014-02-01

Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

Physical and Chemical Stability of Urapidil in 0.9% Sodium Chloride in Elastomeric Infusion Pump.

PubMed

Tomasello, Cristina; Leggieri, Anna; Rabbia, Franco; Veglio, Franco; Baietto, Lorena; Fulcheri, Chiara; De Nicolò, Amedeo; De Perri, Giovanni; D'Avolio, Antonio

2016-01-01

Urapidil is an antihypertensive agent, usually administered through intravenous bolus injection, slow-intravenous infusion, or continuous-drug infusion by perfusor. Since to date no evidences are available on drug stability in elastomeric pumps, patients have to be hospitalized. The purpose of this study was to validate an ultra-performance liquid chromatographic method to evaluate urapidil stability in an elastomeric infusion pump, in order to allow continuous infusion as home-care treatment. Analyses were conducted by diluting urapidil in an elastomeric pump. Two concentrations were evaluated: 1.6 mg/mL and 3.3 mg/mL. For the analyses, a reverse-phase ultra-performance liquid chromatographic- photodiode array detection instrument was used. Stressed degradation, pH changes, and visual clarity were used as stability indicators up to 10 days after urapidil solution preparation. The drug showed no more than 5% degradation during the test period at room temperature. No pH changes and no evidences of incompatibility were observed. Stress tests resulted in appreciable observation of degradation products. Considering the observed mean values, urapidil hydrochloride in sodium chloride 0.9% in elastomeric infusion pumps is stable for at least 10 days. These results indicate that this treatment could be administered at home for a prolonged duration (at least 7 days) with a satisfactory response. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Propionate supplementation improves nitrogen use by reducing urea flux in sheep.

PubMed

Agarwal, U; Hu, Q; Bequette, B J

2015-10-01

Feeding and postruminal infusion of propionate is known to increase N retention in ruminants. Our aim was to determine the role of rumen propionate on urea N recycling and gluconeogenesis in growing sheep. In Exp. 1, wether sheep ( = 6; 32.5 ± 3.57 kg BW) fitted with a rumen cannula were fed to 1.8 × ME requirement a concentrate-type ration (172 g CP/kg DM and 10.4 MJ ME/kg DM) and continuously infused into the rumen with isoenergetic (10% of dietary ME intake) solutions of either sodium acetate (control) or sodium propionate for 9-d periods in a crossover design. In Exp. 2, a different group of wether sheep ( = 5; 33.6 ± 3.70 kg BW) fitted with a rumen cannula were fed, on an isonitrogenous basis, either a control (151 g CP/kg DM and 8.4 MJ ME/kg DM) or sodium propionate-supplemented (139 g CP/kg DM and 8.9 MJ ME/kg DM) diet at 2-h intervals. [N] urea was continuously infused intravenously for the last 5 d of each period, and total urine was collected by vacuum and feces were collected by a harness bag. Over the last 12 h, [C]glucose was continuously infused intravenously and hourly blood samples were collected during the last 5 h. Propionate treatments increased ( < 0.001) the proportion of rumen propionate in both experiments. In Exp. 1, N retention was not affected by propionate infusion as compared with isoenergetic acetate. There was no effect on urea entry (synthesis) rate (UER) in Exp. 1; however, sodium propionate infusion tended ( < 0.1) to increase urinary urea elimination (UUE). In Exp. 2, feeding propionate increased ( < 0.01) N retention by 0.8 g N/d. In addition, UER was reduced by approximately 2 g urea N/d, leading to a reduction ( < 0.05) in UUE (7.0 vs. 6.2 g urea N/d). Between the 2 experiments, the proportion of UER recycled to the gut was greater with the forage-type diet in Exp. 2 (approximately 60%) compared with the concentrate-type diet in Exp. 1 (approximately 40%), although urea N fluxes across the gut remained unchanged in both experiments. In Exp. 1, glucose entry and gluconeogenesis were greater ( < 0.05) and plasma glucose tended ( < 0.1) to be greater with sodium propionate infusion than with sodium acetate infusion, but there was no difference in Cori cycling. In Exp. 2, glucose entry, gluconeogenesis, Cori cycling, and plasma glucose increased ( < 0.05) with dietary propionate. Our studies indicate that propionate inclusion in feed, but not continuous infusion in to the rumen, improves N utilization in growing sheep. The propionate effect is likely mediated by providing additional precursors for gluconeogenesis.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats

NASA Technical Reports Server (NTRS)

Morrow, B. A.; Holt, M. R.; Starcevic, V. P.; Keil, L. C.; Severs, W. B.

1992-01-01

Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non-traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics.

Safety and Efficacy of Pegfilgrastim When Given Less Than 14 Days Before the Next Chemotherapy Cycle: Review of Every 14-Day Chemotherapy Regimen Containing 5-FU Continuous Infusion.

PubMed

Donkor, Kofi N; Selim, Julie H; Waworuntu, Ariani; Lewis, Kelsey

2017-10-01

Pegfilgrastim should not be given <14 days from the next chemotherapy because of concerns for cytopenias. Some clinicians are prescribing pegfilgrastim to be given <14 days in patients receiving 5-fluorouracil continuous infusion (5-FUCI) regimens. To determine the effectiveness and safety of pegfilgrastim administered <14 days from the next chemotherapy in patients receiving 5-FUCI administered >46 hours. Single-institution retrospective cohort study of patients who received 5-FUCI administered >46 hours from June 2013 to December 2015. The unit of measurement was chemotherapy cycles. End points included the safety and efficacy of giving pegfilgrastim <14 days from the next chemotherapy (Pegfilgrastim-Less-Than-14-Days-Group) and comparing that to pegfilgrastim given ≥14 days (Pegfilgrastim-More-Than-14-Days-Group), filgrastim only (Filgrastim-Group), and no colony stimulating factors (No-CSF-Group). Generalized estimating equations (GEEs) were used to compare mean absolute neutrophil count (ANC) and white blood cell count (WBC). Poisson regression models with GEE were used to estimate relative risk (RR) for neutropenia. There were no incidences of neutropenia, febrile neutropenia (FN), or hospitalizations for FN with the Pegfilgrastim-Less-Than-14-Days-Group. There was also a high mean ANC of 9.9 (5.7) × 10 9 /L. Mean ANC and WBC were statistically significantly less with the Filgrastim-Group, No-CSF-Group, and Pegfilgrastim-More-Than-14-Days-Group compared with the Pegfilgrastim-Less-Than-14-Days-Group. The Filgrastim-Group and the No-CSF-Group had a 32% (1.10-1.56, P = 0.002) and 8% (1.04-1.12, P < 0.001) increased risk of incidence of neutropenia, respectively, compared with the Pegfilgrastim-Less-Than-14-Days-Group. The risk of incidence of neutropenia was the same with the Pegfilgrastim-More-Than-14-Days-Group and Pegfilgrastim-Less-Than-14-Days-Group (0.95-1.04, P = 0.821). This study shows a promising possibility that administering pegfilgrastim <14 days from the next chemotherapy cycle could be a safe and effective practice. However, better controlled clinical trials are needed.

A Comparison of Dexmedetomidine and Clonidine in Attenuating the Hemodynamic Responses at Various Surgical Stages in Patients Undergoing Elective Transnasal Transsphenoidal Resection of Pituitary Tumors

PubMed Central

Jan, Summaira; Ali, Zulfiqar; Nisar, Yasir; Naqash, Imtiaz Ahmad; Zahoor, Syed Amer; Langoo, Shabir Ahmad; Azhar, Khan

2017-01-01

Background: Transsphenoidal approach to pituitary tumors is a commonly performed procedure with the advantage of a rapid midline access to the sella with minimal complications. It may be associated with wide fluctuations in hemodynamic parameters due to intense noxious stimulus at various stages of the surgery. As duration of the surgery is short and the patients have nasal packs, it is prudent to use an anesthestic technique with an early predictable recovery. Materials and Methods: A total of 60 patients of either sex between 18 and 65 years of age, belonging to the American Society of Anesthesiologists I and II who were undergoing elective transnasal transsphenoidal pituitary surgery were chosen for this study. Patients were randomly allocated into two groups, Group C (clonidine) and Group D (dexmedetomidine), with each group consisting of 30 patients. Patients in Group C received 200 μg tablet of clonidine and those in Group D received a pantoprazole tablet as placebo at the same time. Patients in the Group D received an intravenous infusion of dexmedetomidine diluted in 50 ml saline (200 μg in 50 ml saline) 10 min before induction and patients in Group C received 0.9% normal saline (50 ml) as placebo. The hemodynamic variables (heart rate, mean arterial pressure) were noted at various stages of the surgery. Statistical analysis of the data was performed. Results: A total of 60 patients were recruited. The mean age, sex, weight and duration of surgery among the two groups were comparable (P > 0.05). Both dexmedetomidine and clonidine failed to blunt the increase in hemodynamic responses (heart rate and blood pressure) during intubation, nasal packing, speculum insertion and extubation. However when the hemodynamic response was compared between the patients receiving dexmedetomidine and clonidine it was seen that patients who received dexmedetomidine had a lesser increase in heart rate and blood pressure (P < 0.05) when compared to clonidine. Conclusions: A continuous intravenous infusion of dexmedetomidine as compared to oral clonidine improved hemodynamic stability in patients undergoing transnasal transsphenoidal resection of pituitary tumors. PMID:29284879

A Comparison of Dexmedetomidine and Clonidine in Attenuating the Hemodynamic Responses at Various Surgical Stages in Patients Undergoing Elective Transnasal Transsphenoidal Resection of Pituitary Tumors.

PubMed

Jan, Summaira; Ali, Zulfiqar; Nisar, Yasir; Naqash, Imtiaz Ahmad; Zahoor, Syed Amer; Langoo, Shabir Ahmad; Azhar, Khan

2017-01-01

Transsphenoidal approach to pituitary tumors is a commonly performed procedure with the advantage of a rapid midline access to the sella with minimal complications. It may be associated with wide fluctuations in hemodynamic parameters due to intense noxious stimulus at various stages of the surgery. As duration of the surgery is short and the patients have nasal packs, it is prudent to use an anesthestic technique with an early predictable recovery. A total of 60 patients of either sex between 18 and 65 years of age, belonging to the American Society of Anesthesiologists I and II who were undergoing elective transnasal transsphenoidal pituitary surgery were chosen for this study. Patients were randomly allocated into two groups, Group C (clonidine) and Group D (dexmedetomidine), with each group consisting of 30 patients. Patients in Group C received 200 μg tablet of clonidine and those in Group D received a pantoprazole tablet as placebo at the same time. Patients in the Group D received an intravenous infusion of dexmedetomidine diluted in 50 ml saline (200 μg in 50 ml saline) 10 min before induction and patients in Group C received 0.9% normal saline (50 ml) as placebo. The hemodynamic variables (heart rate, mean arterial pressure) were noted at various stages of the surgery. Statistical analysis of the data was performed. A total of 60 patients were recruited. The mean age, sex, weight and duration of surgery among the two groups were comparable ( P > 0.05). Both dexmedetomidine and clonidine failed to blunt the increase in hemodynamic responses (heart rate and blood pressure) during intubation, nasal packing, speculum insertion and extubation. However when the hemodynamic response was compared between the patients receiving dexmedetomidine and clonidine it was seen that patients who received dexmedetomidine had a lesser increase in heart rate and blood pressure ( P < 0.05) when compared to clonidine. A continuous intravenous infusion of dexmedetomidine as compared to oral clonidine improved hemodynamic stability in patients undergoing transnasal transsphenoidal resection of pituitary tumors.

A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial.

PubMed

Siebert, Johan N; Ehrler, Frederic; Combescure, Christophe; Lacroix, Laurence; Haddad, Kevin; Sanchez, Oliver; Gervaix, Alain; Lovis, Christian; Manzano, Sergio

2017-02-01

During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean TDD was 214 s (95% CI 171-256) and 391 s (95% CI 298-483), respectively (177.3 s reduction, P=.002). Medication errors were reduced from 70% to 0% (P<.001) by using PedAMINES when compared with conventional methods. In this simulation-based study, PedAMINES dramatically reduced TDP, to delivery and the rate of medication errors. ©Johan N Siebert, Frederic Ehrler, Christophe Combescure, Laurence Lacroix, Kevin Haddad, Oliver Sanchez, Alain Gervaix, Christian Lovis, Sergio Manzano. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.02.2017.

Intravenous medication safety and smart infusion systems: lessons learned and future opportunities.

PubMed

Keohane, Carol A; Hayes, Judy; Saniuk, Catherine; Rothschild, Jeffrey M; Bates, David W

2005-01-01

The Institute of Medicine report To Err Is Human: Building a Safe Health System greatly increased national awareness of the need to improve patient safety in general and medication safety in particular. Infusion-related errors are associated with the greatest risk of harm, and "smart" (computerized) infusion systems are currently available that can avert high-risk errors and provide previously unavailable data for continuous quality improvement (CQI) efforts. As healthcare organizations consider how to invest scarce dollars, infusion nurses have a key role to play in assessing need, evaluating technology, and selecting and implementing specific products. This article reviews the need to improve intravenous medication safety. It describes smart infusion systems and the results they have achieved. Finally, it details the lessons learned and the opportunities identified through the use of smart infusion technology at Brigham and Women's Hospital in Boston, Massachusetts.

[Dose-intensive chemotherapy with continuous infusion 5-fluorouracil].

PubMed

Tichler, T; Ghodsizade, E; Katz, A; Rath, P; Berger, R; Brenner, H

1999-11-01

54 patients with advanced malignancy refractory to chemotherapy were studied to evaluate efficacy and toxicity of continuous infusion of 5-fluorouracil (5FU) given for 3 weeks. We report results of the first 156 courses given in combination with other drugs. 19 (37%) of the 54 responded, including 3 (6%) with complete response. Toxicity was acceptable, with mucositis in 13 (26%) and 3 (6%) with grade II-III toxicity. Results and toxicity profile were compatible with further disease-oriented studies using this dose-intensive program.

Specification and simulation of behavior of the Continuous Infusion Insulin Pump system.

PubMed

Babamir, Seyed Morteza; Dehkordi, Mehdi Borhani

2014-01-01

Continuous Infusion Insulin Pump (CIIP) system is responsible for monitoring diabetic blood sugar. In this paper, we aim to specify and simulate the CIIP software behavior. To this end, we first: (1) presented a model consisting of the CIIP system behavior in response to its environment (diabetic) behavior and (2) we formally defined the safety requirements of the system environment (diabetic) in the Z formal modeling language. Such requirements should be satisfied by the CIIP software. Finally, we programmed the model and requirements.

Intermittent clinical proteinuria and renal function in diabetes: evolution and the effect of glycaemic control.

PubMed Central

Bending, J J; Viberti, G C; Watkins, P J; Keen, H

1986-01-01

The evolution of renal disease was studied in 12 insulin dependent diabetics selected for intermittent clinical proteinuria. After a run in period during which patients were studied three monthly for at least 12 months members of pairs of patients matched for age and duration of diabetes were allocated either to receive continuous subcutaneous insulin infusion or to continue with their usual conventional insulin injection therapy (controls) and studied three monthly for a further year. Mean (SEM) plasma glucose concentration and glycosylated haemoglobin (HbA1) value improved significantly in the insulin infusion group (glucose 10.1 (1.0) v 5.3 (0.3) mmol/l (182 (18) v 95 (5) mg/100 ml); HbA1 9.6 (0.8) v 7.6 (0.5)%; p less than 0.001 and p less than 0.005, run in v experimental periods) but not in the control group. Blood pressure was kept normal throughout. Glomerular filtration rate fell significantly in the insulin infusion and control groups throughout the study, from mean (SEM) baseline values of 114 (16) and 119 (15) ml/min/1.73 m2 to final values of 92 (15) and 95 (13) ml/min/1.73 m2 respectively (p less than 0.05 and p less than 0.01). The mean rate of decline in glomerular filtration rate did not change significantly in either group (run in v experimental periods: insulin infusion group 1.0 v 0.8 ml/min/month; controls 0.8 v 0.9 ml/min/month). Mean (SEM) plasma creatinine concentration rose slightly in the insulin infusion group only (93 (5) to 109 (11) mumol/l (1.1 (0.06) to 1.2 (0.1) mg/100 ml), 0.1 greater than p greater than 0.05; controls 94 (6) to 96 (6) mumol/l (1.1 (0.07) and 1.1 (0.07) mg/100 ml]. The urinary excretion rate of albumin varied widely and unpredictably throughout, while beta 2 microglobulin excretion remained normal and unchanged in both groups. Thus a at the stage of intermittent clinical proteinuria when albumin excretion rate is unpredictably variable (breaking through the "clinically positive" threshold only episodically) renal function, though still in the "normal" range, is already declining progressively; and the study failed to show that sustained improvement in mean glycaemia exerts a significant effect on this early deterioration of renal function. PMID:3080101

Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

PubMed Central

Guo, Honglei; Li, Hongmei; Ling, Lilu

2016-01-01

Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo. PMID:27721575

Safety Risks Among Home Infusion Nurses and Other Home Health Care Providers

PubMed Central

Galligan, Catherine; Quinn, Margaret

2017-01-01

In the United States, home health care (HHC) is a rapidly growing industry and home infusion therapy is a rapidly growing market. HHC can present substantial occupational safety and health (OSH) risks. This article summarizes major OSH risks relevant to home infusion therapy by illustrating them through real-life scenarios collected systematically using qualitative research methods by the National Institute for Occupational Safety and Health-funded research projects at the University of Massachusetts Lowell. The need for home infusion therapy will continue to grow in the future, and safety interventions to prevent or minimize OSH risks are essential. PMID:28683000

Cutaneous manifestations of phosphate solution extravasation.

PubMed

Verykiou, S; Aljefri, K; Gopee, H; Taheri, L; Charlton, F; Langtry, J A; Blasdale, C

2018-01-01

Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations. © 2017 British Association of Dermatologists.

Severe skull base osteomyelitis caused by Pseudomonas aeruginosa with successful outcome after prolonged outpatient therapy with continuous infusion of ceftazidime and oral ciprofloxacin: a case report.

PubMed

Conde-Díaz, Cristina; Llenas-García, Jara; Parra Grande, Mónica; Terol Esclapez, Gertrudis; Masiá, Mar; Gutiérrez, Félix

2017-02-21

Skull base osteomyelitis is an uncommon disease that usually complicates a malignant external otitis with temporal bone involvement. It affects predominantly diabetic and immunocompromised males and has a high mortality rate. Pseudomonas aeruginosa is the most common causative organism. Currently, there is no consensus about the best therapeutic option. Here we describe a case of severe skull base osteomyelitis caused by Pseudomonas aeruginosa with progressive palsy of cranial nerves that was successfully managed with prolonged outpatient continuous infusion of ceftazidime plus oral ciprofloxacin. A 69-year-old Caucasian man presented with dysphagia, headache, and weight loss. He complained of left earache and purulent otorrhea. Over the following weeks he developed progressive palsy of IX, X, VI, and XII cranial nerves and papilledema. A petrous bone computed tomography scan showed a mass in the left jugular foramen with a strong lytic component that expanded to the cavum. A biopsy was then performed and microbiological cultures grew Pseudomonas aeruginosa. After 6 weeks of parenteral antibiotic treatment, our patient was discharged and treatment was continued with a domiciliary continuous infusion of a beta-lactam through a peripherally inserted central catheter, along with an oral fluoroquinolone for 10 months. Both radiological and clinical responses were excellent. Skull base osteomyelitis is a life-threating condition; clinical suspicion and correct microbiological identification are key to achieve an accurate and timely diagnosis. Due to the poor outcome of Pseudomonas aeruginosa skull base osteomyelitis, prolonged outpatient parenteral antibiotic therapy administered by continuous infusion could be a valuable option for these patients.

[Clinical evaluation and problem of intra-arterial infusion chemotherapy of liver metastasis from digestive organ cancer].

PubMed

Ohya, T; Fukunaga, J; Kitahama, H; Okuyama, A; Seki, T; Tsurui, K; Saka, M; Sasagawa, M; Hishinuma, S; Kotake, K

1990-08-01

Intra-arterial infusion chemotherapy using an implantable reservoir was used for 22 patients with liver metastasis from September 1986 to March 1990. The material consisted of 8 subjects with gastric cancer and 14 with colorectal cancer. One had metastasis in one lobe (H1), 10 had a few scattered metastases in both lobes (H2) and 11 had numerous metastases in both lobes (H3). In 5 cases, a reservoir was implanted to prevent the recurrence after hepatectomy. Infusion catheter was placed in the proper hepatic artery in 5 cases via the gastroduodenal artery at laparotomy and it was carried out subcutaneously via the femoral artery in 17 cases. In all cases intra-arterial infusion of 5-FU was continuously administered followed by intermittent one shot injection of ADM. The clinical effectiveness of the therapy was well evaluated. One-year cumulative survival rate of all cases by Kaplan-Meier method was 55% and that of H2 cases was 78%. No recurrence was noted in post hepatectomy cases. Eight cases (36.3%) showed remarkable complications, which made it impossible to continue intra-arterial infusion chemotherapy: hepatic artery occlusion (3 cases), infection (2 cases), abdominal pain (1 case), hematoma in the implanted site (1 case) and dislocation of the infusion catheter (1 case). From the present study, it is considered that intra-arterial infusion chemotherapy is a useful procedure for the control of liver metastasis. Regimens for improved chemotherapy and the maintenance of more useful and safer catheters should therefore be investigated for further development of the therapeutical estimation.

Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

PubMed

Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

2000-01-01

Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

Insulin Pump Malfunction During Hospitalization: Two Case Reports.

PubMed

Faulds, Eileen R; Wyne, Kathleen L; Buschur, Elizabeth O; McDaniel, Jodi; Dungan, Kathleen

2016-06-01

Insulin pump malfunctions and failures continue to occur; however, more severe malfunctions such as the "runaway pump" phenomenon are rarely reported. This article describes two cases of pump malfunction in which pump users appear to have received an unsolicited bolus of insulin resulting in severe episodes of hypoglycemia during hospitalization. Both cases of insulin pump malfunction occurred in the inpatient setting at a large academic medical center in the United States. An analysis of the corresponding insulin pump downloads was performed. The Food and Drug Administration's (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database was searched for similar cases involving Medtronic (Northridge, CA) insulin pumps using the terms "pump," "infusion," "insulin AND malfunction AND Medtronic." The two cases described show remarkable similarities, each demonstrating a severe hypoglycemic event preceded by an infusion site change followed by an alarm. In both cases a rapid spraying of insulin was reported. The insulin pump downloads validated much of the patients' and medical staff's descriptions of events. The FDA's MAUDE database search revealed 425 cases meeting our search term criteria. All cases were reviewed. Seven cases were identified involving independent movement of the reservoir piston. The cases detailed are the first to describe an insulin pump malfunction of this nature in the hospital setting involving unsolicited insulin boluses leading to severe hypoglycemia. The cases are particularly compelling in that they were witnessed by medical personnel. Providers and patients should receive instruction education on the recognition and management of insulin pump malfunction.

Pain control in patients with hepatocellular carcinoma treated by percutaneous radiofrequency ablation: comparison of the efficacy of one-shot and continuous intravenous fentanyl delivery.

PubMed

Yokoyama, Koichi; Ikeda, Osamu; Kawanaka, Koichi; Nakasone, Yutaka; Inoue, Seijiro; Tamura, Yoshitaka; Yamashita, Yasuyuki

2014-12-01

Hepatic percutaneous radiofrequency ablation (RFA) is usually performed with the patient under deep intravenous (i.v.) sedation or general anesthesia. Nonetheless, many patients report pain during and/or after the procedure. To perform a prospective study of pain control obtained by the i.v. one-shot delivery and the continuous i.v. infusion of fentanyl in patients with hepatocellular carcinoma (HCC) treated by RFA. Between April 2007 and March 2010, 83 patients with 106 HCCs underwent percutaneous RFA. All HCCs were addressed by computed tomography (CT)-guided percutaneous RFA performed within 5 h of embolization of the tumor vessels with iodized oil and gelatin sponges. Standard anesthesia consisted of 10 mL of 1% lidocaine injected locally. For conscious sedation, group one patients (n = 41) were injected i.v. with 100 µg of fentanyl before and 100 µg of fentanyl 30 min after percutaneous RFA. In group two (n = 42) we delivered fentanyl by continuous i.v. infusion at 100 µg/h during RFA. Upon request, patients in both groups also received 5 mg of diazepam i.v. for pain during the RFA procedure. The severity of pain experienced by all patients was evaluated on a visual analogue scale (VAS) and complications elicited by the anesthesia regimens were recorded. We also assessed the effectiveness of the treatment on sequential follow-up CT and/or magnetic resonance imaging (MRI) at 3-month intervals. Percutaneous RFA was technically successful in all 83 patients. Two patients in group one (4.8%) and one patient in group two (2.4%) manifested residual enhancement 3 months post RFA. There was no significant difference in the local recurrence rate between the two groups. At 4.0 ± 1.8 for group one and 3.4 ± 1.9 for group two, the VAS score was not significantly different. Major fentanyl or diazepam toxicity was recorded in 11 patients (24.4%) in group one and two patients (4.8%) in group two; the difference was statistically significant (P < 0.01). The continuous infusion of fentanyl provided effective and safe analgesia in HCC patients undergoing percutaneous RFA. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Lung protein leakage in feline septic shock.

PubMed

Schützer, K M; Larsson, A; Risberg, B; Falk, A

1993-06-01

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

Symptomatic improvement reported after receiving Reiki at a cancer infusion center.

PubMed

Marcus, Dawn A; Blazek-O'Neill, Betsy; Kopar, Jennifer L

2013-03-01

To evaluate patient-perceived benefits from receiving Reiki at a cancer infusion center. During a 6-month period, adults at a university hospital receiving Reiki through volunteer services were invited to complete a survey asking about perceived changes after Reiki. Changes in pain, mood, distress, sleep, and appetite were rated on a 5-point scale from no benefit to great benefit. Surveys were distributed after completing treatment and were returned in postage-paid envelops. A total of 145 surveys were completed (34.5% response rate), with 47 participants seen in the cancer infusion center and 98 in other areas of the hospital. Reiki was rated as a positive experience by 94% at the cancer center and 93% of others, with 92% at the cancer center and 86% of others interested in receiving additional Reiki sessions. Symptomatic improvement was similar for people at the cancer center and others, respectively, with much to great improvement for 89% and 86% for relaxation, 75% and 75% for anxiety/worry, 81% and 78% for improved mood, 43% and 35% for improved sleep, 45% and 49% for reduced pain, 38% and 43% for reduced isolation/loneliness, 75% and 63% for improved attitude, and 30% and 30% for improved appetite. Response was unaffected by previous exposure to Reiki, massage, or other touch therapy. Reiki results in a broad range of symptomatic benefits, including improvements in common cancer-related symptoms.

Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials.

PubMed

Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M

2013-02-01

Renal impairment increases mortality among patients with spontaneous bacterial peritonitis (SBP), despite administration of non-nephrotoxic antibiotics. Albumin infusion has been reported to reduce renal impairment and mortality in patients with SBP. We performed a meta-analysis of randomized controlled trials (RCTs) to quantify the effect of albumin infusion on renal impairment and mortality in patients with SBP. We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov for RCTs that evaluated albumin treatment for patients with SBP; we also performed searches by additional methods. Four trials of 288 total patients were included in our analysis. Data were quantitatively combined under a fixed-effects model. We found no evidence of statistically significant heterogeneity or publication bias among the studies analyzed. Albumin was compared with no albumin in 3 trials and with artificial colloid in 1 trial. All patients received antibiotics. The incidence of renal impairment in control groups was 44 of 144 (30.6%), compared with 12 of 144 (8.3%) in groups given albumin. The pooled odds ratio for a reduction in renal impairment after albumin infusion was 0.21 (95% confidence interval, 0.11-0.42). Odds ratios for renal impairment after albumin therapy ranged from 0.19-0.30 among the individual studies. Mortality among controls was 51 of 144 (35.4%), compared with 23 of 144 (16.0%) among patients who received albumin. The pooled odds ratio for decreased mortality after infusion of albumin was 0.34 (95% confidence interval, 0.19-0.60). Odds ratios for mortality in individual RCTs ranged from 0.16-0.55. In a meta-analysis of 4 RCTs (288 patients), albumin infusion prevented renal impairment and reduced mortality among patients with SBP. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Predicting the effectiveness of virtual reality relaxation on pain and anxiety when added to PCA morphine in patients having burns dressings changes.

PubMed

Konstantatos, A H; Angliss, M; Costello, V; Cleland, H; Stafrace, S

2009-06-01

Pain arising in burns sufferers is often severe and protracted. The prospect of a dressing change can heighten existing pain by impacting both physically and psychologically. In this trial we examined whether pre-procedural virtual reality guided relaxation added to patient controlled analgesia with morphine reduced pain severity during awake dressings changes in burns patients. We conducted a prospective randomized clinical trial in all patients with burns necessitating admission to a tertiary burns referral centre. Eligible patients requiring awake dressings changes were randomly allocated to single use virtual reality relaxation plus intravenous morphine patient controlled analgesia (PCA) infusion or to intravenous morphine patient controlled analgesia infusion alone. Patients rated their worst pain intensity during the dressing change using a visual analogue scale. The primary outcome measure was presence of 30% or greater difference in pain intensity ratings between the groups in estimation of worst pain during the dressing change. Of 88 eligible and consenting patients having awake dressings changes, 43 were assigned to virtual reality relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion alone. The group receiving virtual reality relaxation plus morphine PCA infusion reported significantly higher pain intensities during the dressing change (mean=7.3) compared with patients receiving morphine PCA alone (mean=5.3) (p=0.003) (95% CI 0.6-2.8). The addition of virtual reality guided relaxation to morphine PCA infusion in burns patients resulted in a significant increase in pain experienced during awake dressings changes. In the absence of a validated predictor for responsiveness to virtual reality relaxation such a therapy cannot be recommended for general use in burns patients having awake dressings changes.

Ex Vivo Expanded Natural Killer Cells Demonstrate Robust Proliferation In Vivo In High-Risk Relapsed Multiple Myeloma Patients

PubMed Central

Szmania, Susann; Lapteva, Natalia; Garg, Tarun; Greenway, Amy; Lingo, Joshuah; Nair, Bijay; Stone, Katie; Woods, Emily; Khan, Junaid; Stivers, Justin; Panozzo, Susan; Campana, Dario; Bellamy, William T.; Robbins, Molly; Epstein, Joshua; Yaccoby, Shmuel; Waheed, Sarah; Gee, Adrian; Cottler-Fox, Michele; Rooney, Cliona; Barlogie, Bart; van Rhee, Frits

2015-01-01

Highly activated/expanded natural killer (NK) cells can be generated via stimulation with the HLA-deficient cell line K562 genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence and activity of expanded NK cells generated from myeloma patients (auto-NK) or haplo-identical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone and fludarabine. NK cells were shipped overnight either cryopreserved or fresh. In 8 patients, up to 1×108 NK cells/kg were infused on day 0 and followed by daily administrations of IL2. Significant in vivo expansion was observed only in the 5 patients receiving fresh products, peaking at or near day 7, with the highest NK cell counts in 2 subjects who received cells produced in a high concentration of IL2 (500 units/mL). Seven days after infusion, donor NK cells comprised > 90% of circulating leukocytes in fresh allo-NK cell recipients, and cytolytic activity against allogeneic myeloma targets was retained in vitro. Among the 7 evaluable patients, there were no serious adverse events that could be related to NK cell infusion. One patient had a partial response and in another the tempo of disease progression decreased; neither patient required further therapy for 6 months. In the 5 remaining patients, disease progression was not affected by NK cell infusion. In conclusion, infusion of large numbers of expanded NK cells was feasible and safe; infusing fresh cells was critical to their expansion in vivo. PMID:25415285

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.

PubMed

Altier, N; Stewart, J

1998-04-01

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.

Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer.

PubMed

Eltweri, A M; Thomas, A L; Fisk, H L; Arshad, A; Calder, P C; Dennison, A R; Bowrey, D J

2017-06-01

It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. Patients with advanced oesophagogastric cancer (n = 21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven ® (fish oil supplement containing EPA and DHA) at a rate of 2 ml/kg body weight for 4 h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. Twenty patients received at least one Omegaven ® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. Clinical Trials.Gov NCT01870791. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Intravenous sulprostone infusion in the treatment of retained placenta.

PubMed

Stefanovic, Vedran; Paavonen, Jorma; Loukovaara, Mikko; Halmesmäki, Erja; Ahonen, Jouni; Tikkanen, Minna

2013-04-01

To analyze the effectiveness of intravenous sulprostone infusion for the treatment of retained placenta without massive primary hemorrhage among women at an university hospital over a three-year period. Retrospective observational study. University teaching hospital. 126 consecutive women with placental retention and intravenous sulprostone infusion as primary treatment performed from October 2007 up to December 2011. Hospital records of women who received sulprostone infusion to attempt placental expulsion were reviewed. Primary endpoints of the study were expulsion of placenta and the total amount of blood loss during delivery. The placenta was successfully expelled in 39.7% of cases, whereas 60.3% of women underwent manual removal of placenta. Blood loss was significantly lower in women with successful placental expulsion than in women who had manual removal of the placenta (582 ± 431 ml vs. 1275 ± 721 ml, p < 0.0001). Sulprostone infusion did not cause adverse effects or significant postpartum morbidity. Intravenous sulprostone infusion is safe and reduces both blood loss and the need for manual removal of the placenta. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Superselective Urokinase Infusion Therapy for Dorsalis Pedis Artery Occlusion in Buerger's Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota, Yasushi; Kichikawa, Kimihiko; Uchida, Hideo

1997-09-15

Occlusion of the proximal left dorsalis pedis artery (DPA) in a patient with Buerger's disease was treated by continuous urokinase intraarterial infusion using a microcatheter. Recanalization of the DPA and healing of a toe ulcer were achieved. The patient remains asymptomatic during a 4-year follow-up.

Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

PubMed

Tadros, Elizabeth M; Frank, Nicholas; De Witte, Fiamma Gomez; Boston, Raymond C

2013-07-01

To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). 6 healthy adult mares and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

[A case of coronary artery spasm during epidural anesthesia with continuous infusion of propofol].

PubMed

Inoue, Hisashi; Ogawa, Katsumi; Takano, Yoshito; Sato, Isao; Okuda, Yasuhisa

2003-07-01

A 50-year-old male patient was scheduled for left partial pulmonary resection and biopsy. The patient had neither complication nor history of ischemic heart disease. After arriving in the operation room, an epidural catheter was inserted into the epidural space at the T 4-5 intervertebral space. Anesthesia was induced with intravenous propofol 100 mg, fentanyl 100 microgram and vecuronium 6 mg and then a double lumen endotracheal tube was inserted. Anesthesia was maintained with O2 and air (FIO2 0.3-1.0), continuous infusion of propofol, intermittent intravenous administration of fentanyl and epidural injection of 1% lidocaine. Forty-five minutes after the start of operation, ECG showed an elevation of ST segment and soon it passed into ventricular tachycardia and ventricular fibrillation. The patient was treated with cardiopulmonary resuscitation. Fifteen minutes later, ECG returned to sinus rhythm but the elevation of ST segment remained. We considered that these cardiac events were due to coronary spasm, and started continuous infusion of nitroglycerin and nicorandil. One hour later, ST segment returned to normal. The possible inducing factors in this case were altered balance between sympathetic and parasympathetic nervous activity caused by infusion of propofol and epidural block, and alpha-stimulation caused by ephedrine.

Intraduodenal infusion of a combination of tastants decreases food intake in humans.

PubMed

van Avesaat, Mark; Troost, Freddy J; Ripken, Dina; Peters, Jelmer; Hendriks, Henk Fj; Masclee, Ad Am

2015-10-01

Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and umami) on food intake, hunger and fullness, gastrointestinal symptoms, and gastrointestinal peptide release. Fifteen healthy volunteers [6 male; mean ± SEM age: 23.9 ± 2.0 y; mean ± SEM body mass index (in kg/m(2)): 22.4 ± 0.3] received 5 treatments in a double-blind, randomized, placebo-controlled crossover design. Test days started with the insertion of a nasoduodenal catheter followed by a standardized liquid breakfast. Participants received an intraduodenal infusion 150 min after breakfast, containing quinine (bitter), rebaudioside A (sweet), monosodium glutamate (umami), a combination of the 3 tastants, or placebo (tap water) over a period of 60 min. Food intake was measured during an ad libitum meal, and visual analog scales were used to monitor gastrointestinal complaints and hunger and fullness scores. Blood samples were drawn at regular intervals for cholecystokinin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) analysis. Infusion of the combination of tastants substantially decreased food intake (422 ± 97 compared with 486 ± 104 kcal for placebo, P < 0.05), whereas both a combination of tastants and umami decreased hunger scores compared with placebo. No change in cholecystokinin, GLP-1, or PYY concentrations was observed during the infusions. Intraduodenal infusions of the tastants did not result in gastrointestinal symptoms. Intraduodenal infusion of umami and a combination of tastants inhibits feelings of hunger, but only the latter also reduces food intake. However, these alterations were not accompanied by changes in the plasma concentrations of the gut-derived peptides cholecystokinin, GLP-1, or PYY. This trial was registered at clinicaltrials.gov as NCT01956838. © 2015 American Society for Nutrition.

Sequence of Fibrinogen Proteolysis and Platelet Release after Intrauterine Infusion of Hypertonic Saline

PubMed Central

Nossel, H. L.; Wasser, J.; Kaplan, K. L.; Lagamma, K. S.; Yudelman, I.; Canfield, R. E.

1979-01-01

Plasma fibrinopeptide B (Bβ1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bβ1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bβ1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bβ1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bβ42)-alanine (Bβ43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (βTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases βTG and PF4 from platelets. Later plasmin cleaves Bβ1-42 from fibrin I to produce fragment X, which is further degraded to form serum fibrinogen degradation products. This sequence of proteolysis indicates that plasmin action on fibrin I serves as a mechanism that regulates fibrin II formation by removing the Bβ chain cleavage site, which is required for thrombin action in converting fibrin I to fibrin II. PMID:500818

Postoperative analgesic efficacy of single-shot and continuous transversus abdominis plane block after laparoscopic cholecystectomy: A randomized controlled clinical trial.

PubMed

Choi, Yun-Mi; Byeon, Gyeong-Jo; Park, Soon-Ji; Ok, Young-Min; Shin, Sang-Wook; Yang, Kwangho

2017-06-01

To compare the analgesic efficacy of ultrasound-guided single-shot and continuous transversus abdominis plane (TAP) block to that of IV-PCA in patients undergoing laparoscopic cholecystectomy. Prospective randomized controlled trial. Post-anesthesia care unit and General ward. 108 American Society of Anesthesiologist (ASA) physical status I-II patients undergoing laparoscopic cholecystectomy. Group A received IV-PCA; group B received both ultrasound-guided single-shot TAP block with 0.2% ropivacaine (20mL) and IV-PCA; and group C received continuous TAP block using an ultrasound-guidance-inserted indwelling catheter. In group C, infusion of 0.2% ropivacaine at a basal rate of 3mL/h, bolus dose of 4mL, and a lockout interval of 30min was maintained for 48h postoperatively. The primary outcome was evaluated analgesic efficacy using the numeric rating scale (NRS) for 48h postoperatively. Other outcomes included the number of patients requiring additional analgesics, patient satisfaction with postoperative pain control, and incidence of postoperative adverse events. Compared to other groups, group C had higher deep abdominal NRS at 1h postoperatively (P<0.05), and lower incidence of postoperative urinary retention (P<0.05). There were no significant intergroup differences in the number of patients requiring additional analgesics, and patient satisfaction with postoperative pain control. Compared to IV-PCA with or without single-shot TAP block, ultrasound-guided continuous TAP block provided similar analgesia in somatic pain and less analgesia in visceral pain. Moreover, the latter resulted in a lower incidence of postoperative urinary retention. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases: A multicenter study

PubMed Central

Viola, Anna; Costantino, Giuseppe; Privitera, Antonino Carlo; Bossa, Fabrizio; Lauria, Angelo; Grossi, Laurino; Principi, Maria Beatrice; Della Valle, Nicola; Cappello, Maria

2017-01-01

AIM To assess the impact of short infliximab (IFX) infusion on hospital resource utilization and costs. METHODS All inflammatory bowel diseases (IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated. RESULTS One hundred and twenty-five patients were recruited (64 with ulcerative colitis and 61 with Crohn’s disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years (SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501 (30.5% short infusions). In the analyzed cohort, 1143 h were saved (762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving (-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled (infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase (observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient (average -€17.300 on the whole cohort). CONCLUSION A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital’s perspective, as it contributes to increase infusion units capacity, and the patients’ perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity. PMID:28533923

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

PubMed Central

Levy, AnneMarie; Limebeer, Cheryl L.; Ferdinand, Justin; Shillingford, Ucal; Parker, Linda A.; Leri, Francesco

2014-01-01

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets. PMID:24561923

Moderate glucose supply reduces hemolysis during systemic inflammation

PubMed Central

Jägers, Johannes; Brauckmann, Stephan; Kirsch, Michael; Effenberger-Neidnicht, Katharina

2018-01-01

Background Systemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation. Materials and methods Systemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS) infusion (1 mg LPS/kg and h, 300 min). Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h) or excessively (210 mg glucose/kg and h) during systemic inflammation. Vital parameters (eg, systemic blood pressure) as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase) were measured hourly. Clot formation was analyzed by thromboelastometry. Results Continuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia), changes in hemodynamics (tachycardia and hypertension), and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation). It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase), alterations in blood coagulation (disturbed clot formation), and massive hemolysis. Both moderate and excessive glucose supply reduced LPS-induced increase in systemic blood pressure. Excessive but not moderate glucose supply increased blood glucose level and enhanced tissue injury. Glucose supply did not reduce LPS-induced alterations in coagulation, but significantly reduced hemolysis induced by LPS. Conclusion Intravenous glucose infusion can diminish LPS-related changes in hemodynamics, glucose metabolism, and, more interestingly, LPS-induced hemolysis. Since cell-free hemoglobin is known to be a predictor for patient’s survival, a reduction of hemolysis by 35% only by the addition of a small amount of glucose is another step to minimize mortality during systemic inflammation. PMID:29559805

The reliability of using the single-biopsy approach to assess basal muscle protein synthesis rates in vivo in humans.

PubMed

Burd, Nicholas A; Groen, Bart B L; Beelen, Milou; Senden, Joan M G; Gijsen, Annemie P; van Loon, Luc J C

2012-07-01

It has recently been proposed that basal muscle protein synthesis can be effectively assessed by measuring the background enrichment in total plasma protein, thereby omitting the initial biopsy, and determining the difference in enrichment from a single muscle biopsy obtained during a primed continuous infusion of isotope-labeled amino acids. We determined the reliability of calculating basal mixed muscle protein fractional synthetic rates (FSRs) from mixed plasma proteins and a single muscle biopsy compared against the sequential muscle biopsy approach. Ten men (age, 23 ± 1 years; body mass index, 22 ± 1 kg∙m(-2)) received muscle biopsies of the vastus lateralis after 2 and 4 hours of a primed continuous infusion of l-[ring-(13)C(6)]phenylalanine. Mixed muscle protein FSR was calculated from baseline plasma enrichments and muscle protein enrichments determined from the biopsy at 2 hours (1BX SHORT) or 4 hours (1BX LONG), or between muscle protein enrichments at 2 and 4 hours (2BX) of the infusion. No differences (P = .50) were observed in mixed muscle protein FSR, using plasma [ring-(13)C(6)]phenylalanine enrichments as the precursor, between the 1BX SHORT (0.031% ± 0.010%∙h(-1)), 1BX LONG (0.032% ± 0.007%∙h(-1)), or 2BX (0.035% ± 0.011%∙h(-1)) approach. A significant correlation was observed between the calculated muscle protein FSR assessed using the 1BX LONG and 2BX approach (r = 0.7, P = .02). Our data demonstrate that the single-biopsy approach, irrespective of whether the biopsy is obtained at 2 or 4 hours, can be used as a surrogate for the sequential-biopsy approach to determine basal muscle protein synthesis in a group. Copyright © 2012 Elsevier Inc. All rights reserved.

Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil.

PubMed

Bourgoin, Aurélie; Albanèse, Jacques; Wereszczynski, Nicolas; Charbit, Martine; Vialet, Renaud; Martin, Claude

2003-03-01

The aim of the study was to compare the safety concerning cerebral hemodynamics of ketamine and sufentanil used for sedation of severe head injury patients, both drugs being used in combination with midazolam. Prospective, randomized, double-blind study. Intensive care unit in a trauma center. Twenty-five patients with severe head injury. Twelve patients received sedation with a continuous infusion of ketamine-midazolam and 13 with a continuous infusion of sufentanil-midazolam. All patients were mechanically ventilated with moderate hyperventilation. Prognostic indicators (age, Glasgow Coma Scale scores, computed tomography diagnosis, and Injury Severity Scale score) were similar in the two groups at study entry. Measurements were carried out during the first 4 days of sedation. The average infusion rates during this time were 82 +/- 25 micro x kg x min ketamine and 1.64 +/- 0.5 microg x kg x min midazolam in the ketamine group and 0.008 +/- 0.002 microg x kg x min sufentanil and 1.63 +/- 0.37 microg x kg x min midazolam in the sufentanil group. No significant differences were observed between the two groups in the mean daily values of intracranial pressure and cerebral perfusion pressure. The numbers of intracranial pressure elevations were similar in both groups. The requirements of neuromuscular blocking agents, propofol, and thiopental were similar. Heart rate values were significantly higher in the ketamine group on therapy days 3 and 4 ( <.05). With regard to arterial pressure control, more fluids were given on the first therapy day and there was a trend toward greater use of vasopressors in the sufentanil group. Sedative costs were similar in the two groups. The results of this study suggest that ketamine in combination with midazolam is comparable with a combination of midazolam-sufentanil in maintaining intracranial pressure and cerebral perfusion pressure of severe head injury patients placed under controlled mechanical ventilation.

The role of disodium pamidronate in the management of bone pain due to malignancy.

PubMed

Groff, L; Zecca, E; De Conno, F; Brunelli, C; Boffi, R; Panzeri, C; Cazzaniga, M; Ripamonti, C

2001-07-01

A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T0 after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies.

Pascal's wager: combining continuous glucose monitoring and continuous subcutaneous insulin infusion.

PubMed

Kerr, David; Olateju, Tolu

2010-06-01

Pascal's Wager is a suggestion posed by the French Philosopher, Blaise Pascal, that even though the existence of God cannot be determined through reason, a person should wager that God exists because he or she has everything to gain and nothing to lose. In the area of consideration here, the optimum experimental trial of the combined use of continuous subcutaneous insulin infusion and real-time continuous glucose monitoring in free-living individuals with type 1 diabetes providing rock-solid evidence of clinical benefit has not been performed. Nevertheless, there is considerable enthusiasm for combining the technologies among healthcare professionals, patients, and manufacturers based on the belief that this approach to diabetes care must be beneficial beyond the available evidence (i.e., reason).

Cell Saver for Adult Spinal Deformity Surgery Reduces Cost.

PubMed

Gum, Jeffrey L; Carreon, Leah Yacat; Kelly, Michael P; Hostin, Richard; Robinson, Chessie; Burton, Douglas C; Polly, David W; Shaffrey, Christopher I; LaFage, Virginie; Schwab, Frank J; Ames, Christopher P; Kim, Han Jo; Smith, Justin S; Bess, R Shay

2017-07-01

Retrospective cohort. To determine if the use of cell saver reduces overall blood costs in adult spinal deformity (ASD) surgery. Recent studies have questioned the clinical value of cell saver during spine procedures. ASD patients enrolled in a prospective, multicenter surgical database who had complete preoperative and surgical data were identified. Patients were stratified into (1) cell saver available during surgery, but no intraoperative autologous infusion (No Infusion group), or (2) cell saver available and received autologous infusion (Infusion group). There were 427 patients in the Infusion group and 153 in the No infusion group. Patients in both groups had similar demographics. Mean autologous infusion volume was 698 mL. The Infusion group had a higher percentage of EBL relative to the estimated blood volume (42.2%) than the No Infusion group (19.6%, p < .000). Allogeneic transfusion was more common in the Infusion group (255/427, 60%) than the No Infusion group (67/153, 44%, p = .001). The number of allogeneic blood units transfused was also higher in the Infusion group (2.4) than the No Infusion group (1.7, p = .009). Total blood costs ranged from $396 to $2,146 in the No Infusion group and from $1,262 to $5,088 in the Infusion group. If the cost of cell saver blood was transformed into costs of allogeneic blood, total blood costs for the Infusion group would range from $840 to $5,418. Thus, cell saver use yielded a mean cost savings ranging from $330 to $422 (allogeneic blood averted). Linear regression showed that after an EBL of 614 mL, cell saver becomes cost-efficient. Compared to transfusing allogeneic blood, cell saver autologous infusion did not reduce the proportion or the volume of allogeneic transfusion for patients undergoing surgery for adult spinal deformity. The use of cell saver becomes cost-efficient above an EBL of 614 mL, producing a cost savings of $330 to $422. Level III. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Costs of providing infusion therapy for patients with inflammatory bowel disease in a hospital-based infusion center setting.

PubMed

Afzali, Anita; Ogden, Kristine; Friedman, Michael L; Chao, Jingdong; Wang, Anthony

2017-04-01

Inflammatory bowel disease (IBD) (e.g. ulcerative colitis [UC] and Crohn's disease [CD]) severely impacts patient quality-of-life. Moderate-to-severe disease is often treated with biologics requiring infusion therapy, adding incremental costs beyond drug costs. This study evaluates US hospital-based infusion services costs for treatment of UC or CD patients receiving infliximab or vedolizumab therapy. A model was developed, estimating annual costs of providing monitored infusions using an activity-based costing framework approach. Multiple sources (published literature, treatment product inserts) informed base-case model input estimates. The total modeled per patient infusion therapy costs in Year 1 with infliximab and vedolizumab was $38,782 and $41,320, respectively, and Year 2+, $49,897 and $36,197, respectively. Drug acquisition cost was the largest total costs driver (90-93%), followed by costs associated with hospital-based infusion provision: labor (53-56%, non-drug costs), allocated overhead (23%, non-drug costs), non-labor (23%, non-drug costs), and laboratory (7-10%, non-drug costs). Limitations included reliance on published estimates, base-case cost estimates infusion drug, and supplies, not accounting for volume pricing, assumption of a small hospital infusion center, and that, given the model adopts the hospital perspective, costs to the patient were not included in infusion administration cost base-case estimates. This model is an early step towards a framework to fully analyze infusion therapies' associated costs. Given the lack of published data, it would be beneficial for hospital administrators to assess total costs and trade-offs with alternative means of providing biologic therapies. This analysis highlights the value to hospital administrators of assessing cost associated with infusion patient mix to make more informed resource allocation decisions. As the landscape for reimbursement changes, tools for evaluating the costs of infusion therapy may help hospital administrators make informed choices and weigh trade-offs associated with providing infusion services for IBD patients.

Quality-improvement analytics for intravenous infusion pumps.

PubMed

Skledar, Susan J; Niccolai, Cynthia S; Schilling, Dennis; Costello, Susan; Mininni, Nicolette; Ervin, Kelly; Urban, Alana

2013-04-15

The implementation of a smart-pump continuous quality-improvement (CQI) program across a large health system is described, with an emphasis on key metrics for outcomes analyses and program refinement. Three years ago, the University of Pittsburgh Medical Center health system launched a CQI initiative to help ensure the safe use of 6000 smart pumps in its 14 inpatient facilities. A centralized team led by pharmacists is responsible for the retrieval and interpretation of smart-pump data, which is continuously transmitted to a main server. CQI findings are regularly posted on the health system's interdisciplinary intranet. Monitored metrics include rates of compliance with preprogrammed infusion limits, the top 20 drugs involved in alerts, drugs associated with alert-override rates of ≥90%, numbers of alerts by infusion type, nurse responses to alerts, and alert rate per drug library update. Based on the collected CQI data and site-specific requests, four systemwide updates of the smart-pump drug library were performed during the first 18 months of the program, reducing "nuisance alerts" by about 10% per update cycle and enabling targeted interventions to reduce rapid-infusion errors, other adverse drug events (ADEs), and pump-programming workarounds. Over one 12-month period, bedside alerts prompted nurses to reprogram or cancel continuous infusions an average of 400 times per month, potentially averting i.v. medication ADEs. A smart-pump CQI program is an effective tool for enhancing the safety of i.v. medication administration. The ongoing refinement of the drug library through the development and implementation of key interventions promotes the growth and sustainability of the smart-pump initiative systemwide.

Tissue distribution of sup 3 H-nicotine in rats after bolus or constant injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, P.; Pasley, J.N.; Rayford, P.L.

1989-01-01

Two groups of rats, (N = 7), were fasted for 24 hrs prior to the study. On the day of the experiment, the animals were anesthetized and infused with either 5 ml nicotine solution (200 {mu}g/L) in saline containing 5 {mu}c {sup 3}H-nicotine, (sp. activity 50-80 mCi/mol) for 90 minutes or injected as a bolus with 0.5 ml of the same nicotine (200 {mu}g/L) solution. The animals were sacrificed 60 minutes after the injection or after the infusion was stopped. Blood and tissue samples were counted by liquid scintillation counting. Percent distribution of {sup 3}H-nicotine per gm of tissue wasmore » calculated from the total radioactivity recovered in individual tissues over the total activity injected into the rat and the values were compared using student's t test. Results: Distribution of {sup 3}H-nicotine was found highest in kidney (45-49%) among all tissues examined and was not different between routes of administration. Significantly higher retention of {sup 3}H-nicotine was found with continuous infusion in esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle when {sup 3}H-nicotine retentions were compared with bolus injection. In contrast, the distribution of {sup 3}H-nicotine in adrenal gland, was significantly lower in continuous infusion group. Distribution in blood was 6 fold higher in continuous infusion (7.26%) compared to bolus (1.11%) injection. The distribution {sup 3}H-nicotine in other tissues were not different by either routes of injection.« less

Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study.

PubMed

Cheng, Hsiu-Chi; Wu, Chung-Tai; Chang, Wei-Lun; Cheng, Wei-Chun; Chen, Wei-Ying; Sheu, Bor-Shyang

2014-12-01

Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores <6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores <6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs 28.7%, p=0.002). Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. NCT01591083. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Suppression of gastrin release and gastric secretion by gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP).

PubMed Central

Villar, H V; Fender, H R; Rayford, P L; Bloom, S R; Ramus, N I; Thompson, J C

1976-01-01

Five dogs prepared with Heidenhain pouches received infusions of saline, GIP and VIP before and after a standard meat meal. Blood samples were obtained under basal conditions and at subsequent intervals for measurement of gastrin, insulin, GIP and VIP by radioimmunoassay. GIP and VIP infusions had no effect on basal levels of gastrin. GIP and VIP (in common with secretin and glucagon) were found to suppress food-stimulated release of gastrin and gastrin-stimulated acid secretion from the Heidenhain pouch. Insulin levels were significantly elevated during GIP and VIP infusions. Food released GIP (and perhaps VIP. PMID:938120

Effect of time to infusion of autologous stem cells (24 vs. 48 h) after high-dose melphalan in patients with multiple myeloma.

PubMed

Talamo, Giampaolo; Rakszawski, Kevin L; Rybka, Witold B; Dolloff, Nathan G; Malysz, Jozef; Berno, Tamara; Zangari, Maurizio

2012-08-01

High-dose melphalan (HD-Mel) is considered the current standard of care among the preparative regimens used in autologous peripheral blood stem cell transplantation (SCT) for multiple myeloma (MM), but optimal time and schedule of administration is not defined. We retrospectively analyzed outcomes and toxicities of HD-Mel administered on day -2 vs. day -1 before autologous stem cells infusion. A total of 138 consecutive MM patients treated at Penn State Hershey Cancer Institute between 2007 and 2010 were included in this study. No difference in time to hematopoietic recovery, common SCT-related toxicities, and clinical outcomes was seen between patients who received HD-Mel on day -2 (group A, n = 47), and those who received it on day -1 (group B, n = 91). Prompt and full hematopoietic recovery occurred even when stem cells were infused between 8 and 24 h after completion of chemotherapy. In the absence of prospective and randomized data, we conclude that a single I.V. infusion of HD-Mel on day -1 is a safe and effective practice, and the so-called 'day of rest' before the transplant appears not to be necessary. © 2012 John Wiley & Sons A/S.

Transcriptomic Impacts of Rumen Epithelium Induced by Butyrate Infusion in Dairy Cattle in Dry Period

PubMed Central

Baldwin, Ransom L; Li, Robert W; Jia, Yankai; Li, Cong-Jun

2018-01-01

The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function. Ruminal infusion of butyrate was following 0-hour sampling (baseline controls) and continued for 168 hours at a rate of 5.0 L/day of a 2.5 M solution as a continuous infusion. Following the 168-hour infusion, the infusion was stopped, and cows were maintained on the basal lactation ration for an additional 168 hours for sampling. Rumen epithelial samples were serially collected via biopsy through rumen fistulae at 0-, 24-, 72-, and 168-hour (D1, D3, D7) and 168-hour post-infusion (D14). In comparison with pre-infusion at 0 hours, a total of 3513 genes were identified to be impacted in the rumen epithelium by butyrate infusion at least once at different sampling time points at a stringent cutoff of false discovery rate (FDR) < 0.01. The maximal effect of butyrate was observed at day 7. Among these impacted genes, 117 genes were responsive consistently from day 1 to day 14, and another 42 genes were lasting through day 7. Temporal effects induced by butyrate infusion indicate that the transcriptomic alterations are very dynamic. Gene ontology (GO) enrichment analysis revealed that in the early stage of rumen butyrate infusion (on day 1 and day 3 of butyrate infusion), the transcriptomic effects in the rumen epithelium were involved with mitotic cell cycle process, cell cycle process, and regulation of cell cycle. Bioinformatic analysis of cellular functions, canonical pathways, and upstream regulator of impacted genes underlie the potential mechanisms of butyrate-induced gene expression regulation in rumen epithelium. The introduction of transcriptomic and bioinformatic technologies to study nutrigenomics in the farm animal presented a new prospect to study multiple levels of biological information to better apprehend the whole animal response to nutrition, physiological state, and their interactions. The nutrigenomics approach may eventually lead to more precise management of utilization of feed resources in a more effective approach. PMID:29785087

Calcium EDTA toxicity: renal excretion of endogenous trace metals and the effect of repletion on collagen degradation in the rat.

PubMed

Braide, V B

1984-01-01

Studies on total hydroxyproline concentrations in urine of rats infused with toxic doses of CaEDTA at 6 mmol/kg per 24 hr for 48 hr or injected i.p. with the chelate at 4.8 mmol/kg/day for 10 days, indicate a two- to six-fold increase in urine excretion of the imino acid. This is due to increased degradation of collagen induced by CaEDTA. CaEDTA infusion was also shown to enhance urine excretion of some trace metals (Zn, Mn, Cu and Fe). Rats infused with CaEDTA for 36 hr showed a gradual fall in concentration of hydroxyproline in the urine, following cessation of chelate infusion. The decline in hydroxyproline concentrations was faster in rats receiving trace metal (Zn, Co, Mn or Ni) treatment during the post-CaEDTA infusion period; suggesting that the metals may affect collage, making the protein less susceptible to degradation in the body.

Design and rationale of Heart and Lung Failure – Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children☆

PubMed Central

Agus, Michael SD; Hirshberg, Ellie; Srinivasan, Vijay; Faustino, Edward Vincent; Luckett, Peter M; Curley, Martha AQ; Alexander, Jamin; Asaro, Lisa A; Coughlin-Wells, Kerry; Duva, Donna; French, Jaclyn; Hasbani, Natalie; Sisko, Martha T; Soto-Rivera, Carmen L; Steil, Garry; Wypij, David; Nadkarni, Vinay M

2017-01-01

Objectives Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design Multi-center randomized clinical trial. Setting Pediatric ICUs at 35 academic hospitals. Patients Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions Patients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions This trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control. PMID:28042054

Evaluation of the Cardiovascular and Subjective Effects of Rivastigmine In Combination With Methamphetamine in Methamphetamine-Dependent Human Volunteers

PubMed Central

De La Garza, R.; Shoptaw, S.; Newton, T. F.

2008-01-01

Acetylcholine (ACh) has been implicated in the reinforcing and locomotor activating effects produced by methamphetamine. Of interest, recent data suggest that acetylcholinesterase (AChE) inhibitors attenuate methamphetamine-seeking behavior in rats. We conducted this study in order to determine the safety (adverse events, mood changes, cardiovascular effects) and preliminary efficacy (subjective effects) of the AChE inhibitor rivastigmine when tested in combination with methamphetamine. Twenty-three non-treatment seeking methamphetamine-dependent participants resided in an inpatient unit at UCLA for two-weeks, and completed this double-blind, between-subjects, placebo-controlled study. Prior to randomization to study drug, infusions of saline (day 4; o mg) and methamphetamine (day 5; 30 mg, IV) were given to all participants at 11:30 a.m. in single-blinded fashion. On day 7 and continuing through day 11, participants were randomized to receive oral placebo (0 mg, N=7) or rivastigmine (1.5 mg, N=7; 3 mg, N=9). On day 11, the subjects received saline and methamphetamine infusions again (randomized to either 11:30 a.m. or 2:30 p.m.), under double-blind conditions. The data analyses compared across-study measures of adverse events and mood, and a post-randomization analysis of cardiovascular and subjective effects (on Day 11). The data reveal that rivastigmine was not associated with increased adverse events or alterations in mood. As expected, acute methamphetamine exposure (30 mg, IV) increased heart rate and blood pressure, as well as several positive subjective effects, ARCI ratings, and reported monetary value (p<0.05). The data indicated that rivastigmine, at 3 mg, significantly attenuated methamphetamine-induced increases in diastolic blood pressure, and self-reports of “anxious” and “desire” (p<0.05). Taken together, the findings in the current report suggest that pharmacological manipulations that enhance brain ACh warrant continued investigation as potential treatments for methamphetamine addiction. PMID:18248689

Intravenous magnesium sulfate for vaso-occlusive episodes in sickle cell disease.

PubMed

Goldman, Ran D; Mounstephen, William; Kirby-Allen, Melanie; Friedman, Jeremy N

2013-12-01

Vaso-occlusive episodes (VOEs) are the most common complication of sickle cell disease in children. Treatment with magnesium seems to improve cellular hydration and may result in reduced vaso-occlusion. This study aimed to determine if intravenous (IV) magnesium sulfate (MgSO4) reduces length of stay (LOS) in hospital, pain scores, and cumulative analgesia when compared with placebo. Randomized, double-blind, placebo-controlled trial in children aged 4 to 18 years requiring admission to hospital with a sickle cell disease VOE requiring IV analgesia. Participating children received IV MgSO4 (100 mg/kg) every 8 hours or placebo in addition to standard therapy. We used a t test or Mann-Whitney test (continuous variables), Fisher's exact test, or χ2 test (frequencies). P values were considered significant if <.05, and 95% confidence intervals were calculated for the difference between groups. One hundred six children were randomly assigned to the study, and 104 were included. Fifty-one (49%) received MgSO4. Children's mean age was 12.4 years (range: 4-18 years; SD: 3.8 years), and 56 (54%) were females. There was no significant difference in the primary outcome measure, LOS in hospital, with a mean of 132.6 and 117.7 hours in the MgSO4 and placebo groups, respectively (P = .41). There was no significant difference between groups for the secondary outcomes of mean pain scores (4.9 ± 2.6 vs 4.8 ± 2.6, respectively; P = .92) or analgesic requirements (continuous morphine infusion [P = .928], boluses of IV morphine [P = .82], acetaminophen [P = .34], ibuprofen [P = .15], naproxen [P = .10]). Only minor adverse events were recorded in both groups. Pain at the infusion site was more common in the MgSO4 group. IV MgSO4 was well tolerated but had no effect on the LOS in hospital, pain scores, or cumulative analgesia use in admitted children with a VOE.

Use of di(2-ethylhexyl)phthalate-containing infusion systems increases the risk for cholestasis.

PubMed

von Rettberg, Heike; Hannman, Torsten; Subotic, Ulrike; Brade, Joachim; Schaible, Thomas; Waag, Karl Ludwig; Loff, Steffan

2009-08-01

Most polyvinylchloride infusion systems are plasticized with up to 60% of di(2-ethylhexyl)phthalate (DEHP). DEHP is easily extracted from the tubing by total parenteral nutrition (TPN) solutions and has been shown to have toxic effects on various organ systems including the liver in animals and humans. A role was postulated for DEHP in the development of hepatobiliary dysfunction in premature and newborn infants receiving parenteral nutrition, and the incidence of cholestasis was investigated after changing from polyvinylchloride infusion systems to polyvinylchloride-free infusion systems. Two 3-year periods from 1998 to 2004 were investigated retrospectively before and after changing from polyvinylchloride to polyvinylchloride-free infusion systems in our department. This resulted in 1 group of 30 patients treated with polyvinylchloride lines and a second group of 46 patients treated with polyvinylchloride-free lines. The 2 groups were examined for the incidence of cholestasis and other possible contributing factors. Statistics were performed by using SAS software (SAS Institute, Cary, NC). After changing infusion systems, the incidence of cholestasis dropped from 50% to 13%. Using DEHP-plasticized polyvinylchloride infusion systems for TPN increased the risk for cholestasis by a factor of 5.6. The use of polyvinylchloride lines correlated strongly with the development of TPN-associated cholestasis (P = .0004). Using DEHP-containing polyvinylchloride infusions systems contributes to the development of cholestasis. Therefore, the use of DEHP-free infusion systems for TPN is recommended, especially in premature and newborn infants.

Perioperative management in orthotopic liver transplantation: results of an Italian national survey.

PubMed

Biancofiore, G; Della Rocca, G

2012-06-01

No data are available on the perioperative approach during orthotopic liver transplantation (OLT) in Italy, apart from sporadically single center studies. The Department of Anesthesia cooperating with each Italian licensed OLT center received a questionnaire regarding preoperative evaluation, intraoperative anesthesia management, anesthetic drugs, blood components therapy, perioperative monitoring, supportive therapies, postoperative care, staff and organization. Twenty-two centers were surveyed and 17 returned the questionnaire. Center specific protocols for OLT anesthesia exist in 12 centers. Balanced anesthesia (volatile anesthetic agents and continuous infusion of opioids) is the standard anesthetic method. In 14 cases a thromboelastogram is available; one center reported not to have a rapid infusion device available. Pulmonary artery catheterization with a continuous cardiac output device is the most used hemodynamic monitoring system; in case of hemodynamic instability, the combination of dopamine/noradrenaline resulted the first choice before vascular clamping whereas noradrenaline alone after graft's reperfusion. No difference about which intraoperative phase is mostly characterized by the use of blood components was reported. Postoperative care is provided on anesthesiological-guided Intensive Care Units (ICU) in all the surveyed centers and in three centers the ICU is dedicated only to transplant patients. The results of this survey show that in Italy the perioperative management of patients undergoing OLT is not homogeneous. This database allows to debate on the best practices and pathways for perioperative management of these patients, and to stimulate future clinical trials aimed to assess the different component and steps forwards of the whole process.

Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products.

PubMed

Nowicki, Theodore S; Escuin-Ordinas, Helena; Avramis, Earl; Chmielowski, Bartosz; Chodon, Thinle; Berent-Maoz, Beata; Wang, Xiaoyan; Kaplan-Lefko, Paula; Yang, Lili; Baltimore, David; Economou, James S; Ribas, Antoni; Comin-Anduix, Begoña

2018-06-01

Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort's superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols.

Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products

PubMed Central

Nowicki, Theodore S.; Escuin-Ordinas, Helena; Avramis, Earl; Chmielowski, Bartosz; Chodon, Thinle; Berent-Maoz, Beata; Wang, Xiaoyan; Kaplan-Lefko, Paula; Yang, Lili; Baltimore, David; Economou, James S.; Ribas, Antoni

2018-01-01

Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort’s superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols. PMID:29470191

Bridging Grafts and Transient Nerve Growth Factor Infusions Promote Long-Term Central Nervous System Neuronal Rescue and Partial Functional Recovery

NASA Astrophysics Data System (ADS)

Tuszynski, Mark H.; Gage, Fred H.

1995-05-01

Grafts of favorable axonal growth substrates were combined with transient nerve growth factor (NGF) infusions to promote morphological and functional recovery in the adult rat brain after lesions of the septohippocampal projection. Long-term septal cholinergic neuronal rescue and partial hippocampal reinnervation were achieved, resulting in partial functional recovery on a simple task assessing habituation but not on a more complex task assessing spatial reference memory. Control animals that received transient NGF infusions without axonal-growth-promoting grafts lacked behavioral recovery but also showed long-term septal neuronal rescue. These findings indicate that (i) partial recovery from central nervous system injury can be induced by both preventing host neuronal loss and promoting host axonal regrowth and (ii) long-term neuronal loss can be prevented with transient NGF infusions.

The Influence of Insulin Injections and Infusions on Eating and Blood Glucose Level in the Rat,

DTIC Science & Technology

then a sudden rise ensues. Continuous infusion of insulin in normal rats induces hyperphagia : blood glucose decreases slowly to 50 mg%; at which...insulin into static obese hypothalamic subjects (whose daily food intake is fairly normal) leads to renewed hyperphagia , but the fluctuations in blood

Long-term leucine induced stimulation of muscle protein synthesis is amino acid dependent

USDA-ARS?s Scientific Manuscript database

Infusing leucine for 1 h increases skeletal muscle protein synthesis in the neonate, but this is not sustained for 2 h unless the corresponding fall in amino acids is prevented. This study aimed to determine whether a continuous leucine infusion can stimulate protein synthesis for a prolonged period...

Growth Infusion: Embedding Staff Development in a Culture of Learning

ERIC Educational Resources Information Center

Bennett, Betty J.

2017-01-01

To address increasing accountability demands, instructional leaders must find ways to expand the current reality of faculty development to create a culture where continuous growth and learning are the standard for professional behavior. Growth Infusion is a framework for creating such a culture. The framework is a result of an extensive search for…

Severe infusion reactions to fabry enzyme replacement therapy: rechallenge after tracheostomy.

PubMed

Nicholls, K; Bleasel, K; Becker, G

2012-01-01

A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.

Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment.

PubMed

Hendriksz, Christian; Santra, Saikat; Jones, Simon A; Geberhiwot, Tarekegn; Jesaitis, Lynne; Long, Brian; Qi, Yulan; Hawley, Sara M; Decker, Celeste

2018-04-01

Elosulfase alfa is an enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis IVA), a multisystemic progressive lysosomal storage disorder. This report includes the primary treatment outcomes and immunogenicity profile of elosulfase alfa in patients with Morquio A syndrome from 2 sequential studies, MOR-002 (ClinicalTrials.govNCT00884949) and MOR-100 (NCT01242111), representing >5 years of clinical study data. MOR-002 was an open-label, single-arm phase 1/2 study that evaluated the pharmacokinetics, safety, immunogenicity, and preliminary efficacy of 3 sequential doses of elosulfase alfa (0.1, 1.0, and 2.0 mg/kg/week) in patients with Morquio A syndrome (n = 20) over 36 weeks, followed by an optional 36- to 48-week treatment period using elosulfase alfa 1.0 mg/kg once weekly (qw). During the 0.1 mg/kg dosing phase, 1 patient discontinued due to a type I hypersensitivity adverse event (AE), and that patient's sibling voluntarily discontinued in the absence of AEs. An additional patient discontinued due to recurrent infusion reactions during the 1.0 mg/kg continuation phase. The remaining 17 patients completed MOR-002 and enrolled in MOR-100, an open-label, long-term extension study that further evaluated safety and clinical outcomes with elosulfase alfa administered at 2.0 mg/kg qw. During the course of MOR-100, patients were given the option of receiving elosulfase alfa infusions at home with nursing assistance. Over the course of both studies, all patients experienced ≥1 AE and most patients experienced a drug-related AE, generally of mild or moderate severity. Hypersensitivity reactions reported as related to study drug occurred in 25% of patients. Thirteen patients who chose to receive infusions at home had the same tolerability and safety profile, as well as comparable compliance rates, as patients who chose to receive on-site infusions. All patients developed antibodies to elosulfase alfa. Positivity for neutralizing antibodies was associated with increased drug half-life and decreased drug clearance. Despite formation of antidrug-binding (total antidrug antibodies, TAb) and in vitro neutralizing antibodies (NAb) in all patients, these types of immunogenicity to elosulfase alfa were not correlated with safety or clinical outcomes. In contrast with the reported natural history of Morquio A, no trends toward decreasing endurance, respiratory function, or ability to perform activities of daily living were observed in this cohort over the 5-year period. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone.

PubMed

Maddocks, I; Somogyi, A; Abbott, F; Hayball, P; Parker, D

1996-09-01

We have observed among patients of the Southern Community Hospice Programme that up to 25% experience acute delirium when treated with morphine and improve when the opioid is changed to oxycodone or fentanyl. This study aimed to confirm by a prospective trial that oxycodone produces less delirium than morphine in such patients. Oxycodone was administered by a continuous subcutaneous infusion, as this allowed more flexible and reliable dosing, and patients were monitored for any adverse reactions to the drug. Thirteen patients completed the study. Statistically significant improvements in mental state and nausea and vomiting occurred following a change from morphine to oxycodone. Pain scores improved but did not reach a level of statistical significance. The phenotype status of the patients was tested to establish their capacity to metabolize oxycodone. One patient who did not achieve adequate pain control proved to be a poor metabolizer. These results show that oxycodone administered by the subcutaneous route can provide effective analgesia without significant side effects in patients with morphine-induced delirium. This treatment allows patients to remain more comfortable and lucid in their final days. A small proportion of patients who do not metabolize oxycodone effectively may not receive this benefit.

Insulin pump patient characteristics and glucose control in the hospitalized setting.

PubMed

Kannan, Subramanian; Satra, Ankita; Calogeras, Ellen; Lock, Patricia; Lansang, M Cecilia

2014-05-01

Patients' knowledge of their insulin pumps and glucose control during hospitalization has not been studied. The aim was to study the determinants of glycemic control in patients using continuous subcutaneous insulin infusion (CSII) in the hospital. Three groups of patients were identified: those who did not need any inpatient education and continued on CSII (gorup A), those who received education then continued on CSII (group B), and those for whom CSII was not appropriate and were treated with multiple daily insulin injections (gorup C). We compared the measures of glycemic control between the 3 groups and analyzed which variables impacted glucose control. There were 50 patients, with 51 hospital admissions, 57% males, mean age 48 ± 13 years, 86% had type 1 diabetes (T1DM). The mean DM duration was 26 ± 14 years, mean duration of CSII use was 8.7 ± 6 years, and mean HbA1c was 7.6 ± 1.4%. The mean duration of hospital stay was 5.6 ± 4.6 days. Mean blood glucose (BG) and frequency of hyperglycemia and hypoglycemic events among the 3 groups adjusted for their duration of hospital stay were not statistically different. None of the patients developed diabetic ketoacidosis while using their pump. Stepwise multivariate analysis revealed knowledge of hypoglycemia correction was the single most important predictor of mean BG (P < .001). Patients who received inpatient education performed similarly to patients who did not need inpatient education. Patients who receive inpatient education on CSII fare similar as patients who did not require inpatient education. © 2014 Diabetes Technology Society.

Management of life-threatening calcium channel blocker overdose with continuous veno-venous hemodiafiltration with charcoal hemoperfusion

PubMed Central

Garg, Suneel K.; Goyal, Pankaj K.; Kumar, Rahul; Juneja, Deven; Bhasin, Alka; Singh, Omender

2014-01-01

Cases of calcium channel blocker overdose reported from India are few, and although rare, they are associated with high mortality. Management includes fluids, vasopressors, calcium gluconate or chloride, glucagon infusion, and hyperinsulinemia-euglycemia therapy along with some rescue therapies tried in anecdotal reports. We report here a case of life-threatening overdose of amlodipine with shock, refractory to conventional therapies. Salvage therapy with continuous veno-venous hemodiafiltration using charcoal hemoperfusion with prior infusion of intravenous lipid emulsion resulted in a successful outcome. PMID:24987241

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Chronic intracerebroventricular infusion of nociceptin/orphanin FQ increases food and ethanol intake in alcohol-preferring rats.

PubMed

Cifani, Carlo; Guerrini, Remo; Massi, Maurizio; Polidori, Carlo

2006-11-01

Central administration of low doses of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, have been shown to reduce ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behavior in alcohol preferring rats. The present study evaluated the effect of continuous (7 days) lateral brain ventricle infusions of N/OFQ (0, 0.25, 1, 4, and 8 microg/h), by means of osmotic mini-pumps, on 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats provided 2h or 24h access to it. N/OFQ dose-dependently increased food intake in msP rats. On the other hand, in contrast to previous studies with acute injections, continuous lateral brain ventricle infusion of high doses of N/OFQ increased ethanol consumption when the ethanol solution was available for 24h/day or 2h/day. The present study demonstrates that continuous activation of the opioidergic N/OFQ receptor does not blunt the reinforcing effects of ethanol. Moreover, the data suggest that continuous activation of the opioidergic N/OFQ receptor is not a suitable way to reduce alcohol abuse.

Intraosseous infusion in elective and emergency pediatric anesthesia: when should we use it?

PubMed

Neuhaus, Diego

2014-06-01

Difficulties to establish a venous access may also occur in routine pediatric anesthesia and lead to hazardous situations. Intraosseous infusion is a well tolerated and reliable but rarely used alternative technique in this setting. According to recent surveys, severe complications of intraosseous infusion stay a rare event. Minor complications and problems in getting an intraosseous infusion started on the other side seem to be more common than generally announced. The EZ-IO intraosseous infusion system has received expanded EU CE mark approval for an extended dwell time of up to 72 h and for insertion in pediatric patients in the distal femur. Key values of blood samples for laboratory analysis can be obtained with only 2 ml of blood/marrow waste and do also offer reliable values using an I-Stat point-of-care analyzer. Most problems in using an intraosseous infusion are provider-dependent. In pediatric anesthesia, the perioperative setting should further contribute to reduce these problems. Nevertheless, regular training, thorough anatomical knowledge and prompt availability especially in the pediatric age group are paramount to get a seldom used technique work properly under pressure. More longitudinal data on large cohorts were preferable to further support the safety of the intraosseous infusion technique in pediatric patients.

Modulation of salivation and heartburn in response to the site of acid infusion in the human oesophagus.

PubMed

Dutta, S K; Agrawal, K; Mahmoud, M A

2010-09-01

The pathogenesis of gastro-oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail. To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus. Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t-tests, analysis of variance) were used to determine the significance of results. Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach. These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus. 2010 Blackwell Publishing Ltd.

[Effect of amino acid and glucose infusion on perioperative body temperature and postoperative infection in patients undergoing total knee arthroplasty].

PubMed

Fujita, Yasuki; Yamaguchi, Sayo; Nakamura, Kayo; Horiguchi, Yuu; Ikeda, Daisuke; Kaneko, Michiko; Tomioka, Keiko; Tokunaga, Chiharu; Iwakura, Takeo

2012-01-01

We investigated whether the perioperative amino acid infusion with glucose is effective for preventing perioperative hypothermia and postoperative infection in patients undregoing total knee arthroplasty (TKA). Forty patients undergoing TKA under general anesthesia were enrolled in this study. The patients were randomly allocated to two groups: AA group (n = 22), to which amino acid was infused, and AAGlu group (n = 18), to which amino acid and glucose were infused. The infusions were started before the anesthetic induction. Remifentanil was administered during the surgery, and the dose of remifentanil was adjusted to keep stable hemodynamics. The levels of blood glucose and body temperature were evaluated. We also recorded the frequency of additional use of nonsteroidal anti-inflammatory drugs, the days required until the wound closure, and complications in the post-operative period. The levels of blood glucose in AAGlu group were significantly higher than those of AA group (P < 0.05). However, no significant differences were found in perioperative body temperature, postoperative days required until the wound closure and the frequency of additional use of analgesics between the groups. These results suggest that in patients undergoing TKA receiveing amino acid infusion perioperatively, thermogenic effect and prevention of postoperative infection are similar whether exogenous glucose is infused or not.

A study of estrogen metabolic clearance rates and transfer factors

PubMed Central

Hembree, W. C.; Bardin, C. W.; Lipsett, M. B.

1969-01-01

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E2) and estrone (E1) during 2-hr and 12-hr infusions. When estradiol-3H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-3H levels increased slowly throughout the infusion. When estrone-3H was infused, constancy of estrone-3H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios CE1E2 and CE2E1 continually changed and transfer factors could not be calculated. The apparent “MCR'S” calculated on the basis of the 2-hr studies expressed as liters/24 hr per m2 ±SD were: “MCRE1” (women) 980 ±94, (men) 1170 ±95; “MCRE2” (women) 615 ±17, (men) 830 ±30. The estradiol “MCR's” differed significantly between men and women. “MCRE2” was the same using either estradiol-14C or -3H and was unchanged by the infusion of 170 μg of estradiol daily. Postmenopausal women had estrogen “MCR's” in the same range as premenopausal women. Excess glucocorticoids increased the “MCRE2.” PMID:5822587

Intermittent subcutaneous methadone administration in the management of cancer pain.

PubMed

Centeno, Carlos; Vara, Francisco

2005-01-01

Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the subcutaneous methadone route were minimal. Subcutaneous intermittent administration of methadone appears to be a useful alternative to oral administration in selected clinical situations when oral administration is not feasible.

Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized.

PubMed

Pickup, J C

2015-01-01

Continuous subcutaneous insulin infusion was initially developed as a research procedure in the 1970s but quickly became a routine treatment for selected people with Type 1 diabetes. Continuous subcutaneous insulin infusion and other diabetes technologies, such as continuous glucose monitoring, are now an established and evidence-based part of diabetes care, but there has been some confusion about effectiveness and best use, particularly because of conflicting results from meta-analyses. This is because literature summary meta-analyses (including all trials) are inappropriate for therapeutic and economic decision-making; such meta-analyses should only include trials representative of groups likely to benefit. For example, for continuous subcutaneous insulin infusion, this would be those with continued disabling hypoglycaemia or elevated HbA1c levels. Alternatively, individual patient data meta-analysis allows modelling of covariates that determine effect size, e.g. in the case of continuous glucose monitoring, baseline HbA1c and frequency of sensor usage. Diabetes technology is therefore an example of personalized medicine, where evaluation and use should be both appropriate and targeted. This will also apply to future technologies such as new 'patch' pumps for Type 2 diabetes, closed-loop insulin delivery systems and nanomedicine applications in diabetes that we are currently researching. These include fluorescence lifetime-based non-invasive glucose monitoring and nanoencapsulation of islets for improved post-transplant survival. © 2014 The Author. Diabetic Medicine © 2014 Diabetes UK.

Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Peters, Anne L; Ahmann, Andrew J; Battelino, Tadej; Evert, Alison; Hirsch, Irl B; Murad, M Hassan; Winter, William E; Wolpert, Howard

2016-11-01

To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

Effect of intravenous zoledronic acid infusion on electrocardiographic parameters in patients with osteoporosis.

PubMed

Aktas, I; Nazikoglu, C; Kepez, A; Ozkan, F U; Kaysin, M Y; Akpinar, P; Dogan, Z; Ileri, C; Saymaz, S; Erdogan, O

2016-12-01

We evaluated the effects of zoledronic acid (ZA) therapy on electrocardiographic (ECG) parameters for the first time in the literature. Measurements were performed on ECGs obtained before and after ZA infusion on the same day as well as 1 month after the infusion. ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias. The aim of the present study was to evaluate the early and late effects of ZA therapy on ECG parameters which might be associated with the tendency for atrial and ventricular arrhythmias. Consecutive patients with osteoporosis who were admitted to our clinic between December 2013 and December 2014 and who were scheduled to receive ZA infusion constituted our study population. Twelve-lead surface ECGs were obtained from all patients before and after ZA infusion on the same day as well as 1 month after the infusion. All ECG parameters were measured and compared with each other for each patient. Data of 100 patients were used in the analysis (9 male; 70.5 ± 11.6 years of age). There were no significant differences between repeated measurements regarding pmax, pmin, and p dispersion values. QT max and QT min values were significantly increased after infusion; however, there were no significant changes in QT dispersion, Tp-e interval, and Tp-e dispersion values. ZA infusion did not affect P wave dispersion both at the immediate post-infusion period and 1 month after infusion. QT values were significantly increased early after ZA infusion; however, there were no significant differences in parameters reflecting disparity of ventricular recovery times and transmural dispersion of ventricular repolarization. Based on these observations, it may be suggested that ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Implantation of programmable infusion pumps for insulin delivery in type I diabetic patients.

PubMed

Walter, H; Günther, A; Kronski, D; Flaschenträger, T; Mehnert, H

1989-06-01

Five type I diabetic patients were followed prospectively during treatment with continuous subcutaneous insulin infusion by externally worn pumps and during the first 12 months after implantation of a remote-controlled insulin infusion device (ID1, Siemens AG). Stabilized insulin (Hoe 21 GH, Hoechst AG) was infused intravenously in two and intraperitoneally in three patients. Total observation time was 47.2 patient-months after implantation. Two devices had to be explanted prematurely, one because of a technical failure after 101 days, one due to a skin necrosis over the implant after 236 days. HbA1, frequency of hypoglycemia, total insulin dose, and basal rate infusion did not change after implantation. There was a reduction in the insulin antibodies 6 months after start of intravenous or intraperitoneal insulin delivery. Fasting plasma free insulin levels could be normalized only by intraperitoneal insulin infusion. Although a technical and a surgical problem was observed, our data show the successful implantation and clinical use of programmable dosing devices and stabilized insulin.

Professional ethics. A case study of infusion nurse consultants.

PubMed

Adams, J

2000-01-01

As the healthcare system continues to reform, opportunities exist for infusion nurses to expand their practice into the business world. Traditionally, biomedical ethics have been used in nursing education as a framework for identifying and responding to ethical dilemmas. However, in the business world, professional ethics may be more subtle and insidious. A case study of ten infusion nurse consultants and their experiences with professional ethical issues is presented. Data were obtained using interviews, and content analysis revealed emergent themes of integrity and intuitive knowing with related categories.