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

Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter Perioperative Outcomes Group.

PubMed

Berman, Mitchell F; Iyer, Nikhil; Freudzon, Leon; Wang, Shuang; Freundlich, Robert E; Housey, Michelle; Kheterpal, Sachin

2017-10-01

Continuous medication infusions are commonly used during surgical procedures. Alarm settings for infusion pumps are considered important for patient safety, but limits are not created in a standardized manner from actual usage data. We estimated 90th and 95th percentile infusion rates from a national database for potential use as upper limit alarm settings. We extracted infusion rate data from 17 major hospitals using intraoperative records provided by Multicenter Perioperative Outcomes Group for adult surgery between 2008 and 2014. Seven infusions were selected for study: propofol, remifentanil, dexmedetomidine, norepinephrine, phenylephrine, nitroglycerin, and esmolol. Each dosage entry for an infusion during a procedure was included. We estimated the 50th, 90th, and 95th percentile levels for each infusion across institutions, and performed quantile regression to examine factors that might affect the percentiles rates, such as use in general anesthesia versus sedation. The median 90th and 95th percentile infusion rates (with interquartile range) for propofol were 150 (140-150) and 170 (150-200) μg/kg/min. Quantile regression demonstrated higher 90th and 95th percentile rates during sedation for gastrointestinal endoscopy than for all surgical procedures performed under general anesthesia. For selected vasoactive medications, the corresponding median 90th and 95th percentile rates (with interquartile range) were norepinephrine 14.0 (9.8-18.1) and 18.3 (12.6-23.9) μg/min, and phenylephrine 60 (55-80) and 80 (75-100) μg/min. Alarm settings based on infusion rate percentile limits would be triggered at predictable rates; ie, the 95th percentile would be exceeded and an alarm sounded during 1 in 20 infusion rate entries. As a result, institutions could establish pump alarm settings consistent with desired alarm frequency using their own or externally validated usage data. Further study will be needed to determine the optimal percentile for infusion alarm settings.

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

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.

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.

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

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.

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

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.

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.

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.

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.

Low-Dose Ketamine Infusion for Emergency Department Patients with Severe Pain.

PubMed

Ahern, Terence L; Herring, Andrew A; Miller, Steve; Frazee, Bradley W

2015-07-01

Use of low-dose ketamine infusions in the emergency department (ED) has not previously been described, despite routine use in perioperative and other settings. Our hypothesis was that a low-dose ketamine bolus followed by continuous infusion would 1) provide clinically significant and sustained pain relief; 2) be well tolerated; and 3) be feasible in the ED. We prospectively administered 15 mg intravenous ketamine followed immediately by continuous ketamine infusion at 20 mg/h for 1 hour. Optional morphine (4 mg) was offered at 20, 40, and 60 minutes. Pain intensity, vitals signs, level of sedation, and adverse reactions were assessed for 120 minutes. A total of 38 patients were included with a median initial numerical rating scale (NRS) pain score of 9. At 10 minutes, the median reduction in pain score was 4, with 7 patients reporting a score of 0. At 60 and 120 minutes, 25 and 26 patients, respectively, reported clinically significant pain reduction (decrease NRS score > 3). Heart rate, blood pressure, respiratory rate, and oxygen saturation remained stable. Mild or moderate side effects including dizziness, fatigue, and headache were common. Patient satisfaction was high; 85% reported they would have this medication again for similar pain. A low-dose ketamine infusion protocol provided significant pain relief with mostly mild side effects and no severe adverse events. Wiley Periodicals, Inc.

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.

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.

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.

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. 

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.

Aggressive Treatment of Life-Threatening Hypophosphatemia During Recovery From Fulminant Hepatic Failure: A Case Report.

PubMed

Bissell, Brittany D; Davis, Jason E; Flannery, Alexander H; Adkins, David A; Thompson Bastin, Melissa L

2018-06-01

Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.

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

Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit.

PubMed

Honey, Brooke L; Harrison, Donald L; Gormley, Andrew K; Johnson, Peter N

2010-01-01

Dexmedetomidine is an α(2)-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events. Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose. Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events. Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

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.

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.

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

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 ).

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

Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic.

PubMed

Diamond, Peter R; Farmery, Andrew D; Atkinson, Stephanie; Haldar, Jag; Williams, Nicola; Cowen, Phil J; Geddes, John R; McShane, Rupert

2014-06-01

Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4-7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25-168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop. © The Author(s) 2014.

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.

Continuous-infusion local anesthetic pain pump use and seroma formation with abdominal procedures: is there a correlation?

PubMed

Smith, Melissa M; Hovsepian, Raffi V; Markarian, Mark K; Degelia, Amber L; Paul, Malcolm D; Evans, Gregory R D; Wirth, Garrett A

2008-11-01

Seroma formation is the most commonly occurring complication in plastic surgery abdominal procedures. Continuous local anesthetic pain pump delivery systems are often used to decrease postoperative pain. An unreported concern with use of these devices in abdominal procedures is the effect of continuous fluid infiltration of the surgical site and a possible increase in the incidence of seroma formation. The authors performed a retrospective chart review to evaluate all patients (n = 159) who underwent abdominal procedures (abdominoplasty, panniculectomy, and transverse rectus abdominis myocutaneous flap harvest) over a 3-year period. Patient charts were evaluated for sex, age, body mass index, procedure performed, surgeon, operation length, pain pump use, postoperative seroma formation, and any complications. In cases with pain pump use, catheter placement location, anesthetic medication and strength, continuous-infusion rate, and duration of pain pump use were also reviewed. If a postoperative seroma formation was identified, treatment and outcomes were also recorded. The overall seroma formation rate was 11.3 percent (18 of 159 patients). Other complications occurred at a rate of 2.5 percent (four of 159). The incidence of seroma was 11.0 percent (11 of 100) in patients with pain pump use versus 11.9 percent (7 of 59) in those who did not use a pain pump. There was no statistically significant difference (p = 0.9) in the incidence of seroma formation between those who did and did not use a pain pump device. There was no correlation between increased rate of seroma formation and use of a continuous-infusion local anesthetic pain pump system in our patient population.

[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.

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.

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.

Insulin pump therapy: what is the evidence for using different types of boluses for coverage of prandial insulin requirements?

PubMed

Heinemann, Lutz

2009-11-01

Bolus infusion of insulin along with a meal is a standard procedure with continuous subcutaneous insulin infusion. Modern insulin pumps allow applying this bolus in four different ways: infusion of the total dose at once or splitting the dose into two boluses, infusion of a part of the bolus in the usual manner plus infusion of the other part over a prolonged period of time (with a higher infusion rate than the basal rate), or infusion of the total dose in the form of an elevated basal rate. Depending on the composition of the given meal and its glycemic index, this is an attempt to match the circulating insulin levels to the rate of glucose absorption from the gut in order to minimize postprandial glycemic excursions. However, in the framework of evidence-based medicine, the benefits of this approach should be proven in appropriately designed clinical studies. Performance of meal-related studies requires careful attention to many aspects in order to allow meaningful evaluation of a given intervention (i.e., type of bolus). Critical evaluation of the clinical experimental studies and the one clinical study published about the impact of different types of boluses on postprandial metabolic control revealed fundamental shortcomings in study design and performance in these studies. Insufficient establishment of comparable preprandial glycemia and insulinemia on the different study days within and between the patients studied is one key aspect. Therefore, the recommendation made in most of these studies (i.e., use of dual-wave bolus) has to be accepted with care, until we have better evidence.

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.

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.

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.

Role of rumen butyrate in regulation of nitrogen utilization and urea nitrogen kinetics in growing sheep.

PubMed

Agarwal, U; Hu, Q; Baldwin, R L; Bequette, B J

2015-05-01

Butyrate, a major rumen VFA, has been indirectly linked to enhancement of urea recycling on the basis of increased expression of urea transporter in the rumen epithelia of steers fed a rumen butyrate-enhancing diet. Two studies were conducted to quantify the effect of elevated rumen butyrate concentrations on N balance, urea kinetics and rumen epithelial proliferation. Wether sheep (n= 4), fitted with a rumen cannula, were fed a pelleted ration (∼165 g CP/kg DM, 10.3 MJ ME/kg DM) at 1.8 × ME requirement. In Exp. 1, sheep were infused intraruminally with either an electrolyte buffer solution (Con-Buf) or butyrate dissolved in the buffer solution (But-Buf) during 8-d periods in a balanced crossover design. In Exp. 2, sheep were infused intraruminally with either sodium acetate (Na-Ac) or sodium butyrate (Na-But) for 9 d. All solutions were adjusted to pH 6.8 and 8.0 in Exp. 1 and 2, respectively, and VFA were infused at 10% of ME intake. [15N2] urea was continuously infused intravenously for the last 5 d of each period, and total urine and feces were collected. In Exp. 1, 2H5-phenylalanine was continuously infused intravenously over the last 12 h, after which a biopsy from the rumen papillae was taken for measurement of fractional protein synthesis rate (FSR). Butyrate infusion treatments increased (P = 0.1 in Exp. 1; P < 0.05 in Exp. 2) the proportion of rumen butyrate, and acetate infusion increased (P < 0.05) rumen acetate. All animals were in positive N balance (4.2 g N/d in Exp. 1; 7.0 g N/d in Exp. 2), but no difference in N retention was observed between treatments. In Exp. 2, urea entry (synthesis) rate was reduced ( < 0.05) by Na-But compared with the Na-Ac control. In Exp. 1, although But-Buf infusion increased the FSR of rumen papillae (35.3% ± 1.08%/d vs. 28.7% ± 1.08%/d; P < 0.05), urea kinetics were not altered by But-Buf compared with Con-Buf. These studies are the first to directly assess the role of butyrate in urea recycling and its effects on rumen papillae protein turnover in growing lambs. Under the feeding conditions used and the rate of continuous butyrate infusion into the rumen in the present studies, butyrate does not affect overall N retention in growing sheep. However, butyrate may play a role in the redistribution of urea N fluxes in the overall scheme of N metabolism.

Cost-effectiveness analysis of levobupivacaine 0.5 %, a local anesthetic, infusion in the surgical wound after modified radical mastectomy.

PubMed

Ferreira Laso, Lourdes; López Picado, Amanda; Antoñanzas Villar, Fernando; Lamata de la Orden, Laura; Ceballos Garcia, Mar; Ibañez López, Carolina; Pipaon Ruilope, Lorena; Lamata Hernandez, Felix; Valero Martinez, Cesar; Aizpuru, Felipe; Hernandez Chaves, Roberto

2015-09-01

Effective treatment of postoperative pain contributes to decreasing the rate of complications as well as the total cost of the operated patients. The aim of this study was to analyze the costs and the efficiency of use of continuous infusion of levobupivacaine 0.5 % with the help of an infusion pump in modified radical mastectomy. A cost calculation of the analgesic procedures (continuous infusion of levobupivacaine 0.5 % [levobupivacaine group (LG)] or saline [saline group (SG)] (2 ml/h 48 h) has been carried out based on the data of a previous clinical trial (double-blind randomized study) of patients who underwent modified radical mastectomy surgery. The measure of the effectiveness was the point reduction of pain derived from the verbal numeric rating scale (VNRS). The usual incremental cost-effectiveness ratio (ICER) was performed. Considering only the intravenous analgesia, overall costs were lower in LG, as less analgesia was used (EUR14.06 ± 7.89 vs. 27.47 ± 14.79; p < 0.001). In this study the costs of the infusion pump were not calculated as it was used by both groups and they offset each other. However, if the infusion pump costs were included, costs would be higher in the LG, (EUR91.89 ± 7.89 vs. 27.47 ± 14.79; p < 0.001) and then the ICER was -8.51, meaning that for every extra point of decrease in the pain verbal numerical rating score over the 2-day period, the cost increased by EUR8.51. Infiltration of local anesthetics is an effective technique for controlling postoperative pain and the associated added costs are relatively low in relation to the total cost of mastectomy, therefore providing patients with a higher quality of care in the prevention of pain. clinicaltrials.gov: reference number NCT01389934. http://clinicaltrials.gov/show/NCT01389934

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

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.

Cardiovascular, respiratory, electrolyte and acid-base balance during continuous dexmedetomidine infusion in anesthetized dogs.

PubMed

Congdon, Jonathan M; Marquez, Megan; Niyom, Sirirat; Boscan, Pedro

2013-09-01

To evaluate the cardiovascular, respiratory, electrolyte and acid-base effects of a continuous infusion of dexmedetomidine during propofol-isoflurane anesthesia following premedication with dexmedetomidine. Prospective experimental study. Five adult male Walker Hound dogs 1-2 years of age averaging 25.4 ± 3.6 kg. Dogs were sedated with dexmedetomidine 10 μg kg(-1) IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg(-1) ) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg(-1) IV was administered over 5 minutes followed by an infusion of 0.5 μg kg(-1)  hour(-1) . Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid-base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD. No statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute(-1) , 78 ± 18 beats minute(-1) and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute(-1) , 78 ± 14 beats minute(-1) and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO2 , PaCO2 , pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion. Dexmedetomidine infusion using a loading dose of 0.5 μg kg(-1) IV followed by a constant rate infusion of 0.5 μg kg(-1)  hour(-1) does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg(-1) , in propofol-isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Randomized Trial of Infusion Set Function: Steel Versus Teflon

PubMed Central

Patel, Parul J.; Benasi, Kari; Ferrari, Gina; Evans, Mark G.; Shanmugham, Satya; Wilson, Darrell M.

2014-01-01

Abstract Background: This study compared infusion set function for up to 1 week using either a Teflon® (Dupont™, Wilmington, DE) catheter or a steel catheter for insulin pump therapy in type 1 diabetes mellitus. Subjects and Methods: Twenty subjects participating in a randomized, open-labeled, crossover study were asked to wear two Quick-Set® and two Sure-T® infusion sets (both from Medtronic Minimed, Northridge, CA) until the infusion set failed or was worn for 1 week. All subjects wore a MiniMed continuous glucose monitoring system for the duration of the study. Results: One subject withdrew from the study. There were 38 weeks of Sure-T wear and 39 weeks of Quick-Set wear with no difference in the survival curves of the infusion sets. There was, however, a 15% initial failure rate with the Teflon infusion set. After 7 days, both types of infusion sets had a 64% failure rate. Overall, 30% failed because of hyperglycemia and a failed correction dose, 13% were removed for pain, 10% were pulled out by accident, 10% had erythema and/or induration of>10 mm, 5% fell out because of loss of adhesion, and 4% were removed for infection. The main predictor of length of wear was the individual subject. There was no increase in hyperglycemia or daily insulin requirements when an infusion set was successfully used for 7 days (n=25 of 77 weeks). Conclusions: We found no difference between steel and Teflon infusion sets in their function over 7 days, although 15% of Teflon sets failed because of kinking on insertion. The strongest predictor of prolonged 7-day infusion set function was the individual subject, not the type of infusion set. PMID:24090124

Home therapy with continuous infusion of factor VIII after minor surgery or serious haemorrhage.

PubMed

Varon, D; Schulman, S; Bashari, D; Martinowitz, U

1996-10-01

Administration of factor VIII (F VIII) concentrates by continuous infusion is now routinely used at several haemophilia centers but almost exclusively for hospitalized patients. We evaluated various aspects of home therapy with continuous infusion of an immunoaffinity purified F VIII concentrate (Monoclate P®, Armour) in patients who would normally have been treated with high doses in bolus injections or with continuous infusion as in-patients. Twenty haemophilia A patients, eight after minor surgery and 12 for serious haemorrhage, received continuous infusion with undiluted F VIII by a minipump for a mean of 0.9 days in the hospital, followed by 3.3 days at home. Infusion bags were exchanged every 2.5 days. No haemorrhagic complications occurred, and five haemorrhages that had been resistant to treatment with bolus injections responded promptly to the continuous infusion. There were no technical problems and patient compliance and acceptance was good. We find this mode of therapy safe, efficacious and convenient for the patients as well as for the staff.

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC.

PubMed

Uehara, Roberto Palermo; Sá, Victor Hugo Lara de; Koshimura, Erika Tae; Prudente, Fernanda Vilas Boas; Tucunduva, Luciana Tomanik Cardozo de Mello; Gonçalves, Marina Sahade; Samano, Eliana Sueco Tibana; del Giglio, Auro

2005-09-01

Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

PubMed

Daniel, Shoshana R; McDermott, John D; Le, Cathy; Pierce, Christine A; Ziskind, Michael A; Ellis, Lorie A

2018-05-25

To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. Findings may not be representative of care delivery for all RA infusion practices or RA patients. Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

[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.

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.

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

Randomized trial of intermittent or continuous amnioinfusion for variable decelerations.

PubMed

Rinehart, B K; Terrone, D A; Barrow, J H; Isler, C M; Barrilleaux, P S; Roberts, W E

2000-10-01

To determine whether continuous or intermittent bolus amnioinfusion is more effective in relieving variable decelerations. Patients with repetitive variable decelerations were randomized to an intermittent bolus or continuous amnioinfusion. The intermittent bolus infusion group received boluses of 500 mL of normal saline, each over 30 minutes, with boluses repeated if variable decelerations recurred. The continuous infusion group received a bolus infusion of 500 mL of normal saline over 30 minutes and then 3 mL per minute until delivery occurred. The ability of the amnioinfusion to abolish variable decelerations was analyzed, as were maternal demographic and pregnancy outcome variables. Power analysis indicated that 64 patients would be required. Thirty-five patients were randomized to intermittent infusion and 30 to continuous infusion. There were no differences between groups in terms of maternal demographics, gestational age, delivery mode, neonatal outcome, median time to resolution of variable decelerations, or the number of times variable decelerations recurred. The median volume infused in the intermittent infusion group (500 mL) was significantly less than that in the continuous infusion group (905 mL, P =.003). Intermittent bolus amnioinfusion is as effective as continuous infusion in relieving variable decelerations in labor. Further investigation is necessary to determine whether either of these techniques is associated with increased occurrence of rare complications such as cord prolapse or uterine rupture.

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.

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 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.

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.

Insulin production rate in normal man as an estimate for calibration of continuous intravenous insulin infusion in insulin-dependent diabetic patients.

PubMed

Waldhäusl, W K; Bratusch-Marrain, P R; Francesconi, M; Nowotny, P; Kiss, A

1982-01-01

This study examines the feasibility of deriving the 24-h insulin requirement of insulin-dependent diabetic patients who were devoid of any endogenous insulin release (IDD) from the insulin-production rate (IPR) of healthy man (basal, 17 mU/min; stimulated 1.35 U/12.5 g glucose). To this end, continuous intravenous insulin infusion (CIVII) was initiated at a precalculated rate of 41.2 +/- 4.6 (SD) U/24 h in IDD (N - 12). Blood glucose profiles were compared with those obtained during intermittent subcutaneous (s.c.) insulin therapy (IIT) and those of healthy controls (N = 7). Regular insulin (Hoechst CS) was infused with an adapted Mill Hill Infuser at a basal infusion rate of 1.6 U/h (6:00 a.m. to 8:00 p.m.), and of 0.8 U/h from 8:00 p.m. to 6:00 a.m. Preprandial insulin (3.2-6.4 U) was added for breakfast, lunch, and dinner. Daily individual food intake totaled 7688 +/- 784 kJ (1836 +/- 187 kcal)/24 h including 184 +/- 37 g of glucose. Proper control of blood glucose (BG) (mean BG 105 +/- 10 mg/dl; mean amplitude of glycemic excursions 54 +/- 18 mg/dl; and 1 h postprandial BG levels not exceeding 160 mg/dl) and of plasma concentrations of beta-hydroxybutyrate and lactate was maintained by 41.4 +/- 4.4 U insulin/24 h. Although BG values only approximated the upper normal range as seen in healthy controls, they were well within the range reported by others during CIVII. Therefore, we conclude that in adult IDD completely devoid of endogenous insulin (1) the IPR of normal man can be used during CIVII as an estimate for the patient's minimal insulin requirement per 24 h, and (2) this approach allows for a blood glucose profile close to the upper range of a normal control group. Thus, deriving a patient's daily insulin dose from the insulin production rate of healthy man may add an additional experimental protocol which aids in making general calculations of a necessary insulin dose instead of using trial and error or a closed-loop insulin infusion system.

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

Antibody-containing cell response in lymph of sheep after intra-intestinal infusion of ovalbumin with and without DEAE-dextran.

PubMed Central

Beh, K J

1979-01-01

The output of antibody-containing cells (ACC) was monitored in efferent ileal lymph after continuous infusion of ovalbumin into the ileum of sheep with and without the adjuvant DEAE-dextran. When ovalbumin was infused at the slow rate of 5 ml/h, maximum outputs of 2.9 x 10(5) and 2.4 x 10(5 ACC/h were observed on days 9 and 16 respectively. When infused at the faster rate of 15 ml/h, peak levels of 6.9 x 10(5) and 11.7 x 10(5) ACC/h were recorded on days 10 and 16 respectively. The maximum response was substantially enhanced when ovalbumin was infused simultaneously with DEAE-dextran when a mean output of 51.7 x 10(5) ACC/h occurred on day 10. With all treatments the distribution of ACC amongst various immunoglobulin classes was similar. During the first few days of the response IgM-specific ACC predominated and later IgG1-specific ACC were most abundant. Throughout the response a substantial proportion (10-81%) of ACC in efferent ileal lymph were IgA-specific. PMID:572818

A Mobile Device App to Reduce Medication Errors and Time to Drug Delivery During Pediatric Cardiopulmonary Resuscitation: Study Protocol of a Multicenter Randomized Controlled Crossover Trial.

PubMed

Siebert, Johan N; Ehrler, Frederic; Lovis, Christian; Combescure, Christophe; Haddad, Kevin; Gervaix, Alain; Manzano, Sergio

2017-08-22

During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusions is complex and time-consuming. The need for individual specific weight-based drug dose calculation and preparation places children at higher risk than adults for medication errors. Following an evidence-based and 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. In a prior single center randomized controlled trial, medication errors were reduced from 70% to 0% by using PedAMINES when compared with conventional preparation methods. The purpose of this study is to determine whether the use of PedAMINES in both university and smaller hospitals reduces medication dosage errors (primary outcome), time to drug preparation (TDP), and time to drug delivery (TDD) (secondary outcomes) during pediatric CPR when compared with conventional preparation methods. This is a multicenter, prospective, randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drug infusion rate table in the preparation of continuous drug infusion. The evaluation setting uses a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin. The study involving 120 certified nurses (sample size) will take place in the resuscitation rooms of 3 tertiary pediatric emergency departments and 3 smaller hospitals. After epinephrine-induced return of spontaneous circulation, nurses will be asked to prepare a continuous infusion of dopamine using either PedAMINES (intervention group) or the infusion table (control group) and then prepare a continuous infusion of norepinephrine by crossing the procedure. The primary outcome is the medication dosage error rate. The secondary outcome is the time in seconds elapsed since the oral prescription by the physician to drug delivery by the nurse in each allocation group. TDD includes TDP. Stress level during the resuscitation scenario will be assessed for each participant by questionnaire and recorded by the heart rate monitor of a fitness watch. The study is formatted according to the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of Electronic and Mobile Health Applications and Online TeleHealth (CONSORT-EHEALTH) and the Reporting Guidelines for Health Care Simulation Research. Enrollment and data analysis started in March 2017. We anticipate the intervention will be completed in late 2017, and study results will be submitted in early 2018 for publication expected in mid-2018. Results will be reported in line with recommendations from CONSORT-EHEALTH and the Reporting Guidelines for Health Care Simulation Research . This paper describes the protocol used for a clinical trial assessing the impact of a mobile device app to reduce the rate of medication errors, time to drug preparation, and time to drug delivery during pediatric resuscitation. As research in this area is scarce, results generated from this study will be of great importance and might be sufficient to change and improve the pediatric emergency care practice. ClinicalTrials.gov NCT03021122; https://clinicaltrials.gov/ct2/show/NCT03021122 (Archived by WebCite at http://www.webcitation.org/6nfVJ5b4R). ©Johan N Siebert, Frederic Ehrler, Christian Lovis, Christophe Combescure, Kevin Haddad, Alain Gervaix, Sergio Manzano. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.08.2017.

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.

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.

Key variables influencing patterns of lava dome growth and collapse

NASA Astrophysics Data System (ADS)

Husain, T.; Elsworth, D.; Voight, B.; Mattioli, G. S.; Jansma, P. E.

2013-12-01

Lava domes are conical structures that grow by the infusion of viscous silicic or intermediate composition magma from a central volcanic conduit. Dome growth can be characterized by repeated cycles of growth punctuated by collapse, as the structure becomes oversized for its composite strength. Within these cycles, deformation ranges from slow long term deformation to sudden deep-seated collapses. Collapses may range from small raveling failures to voluminous and fast-moving pyroclastic flows with rapid and long-downslope-reach from the edifice. Infusion rate and magma rheology together with crystallization temperature and volatile content govern the spatial distribution of strength in the structure. Solidification, driven by degassing-induced crystallization of magma leads to the formation of a continuously evolving frictional talus as a hard outer shell. This shell encapsulates the cohesion-dominated soft ductile core. Here we explore the mechanics of lava dome growth and failure using a two-dimensional particle-dynamics model. This meshless model follows the natural evolution of a brittle carapace formed by loss of volatiles and rheological stiffening and avoids difficulties of hour-glassing and mesh-entangelment typical in meshed models. We test the fidelity of the model against existing experimental and observational models of lava dome growth. The particle-dynamics model follows the natural development of dome growth and collapse which is infeasible using simple analytical models. The model provides insight into the triggers that lead to the transition in collapse mechasnism from shallow flank collapse to deep seated sector collapse. Increase in material stiffness due to decrease in infusion rate results in the transition of growth pattern from endogenous to exogenous. The material stiffness and strength are strongly controlled by the magma infusion rate. Increase in infusion rate decreases the time available for degassing induced crystallization leading to a transition in the growth pattern, while a decrease in infusion rate results in larger crystals causing the material to stiffen leading to formation of spines. Material stiffness controls the growth direction of the viscous plug in the lava dome interior. Material strength and stiffness controled by rate of infusion influence lava dome growth more significantly than coefficient of frictional of the talus.

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine.

PubMed

Drexel, H; Dzien, A; Spiegel, R W; Lang, A H; Breier, C; Abbrederis, K; Patsch, J R; Braunsteiner, H

1989-02-01

In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty-eight in-patients with cancer pain received a short-term infusion lasting 2-42 days, and 8 out-patients underwent long-term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P less than 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5-48 mg (median 19 mg) of morphine was required daily, significantly (P less than 0.001) less than the 10-90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long-term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low-dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

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.

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

Effect of flow rate and insulin priming on the recovery of insulin from microbore infusion tubing.

PubMed

Fuloria, M; Friedberg, M A; DuRant, R H; Aschner, J L

1998-12-01

A retrospective medical record review of 13 consecutive, hyperglycemic, extremely low birth weight (ELBW) infants treated with continuous insulin infusions revealed a 14- to 24-hour delay (mean, 19 hours) in blood glucose normalization despite stepwise increases in insulin infusion rates. This in vitro study examined the effects of flow rate and insulin priming on insulin recovery from polyvinyl chloride (PVC) tubing and polyethylene (PE)-lined PVC tubing infused with a standard insulin stock solution. Stock insulin solution (0.2 U/mL) was infused through microbore PVC or PE-lined tubing at flow rates of 0.05 and 0.2 mL/h. To determine if saturation of nonspecific binding sites would alter effluent insulin concentration, we compared insulin recovery from tubing previously flushed with the stock solution and tubing primed with 5 U/mL of insulin for 20 minutes. Effluent samples, which were collected at baseline and at six time points during a 24-hour period, were immediately frozen at -20 degreesC. Insulin concentration was measured by IMx immunoassay. Data were analyzed using general linear modeling with repeated measures. At 0.05 mL/h flow rate, insulin recovery from unprimed PVC tubing at 1, 2, 4, and 8 hours was 17%, 11%, 27%, and 55%, respectively, with 100% recovery at 24 hours. From insulin-primed tubing, insulin recovery was approximately 70% at 1, 2, and 4 hours, and close to 100% at 8 hours. At a faster flow rate of 0.2 mL/h, insulin recovery at 1, 2, 4, and 8 hours was 22%, 38%, 67%, and 75% vs 42%, 85%, 91% and 95% from unprimed and insulin-primed PVC tubing, respectively. Similar results were obtained from unprimed and insulin-primed PE-lined tubing at 0.2 mL/h flow rate. Priming of microbore tubing with 5 U/mL of insulin solution for 20 minutes to block nonspecific binding sites enhances delivery of a standard insulin stock at infusion rates typically used to treat hyperglycemic ELBW infants. We conclude that priming the tubing with a higher concentration of insulin before initiation of standard insulin infusion therapy should accelerate achievement of steady-state insulin delivery and correction of hyperglycemia in ELBW infants.

Continuous subcutaneous insulin infusion: Special needs for children.

PubMed

Adolfsson, Peter; Ziegler, Ralph; Hanas, Ragnar

2017-06-01

Continuous subcutaneous insulin infusion (CSII) is a very common therapy for children with type 1 diabetes. Due to physiological differences they have other requirements for their insulin pump than adults. The main difference is the need for very low basal rates. Even though most available insulin pumps reach a high accuracy at usual basal rates, accuracy decreases for lower rates. In addition, the lowest delivered amount at 1 time is limiting the fine tuning of the basal rate as well as the option for temporary basal rates. Alarms in case of occlusions depend on accumulation of a certain amount of insulin in the catheter, and therefore the time until such an alarm is triggered is much longer with lower basal rates. Accordingly, the risk for hyperglycemia developing into diabetic ketoacidosis increases. The availability of bolus advisors facilitates the calculation of meal and correction boluses for children and their parents. However, there are some differences between the calculators, and the settings that the calculation is based on are very important. Better connectivity, for example with a system for continuous glucose monitoring, might help to further increase safety in the use of CSII in children. When selecting an insulin pump for a child, the features and characteristics of available pumps should be properly compared to ensure an effective and safe therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Cardiovascular effects of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane.

PubMed

Araújo, Marcelo A; Dias, Bianca P; Bovino, Fernanda; Deschk, Maurício; Abimussi, Caio Jx; Oliva, Valéria Nls; Rodrigues, Celso A; Santos, Paulo Sp

2014-03-01

To assess the cardiovascular changes of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane during mechanical ventilation. Prospective, randomized, cross-over, experimental trial. A total of eight, healthy, male Holstein calves, aged 10 ± 1 months and weighing 114 ± 11 kg were included in the study. Calves were administered xylazine followed by ketamine and midazolam, orotracheal intubation and maintenance on isoflurane (1.3%) using mechanical ventilation. Forty minutes after induction, lidocaine (2 mg kg⁻¹ bolus) or an equivalent volume of saline (0.9%) was administered IV followed by a continuous rate infusion (100 μg kg⁻¹ minute⁻¹) of lidocaine (treatment L) or saline (treatment C). Heart rate (HR), systolic, diastolic and mean arterial pressures (SAP, DAP and MAP), central venous pressure (CVP), mean pulmonary arterial pressure (mPAP), pulmonary arterial occlusion pressure (PAOP), cardiac output, end-tidal carbon dioxide (Pe'CO2 ) and core temperature (CT) were recorded before lidocaine or saline administration (Baseline) and at 20-minute intervals (T20-T80). Plasma concentrations of lidocaine were measured in treatment L. The HR was significantly lower in treatment L compared with treatment C. There was no difference between the treatments with regards to SAP, DAP, MAP and SVRI. CI was significantly lower at T60 in treatment L when compared with treatment C. PAOP and CVP increased significantly at all times compared with Baseline in treatment L. There was no significant difference between times within each treatment and between treatments with regards to other measured variables. Plasma concentrations of lidocaine ranged from 1.85 to 2.06 μg mL⁻¹ during the CRI. At the studied rate, lidocaine causes a decrease in heart rate which is unlikely to be of clinical significance in healthy animals, but could be a concern in compromised animals. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

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

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.

Treatment of Parkinson's disease could be regulated by movement sensors: subcutaneous infusion of varying apomorphine doses according to the intensity of motor activity.

PubMed

Rodríguez-Molinero, Alejandro; Pérez-Martínez, David A; Català, Andreu; Cabestany, Joan; Yuste, Antonio

2009-04-01

Most recent therapeutic solutions to treat Parkinson's disease seek continuous administration of dopaminergic agonists, as for example rigotine patches or apomorphine infusion pumps. Such drug-delivery devices are aimed at preventing fluctuations in drug plasma levels, which could cause certain symptoms such as wearing-off periods or dyskinesia. However, we postulate that drug plasma levels should not keep constant, but rather adjust to the varying intensity of the different user's activities. The rationale behind this is that the drug amount appropriate to treat a patient at rest is lower than that required to treat the same patient when engaged in physical activity. We propose dynamic real-time dose adjustment, so that the doses increase as the patient starts performing physical activity, thus preventing off periods such as "freeze" phenomenon, and the doses reduce during the resting periods, thus preventing adverse effects. Small portable movement sensors are currently available, which detect the amount and type of activity in a continuous way. Combining such technology with infusion pumps to produce modified pumps capable of adjusting the infusion rate to the user's activity, seems to be feasible in the short-term.

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.

Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

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

Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control.

PubMed

Rasmussen, Keith G

2014-08-01

To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

The U.S. home infusion market.

PubMed

Monk-Tutor, M R

1998-10-01

Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

[Continuous drug infusion in terminal cancer].

PubMed

Ottesen, S; Manger, A T; Monrad, L

1992-05-30

Today's technology provides portable pumps which facilitate continuous infusion of drugs to relieve suffering in terminal disease. Subcutaneous and epidural infusion is now frequently used in our hospital. The most common indications are gastrointestinal obstruction, impaired absorption of drugs, refractory side effects of oral medication or poor compliance because good pain relief is no longer possible orally. During the last days of life, this method may be the only possible approach to good comfort and relief from terminal agitation and anxiety. Of the patients referred to the advisory group for seriously ill and dying in 1990, 64% received subcutaneous infusions and 15% epidural infusions during the last days or weeks of life. Continuous infusion of drugs from portable pumps has become an almost indispensible method of treatment in an ordinary clinic.

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.

Pantoprazole before Endoscopy in Patients with Gastroduodenal Ulcer Bleeding: Does the duration of Infusion and Ulcer Location Influence the Effects?

PubMed Central

Rácz, Istvan; Szalai, Milan; Dancs, Nora; Kárász, Tibor; Szabó, Andrea; Csöndes, Mihaly; Horváth, Zoltan

2012-01-01

The aim of this study was to investigate the effect of preemptive pantoprazole infusion on early endoscopic findings in patients with acute ulcer bleeding. Records of 333 patients admitted with acute ulcer bleeding were analyzed. Ulcer bleeders were given either 80 mg bolus of pantoprazole followed by continuous infusion of 8 mg per hour or saline infusion until endoscopy. In 93 patients saline infusion whereas in 240 patients bolus plus infusion of pantoprazole was administrated with mean (±SD) durations of 5.45 ± 12.9 hours and 6.9 ± 13.2 hours, respectively (P = 0.29). Actively bleeding ulcers were detected in 46/240 (19.2%) of cases in the pantoprazole group as compared with 23/93 (24.7%) in the saline infusion group (P = 0.26). Different durations of pantoprazole infusion (0–4 hours, >4 hours, and >6 hours) had no significant effect on endoscopic and clinical outcome parameters in duodenal ulcer bleeders. Gastric ulcer bleeders on pantoprazole infusion longer than 4 and 6 hours before endoscopy had actively bleeding ulcers in 4.3% and 5% compared to the 19.5% active bleeding rate in the saline group (P = 0.02 and P = 0.04). Preemptive infusion of high-dose pantoprazole longer than 4 hours before endoscopy decreased the ratio of active bleeding only in gastric but not in duodenal ulcer patients. PMID:23125849

Comparison of clinical efficacy among remifentanil, nicardipine, and remifentanil plus nicardipine continuous infusion for hypotensive anesthesia during arthroscopic shoulder surgery.

PubMed

Kim, Joon Yub; Song, Seong Hun; Cho, Jae Ho; Cho, Hyung Rae

2017-01-01

Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility. The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil, nicardipine, and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery. For this study, we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and randomly allocated them into remifentanil (group R, n = 15), nicardipine (group N, n = 15), and remifentanil plus nicardipine (group RN, n = 15) groups. During the surgeries, these drugs were administered with continuous infusion. We analyzed the mean arterial pressure (MAP) and heart rate during surgery, stay time in the recovery room, visual analogue scale (VAS) scores, use of antiemetics in the recovery room, and postoperative blood urea nitrogen and creatinine changes. The VAS score in the recovery room was higher for group R (mean 5.6, SD 1.4) than for groups N (mean 3.9, SD 0.9) and RN (mean 4.0, SD 1.1; p = 0.000). There were no statistical differences regarding other clinical variables among the three groups (all p > 0.05) except for MAP at 120 min of surgery between groups N and RN (N: 84.67 (SD 10.7) mmHg, RN: 65.4 (SD 9.2) mmHg, p = 0.027). The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit.

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.

Administration of drugs by infusion pumps in palliative medicine.

PubMed

Thorsen, A B; Yung, N S; Leung, A C

1994-03-01

A retrospective study was carried out in 100 adult patients with advanced malignant disease. They were given subcutaneous continuous infusions of medication for symptom relief. The drugs were administered through a butterfly needle inserted subcutaneously in the anterior chest wall using a battery-operated infusion pump. The indications for using this technique were inability to swallow due to deteriorating general condition, oesophageal obstruction, intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor pain control with oral opiates. All patients received morphine; other drugs administered through the syringe driver included hyoscine, metoclopramide, cyclizine, dexamethasone and midazolam. Ninety-four patients continued subcutaneous infusion until death. The mean duration of treatment was 9.1 days. The treatment was well tolerated by the patients and controlled their symptoms satisfactorily in the great majority. The use of continuous subcutaneous infusion via a syringe driver gives good symptom control. In the last days of life when the patients have difficulty tolerating oral medication, continuous subcutaneous infusion is a superior alternative to frequent intermittent parenteral injections.

[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.

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.

Effect of infusion regime on doxorubicin pharmacokinetics in the cat.

PubMed

Hahn, K A; Frazier, D L; Cox, S K; Legendre, A M

1997-01-01

In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin infusion (mg per minute per m2 or mg per minute per kg) correlated positively with clearance and the distribution rate constant alpha, and it inversely correlated with area under the plasma concentration versus time curve (AUC). These findings suggest that a slower infusion rate results in a greater AUC and longer distribution phase than a faster infusion rate and indicates the importance of normalizing dosage regimes by infusion rate rather than by infusion duration when considering dose-response phenomena in veterinary patients.

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.

Information Technology and the Curriculum: A Status Report

ERIC Educational Resources Information Center

Perry, Claudia A.

2004-01-01

Information technology infuses all aspects of modern life, and the growth of digital information continues at an unprecedented rate. Widely influential documents, such as the National Research Council's "Being Fluent with Information Technology" and the American Library Association's "Information Literacy Competency Standards for Higher…

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.

Continuous wound infusion and local infiltration analgesia for postoperative pain and rehabilitation after total hip arthroplasty.

PubMed

Fusco, Pierfrancesco; Cofini, Vincenza; Petrucci, Emiliano; Scimia, Paolo; Fiorenzi, Maurizio; Paladini, Giuseppe; Behr, Astrid U; Borghi, Battista; Flamini, Stefano; Pizzoferrato, Renzo; Colafarina, Olivo; Di Francesco, Alexander; Tabacco, Tito; Necozione, Stefano; Marinangeli, Franco

2018-05-01

Total hip arthroplasty is one of the most common procedures in orthopedic surgery. We hypothesized that local infiltration of analgesia and continuous wound infusion of anesthetics in the first 72 hours after surgery could provide more effective postoperative analgesia with better rehabilitation. A double-blind, randomized, controlled study was conducted with 96 patients who underwent total hip arthroplasty. The patients were randomized to receive either a local infiltration analgesia and continuous wound infusion of anesthetics or a local infiltration analgesia and continuous wound infusion of saline solution. The patients in both groups received subarachnoid anesthesia and a local infiltration analgesia. A multihole catheter was placed next to the implant and connected to an electronic pump containing a 300-mL solution of 0.2% levobupivacaine (experimental group) or saline (control group). A total of 96 consecutive patients were enrolled and randomized. Of these, 48 patients received local infiltration analgesia and continuous wound infusion of local anesthetics, and the remainder received local infiltration analgesia and continuous wound infusion of saline solution. The analysis showed a significant main effect of treatment on the postoperative incident of pain (Ftreat(1,93)=22.62, P=0.000) and on resting pain during the post-surgery follow-up (Ftreat(1,93)=15.62, P=0.0002). The pain scores during the rehabilitation period were significantly less in the experimental group. Analgesic consumption was less in the experimental group. The addition of continuous wound infusion of anesthetics to local infiltration analgesia provided an extended analgesic effect associated with good rehabilitation performance.

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.

Impact of intravenous magnesium infusion rate during ambulatory replacements on serum magnesium concentrations after allogeneic stem cell transplant.

PubMed

Snyder, Matthew; Shillingburg, Alexandra; Newton, Michael; Hamadani, Mehdi; Kanate, Abraham S; Craig, Michael; Cumpston, Aaron

2016-10-01

For an outpatient cancer center to operate efficiently, optimizing the use of chair time is essential. Allogeneic hematopoietic cell transplant (allo-HCT) recipients are seen frequently in this setting after hospital discharge and regularly for several months thereafter. Aggressive electrolyte replacement is commonly required in these patients, primarily due to renal wasting with calcineurin inhibitor use. Frequent intravenous (IV) magnesium repletion, requiring several hours of infusion time, is often needed in these patients to adequately manage their magnesium deficiencies. The purpose of this study is to explore the impact of extending the infusion rate of intravenous magnesium sulfate on the frequency and degree of IV magnesium replacements required in allo-HCT recipients. We conducted a retrospective study to compare two cohorts of patients administered IV magnesium sulfate at a rate of 4 g/1 h versus 4 g/2 h. A total of 103 continuous patients were assessed in two groups as cohort 1 at the 4 g/1 h rate and cohort 2 at the 4 g/2 h rate. Cohort 1 required less IV magnesium per outpatient visit (median 2.2 vs. 2.9 g/visit, P = 0.0211) and less total IV magnesium replacement through day +100 (median 68 vs. 85 g, P = 0.0479) than cohort 2. These data suggest that there is no apparent benefit of prolonging magnesium infusion from 1 to 2 h in our outpatient allo-HCT population.

Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

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

Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com; Zhou, Ying, E-mail: yingzhou526@gmail.com; Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com

Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalizedmore » by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.« less

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

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.

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

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.

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

The Relationship of the Anthropometric Variables to the Infusion Rate of Rocuronium in the Elderly

PubMed Central

Koo, Bon Nyeo; Bai, Sun Jun; Lee, Woo Chang

2005-01-01

We have determined the infusion rates of rocuronium in the elderly and young adult patients during sevoflurane and nitrous oxide anesthesia. The correlation of some anthropometric predictors with infusion rate of rocuronium was also investigated for both elderly and young adult. Participating patients were assigned to one of two groups: 1) young adult patients aged 20 to 50 years (n = 30); 2) elderly patients aged over 65 years (n = 30). The anthropometric variables such as height, weight, ratio of weight to body surface area, subscapularis and suprailiac skin folds, body surface area, body mass index and % ideal body weight were evaluated as predictors for infusion rate. The infusion rate in elderly patients was significantly less compared with that in young adult patients (p < 0.05). In elderly patients, no anthropometric predictor was related to the infusion rate of rocuronium. This suggests that the infusion rate of rocuronium for an elderly patient needs to be individualized by monitoring neuromuscular transmission to avoid excessive dose. PMID:16259061

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

PubMed Central

Clendinnen, B. Guy; Reeder, David D.; Brandt, E. N.; Thompson, James C.

1973-01-01

Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2·54 min to 5·15 min at the low rate, and from 2·85 min to 7·88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin. PMID:4719213

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.

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.

Accuracy of intravenous infusion pumps in continuous renal replacement therapies.

PubMed

Jenkins, R; Harrison, H; Chen, B; Arnold, D; Funk, J

1992-01-01

Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use.

Paediatric electronic infusion calculator: An intervention to eliminate infusion errors in paediatric critical care.

PubMed

Venkataraman, Aishwarya; Siu, Emily; Sadasivam, Kalaimaran

2016-11-01

Medication errors, including infusion prescription errors are a major public health concern, especially in paediatric patients. There is some evidence that electronic or web-based calculators could minimise these errors. To evaluate the impact of an electronic infusion calculator on the frequency of infusion errors in the Paediatric Critical Care Unit of The Royal London Hospital, London, United Kingdom. We devised an electronic infusion calculator that calculates the appropriate concentration, rate and dose for the selected medication based on the recorded weight and age of the child and then prints into a valid prescription chart. Electronic infusion calculator was implemented from April 2015 in Paediatric Critical Care Unit. A prospective study, five months before and five months after implementation of electronic infusion calculator, was conducted. Data on the following variables were collected onto a proforma: medication dose, infusion rate, volume, concentration, diluent, legibility, and missing or incorrect patient details. A total of 132 handwritten prescriptions were reviewed prior to electronic infusion calculator implementation and 119 electronic infusion calculator prescriptions were reviewed after electronic infusion calculator implementation. Handwritten prescriptions had higher error rate (32.6%) as compared to electronic infusion calculator prescriptions (<1%) with a p  < 0.001. Electronic infusion calculator prescriptions had no errors on dose, volume and rate calculation as compared to handwritten prescriptions, hence warranting very few pharmacy interventions. Use of electronic infusion calculator for infusion prescription significantly reduced the total number of infusion prescribing errors in Paediatric Critical Care Unit and has enabled more efficient use of medical and pharmacy time resources.

Novel monorail infusion catheter for volumetric coronary blood flow measurement in humans: in vitro validation.

PubMed

van 't Veer, Marcel; Adjedj, Julien; Wijnbergen, Inge; Tóth, Gabor G; Rutten, Marcel C M; Barbato, Emanuele; van Nunen, Lokien X; Pijls, Nico H J; De Bruyne, Bernard

2016-08-20

The aim of this study is to validate a novel monorail infusion catheter for thermodilution-based quantitative coronary flow measurements. Based on the principles of thermodilution, volumetric coronary flow can be determined from the flow rate of a continuous saline infusion, the temperature of saline when it enters the coronary artery, and the temperature of the blood mixed with the saline in the distal part of the coronary artery. In an in vitro set-up of the systemic and coronary circulation at body temperature, coronary flow values were varied from 50-300 ml/min in steps of 50 ml/min. At each coronary flow value, thermodilution-based measurements were performed at infusion rates of 15, 20, and 30 ml/min. Temperatures and pressures were simultaneously measured with a pressure/temperature sensor-tipped guidewire. Agreement of the calculated flow and the measured flow as well as repeatability were assessed. A total of five catheters were tested, with a total of 180 measurements. A strong correlation (ρ=0.976, p<0.0001) and a difference of -6.5±15.5 ml/min were found between measured and calculated flow. The difference between two repeated measures was 0.2%±8.0%. This novel infusion catheter used in combination with a pressure/temperature sensor-tipped guidewire allows accurate and repeatable absolute coronary flow measurements. This opens a window to a better understanding of the coronary microcirculation.

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

Siphon effects on continuous subcutaneous insulin infusion pump delivery performance.

PubMed

Zisser, Howard C; Bevier, Wendy; Dassau, Eyal; Jovanovic, Lois

2010-01-01

The objective was to quantify hydrostatic effects on continuous subcutaneous insulin infusion (CSII) pumps during basal and bolus insulin delivery. We tested CSII pumps from Medtronic Diabetes (MiniMed 512 and 515), Smiths Medical (Deltec Cozmo 1700), and Insulet (OmniPod) using insulin aspart (Novolog, Novo Nordisk). Pumps were filled and primed per manufacturer's instructions. The fluid level change was measured using an inline graduated glass pipette (100 microl) when the pipette was moved in relation to the pump (80 cm Cosmo and 110 cm Medtronics) and when level. Pumps were compared during 1 and 5 U boluses and basal insulin delivery of 1.0 and 1.5 U/h. Pronounced differences were seen during basal delivery in pumps using 80-100 cm tubing. For the 1 U/h rate, differences ranged from 74.5% of the expected delivery when the pumps were below the pipettes and pumping upward to 123.3% when the pumps were above the pipettes and pumping downward. For the 1.5 U/h rate, differences ranged from 86.7% to 117.0% when the pumps were below or above the pipettes, respectively. Compared to pumps with tubing, OmniPod performed with significantly less variation in insulin delivery. Changing position of a conventional CSII pump in relation to its tubing results in significant changes in insulin delivery. The siphon effect in the tubing may affect the accuracy of insulin delivery, especially during low basal rates. This effect has been reported when syringe pumps were moved in relation to infusion sites but has not been reported with CSII pumps. 2010 Diabetes Technology Society.

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.

Performance of a restrictive flow device and an electronic syringe driver for continuous subcutaneous infusion.

PubMed

Capes, D; Martin, K; Underwood, R

1997-10-01

The aim of this study was to investigate the flow performance of the mechanical Springfusor 30 short model and the electronic Graseby MS16A. Flow rate was measured gravimetrically in a temperature-controlled cabinet. There was no statistically significant difference between the Graseby and Springfusor syringe drivers in the flow rate error at 25 degrees C. The percentage of flow rates within +/-20% accuracy during a 35-min periods at 25 degrees C was significantly less with the Graseby, being 91.9% compared with 100% for the Springfusor. Only 58.2% of flow rates with the Graseby were within the manufacturer claimed accuracy of +/-5%. The flow rate of the Springfusor was affected by temperature; at 30 degrees C the mean flow rate was 10.8% greater than at 25 degrees C. These results indicate that the Springfusor 30 had less flow rate variation than the Graseby MS16A. However, this would not be expected to cause noticeable clinical effects when used for opioid infusion in palliative care.

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.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

PubMed

Muelken, Peter; Schmidt, Clare E; Shelley, David; Tally, Laura; Harris, Andrew C

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

PubMed Central

Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome. PMID:26658557

Discharge prescribing of enteral opioids after initiation as a weaning strategy from continuous opioid infusions in the Intensive Care Unit.

PubMed

Kram, Bridgette; Weigel, Kylie M; Kuhrt, Michelle; Gilstrap, Daniel L

To evaluate the proportion of patients receiving a hospital discharge prescription for a scheduled enteral opioid following initiation as a weaning strategy from a continuous opioid infusion in the Intensive Care Unit (ICU). Retrospective, observational study. Five adult ICUs at a large, quaternary care academic medical center. Endotracheally intubated, opioid-naive adults receiving a continuous opioid infusion with a concomitant scheduled enteral opioid initiated. Exclusion criteria were receipt of fewer than two enteral opioid doses, documentation of a long-acting opioid as a home medication, the indication for the enteral opioid was not a weaning strategy, death during hospital admission or discharge to hospice. None. The proportion of ICU and hospital survivors who received a discharge prescription for a scheduled enteral opioid, total duration of continuous opioid infusion, duration of continuous opioid infusion after initiation of an enteral opioid therapy, total duration of enteral therapy, ICU and hospital length of stay. Of 62 included patients, 19 patients (30.6 percent) received a new prescription for a scheduled enteral opioid at hospital discharge. The median duration of enteral opioid therapy was longer for patients who received a discharge prescription compared to those who did not (20.09 vs 8.89 days, p = 0.02), though the remaining endpoints were not different. Utilizing scheduled enteral opioids as a weaning strategy from continuous opioid infusions may place patients at risk of ICU-acquired physical dependence on opioids.

[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.

Subcutaneous glucagon infusion and continuous glucose monitoring enable effective management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma.

PubMed

Buras, Eric D; Weatherup, Emily; Wyckoff, Jennifer

2018-01-01

Ectopic insulin-like growth factor (IGF)-2 production is a rare complication of an array of epithelial and mesenchymal tumors, and can clinically manifest as life-threatening hypoglycemia. A 49-year-old woman with 13-year history of metastatic hemangiopericytoma, previously treated with multiple rounds of chemotherapy and palliative radiation, presented to the emergency department after a hypoglycemic seizure. On arrival, glucose was 18 mg/dL (1.0 mmol/L) and required continuous dextrose infusion for maintenance within normal limits. Insulin was <2.0 μU/mL, C-peptide 0.1 ng/mL, and beta-hydroxybutyrate <0.2 mmol/L. Random cortisol was 21 μg/dL; sulfonylurea screen, and insulin antibodies were negative. IGF-2 level was 1320 ng/mL; IGF-1 was within normal limits and IGF binding protein (BP)-3 suppressed. Dexamethasone, started at 6 mg twice daily, allowed discontinuation of the glucose infusion. Given concern for nocturnal hypoglycemia, and patient interest in steroid-sparing anti-hypoglycemic regimen, she was also started on overnight continuous subcutaneous glucagon infusion via insulin pump. She was discharged with instructions to maintain a diet high in complex carbohydrates during the day, while utilizing glucagon pump at night. She was also started on continuous glucose monitoring system (CGMS) with an alarm to warn of hypoglycemia. Glucagon infusion rate was later titrated based on CGMS readings. Abdominal CT revealed increasing size of a right upper quadrant mass not previously subjected to radiotherapy. After radiation to this area, hypoglycemia improved, allowing further glucagon titration. In parallel, IGF-2 level declined to 380 ng/mL. Ectopic IGF-2 production is a rare but often fatal complication of many cancers, and should be considered on the differential diagnosis in patients with malignancy and unexplained hypoglycemia. Once hypoglycemia is diagnosed, patients often have end-stage disease. While treatment of the causative tumor is the only definitive intervention, anti-hypoglycemia therapy is a life-saving, temporizing measure. In this case, the patient attained euglycemia and survived 3 months after presentation before ultimately succumbing to other malignancy-related complications. Given efficacy in management of hypoglycemia while awaiting definitive tumor-directed therapy, we submit nighttime subcutaneous glucagon infusion and CGMS are valuable additions to the physician's armamentarium in managing this condition.

Mechanisms for vasopressin effects on intraocular pressure in anesthetized rats

NASA Technical Reports Server (NTRS)

Balaban, C. D.; Palm, D. E.; Shikher, V.; Searles, R. V.; Keil, L. C.; Severs, W. B.

1997-01-01

Continuous intracameral infusions of a balanced salt solution (0.175 microliter min-1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 microliter-1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049-0.35 microliter min-1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 microliter min-1) and a larger periodic component (0.25 microliter min-1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 microliter min-1. As shown previously for 0.175 microliter min-1 constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

PubMed

Kamei, J; Onodera, K; Kawaguchi, M; Shibata, M; Kagawa, M; Wachi, M; Kojima, J

2002-10-01

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

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

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Ludwig, D. A.; Reister, C.; Fanton, J. W.; Ewert, D.; Convertino, V. A.

2001-01-01

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

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.

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

Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of combination therapy with colistin plus β-lactams.

PubMed

Ribera, Alba; Benavent, Eva; Lora-Tamayo, Jaime; Tubau, Fe; Pedrero, Salvador; Cabo, Xavier; Ariza, Javier; Murillo, Oscar

2015-12-01

In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options. This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion. Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%. We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

PubMed Central

Fowler, Christie D.; Kenny, Paul J.

2011-01-01

Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

Intraperitoneal Continuous-Rate Infusion for the Maintenance of Anesthesia in Laboratory Mice (Mus musculus)

PubMed Central

Erickson, Rebecca L; Terzi, Matthew C; Jaber, Samer M; Hankenson, F Claire; McKinstry-Wu, Andrew; Kelz, Max B; Marx, James O

2016-01-01

Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine–xylazine–acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine–xylazine–acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine–xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing. PMID:27657709

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.

Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

PubMed

Al-Niaimi, Ahmed N; Ahmed, Mostafa; Burish, Nikki; Chackmakchy, Saygin A; Seo, Songwon; Rose, Stephen; Hartenbach, Ellen; Kushner, David M; Safdar, Nasia; Rice, Laurel; Connor, Joseph

2015-01-01

SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of <139 mL/dL and a primary outcome of the protocol's impact on SSI rates. We compared SSI rates retrospectively among three groups. Group 1 was composed of patients with DM whose blood glucose was controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics. Copyright © 2014. Published by Elsevier Inc.

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

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.

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

Effect of hyperthyroidism on clearance and secretion of glucagon in man.

PubMed

Dimitriadis, G; Hatziagelaki, E; Mitrou, P; Lambadiari, V; Maratou, E; Raptis, A E; Gerich, J E; Raptis, S A

2011-04-01

Glucagon has been proposed to contribute to the increased glucose production found in hyperthyroidism. However, fasting plasma glucagon levels are not increased in hyperthyroidism suggesting that the activity of the α-cell is normal. Nevertheless, an increase in the clearance rate of glucagon may mask increased glucagon secretion. This study was designed to examine the effects of hyperthyroidism on the kinetics of glucagon. A primed-continuous infusion of glucagon was administered to 9 euthyroid and 9 hyperthyroid subjects at 3 sequential rates (1,200, 3,000 and 6,000 pg/kg/min, each given for 2 h). Arterialized blood was drawn at 15-30 min intervals for determination of glucagon. Fasting plasma glucagon levels were comparable in euthyroids (195±8 pg/ml) and hyperthyroids (231±16 pg/ml). During infusions (1,200, 3,000 and 6,000 pg/kg/min), plasma glucagon increased to 387±19, 624±44 and 977±51 pg/ml in euthyroids and to 348±23, 597±42 and 938±56 pg/ml in hyperthyroids respectively. At these infusion rates, metabolic clearance of glucagon (ml/kg/min) was 6.6±0.5, 7.4±0.6 and 7.9±0.5 in euthyroids and 12.6±2, 8.9±1 and 8.8±0.6 in hyperthyroids, respectively. Metabolic clearance of glucagon differed between hyperthyroids and euthyroids at 1 200 pg/kg/min infusion rate (p=0.001). The basal delivery rate of glucagon (ng/kg/min) was 1.3±0.1 in euthyroids and 2.9±0.6 in hyperthyroids (p=0.0005). In hyperthyroidism, the secretion and metabolic clearance rates of glucagon are increased. These effects may explain the changes in plasma glucagon levels observed in hyperthyroidism and support the important role of glucagon in increasing endogenous glucose production in this condition. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

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

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

PubMed

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

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).

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

Continuous quality improvement using intelligent infusion pump data analysis.

PubMed

Breland, Burnis D

2010-09-01

The use of continuous quality-improvement (CQI) processes in the implementation of intelligent infusion pumps in a community teaching hospital is described. After the decision was made to implement intelligent i.v. infusion pumps in a 413-bed, community teaching hospital, drug libraries for use in the safety software had to be created. Before drug libraries could be created, it was necessary to determine the epidemiology of medication use in various clinical care areas. Standardization of medication administration was performed through the CQI process, using practical knowledge of clinicians at the bedside and evidence-based drug safety parameters in the scientific literature. Post-implementation, CQI allowed refinement of clinically important safety limits while minimizing inappropriate, meaningless soft limit alerts on a few select agents. Assigning individual clinical care areas (CCAs) to individual patient care units facilitated customization of drug libraries and identification of specific CCA compliance concerns. Between June 2007 and June 2008, there were seven library updates. These involved drug additions and deletions, customization of individual CCAs, and alterations of limits. Overall compliance with safety software use rose over time, from 33% in November 2006 to over 98% in December 2009. Many potentially clinically significant dosing errors were intercepted by the safety software, prompting edits by end users. Only 4-6% of soft limit alerts resulted in edits. Compliance rates for use of infusion pump safety software varied among CCAs over time. Education, auditing, and refinement of drug libraries led to improved compliance in most CCAs.

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy

PubMed Central

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2016-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery. PMID:27293475

Control Law Design for Propofol Infusion to Regulate Depth of Hypnosis: A Nonlinear Control Strategy.

PubMed

Khaqan, Ali; Bilal, Muhammad; Ilyas, Muhammad; Ijaz, Bilal; Ali Riaz, Raja

2015-01-01

Maintaining the depth of hypnosis (DOH) during surgery is one of the major objectives of anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but increases the undue load of an anesthetist in operating room working in a multitasking setup. Manual and target controlled infusion (TCI) systems are not good at handling instabilities like blood pressure changes and heart rate variability arising due to interpatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors to motivate automation in anesthesia. The idea of automated system for Propofol infusion excites the control engineers to come up with a more sophisticated and safe system that handles optimum delivery of drug during surgery and avoids postoperative effects. In contrast to most of the investigations with linear control strategies, the originality of this research work lies in employing a nonlinear control technique, backstepping, to track the desired hypnosis level of patients during surgery. This effort is envisioned to unleash the true capabilities of this nonlinear control technique for anesthesia systems used today in biomedical field. The working of the designed controller is studied on the real dataset of five patients undergoing surgery. The controller tracks the desired hypnosis level within the acceptable range for surgery.

Evidence for Increased Beta-Adrenoreceptor Responsiveness Induced by 14 Days of Simulated Microgravity in Humans

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Polet, Jill L.; Engelke, Keith A.; Hoffler, G. W.; Lane, Lynda D.

1996-01-01

We studied hemodynamic responses to alpha and beta receptor agonists in 8 healthy men ( 38+- 2 yrs) before and after 14 days of 6 degree head-down tilt (HDT) to test the hypothesis that increased adrenergic responsiveness is induced by prolonged exposure to microgravity. Immediately following a 30-min baseline period, a steady-state infusion of isoproterenol (ISO) was used to assess beta 1- and beta 2-adrenergic responsiveness. ISO was infused at three graded constant rates of 0.005, 0.01 and 0.02 ug/kg/min. After heart rate and blood pressure had been allowed to return to baseline levels following ISO infusion graded infusion of phenylephrine (PE) was used to assess responsiveness of alpha I-vascular receptors. PE was infused at three graded constant rates of 0.25, 0.50 and 1.00 ug/kg/min. Each infusion interval for both drugs was 9 min. During the infusions, constant monitoring of beat-to-beat blood pressure and heart rate was performed and leg blood flow was measured with occlusion plethysmography at each infusion level. The slopes calculated from linear regressions between ISO and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used to represent alpha- and beta- adrenoreceptor responsiveness. Fourteen days HDT increased the slopes of heart rate (1056 +- 107 to 1553 +- 83 beats/ug/kg/min; P= 0.014) and vasodilation (-469ft +- 111 to -l446 +- 309 PRU/ug/kg/min; P =0.0224) to ISO infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that microgravity causes selective increases in beta 1- and beta 2-adrenergic responsiveness without affecting alpha 1-vascular responses.

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.

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.

Baseline albumin is associated with worsening renal function in patients with acute decompensated heart failure receiving continuous infusion loop diuretics.

PubMed

Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E

2013-06-01

To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.

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.

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.

Sympathetic and cardiovascular responses to venous distension in an occluded limb.

PubMed

Cui, Jian; Leuenberger, Urs A; Gao, Zhaohui; Sinoway, Lawrence I

2011-12-01

We recently showed that a fixed volume (i.e., 40 ml) of saline infused into the venous circulation of an arterially occluded vascular bed increases muscle sympathetic nerve activity (MSNA) and blood pressure. In the present report, we hypothesized that the volume and rate of infusion would influence the magnitude of the sympathetic response. Blood pressure, heart rate, and MSNA were assessed in 13 young healthy subjects during forearm saline infusions (arrested circulation). The effects of different volumes of saline (i.e., 2%, 3%, 4%, or 5% forearm volume at 30 ml/min) and different rates of infusion (i.e., 5% forearm volume at 10, 20, or 30 ml/min) were evaluated. MSNA and blood pressure responses were linked with the infusion volume. Infusion of 5% of forearm volume evoked greater MSNA responses than did infusion of 2% of forearm volume (Δ11.6 ± 1.9 vs. Δ3.1 ± 1.8 bursts/min and Δ332 ± 105 vs. Δ38 ± 32 units/min, all P < 0.05). Moreover, greater MSNA responses were evoked by saline infusion at 30 ml/min than 10 ml/min (P < 0.05). Sonographic measurements confirmed that the saline infusions induced forearm venous distension. The results suggest that volume and rate of saline infusion are important factors in evoking sympathetic activation. We postulate that venous distension contributes to cardiovascular autonomic adjustment in humans.

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units.

PubMed

Maiguy-Foinard, Aurélie; Genay, Stéphanie; Lannoy, Damien; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal; Décaudin, Bertrand

2017-02-01

The aims are to identify critical parameters influencing the drug mass flow rate of infusion delivery to patients during multidrug infusion and to discuss their clinical relevance. A review of literature was conducted in January 2016 using Medline, Google Scholar, ScienceDirect, Web of Science and Scopus online databases. References relating to the accuracy of fluid delivery via gravity-flow intravenous (IV) infusion systems and positive displacement pumps, components of IV administration sets, causes of flow rate variability, potential complications due to flow rate variability, IV therapies especially at low flow rates and drug compatibilities were considered relevant. Several parameters impact the delivery of drugs and fluids by IV infusion. Among them are the components of infusion systems that particularly influence the flow rate of medications and fluids being delivered. By their conception, they may generate significant start-up delays and flow rate variability. Performing multidrug infusion requires taking into account two main points: the common dead volume of drugs delivered simultaneously with potential consequences on the accuracy and amount of drug delivery and the prevention of drug incompatibilities and their clinical effects. To prevent the potentially serious effects of flow rate variability on patients, clinicians should receive instruction on the fluid dynamics of an IV administration set and so be able to take steps to minimise flow rate changes during IV therapy. Copyright © 2016 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

PubMed

Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

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

Local infiltration analgesia followed by continuous infusion of local anesthetic solution for total hip arthroplasty: a prospective, randomized, double-blind, placebo-controlled study.

PubMed

Solovyova, Olga; Lewis, Courtland G; Abrams, Jonathan H; Grady-Benson, John; Joyce, Michael E; Schutzer, Steven F; Arumugam, Sivasenthil; Caminiti, Stephanie; Sinha, Sanjay K

2013-11-06

We studied the efficacy of local infiltration analgesia in surgical wounds with 0.2% ropivacaine (50 mL), ketorolac (15 mg), and adrenaline (0.5 mg) compared with that of local infiltration analgesia combined with continuous infusion of 0.2% ropivacaine as a method of pain control after total hip arthroplasty. We hypothesized that as a component of multimodal analgesia, local infiltration analgesia followed by continuous infusion of ropivacaine would result in reduced postoperative opioid consumption and lower pain scores compared with infiltration alone, and that both of these techniques would be superior to placebo. In this prospective, double-blind, placebo-controlled study, 105 patients were randomized into three groups: Group I, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of 0.2% ropivacaine at 5 mL/hr; Group II, in which patients received infiltration with ropivacaine, ketorolac, and adrenaline followed by continuous infusion of saline solution at 5 mL/hr; and Group III, in which patients received infiltration with saline solution followed by continuous infusion of saline solution at 5 mL/hr.All patients received celecoxib, pregabalin, and acetaminophen perioperatively and patient-controlled analgesia; surgery was performed under general anesthesia. Before wound closure, the tissues and periarticular space were infiltrated with ropivacaine, ketorolac, and adrenaline or saline solution and a fenestrated catheter was placed. The catheter was attached to a pump prefilled with either 0.2% ropivacaine or saline solution set to infuse at 5 mL/hr.The primary outcome measure was postoperative opioid consumption and the secondary outcome measures were pain scores, adverse side effects, and patient satisfaction. There were no differences between groups in the administration of opioids in the operating room, in the recovery room, or on the surgical floor. The pain scores on recovery room admission and discharge and the floor were low and similar between groups. There were no differences in the incidence of adverse side effects among groups. Patient satisfaction with pain management was similar in all groups. Local infiltration analgesia alone or followed by continuous infusion of ropivacaine as part of multimodal analgesia provides no additional analgesic benefit or reduction in opioid consumption compared with placebo following total hip arthroplasty. Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence.

Effect of Starvation on the Turnover and Metabolic Response to Leucine

PubMed Central

Sherwin, Robert S.

1978-01-01

l-Leucine was administered as a primed continuous 3-4-h infusion in nonobese and obese subjects in the postabsorptive state and for 12 h in obese subjects after a 3-day and 4-wk fast. In nonobese and obese subjects studied in the post-absorptive state, the leucine infusion resulted in a 150-200% rise in plasma leucine above preinfusion levels, a small decrease in plasma glucose, and unchanged levels of plasma insulin and glucagon and blood ketones. Plasma isoleucine (60-70%) and valine (35-40%) declined to a greater extent than other amino acids (P < 0.001). After 3 days and 4 wk of fasting, equimolar infusions of leucine resulted in two- to threefold greater increments in plasma leucine as compared to post-absorptive subjects, a 30-40% decline in other plasma amino acids, and a 25-30% decrease in negative nitrogen balance. Urinary excretion of 3-methylhistidine was however, unchanged. Plasma glucose which declined in 3-day fasted subjects after leucine administration, surprisingly rose by 20 mg/100 ml after 4 wk of fasting. The rise in blood glucose occurred in the absence of changes in plasma glucagon and insulin and in the face of a 15% decline in endogenous glucose production (as measured by infusion of [3-3H]glucose). On the other hand, fractional glucose utilization fell by 30% (P < 0.001), thereby accounting for hyperglycemia. The estimated metabolic clearance rate of leucine fell by 48% after 3 days of fasting whereas the plasma delivery rate of leucine was unchanged, thereby accounting for a 40% rise in plasma leucine during early starvation. After a 4-wk fast, the estimated metabolic clearance rate of leucine declined further to 59% below base line. Plasma leucine nevertheless fell to postabsorptive levels as the plasma delivery rate of leucine decreased 65% below postabsorptive values. Conclusions: (a) Infusion of exogenous leucine in prolonged fasting results in a decline in plasma levels of other amino acids, improvement in nitrogen balance and unchanged excretion of 3-methylhistidine, thus suggesting stimulation of muscle protein synthesis, (b) leucine infusion also reduces glucose production and to an even greater extent, glucose consumption, thereby raising blood glucose concentration; and (c) the rise in plasma leucine in early starvation results primarily from a decrease in leucine clearance which drops progressively during starvation. PMID:659610

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.

Acid-base status and cardiovascular function in mink (Mustela vison) anaesthetized with ketamine/midazolam.

PubMed

Wamberg, S; Svendsen, P; Johansen, B

1996-01-01

Heart rate, arterial blood pressure and blood acid-base status were determined in 18 adult female mink (mean (+/- SEM) body weight 1052 +/- 34 g) during long-term anaesthesia with either controlled ventilation (n=12) or spontaneous respiration (n=6). Surgical anaesthesia was induced by intramuscular injection of ketamine hydrochloride (Ketaminol Vet, 40.0 +/- 1.7 mg/kg) and midazolam hydrochloride (Dormicum 2.8 +/- 0.1 mg/kg) and maintained for at least 5 h by continuous intravenous infusion of this drug combination in 0.9% saline. For all animals, the mean rates of infusion of ketamine and midazolam were 48.4 +/- 1.6 and 1.61 +/- 0.12 mg/h, respectively. Following continuous infusion of the anaesthetics in isotonic saline, at a rate of 20 ml/h, a moderate 'dilution acidosis' developed, which could be corrected by replacement of part of the saline with sodium bicarbonate to a final concentration of approximately 25 mmol NaHCO3 per litre. However, when the animals were allowed to breathe spontaneously, an increase in heart rate and a combined respiratory and metabolic acidosis occurred, due to severe respiratory depression. Apart from these effects and a few cases of increased salivation, no adverse effects over time were observed on the arterial blood acid-base status and cardiovascular function of the animals during ketamine/midazolam anaesthesia. It is concluded that the procedure described for long-term anaesthesia in mink is convenient and safe for acute physiological experiments in this species, provided normal body temperature and pulmonary gas exchange is sufficiently maintained. Thus, the need for an adequately controlled artificial ventilation is strongly emphasized. Finally, a proposal for the composition of an intravenous solution, containing ketamine and midazolam hydrochloride, and sodium bicarbonate in saline, suitable for long-term anaesthesia in adult mink is presented.

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...

Pseudoaneurysm embolization and vasopressin infusion for lower gastrointestinal bleeding due to recurrence of urinary bladder carcinoma.

PubMed

Kakizawa, Hideaki; Toyota, Naoyuki; Mita, Koji; Fujimura, Yoshio; Hieda, Masashi; Hirai, Nobuhiko; Tachikake, Toshihiro; Ito, Katsuhide

2006-05-01

We report a case that was successfully treated for massive lower gastrointestinal (LGI) bleeding due to a recurrent urinary bladder carcinoma. Treatment consisted of combination therapy including embolization of an inferior gluteal artery (IGA) pseudoaneurysm and low-dose arterial vasopressin infusion via a sigmoid artery (SA). A 57-year-old man presented with life-threatening sudden, massive LGI bleeding due to an obturator lymph node (LN) metastasis from a urinary bladder carcinoma. Computed tomography showed that the LN recurrence had invaded all the way to the sigmoid colon, and there was a pseudoaneurysm with extravasation inside the recurrence. An angiogram revealed a left IGA pseudoaneurysm. We therefore excluded the pseudoaneurysm by embolization with microcoils. Following this treatment the bleeding decreased, but intermittent LGI bleeding continued. Endoscopic examination showed the tumor with a huge ulcer inside the colonic lumen, and continuous oozing was confirmed. A second angiogram showed no recurrence of the IGA pseudoaneurysm and no apparent findings of bleeding. Then a 3F microcatheter was placed in the SA selectively using a coaxial catheter system, and vasopressin was infused at a rate 0.05 U/min for 12 h. Bleeding completely ceased 2 days later. There were no signs of ischemic gastrointestinal complications. Massive LGI bleeding has not recurred in 5 months.

The Effect of Milrinone on the Right Ventriclular Function in Patients with Reduced Right Ventricular Function Undergoing Off-pump Coronary Artery Bypass Graft Surgery

PubMed Central

Lee, Jong Hwa; Oh, Young Jun; Shim, Yon Hee; Hong, Yong Woo; Yi, Gijong

2006-01-01

This investigation evaluated the effect of continuous milrinone infusion on right ventriclular (RV) function during off-pump coronary artery bypass graft (OPCAB) surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB, with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction, were randomly allocated to either milrinone (0.5 µg/kg/min) or control (saline) group. Hemodynamic variables and RV volumetric data measured by thermodilution method were collected as follows: after anesthesia induction (T1); 10 min after heart displacement for obtuse marginal artery anastomosis (T2); after pericardial closure (T3). Cardiac index and heart rate increased and systemic vascular resistance significantly decreased in milrinone group at T2. Initially lower RVEF of milrinone group was eventually comparable to control group after milrinone infusion. RVEF did not significantly change at T2 and T3 in both groups. RV end-diastolic volume in milrinone group consistently decreased from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus demonstrated potentially beneficial effect on cardiac output and RV afterload in patients with reduced RV function during OPCAB. However, aggressive augmentation of intravascular volume seems to be necessary to maximize the effect of the milrinone in these patients. PMID:17043419

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA.

PubMed

Stiles, David K; Zhang, Zhiming; Ge, Pei; Nelson, Brian; Grondin, Richard; Ai, Yi; Hardy, Peter; Nelson, Peter T; Guzaev, Andrei P; Butt, Mark T; Charisse, Klaus; Kosovrasti, Verbena; Tchangov, Lubomir; Meys, Michael; Maier, Martin; Nechev, Lubomir; Manoharan, Muthiah; Kaemmerer, William F; Gwost, Douglas; Stewart, Gregory R; Gash, Don M; Sah, Dinah W Y

2012-01-01

Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt). Silencing of Htt with RNA interference using direct CNS delivery in rodent models of Huntington's disease has been shown to reduce pathology and promote neuronal recovery. A key translational step for this approach is extension to the larger non-human primate brain, achieving sufficient distribution of small interfering RNA targeting Htt (siHtt) and levels of Htt suppression that may have therapeutic benefit. We evaluated the potential for convection enhanced delivery (CED) of siHtt to provide widespread and robust suppression of Htt in nonhuman primates. siHtt was infused continuously for 7 or 28 days into the nonhuman primate putamen to analyze effects of infusion rate and drug concentration on the volume of effective suppression. Distribution of radiolabeled siHtt and Htt suppression were quantified by autoradiography and PCR, respectively, in tissue punches. Histopathology was evaluated and Htt suppression was also visualized in animals treated for 28 days. Seven days of CED led to widespread distribution of siHtt and significant Htt silencing throughout the nonhuman primate striatum in an infusion rate and dose dependent manner. Htt suppression at therapeutic dose levels was well tolerated by the brain. A model developed from these results predicts that continuous CED of siHtt can achieve significant coverage of the striatum of Huntington's disease patients. These findings suggest that this approach may provide an important therapeutic strategy for treating Huntington's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

A randomised study of perioperative esmolol infusion for haemodynamic stability during major vascular surgery; rationale and design of DECREASE-XIII.

PubMed

Bakker, E J; Ravensbergen, N J; Voute, M T; Hoeks, S E; Chonchol, M; Klimek, M; Poldermans, D

2011-09-01

This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery. A double-blind, placebo-controlled, randomised trial. A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension. This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

In-hospital pediatric cardiac arrest in Spain.

PubMed

López-Herce, Jesús; del Castillo, Jimena; Cañadas, Sonia; Rodríguez-Núñez, Antonio; Carrillo, Angel

2014-03-01

The objective was to analyze the characteristics and prognostic factors of in-hospital pediatric cardiac arrest in Spain. A prospective observational study was performed to examine in-hospital pediatric cardiac arrest. Two hundred children were studied, aged between 1 month and 18 years, with in-hospital cardiac arrest. Univariate and multivariate logistic regression analyses were performed to assess the influence of each factor on survival to hospital discharge. Return of spontaneous circulation was achieved in 74% of the patients and 41% survived to hospital discharge. The survival rate was significantly higher than that reported in a previous Spanish study 10 years earlier (25.9%). In the univariate analysis, the factors related to mortality were body weight higher than 10 kg; continuous infusion of vasoactive drugs prior to cardiac arrest; sepsis and neurological disorders as causes of cardiac arrest, the need for treatment with adrenaline, bicarbonate, and volume expansion, and prolonged cardiopulmonary resuscitation. In the multivariate analysis, the factors related to mortality were hematologic/oncologic diseases, continuous infusion of vasoactive drugs prior to cardiac arrest, cardiopulmonary resuscitation for more than 20 min, and treatment with bicarbonate and volume expansion. Survival after in-hospital cardiac arrest in children has significantly improved in recent years. The factors related to in-hospital mortality were hematologic/oncologic diseases, continuous infusion of vasoactive drugs prior to cardiac arrest, the duration of cardiopulmonary resuscitation, and treatment with bicarbonate and volume expansion. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

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.

Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study.

PubMed

Ozbilgin, Sule; Yurtlu, Derya Aslan; Küçükoztaş, Beyza; Kamacı, Gonca; Korkut, Sezen; Yurtlu, Bülent Serhan; Ensari Güneli, M; Hancı, Volkan; Günerli, Ali

2018-03-16

Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex. Heart rate, electrocardiography, and respiratory rate were monitored. The primary endpoint was time to asystole. Digoxin infusion continued until the animals arrested. The time to asystole for the Sgdx1000 group was significantly longer compared to that for the control group (p < 0.05). The mean lethal dose of digoxin was 5.35 ± 2.06 mg/kg in the saline-treated rats. On the other hand, the mean lethal dose of digoxin was 8.54 ± 1.51 mg/kg in the sugammadex 1000 group (p < 0.05). The mean lethal dose of digoxin was significantly higher than control group (p < 0.05). We found that the 1000 mg/kg dose of sugammadex delayed digoxin cardiotoxicity in a rat model of digoxin toxicity. We conclude that further research must be conducted on the interaction between digoxin and sugammadex.

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

Pharmacodynamic effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses.

PubMed

Lankveld, D P K; Driessen, B; Soma, L R; Moate, P J; Rudy, J; Uboh, C E; van Dijk, P; Hellebrekers, L J

2006-12-01

Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, nonesterified fatty acids, and muscle enzyme levels were measured, as were plasma concentrations of KET and its metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Levels of sedation and muscle tension were scored. Respiration and heart rate significantly increased during the early infusion phase. Glucose and cortisol significantly varied both during and after infusion. During CRI all horses scored 0 on sedation. All but one horse scored 0 on muscle tension, with one mare scoring 1. All other parameters remained within or close to physiological limits without significant changes from pre-CRI values. The mean plasma concentration of KET during the 1.5 mg/kg/h KET CRI was 235 ng/mL. The decline of its plasma concentration-time curve of both KET and norketamine (NKET) following the CRI was described by a two-compartmental model. The metabolic cascade of KET was NKET, hydroxynorketamine (HNK), and 5,6-dehydronorketamine (DHNK). The KET median elimination half-lives (t1/2alpha and t1/2beta) were 2.3 and 67.4 min, respectively. The area under the KET plasma concentration-time curve (AUC), elimination was 76.0 microg.min/mL. Volumes of C1 and C2 were 0.24 and 0.79 L/kg, respectively. It was concluded that a KET CRI of 1.5 mg/kg/h can safely be administered to healthy conscious horses for at least 6 h, although a slight modification of the initial infusion rate regimen may be indicated. Furthermore, in the horse KET undergoes very rapid biotransformation to NKET and HNK and DHNK were the major terminal metabolites.

Continuous Subcutaneous Insulin Infusion in Children: A Pilot Study Validating a Protocol to Avoid Hypoglycemia at Initiation.

PubMed

Manousaki, Despoina; Deladoëy, Johnny; Geoffroy, Louis; Olivier, Patricia

2017-01-01

The occurrence of hypoglycemia and hyperglycemia during the first days after transition to continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes has not been systematically studied in children. The aim of this prospective study was to demonstrate that the protocol applied in our diabetes clinic is safe at CSII initiation in children. We assessed 22 pediatric patients with type 1 diabetes, using continuous glucose monitoring (CGM) before and after CSII initiation (±3 days). After CSII initiation, there was no difference in the rates of hypoglycemic events expressed as relative rates (RRs) per person-reading (RR = 0.85, p  = 0.52, 95% CI 0.52-1.39), as well as in the number of prolonged hypoglycemic events (>1 h) per day (RR = 1.12, p  = 0.56, 95% CI 0.75-1.68). We observed only a trend toward prolonged episodes of hyperglycemia after pump initiation (RR = 1.52, p  = 0.06, 95% CI 0.97-2.35). Our study is the first to assess, through CGM and in a prospective way, the impact of a CSII initiation protocol on glycemic values. Our protocol provides a safe model to avoid hypoglycemia at CSII initiation in children. www.ClinicalTrials.gov, identifier NCT01840358.

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

Triacetin: a potential parenteral nutrient.

PubMed

Bailey, J W; Haymond, M W; Miles, J M

1991-01-01

Triacetin, the water-soluble triglyceride of acetate, was infused in mongrel dogs at isocaloric (N = 6) or hypercaloric (approximately 1.5 REE, N = 7) rates in mongrel dogs for 3 hr. Ketone body and glucose production rates were quantified with [13C2] acetoacetate and [3H]glucose, respectively. Four additional animals were infused with glycerol to serve as controls for the hypercaloric triacetin infusion. Energy expenditure was determined in the isocaloric experiments. no evidence of acute toxicity was observed during triacetin infusion at either rate. Plasma acetate concentrations increased from basal levels to approximately 1 and approximately 13 mmol/liter in the isocaloric and hypercaloric experiments, respectively. Plasma lactate and pyruvate concentrations decreased dramatically after 30 min of both isocaloric and hypercaloric triacetin infusions. Glucose production rates did not increase in either group, but glucose clearance decreased significantly in both groups (p less than 0.05) over the last hour of triacetin infusion. Plasma ketone body concentrations increased from 1.4 to 3.5 and 1.8 to 13.5 mumol/kg.min, respectively, during isocaloric and hypercaloric triacetin infusion. Resting energy expenditure increased from 3.0 +/- 0.3 to 4.0 +/- 0.5 kcal/kg.hr during isocaloric triacetin infusion (p less than 0.05). These studies indicate that triacetin can be administered to dogs at high rates without overt toxicity. The decrease in glucose clearance may represent competition between carbohydrate (glucose) and lipid (acetate). Triacetin infusion resulted in significant increases in ketone body production and concentration. These preliminary data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted.

Saline-Induced Coronary Hyperemia: Mechanisms and Effects on Left Ventricular Function.

PubMed

De Bruyne, Bernard; Adjedj, Julien; Xaplanteris, Panagiotis; Ferrara, Angela; Mo, Yujing; Penicka, Martin; Floré, Vincent; Pellicano, Mariano; Toth, Gabor; Barbato, Emanuele; Duncker, Dirk J; Pijls, Nico H J

2017-04-01

During thermodilution-based assessment of volumetric coronary blood flow, we observed that intracoronary infusion of saline increased coronary flow. This study aims to quantify the extent and unravel the mechanisms of saline-induced hyperemia. Thirty-three patients were studied; in 24 patients, intracoronary Doppler flow velocity measurements were performed at rest, after intracoronary adenosine, and during increasing infusion rates of saline at room temperature through a dedicated catheter with 4 lateral side holes. In 9 patients, global longitudinal strain and flow propagation velocity were assessed by transthoracic echocardiography during a prolonged intracoronary saline infusion. Taking adenosine-induced maximal hyperemia as reference, intracoronary infusion of saline at rates of 5, 10, 15, and 20 mL/min induced 6%, 46%, 111%, and 112% of maximal hyperemia, respectively. There was a close agreement of maximal saline- and adenosine-induced coronary flow reserve (intraclass correlation coefficient, 0.922; P <0.001). The same infusion rates given through 1 end hole (n=6) or in the contralateral artery (n=6) did not induce a significant increase in flow velocity. Intracoronary saline given on top of an intravenous infusion of adenosine did not further increase flow. Intracoronary saline infusion did not affect blood pressure, systolic, or diastolic left ventricular function. Heart rate decreased by 15% during saline infusion ( P =0.021). Intracoronary infusion of saline at room temperature through a dedicated catheter for coronary thermodilution induces steady-state maximal hyperemia at a flow rate ≥15 mL/min. These findings open new possibilities to measure maximal absolute coronary blood flow and minimal microcirculatory resistance. © 2017 American Heart Association, Inc.

Measurement of Muscle Protein Fractional Synthetic Rate by Capillary Gas Chromatography/Combustion Isotope Ratio Mass Spectrometry

PubMed Central

Yarasheski, Kevin E.; Smith, Kenneth; Rennie, Michael J.; Bier, Dennis M.

2014-01-01

The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague–Dawley rats after each was infused at a different rate with (1-13C)leucine for 6–8 h. Muscle leucine enrichment (at.% excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (<0.03 at.% excess). In addition, capillary GC/combustion IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12–14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 ± 0.011% h−1 (mean ± SEM); range = 0.023–0.147% h−1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS. PMID:1420371

Immediate effects of different schedules of somatostatin on portal pressure in patients with liver cirrhosis.

PubMed

Zhang, C; Xu, J-M; Kong, D-R; Min, X-K; Chen, R

2013-06-01

Somatostatin (SST) is used for the treatment of acute variceal bleeding based on its ability to decrease portal pressure and collateral blood flow. To date, no studies have focused on the immediate-early effects (between 1 and 30 min) of SST. The aim of this study was to compare the efficacy of different schedules of SST therapy with placebo on portal pressure in patients with portal hypertension treated with portal-azygous disconnection and to test whether an increase in bolus or infusion dose can improve the clinical efficacy of SST therapy.   Patients were treated with four different schedules: (a) standard dose (n = 11): one 250 μg bolus + a continuous infusion of 250 μg/h; (b) medium dose (n = 10): 500 μg bolus + a continuous infusion of 250 μg/h; (c) high dose (n = 10): 250 μg bolus + a continuous infusion of 500 μg/h; (d) control (n = 10): an injection of placebo (saline) followed by a placebo infusion. Following SST or placebo administration, portal pressure, central venous pressure (CVP), systemic blood pressure and heart rate (HR) were measured at 1, 3, 5, 7, 10 and 30 min.   The three schedules of SST induced a marked, rapid and highly significant decrease in portal pressure. The decline in portal pressure was moderate at 1 min (P < 0·040), achieved a peak effect at 5 min (P < 0·009) and remained decreased at 30 min. The effect of SST on portal pressure was significantly greater than placebo from 1 min after administration. There were no significant differences in portal pressure decrease between the three schedules of SST. The three schedules of SST and the placebo schedule did not induce significant changes in HR, systemic blood pressure and CVP.   This study shows that SST is effective in decreasing portal pressure within 30 min of administration in patients with liver cirrhosis. The clinical schedule used in this study was reasonable and safe. © 2013 Blackwell Publishing Ltd.

Mathematical and physical model of gravity-fed infusion outflow: application to soft-bag-packed solutions.

PubMed

Simon, N; Décaudin, B; Lannoy, D; Barthélémy, C; Lemdani, M; Odou, P

2011-12-01

Gravity-fed infusion (GFI) systems are acknowledged as being unable to keep their flow-rate constant. This may affect drug plasma levels such as aminoglycosides. Numerous factors have previously been cited, but their relative importance has never been quantified so far. The objective of this work is to identify the main factors that influence GFI in vitro outflow and to propose a mathematical model of flow-rate evolution as a function of time. In this model, pressure loss and infusion device creep have been considered as the main variation factors. Concomitantly, two experiments were undertaken. Firstly, the flow-rate evolution of an in vitro infusion of 250 mL of dextrose 5% was assessed. Secondly, the creep occurring on an infusion device was measured through a stress relaxation experiment. The experimental infusion flow-rate decreased by as much as 28.5% over 1 h. Simulated and experimental data are well correlated (r = 0.987; P < 0.0001). The maximum creep effect happens during the first 15 min of infusion. In this work, height of the liquid in the bag and tube creep were found to be the main variation factors in GFI flow-rate. This new mathematical model should help to explain the differences observed in drug plasma levels with gravity-fed devices.

[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.

A supplemental intravenous amino acid infusion sustains a positive protein balance for 24 hours in critically ill patients.

PubMed

Sundström Rehal, Martin; Liebau, Felix; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

2017-12-06

Providing supplemental amino acids to ICU patients during a 3-h period results in improved whole-body net protein balance, without an increase in amino acid oxidation. The primary objective was to investigate if a 24-h intravenous amino acid infusion in critically ill patients has a sustained effect on whole-body protein balance as was seen after 3 h. Secondary objectives were monitoring of amino acid oxidation rate, urea and free amino acid plasma concentrations. An infusion of [1- 13 C]-phenylalanine was added to ongoing enteral nutrition to quantify the enteral uptake of amino acids. Primed intravenous infusions of [ring- 2 H 5 ]-phenylalanine and [3,3- 2 H 2 ]-tyrosine were used to assess whole-body protein synthesis and breakdown, to calculate net protein balance and to assess amino acid oxidation at baseline and at 3 and 24 hours. An intravenous amino acid infusion was added to nutrition at a rate of 1 g/kg/day and continued for 24 h. Eight patients were studied. The amino acid infusion resulted in improved net protein balance over time, from -1.6 ± 7.9 μmol phe/kg/h at 0 h to 6.0 ± 8.8 at 3 h and 7.5 ± 5.1 at 24 h (p = 0.0016). The sum of free amino acids in plasma increased from 3.1 ± 0.6 mmol/L at 0 h to 3.2 ± 0.3 at 3 h and 3.6 ± 0.5 at 24 h (p = 0.038). Amino acid oxidation and plasma urea were not altered significantly. We demonstrated that the improvement in whole-body net protein balance from a supplemental intravenous amino acid infusion seen after 3 h was sustained after 24 h in critically ill patients. This trial was prospectively registered at Australian New Zealand Clinical Trials Registry. ACTRN, 12615001314516 . Registered on 1 December 2015.

Effects of flow rate on the migration of different plasticizers from PVC infusion medical devices

PubMed Central

Eljezi, Teuta; Clauson, Hélène; Lambert, Céline; Bouattour, Yassine; Chennell, Philip; Pereira, Bruno; Sautou, Valérie

2018-01-01

Infusion medical devices (MDs) used in hospitals are often made of plasticized polyvinylchloride (PVC). These plasticizers may leach out into infused solutions during clinical practice, especially during risk-situations, e.g multiple infusions in Intensive Care Units and thus may enter into contact with the patients. The migrability of the plasticizers is dependent of several clinical parameters such as temperature, contact time, nature of the simulant, etc… However, no data is available about the influence of the flow rate at which drug solutions are administrated. In this study, we evaluated the impact of different flow rates on the release of the different plasticizers during an infusion procedure in order to assess if they could expose the patients to more toxic amounts of plasticizers. Migration assays with different PVC infusion sets and extension lines were performed with different flow rates that are used in clinical practice during 1h, 2h, 4h, 8h and 24h, using a lipophilic drug simulant. From a clinical point of view, the results showed that, regardless of the plasticizer, the faster the flow rate, the higher the infused volume and the higher the quantities of plasticizers released, both from infusion sets and extension lines, leading to higher patient exposure. However, physically, there was no significant difference of the migration kinetics linked to the flow rate for a same medical device, reflecting complex interactions between the PVC matrix and the simulant. The migration was especially dependent on the nature and the composition of the medical device. PMID:29474357

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.

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.

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.

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...

Effect of intravenous infusion of an alpha-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold pressor stimulation.

PubMed

Maekawa, K; Kuboki, T; Miyawaki, T; Shimada, M; Yamashita, A; Clark, G T

1999-04-01

This study evaluated the effect of intravenous infusion of a non-selective alpha-adrenergic blocking agent on masseter muscle haemodynamics induced by 4 degrees C cold pressor stimulation (CPS) of the right foot and ankle, which reportedly evokes a rapidly increasing sympathetic nerve activity in human skeletal muscle. Nine healthy non-smoking males (mean age 23.7+/-2.1 year) with no history of chronic muscle pain or migraine participated. The haemoglobin (Hb) concentration in the right masseter was continuously recorded by non-invasive, near-infrared spectroscopy. Heart rate and blood pressure were also recorded. The experiment involved the following sequence: (1) a placebo (physiological saline) with a CPS trial; (2) a 30-sec maximal voluntary clenching (MVC)-only trial; and (3) an alpha-adrenergic blocking agent with a CPS trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the CPS. Physiological saline (20 ml) or phentolamine mesylate (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 15 min before baseline recording and participants were not aware which solution (saline or phentolamine) was being infused. For the MVC trial, each participant performed a 30-sec MVC of his jaw-closing muscles followed by a 15-min rest between each trial. The individual Hb data were adjusted so that the baseline at the beginning of the experiment was equal to zero and all data were normalized as a percentage of the individual's highest absolute Hb change seen after the MVC. The mean baseline Hb concentrations 1 min before CPS were significantly higher in the alpha-blocker trial (83.6%) than in the placebo saline trial (P < 0.001). The change in mean Hb concentration from baseline during CPS in the alpha-blocker trial was significantly less than in the placebo trial (P = 0.006). Mean heart rate before CPS was also significantly higher in the alpha-blocker trial (85.2 beats/min) than in the placebo trial (69.6 beats/min) (P < 0.001). There were no significant differences in the mean systolic and diastolic blood pressures between the placebo and alpha-blocker trials in any time period. The results suggest that non-selective alpha-adrenoceptor blockade increases the blood volume in the masseter muscle. This change might be due to a combination of peripheral vasodilation and an increase in cardiac output.

IL15 Infusion of Cancer Patients Expands the Subpopulation of Cytotoxic CD56bright NK Cells and Increases NK-Cell Cytokine Release Capabilities.

PubMed

Dubois, Sigrid; Conlon, Kevin C; Müller, Jürgen R; Hsu-Albert, Jennifer; Beltran, Nancy; Bryant, Bonita R; Waldmann, Thomas A

2017-10-01

The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56 bright NK-cell subpopulation in that the expansion rates exceeded those of CD56 dim NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56 dim subset. CD56 bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56 bright NK cells gained the ability to kill various target cells at levels that are typical for CD56 dim NK cells. Some increased cytotoxic activities were also observed for CD56 dim NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56 bright NK cells that alone or in combination with tumor-targeting antibodies may be useful in the treatment of cancer. Cancer Immunol Res; 5(10); 929-38. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

ERIC Educational Resources Information Center

Darby, Wendy

2006-01-01

Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

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.

Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations.

PubMed

Rugonyi, Sandra

2008-04-01

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.

The systemic toxicity of equipotent proxymetacaine, oxybuprocaine, and bupivacaine during continuous intravenous infusion in rats.

PubMed

Hung, Ching-Hsia; Liu, Kuo-Sheng; Shao, Dong-Zi; Cheng, Kuang-I; Chen, Yu-Chung; Chen, Yu-Wen

2010-01-01

Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity. After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After i.v. infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate. Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses. Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity.

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.

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.

The action of bombesin on the kidney of the anaesthetized dog.

PubMed

Erspamer, V; Melchiorri, P; Sopranzi, N

1973-07-01

1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.

Influences of brain tissue poroelastic constants on intracranial pressure (ICP) during constant-rate infusion.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2013-01-01

A 3D finite element (FE) model has been developed to study the mean intracranial pressure (ICP) response during constant-rate infusion using linear poroelasticity. Due to the uncertainties in the poroelastic constants for brain tissue, the influence of each of the main parameters on the transient ICP infusion curve was studied. As a prerequisite for transient analysis, steady-state simulations were performed first. The simulated steady-state pressure distribution in the brain tissue for a normal cerebrospinal fluid (CSF) circulation system showed good correlation with experiments from the literature. Furthermore, steady-state ICP closely followed the infusion experiments at different infusion rates. The verified steady-state models then served as a baseline for the subsequent transient models. For transient analysis, the simulated ICP shows a similar tendency to that found in the experiments, however, different values of the poroelastic constants have a significant effect on the infusion curve. The influence of the main poroelastic parameters including the Biot coefficient α, Skempton coefficient B, drained Young's modulus E, Poisson's ratio ν, permeability κ, CSF absorption conductance C(b) and external venous pressure p(b) was studied to investigate the influence on the pressure response. It was found that the value of the specific storage term S(ε) is the dominant factor that influences the infusion curve, and the drained Young's modulus E was identified as the dominant parameter second to S(ε). Based on the simulated infusion curves from the FE model, artificial neural network (ANN) was used to find an optimised parameter set that best fit the experimental curve. The infusion curves from both the FE simulation and using ANN confirmed the limitation of linear poroelasticity in modelling the transient constant-rate infusion.

Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine).

PubMed

Holstege, Christopher P; Wu, Jeffrey; Baer, Alexander B

2002-06-01

A 16-year-old boy presented to the emergency department with rapidly progressing extremity pain, edema, and ecchymosis after envenomation by a copperhead. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) was infused. Six vials were placed in 250 mL of normal saline solution, and the infusion was gradually increased. Fifty minutes after beginning, the infusion was increased to 640 mL/h. Within minutes of the rate increase, the patient experienced full-body urticaria, facial edema, voice change, and tachycardia. The infusion was stopped. Hydroxyzine pamoate, famotidine, methylprednisolone, and a 1-L bolus of normal saline solution were administered intravenously. The symptoms abated, and the remaining FabAV was infused at a slower rate without return of this reaction. This immediate hypersensitivity reaction was most likely a rate-related anaphylactoid reaction that has not been previously reported with FabAV.[Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med. June 2002;39:677-679.

ACR Appropriateness Criteria®  Resectable Rectal Cancer

PubMed Central

2012-01-01

The management of resectable rectal cancer continues to be guided by clinical trials and advances in technique. Although surgical advances including total mesorectal excision continue to decrease rates of local recurrence, the management of locally advanced disease (T3-T4 or N+) benefits from a multimodality approach including neoadjuvant concomitant chemotherapy and radiation. Circumferential resection margin, which can be determined preoperatively via MRI, is prognostic. Toxicity associated with radiation therapy is decreased by placing the patient in the prone position on a belly board, however for patients who cannot tolerate prone positioning, IMRT decreases the volume of normal tissue irradiated. The use of IMRT requires knowledge of the patterns of spreads and anatomy. Clinical trials demonstrate high variability in target delineation without specific guidance demonstrating the need for peer review and the use of a consensus atlas. Concomitant with radiation, fluorouracil based chemotherapy remains the standard, and although toxicity is decreased with continuous infusion fluorouracil, oral capecitabine is non-inferior to the continuous infusion regimen. Additional chemotherapeutic agents, including oxaliplatin, continue to be investigated, however currently should only be utilized on clinical trials as increased toxicity and no definitive benefit has been demonstrated in clinical trials. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:23006527

Use of insulin pumps in India: suggested guidelines based on experience and cultural differences.

PubMed

Kesavadev, Jothydev; Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

2010-10-01

All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of continuous subcutaneous insulin infusion in selected T2DM subjects. This article aims at suggesting guidelines based on clinical experience and cultural diversity for India and developing countries.

Use of Insulin Pumps in India: Suggested Guidelines Based on Experience and Cultural Differences

PubMed Central

Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R.; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

2010-01-01

Abstract All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of continuous subcutaneous insulin infusion in selected T2DM subjects. This article aims at suggesting guidelines based on clinical experience and cultural diversity for India and developing countries. PMID:20807118

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 effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

PubMed

Rittler, Peter; Schiefer, Beatrice; Demmelmair, Hans; Koletzko, Berthold; Vogeser, Michael; Alpers, David H; Jauch, Karl-Walter; Hartl, Wolfgang H

2006-01-01

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).

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

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.

Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.

PubMed

Schnuelle, Peter; Schmitt, Wilhelm H; Weiss, Christel; Habicht, Antje; Renders, Lutz; Zeier, Martin; Drüschler, Felix; Heller, Katharina; Pisarski, Przemyslaw; Banas, Bernhard; Krämer, Bernhard K; Jung, Matthias; Lopau, Kai; Olbricht, Christoph J; Weihprecht, Horst; Schenker, Peter; De Fijter, Johan W; Yard, Benito A; Benck, Urs

2017-03-07

Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µ g/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration. Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.gov identifier: NCT00115115). Follow-up was complete in 99.2%. Graft survival was 72.6% versus 68.7% ( P =0.34), and 83.3% versus 80.4% ( P =0.42) after death-censoring in treatment and control arms according to trial assignment. Although infusion times varied substantially in the treatment arm (range 0-32.2 hours), duration of the dopamine infusion and all-cause graft failure exhibited an exposure-response relationship (hazard ratio, 0.96; 95% confidence interval [95% CI], 0.92 to 1.00, per hour). Cumulative frequency curves of graft survival and exposure time of the dopamine infusion indicated a maximum response rate at 7.10 hours (95% CI, 6.99 to 7.21), which almost coincided with the optimum infusion time for improvement of early graft function (7.05 hours; 95% CI, 6.92 to 7.18). Taking infusion time of 7.1 hours as threshold in subsequent graft survival analyses indicated a relevant benefit: Overall, 81.5% versus 68.5%; P =0.03; and 90.3% versus 80.2%; P =0.04 after death-censoring. We failed to show a significant graft survival advantage on intention-to-treat. Dopamine infusion time was very short in a considerable number of donors assigned to treatment. Our finding of a significant, nonlinear exposure-response relationship disclosed a threshold value of the dopamine infusion time that may improve long-term kidney graft survival. Copyright © 2017 by the American Society of Nephrology.

Target controlled infusion for kids: trials and simulations.

PubMed

Mehta, Disha; McCormack, Jon; Fung, Parry; Dumont, Guy; Ansermino, J

2008-01-01

Target controlled infusion (TCI) for Kids is a computer controlled system designed to administer propofol for general anesthesia. A controller establishes infusion rates required to achieve a specified concentration at the drug's effect site (C(e)) by implementing a continuously updated pharmacokinetic-pharmacodymanic model. This manuscript provides an overview of the system's design, preclinical tests, and a clinical pilot study. In pre-clinical tests, predicted infusion rates for 20 simulated procedures displayed complete convergent validity between two software implementations, Labview and Matlab, at computational intervals of 5, 10, and 15s, but diverged with 20s intervals due to system rounding errors. The volume of drug delivered by the TCI system also displayed convergent validity with Tivatrainer, a widely used TCI simulation software. Further tests, were conducted for 50 random procedures to evaluate discrepancies between volumes reported and those actually delivered by the system. Accuracies were within clinically acceptable ranges and normally distributed with a mean of 0.08 +/- 0.01 ml. In the clinical study, propofol pharmacokinetics were simulated for 30 surgical procedures involving children aged 3 months to 9 years. Predicted C(e) values during standard clinical practice, the accuracy of wake-up times predicted by the system, and potential correlations between patient wake-up times, C(e), and state entropy (SE) were assessed. Neither Ce nor SE was a reliable predictor of wake-up time in children, but the small sample size of this study does not fully accommodate the noted variation in children's response to propofol. A C(e) value of 1.9 mug/ml was found to best predict emergence from anesthesia in children.

Intravenous Insulin Decreases Protein Breakdown in Infants on Extracorporeal Membrane Oxygenation

PubMed Central

Agus, Michael S.D.; Javid, Patrick J.; Ryan, Daniel P.; Jaksic, Tom

2010-01-01

Background/Purpose Infants requiring extracorporeal membrane oxygenation (ECMO) have the highest rates of protein catabolism ever reported. Recent investigations have found that such extreme protein breakdown is refractory to conventional nutritional management. In this pilot study, the authors sought to use the anabolic hormone insulin to reduce the profound protein degradation in this cohort. Methods Four parenterally fed infants on ECMO were enrolled in a prospective, randomized, crossover trial. Subjects were administered an insulin infusion using a 4-hour hyperinsulinemic euglycemic clamp followed by a control saline infusion on consecutive days in random order. Whole-body protein flux and breakdown were quantified using a primed continuous infusion of the stable isotope l-[1-13C]leucine. Statistical analyses were performed using paired t tests. Results Serum insulin levels were increased 15-fold during the insulin clamp compared with the saline control (407 ± 103 v 26 ± 12 µU/mL; P < .05). During the insulin infusion, infants had decreased rates of total leucine flux (214 ± 25 v 298 ± 38 µmol/kg/h; P < .05) and leucine flux derived from protein breakdown (156 ± 40 v 227 ± 54 µmol/kg/h; P < .05) when compared with saline control. Overall, insulin administration produced a 32% reduction in protein breakdown (P < .05). Conclusions In this pilot study, the anabolic hormone insulin markedly reduced protein breakdown in critically ill infants on ECMO. Because elevated protein breakdown correlates with mortality and morbidity, the administration of intravenous insulin may ultimately have broad applicability to the metabolic management of critically ill infants. PMID:15185208

Management of an oral ingestion of transdermal fentanyl patches: a case report and literature review.

PubMed

Faust, Andrew C; Terpolilli, Ralph; Hughes, Darrel W

2011-01-01

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In the ED, the patient was obtunded, dizzy and drowsy. Initial vital signs showed the patient to be afebrile and normotensive with a heart rate of 63, respiratory rate of 16, and oxygen saturation of 100% on 2 liters nasal cannula after administration of 2 milligrams of intravenous naloxone. The patient was treated with whole bowel irrigation and continuous intravenous naloxone infusion for approximately 48 hours without complications. Conclusion. Despite numerous case reports describing oral ingestion of fentanyl patches, information on the management of such intoxication is lacking. We report successful management of such a case utilizing whole bowel irrigation along with intravenous push and continuous infusion naloxone.

Management of an Oral Ingestion of Transdermal Fentanyl Patches: A Case Report and Literature Review

PubMed Central

Faust, Andrew C.; Terpolilli, Ralph; Hughes, Darrel W.

2011-01-01

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In the ED, the patient was obtunded, dizzy and drowsy. Initial vital signs showed the patient to be afebrile and normotensive with a heart rate of 63, respiratory rate of 16, and oxygen saturation of 100% on 2 liters nasal cannula after administration of 2 milligrams of intravenous naloxone. The patient was treated with whole bowel irrigation and continuous intravenous naloxone infusion for approximately 48 hours without complications. Conclusion. Despite numerous case reports describing oral ingestion of fentanyl patches, information on the management of such intoxication is lacking. We report successful management of such a case utilizing whole bowel irrigation along with intravenous push and continuous infusion naloxone. PMID:21629807

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...

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.

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…

Ruminant Nutrition Symposium: Productivity, digestion, and health responses to hindgut acidosis in ruminants.

PubMed

Gressley, T F; Hall, M B; Armentano, L E

2011-04-01

Microbial fermentation of carbohydrates in the hindgut of dairy cattle is responsible for 5 to 10% of total-tract carbohydrate digestion. When dietary, animal, or environmental factors contribute to abnormal, excessive flow of fermentable carbohydrates from the small intestine, hindgut acidosis can occur. Hindgut acidosis is characterized by increased rates of production of short-chain fatty acids including lactic acid, decreased digesta pH, and damage to gut epithelium as evidenced by the appearance of mucin casts in feces. Hindgut acidosis is more likely to occur in high-producing animals fed diets with relatively greater proportions of grains and lesser proportions of forage. In these animals, ruminal acidosis and poor selective retention of fermentable carbohydrates by the rumen will increase carbohydrate flow to the hindgut. In more severe situations, hindgut acidosis is characterized by an inflammatory response; the resulting breach of the barrier between animal and digesta may contribute to laminitis and other disorders. In a research setting, effects of increased hindgut fermentation have been evaluated using pulse-dose or continuous abomasal infusions of varying amounts of fermentable carbohydrates. Continuous small-dose abomasal infusions of 1 kg/d of pectin or fructans into lactating cows resulted in decreased diet digestibility and decreased milk fat percentage without affecting fecal pH or VFA concentrations. The decreased diet digestibility likely resulted from increased bulk in the digestive tract or from increased digesta passage rate, reducing exposure of the digesta to intestinal enzymes and epithelial absorptive surfaces. The same mechanism is proposed to explain the decreased milk fat percentage because only milk concentrations of long-chain fatty acids were decreased. Pulse-dose abomasal fructan infusions (1 g/kg of BW) into steers resulted in watery feces, decreased fecal pH, and increased fecal VFA concentrations, without causing an inflammatory response. Daily 12-h abomasal infusions of a large dose of starch (~4 kg/d) have also induced hindgut acidosis as indicated by decreased fecal pH and watery feces. On the farm, watery or foamy feces or presence of mucin casts in feces may indicate hindgut acidosis. In summary, hindgut acidosis occurs because of relatively high rates of large intestinal fermentation, likely due to digestive dysfunction in other parts of the gut. A better understanding of the relationship of this disorder to other animal health disorders is needed.

A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation.

PubMed

Ilyas, Muhammad; Butt, Muhammad Fasih Uddin; Bilal, Muhammad; Mahmood, Khalid; Khaqan, Ali; Ali Riaz, Raja

2017-01-01

Regulating the depth of hypnosis during surgery is one of the major objectives of an anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but it unduly increases the load of an anesthetist working in a multitasking scenario in the operation theatre. Manual and target controlled infusion systems are not appropriate to handle instabilities like blood pressure and heart rate changes arising due to interpatient and intrapatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors motivating automation in anesthesia administration. The idea of automated system for Propofol infusion excites control engineers to come up with more sophisticated systems that can handle optimum delivery of anesthetic drugs during surgery and avoid postoperative effects. A linear control technique is applied initially using three compartmental pharmacokinetic and pharmacodynamic models. Later on, sliding mode control and model predicative control achieve considerable results with nonlinear sigmoid model. Chattering and uncertainties are further improved by employing adaptive fuzzy control and H ∞ control. The proposed sliding mode control scheme can easily handle the nonlinearities and achieve an optimum hypnosis level as compared to linear control schemes, hence preventing mishaps such as underdosing and overdosing of anesthesia.

A Review of Modern Control Strategies for Clinical Evaluation of Propofol Anesthesia Administration Employing Hypnosis Level Regulation

PubMed Central

Ilyas, Muhammad; Bilal, Muhammad; Mahmood, Khalid; Ali Riaz, Raja

2017-01-01

Regulating the depth of hypnosis during surgery is one of the major objectives of an anesthesia infusion system. Continuous administration of Propofol infusion during surgical procedures is essential but it unduly increases the load of an anesthetist working in a multitasking scenario in the operation theatre. Manual and target controlled infusion systems are not appropriate to handle instabilities like blood pressure and heart rate changes arising due to interpatient and intrapatient variability. Patient safety, large interindividual variability, and less postoperative effects are the main factors motivating automation in anesthesia administration. The idea of automated system for Propofol infusion excites control engineers to come up with more sophisticated systems that can handle optimum delivery of anesthetic drugs during surgery and avoid postoperative effects. A linear control technique is applied initially using three compartmental pharmacokinetic and pharmacodynamic models. Later on, sliding mode control and model predicative control achieve considerable results with nonlinear sigmoid model. Chattering and uncertainties are further improved by employing adaptive fuzzy control and H∞ control. The proposed sliding mode control scheme can easily handle the nonlinearities and achieve an optimum hypnosis level as compared to linear control schemes, hence preventing mishaps such as underdosing and overdosing of anesthesia. PMID:28466018

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

PubMed

Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

2010-01-15

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Continuous Subcutaneous Insulin Infusion versus Multiple Daily Injections of Insulin for the Management of Type 1 Diabetes Mellitus in Pregnancy: Association with Neonatal Chemical Hypoglycemia.

PubMed

Sargent, James A; Roeder, Hilary A; Ward, Kristy K; Moore, Thomas R; Ramos, Gladys A

2015-12-01

We hypothesized that patients with type 1 diabetes mellitus (T1DM) who were managed during their pregnancy with a continuous subcutaneous insulin infusion (CSII) would have a lower incidence of neonatal hypoglycemia (NH) than patients managed with multiple daily injections (MDI) of insulin. This was a retrospective cohort of 95 women with T1DM who delivered singleton, term neonates between 2007 and 2014. The primary outcome was incidence of NH (capillary plasma glucose ≤ 45 mg/dL) in the first 24 hours after birth. The incidence of NH was 66.0% (62/95). The NH rate was significantly higher in women managed with CSII versus MDI (62 vs. 38%, p = 0.024). Neonates with NH had a higher birth weight (3,867 ± 658 vs. 3,414 ± 619 g, p = 0.002). When analyzing intrapartum glucose management, mothers of neonates with NH had significantly less time managed on an insulin infusion (median interquartile range 7 [3.5-30.5] vs. 17.5 [2.0-17.5] hours, p = 0.014). In multivariable analysis, only maternal body mass index (BMI) (p = 0.035) and time on an insulin infusion (p = 0.043) were significantly associated with NH. In our population of patients with T1DM, CSII was more prevalent in the NH group; however, when controlling for other factors, intrapartum glucose management and early maternal BMI were the only variables associated with NH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The chronic infusion of hexamethonium and phenylephrine to effectively clamp sympathetic vasomotor tone. A novel approach.

PubMed

Collister, J P; Osborn, J W

1999-11-01

There are several ways to assess the sympathetic nervous system (i.e. , nerve recording, sympathectomy, etc.), each of which has its own limitations. The present study was conducted to establish a standard, testable chronic ganglionic blockade protocol with a fixed level of adrenergic vasomotor tone. Rats were instrumented with radio telemetry pressure transducers and venous catheters for continuous measurement of arterial pressure and infusion of pharmacologic agents, respectively. After 3 days of control measurements, rats were infused for 9 days with a continuous dose of the ganglionic blocking agent, hexamethonium and the alpha-adrenergic agonist, phenylephrine. In this way, sympathetic tone was effectively "clamped," which maintained a normal level of arterial pressure. Control pressure between hexamethonium + phenylephrine (HEX + PE) treated rats (101+/-2 mm Hg) and saline (VEHICLE) treated rats (101+/-2 mmHg) was not different. By day 9 of the infusion, there was no difference in arterial pressure between groups (VEHICLE: 101+/-3 mm Hg, HEX + PE: 103+/-3 mm Hg) or from the control period, although heart rate was significantly less in HEX + PE rats (VEHICLE: 406+/-9 beats/min vs. HEX + PE: 343+/-6 beats/min). The effectiveness of this technique was validated by measuring cardiac baroreceptor reflex sensitivity, as well as the pressor response to the direct ganglionic stimulating agent, 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP). Compared to VEHICLE rats, HEX + PE rats showed no tachycardic response to depressor stimuli and an absence of a pressor response to DMPP. We conclude that this protocol is a useful technique to chronically, yet reversibly, block the sympathetic nervous system in experimental settings.

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.

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

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.

Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.

PubMed

Maury, Eric; Vitry, Paola; Galbois, Arnauld; Ait-Oufella, Hafid; Baudel, Jean-Luc; Guidet, Bertrand; Offenstadt, Georges

2012-06-14

We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p < 0.001). The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

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.

Effect of intravenous infusion of a beta-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold-pressor stimulation.

PubMed

Maekawa, K; Kuboki, T; Miyawaki, T; Shimada, M; Yamashita, A; Clark, G T

1999-06-01

Eight healthy non-smoking males (mean age: 24.1 +/- 1.1 years) without any history of chronic muscle pain and migraine participated in this study. Haemoglobin (Hb) and oxygen (O2) saturation in the right masseter muscle were continuously recorded with a non-invasive near-infrared spectroscopic device. Heart rate and blood pressure were also recorded. The experiment had three phases: a placebo drug (physiological saline) with cold-pressor trial, a 30-sec maximal voluntary clenching (MVC) trial, and a propranolol with cold-pressor trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the cold-pressor stimulation (4 degrees C). Physiological saline (20 ml) or propranolol hydrochloride (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 20 min before the baseline recording and participants did not know which solution (saline or propranolol) was being infused. For the MVC trial, each participant was asked to perform a 30-sec clench of their jaw-closing muscles. There was a rest period of 15 min between each trial. The individual Hb and O2 data were normalized so that the baseline at the beginning of the experiment was equal to zero, and the Hb and O2 data were normalized as a percentage of the individual's own highest absolute Hb and O2 after and during the MVC, respectively. The results showed that the mean baseline Hb 1 min before cold-pressor stimulation was significantly lower in the beta-blocker trial than in the placebo trial (p = 0.035). The mean change in Hb from baseline during cold-pressor stimulation in the beta-blocker trial was also significantly less than in the placebo trial (p = 0.035). The mean Hb rebound change after the cold-pressor stimulation in the beta-blocker trial was significantly higher than in the placebo trial, and no significant heart-rate differences were observed in the period after cold-pressor stimulation. Overall, the mean heart rate before and during that stimulation was significantly lower in the beta-blocker trial than the placebo trial (p < 0.001). There was no significant mean blood-pressure difference between placebo and beta-blocker trials at any time. These results suggest that beta-adrenoceptor blocking decreases the blood volume in the resting masseter, suppresses the incremental blood-volume change during cold-pressor stimulation, and discloses a hidden vasoconstrictive effect after that stimulation.

Peripheral amiodarone-related phlebitis: an institutional nursing guideline to reduce patient harm.

PubMed

Spiering, Mary

2014-01-01

Intravenous amiodarone is one of the most widely used antiarrythmics for the treatment of atrial fibrillation with rapid ventricular response. Peripheral amiodarone infusion, however, often causes pain during infusion and subsequent phlebitis.Data collection on a cardiac telemetry unit revealed a high rate of phlebitis. A multidisciplinary team developed and implemented amiodarone peripheral infusion guidelines. The pre-guideline phlebitis rate was 85% and post-guideline rate was 38%, representing a 47% change or improvement. An additional finding was that the severity of phlebitis was reduced, as well. The results of this study suggest that the implementation of a peripheral amiodarone infusion guideline reduced the incidence and severity of amiodarone-related phlebitis in the cardiac population.

Infusion pressure and pain during microneedle injection into skin of human subjects.

PubMed

Gupta, Jyoti; Park, Sohyun S; Bondy, Brian; Felner, Eric I; Prausnitz, Mark R

2011-10-01

Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures caused more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines

PubMed Central

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock. PMID:29270582

Using terlipressin in a pediatric patient with septic shock resistant to catecholamines.

PubMed

Erdogan, Seher; Bosnak, Mehmet

2017-01-01

Sepsis and septic shock are important causes of morbidity and mortality in critically ill children. The goal of treatment is to ensure adequate mean arterial pressure to maintain organ perfusion. The growing number of instances of peripheral vascular hyporeactivity to catecholamines has necessitated the search for alternative vasopressors. A 14-year-old boy had septic shock, with a high cardiac index and low systemic vascular resistance index (SVRI) measurements according to pulse contour analysis, despite treatment with dopamine, dobutamine, adrenaline, and noradrenaline infusions. A terlipressin (TP) 10 μg/kg intravenous bolus was administered, followed by a 1 μg/kg/minute continuous infusion. The response to TP treatment was assessed using pulse contour analysis. The mean arterial pressure and SVRI increased, and the cardiac index and heart rate decreased within 10 minutes after bolus administration of TP. Noradrenaline infusion could be reduced to 0.7 μg/kg/minute within 5 hours. The goal in presenting this case was to evaluate the vasoconstrictor effects of TP, a long-acting vasopressin analogue, in septic shock.

Effect of chronic intracerebroventricular angiotensin II infusion on vasopressin release in rats

NASA Technical Reports Server (NTRS)

Sterling, G. H.; Chee, O.; Riggs, R. V.; Keil, L. C.

1980-01-01

The effects of the chronic infusion of angiotensin II into the lateral cerebral ventricle on the release of arginine vasopressin in rats are investigated. Rats were subjected to a continuous infusion of angiotensin at a rate of 1 microgram/h for five days, during which they were offered water, isotonic saline or hypertonic saline ad libitum or 40 ml water/day, and fluid intake, changes in body weight, plasma sodium ion concentrations and plasma and pituitary arginine vasopressin levels were measured. Angiotensin II is found to increase the fluid intake of rats given isotonic saline and decrease plasma sodium ion levels with no changes in plasma or pituitary arginine vasopressin in those given water or isotonic saline. However, in rats given hypertonic saline, plasma sodium concentrations remained at control levels while plasma vasopressin increased, and in water-restricted rats the effects of angiotensin II were intermediate. Results thus demonstrate that angiotensin II-stimulated arginine vasopressin release is reduced under conditions in which plasma sodium ion concentration becomes dilute, compatible with a central role of angiotensin in the regulation of salt and water balance.

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.

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.

The role of neuropeptide Y in the ovine fetal cardiovascular response to reduced oxygenation

PubMed Central

Sanhueza, Emilia M; Johansen-Bibby, Anja A; Fletcher, Andrew J W; Riquelme, Raquel A; Daniels, Alejandro J; Serón-Ferré, Maria; Gaete, Cristián R; Carrasco, Jorge E; Llanos, Aníbal J; Giussani, Dino A

2003-01-01

This study investigated the role of neuropeptide Y (NPY) in mediating cardiovascular responses to reduced oxygenation in the late gestation ovine fetus by: (1) comparing the effects on the cardiovascular system of an exogenous infusion of NPY with those elicited by moderate or severe reductions in fetal oxygenation; and (2) determining the effect of fetal i.v. treatment with a selective NPY-Y1 receptor antagonist on the fetal cardiovascular responses to acute moderate hypoxaemia. Under general anaesthesia, 14 sheep fetuses (0.8–0.9 of gestation) were surgically prepared with vascular and amniotic catheters. In 5 of these fetuses, a Transonic flow probe was also implanted around a femoral artery. Following at least 5 days of recovery, one group of fetuses (n = 9) was subjected to a 30 min treatment period with exogenous NPY (17 μg kg−1 bolus plus 0.85 μg kg−1 min−1 infusion). In this group, fetal blood pressure and heart rate were monitored continuously and the distribution of the fetal combined ventricular output was assessed via injection of radiolabelled microspheres before and during treatment. The second group of fetuses instrumented with the femoral flow probe (n = 5) were subjected to a 3 h experiment consisting of 1 h of normoxia, 1 h of hypoxaemia, and 1 h of recovery during a slow i.v. infusion of vehicle. One or two days later, the acute hypoxaemia protocol was repeated during fetal i.v. treatment with a selective NPY-Y1 receptor antagonist (50 μg kg−1bolus + 1.5 μg kg−1 min−1 infusion). In these fetuses, fetal arterial blood pressure, heart rate and femoral vascular resistance were recorded continuously. The results show that fetal treatment with exogenous NPY mimics the fetal cardiovascular responses to asphyxia, and that treatment of the sheep fetus with a selective NPY-Y1 receptor antagonist does not affect the fetal cardiovascular response to acute moderate hypoxaemia. These results support a greater role for NPY in mediating the fetal cardiovascular responses to acute asphyxia than to acute moderate hypoxaemia. PMID:12563013

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.

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

PubMed Central

2014-01-01

Introduction The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response. Methods The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L). Results Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5). Conclusions This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure. PMID:24887569

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)

Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

PubMed

Giugliano, D; Cozzolino, D; Salvatore, T; Torella, R; D'Onofrio, F

1988-09-01

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in arterial stiffness during continued infliximab treatment in patients with inflammatory arthropathies.

PubMed

Angel, Kristin; Provan, Sella Aarrestad; Hammer, Hilde Berner; Mowinckel, Petter; Kvien, Tore Kristian; Atar, Dan

2011-08-01

Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased risk of cardiovascular disease. TNF-α antagonists may improve vascular function in these patients and thus be beneficial with regard to cardiovascular disease. This study evaluated arterial stiffness and disease activity between two infusions with a TNF-α antagonist (infliximab) in patients with inflammatory arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic pulse wave velocity (aPWV), and disease activity were measured in 17 patients with RA, AS, or PsA who had been treated with infliximab for at least 12 months. The patients were examined immediately before their infliximab infusion and thereafter every 10th day until their next infusion scheduled at week 4-8. AIx and aPWV did not change during the period between two infliximab infusions. The patients had a temporary improvement in the general disease activity assessed on visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02) after the infusion. In the group of patients with RA, the Disease Activity Score (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did not alter aortic pulse wave velocity or augmentation index in patients with inflammatory arthropathies who were on long-term infliximab therapy. Reductions in the general disease activity and DAS28 were not reflected in alterations of aortic stiffness or augmentation index. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

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.

Alfaxalone for maintenance of anaesthesia in ponies undergoing field castration: continuous infusion compared with intravenous boluses.

PubMed

Deutsch, Julia; Ekiri, Abel; de Vries, Annemarie

2017-07-01

To compare alfaxalone as continuous intravenous (IV) infusion with intermittent IV injections for maintenance of anaesthesia in ponies undergoing castration. Prospective, randomized, 'blinded' clinical study. A group of 33 entire male Welsh ponies undergoing field castration. After preanaesthetic medication with IV detomidine (10 μg kg -1 ) and butorphanol (0.05 mg kg -1 ), anaesthesia was induced with IV diazepam (0.05 mg kg -1 ) followed by alfaxalone (1 mg kg -1 ). After random allocation, anaesthesia was maintained with either IV alfaxalone 2 mg kg -1  hour -1 (group A; n = 16) or saline administered at equal volume (group S; n = 17). When necessary, additional alfaxalone (0.2 mg kg -1 ) was administered IV. Ponies were breathing room air. Using simple descriptive scales, surgical conditions and anaesthesia recovery were scored. Total amount of alfaxalone, ponies requiring additional alfaxalone and time to administration, time from induction to end of infusion and end of infusion to standing were noted. Indirect arterial blood pressure, pulse and respiratory rates, end-expiratory carbon dioxide partial pressure and arterial haemoglobin oxygen saturation were recorded every 5 minutes. Data were analysed using Student t, Mann-Whitney U and chi-square tests, where appropriate (p < 0.05). Total amount of alfaxalone administered after induction of anaesthesia (0.75 ± 0.27 versus 0.17 ± 0.23 mg kg -1 ; p < 0.0001) and time to standing (14.8 ± 4 versus 11.6 ± 4 minutes; p = 0.044) were higher in group A compared to group S. Ponies requiring additional alfaxalone boluses [four (group A) versus seven (group S)] and other measured variables were similar between groups; five ponies required oxygen supplementation [three (group A) versus two (group S)]. Continuous IV infusion and intermittent administration of alfaxalone provided similar anaesthesia quality and surgical conditions in ponies undergoing field castration. Less alfaxalone is required when used intermittently. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

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.

[Recent advance in chemotherapy for advanced colorectal cancer].

PubMed

Aiba, K

1996-04-01

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in this field. Although no optimal combination dose schedule of LV is well known, randomized studies have shown improved activity of 5-FU modulation by LV over 5-FU alone for advanced colorectal cancer doubled the response rate by monotherapy (20-25%) vs 10-15%). New drugs are also promising with the response rate of 25% approximately obtained with a new camptothecin derivative CPT-11, and a pure TS inhibitor, Tomudex in phase II trials. It is also necessary to explore the clinical activity of the combination of low-dose cisplatin and 5-FU, chronotherapy, new dihydropyrimidine dehydrogenase inhibitors and new TS inhibitors. We are facing a new era with a new treatment concept of biochemical modulation or an understanding of optimal administrative methods with the key drug, 5-FU. Obviously, we still seek new agents or new laboratory rationales which enable us to extend the survival of patients with advanced colorectal cancer.

Breadboard development of a fluid infusion system

NASA Technical Reports Server (NTRS)

Thompson, R. W.

1974-01-01

A functional breadboard of a zero gravity Intravenous Infusion System (IVI) is presented. Major components described are: (1) infusate pack pressurizers; (2) pump module; (3) infusion set; and (4) electronic control package. The IVI breadboard was designed to demonstrate the feasibility of using the parallel solenoid pump and spring powered infusate source pressurizers for the emergency infusion of various liquids in a zero gravity environment. The IVI was tested for flow rate and sensitivity to back pressure at the needle. Results are presented.

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.

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.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

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.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

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.

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.

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.

Accuracy and consistency of drop delivery in infusion pumps.

PubMed

Yau, K I; Miyasaka, K

1990-04-01

Advances in intensive care medicine has made us more depend on infusion pumps to deliver accurate amounts of fluids to sick newborns, children and adults. When infusing rapid-acting critical drugs to patients, it is important not only to deliver accurate fluid-volume amounts over a specified time, but also to deliver the fluid at a constant rate with minimal fluctuation. The accuracy of drop delivery in four infusion pumps (IVAC 530, IVAC 560, IMED 922 and IMED 960) at different infusion rates were examined in a laboratory setting by using a photoelectric sensor and a computer. When it was not in its cassette-filling period, the IMED 960 was the most accurate at delivering fluid-drops, with a coefficient of variance (CV) of less than 10% at each flow rate. Yet, like other piston-cylinder cassette pumps, its cassette filling time and stabilizing period after cassette filling were longer at lower flow rates. Both the IVAC 530 and the IMED 922 delivered fluids irregularly with large coefficients of variance (CVs). IVAC 560 had the best results for consistency of drop-delivery over a 4-hour period.

Cardiovascular Deconditioning and Venous Air Embolism in Simulated Microgravity in the Rat

NASA Technical Reports Server (NTRS)

Robinson, R. R.; Doursout, M.-F.; Chelly, J. E.; Powell, M. R.; Little, T. M.; Butler,B. D.

1996-01-01

Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

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)

Does gestational age affect the pharmacokinetics and pharmacodynamics of lidocaine in mother and fetus?

PubMed

Pedersen, H; Santos, A C; Morishima, H O; Finster, M; Plosker, H; Arthur, G R; Covino, B G

1988-03-01

The pharmacokinetics and pharmacodynamics of lidocaine were studied in nine chronically prepared pregnant ewes and their fetuses at a mean ( +/- SE) gestation of 119 +/- 1.0 days, and the results were compared to the data previously published for ten animals at 138 +/- 1.2 days of gestation (term 148 days). Lidocaine was infused intravenously to the mother at a constant rate of 0.1 mg.kg-1.min-1 over a period of 180 min, in order to reach a steady-state maternal plasma lidocaine concentration of approximately 2 micrograms/ml. Maternal and fetal blood samples and maternal urine were collected at intervals throughout the infusion for determination of pH, blood gases, and lidocaine concentrations. Maternal and fetal heart rate, blood pressure, and intraamniotic pressure were continuously recorded. Fetal cardiac output and organ blood flow were determined before and at the end of lidocaine infusion using radionuclide-labeled microspheres. Lidocaine tissue concentrations were determined in several maternal and fetal organs excised at the end of infusion. In both groups, the steady-state plasma concentrations of lidocaine were similar; namely, 2.3 +/- 0.17 and 2.1 +/- 0.21 micrograms/ml in preterm and term ewes, respectively. There were also no significant differences in steady-state plasma drug concentrations in preterm and term fetuses (1.3 +/- 0.11 and 1.2 +/- 0.15 micrograms/ml). The mean fetal maternal concentration ratios (F/M) were the same; namely, 0.6. Maternal urinary excretion of lidocaine correlated with urine pH, being greater in the more acid urine. Tissue uptake of drug tended to be higher in the preterm than term mothers, but only significantly so in the brain and adrenals.(ABSTRACT TRUNCATED AT 250 WORDS)

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

[How to promote the respect of good infusion practices by meeting health care professionals?].

PubMed

Le Reste, C; Fiedler, A; Dubois, S; Dewailly, A; Le Du, I; Cogulet, V

2016-05-01

Health care professionals often forget that there are risks associated with infusion therapy even if it is a common care. In order to assess this practice and to draw potential improvement actions, an audit of local gravity-flow intravenous infusion practices was conducted. The audit, based on a grid including 66 items from the medical prescription to the end of the infusion therapy administration, was conducted in the 6 units which use the most gravity-flow intravenous infusion devices. A multidisciplinary working group was created to decide and organize priority corrective measures in order to improve infusion practices and quality of healthcare. The audit enabled to observe 90hours of nurse's practices (96 infusions) and highlighted heterogeneity in infusion, in some cases inappropriate infusion practices and misuse of infusion devices. We found 4 main issues: labelling infusion therapy, training of health care professionals on good practices, support the purchase of infusion pumps and standardize perfusion line. An interactive educational program for nurses (workshops) was organized to enhance the respect of good practices: infusion identification at any time, respect of hygiene rules, flow rate regulation by counting drops, appropriate use of pumps and flow rate regulators. The audit drew up work priorities. The workshops made easier exchanges between professionals and had a warm welcome that's why it is essential to carry on such training. This collaborative approach between pharmacists, nurses, hygienists and biomedical technicians contribute to drug management improvement and promote optimal patient care. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

76 FR 8637 - Medical Devices; Medical Device Data Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... would alter the parameters on an infusion pump. The MDDS could pass that control signal to the infusion... proposed Sec. 880.6310(a). Commenters also asked whether a system that sends data to an infusion pump to... signal to an infusion pump to control the flow rate would not be an MDDS because, as the revised final...

Continuous nasogastric tube feeding: monitoring by combined use of refractometry and traditional gastric residual volumes.

PubMed

Chang, W-K; McClave, S-A; Chao, Y-C

2004-02-01

Traditional use of gastric residual volumes (GRVs) is insensitive and cannot distinguish retained enteral formula from the large volume of endogenous secretions. We designed this prospective study to determine whether refractometry and Brix value (BV) measurements could be used to monitor gastric emptying and tolerance in patients receiving continuous enteral feeding. Thirty-six patients on continuous nasogastric tube feeding were divided into two groups; patients with lower GRVs (<75 ml) in Group 1, patients with higher GRVs (>75 ml) in Group 2. Upon entry, all gastric contents were aspirated, the volume was recorded (Asp GRV), BV measurements were made by refractometry, and then the contents were reinstilled but diluted with 30 ml additional water. Finally, a small amount was reaspirated and repeat BV measurements were made. Three hours later, the entire procedure was repeated a second time. The BV ratio, calculated (Cal) GRV, and volume of formula remaining were calculated by derived equations. Mean BV ratios were significantly higher for those patients in Group 2 compared to those in Group 1. All but one of the 22 patients (95%) in Group 1 had a volume of formula remaining in the stomach estimated on both measurements to be less than the hourly infusion rate (all these patients had BV ratios <70%). In contrast, six of the 14 patients in Group 2 (43%) on both measurements were estimated to have volumes of formula remaining that were greater than the hourly infusion rate (all these patients had BV ratios >70%). Three of the Group 2 patients (21%) whose initial measurement showed evidence for retention of formula, improved on repeat follow-up measurement assuring adequate gastric emptying. The remaining five patients from Group 2 (35%) had a volume of formula remaining that was less than the hourly infusion rate on both measurements. The pattern of Asp GRVs and serial pre- and post-dilution BVs failed to differentiate these patients in Group 2 with potential emptying problems from those with sufficient gastric emptying. Refractometry and measurement of the BV may improve the clinical utilization of GRVs, by its ability to identify the component of formula within gastric contents and track changes in that component related to gastric emptying.

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.

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

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.

Relationship between frequency and impedance change in an infusion rate measurement system employing a capacitance sensor - biomed 2011.

PubMed

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

2011-01-01

We have been searching for a suitable frequency range for an electrical impedance measurement infusion solution drip monitoring system, which we have previously reported. This electrical impedance, which is formed between two electrodes wrapped around the infusion supply polyvinyl-chloride tube and around the drip chamber, is changed by the growth and fall of each drop of fluid. Thus, the drip rate can be detected by measuring this impedance. However, many different kinds of infusion solutions such as glucose, amino acid, soya oil, and lactated Ringer’s solution are used in hospitals and care facilities. Therefore, it was necessary to find a suitable frequency for driving the capacitance-change sensor with a wide range of infusion solutions. In this study, the sensor electrical impedance change of 16 infusion solutions was measured from 1 kHz up to 1 MHz. The drip impedance produced by 5% glucose solution, 10% glucose solution and soya oil indicated the maximum sensor output change at 10 kHz, 20 kHz, and 70 kHz, respectively. The other 13 infusion solutions increased up to 10 kHz, and were constant from 10 kHz to 1 MHz. However, the growth, fall, and drip rate of the drops of all the infusion solutions were monitored by measuring the impedance change from 10 kHz to 30 kHz. Our experimental results indicated that most suitable excitation range for the infusion monitoring system is from 10 kHz to 30 kHz. Thus, we can now “fine-tune” the system for optimal sensing.

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.

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.

Dependence of intestinal glucose absorption on sodium, studied with a new arterial infusion technique

PubMed Central

Fisher, R. B.; Gardner, M. L. G.

1974-01-01

1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated. 2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974). 3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled. 4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion. 5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline. 6. Ouabain (10-4 M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l. 7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone. 8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration. PMID:4422318

Continuous subcutaneous insulin infusion therapy and multiple daily insulin injections in type 1 diabetes mellitus: a comparative overview and future horizons.

PubMed

Thabit, Hood; Hovorka, Roman

2016-01-01

Continuous subcutaneous insulin infusion (CSII) therapy is currently accepted as a treatment strategy for type 1 diabetes. Transition from multiple daily injection therapy (MDI; including basal-bolus regimens) to CSII is based on expectations of better metabolic control and fewer hypoglycaemic events. Evidence to date has not been always conclusive. Evidence for CSII and MDI in terms of glycaemic control, hypoglycaemia and psychosocial outcomes is reviewed in the adult and paediatric population with type 1 diabetes. Findings from studies on threshold-based insulin pump suspension and predictive low glucose management (PLGM) are outlined. Limitations of current CSII application and future technological developments are discussed. Glycaemic control and quality of life (QOL) may be improved by CSII compared to MDI depending on baseline HbA1c and hypoglycaemia rates. Future studies are expected to provide evidence on clinical and cost effectiveness in those who will benefit the most. Training, structured education and support are important to benefit from CSII. Novel technological approaches linking continuous glucose monitoring (CGM) and CSII may help mitigate against frequent hypoglycaemia in those at risk. Development of glucose-responsive automated closed-loop insulin delivery systems may reduce the burden of disease management and improve outcomes in type 1 diabetes.

[Case of Leriche's syndrome treated with safe and effective analgesia after laparotomy by transversus abdominis plane block, rectus sheath block, and continuous wound infusion with ropivacaine].

PubMed

Hotta, Arisa; Yagi, Yuuki; Hakata, Saaya; Tsumura, Yae; Shimizu, Motoko; Kukida, Ayako; Nakamoto, Ai; Yoshikawa, Noriko; Oohira, Naoko; Tatekawa, Shigeki

2013-12-01

Ultrasound-guided peripheral nerve blocks in the abdominal wall, such as transversus abdominis plane block (TAP block) and rectus sheath block, are now widely used. We report a case of Leriche's syndrome treated with safe and effective analgesia after laparotomy by abdominal wall block and continuous infusion. A 61-year-old man diagnosed with Leriche's syndrome underwent Y-graft replacement for an abdominal aortic aneurysm. Preoperative enhanced and 3-dimensional CTs showed many collateral arterial systems, especially in the right abdominal wall. It was suggested that the right internal iliac artery had been completely occluded, and the left one showed severe stenosis. After the induction of general anesthesia, we recognized collateral arteries through an ultrasound view as on preoperative CTs. We lowered the pulse repetition frequency more than usual in order not to injure them. We injected 0.1875% ropivacaine 60 ml as TAP block, and 20 ml as rectus sheath block. When the wound was closed, a catheter was passed through an 18-gauge Tuohy needle placed above the fascia along the supraumbilical site. After the operation, 0.2% ropivacaine was continuously delivered at a rate of 6 ml hr-1 through the catheter. We could provide the patient with effective analgesia after surgery.

[Home anti-cancer therapy with a venous port].

PubMed

Muto, A; Ashino, Y; Miyazawa, M; Sato, M; Kanno, A; Kawahara, Y; Fujita, Y; Matsushiro, T

2000-12-01

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

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.

Rapid Bolus Administration Does not Increase The Extravasation Rate of Albumin: A Randomized Controlled Trial in The Endotoxemic Pig.

PubMed

von Seth, Magnus; Lipcsey, Miklós; Engström, Peter; Larsson, Anders; Hillered, Lars; Maripuu, Enn; Widström, Charles; Sjölin, Jan

2017-04-01

Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL × kg 5% albumin labeled with Technetium-99m, either as a rapid 15-min bolus (Bolus group, n = 16) or as a 2-h infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate, and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney, and lung was analyzed post mortem.The plasma area under the curve activity0-6 h was 4.4 ± 0.9 × 10 in the Bolus group and 4.4 ± 1.1 × 10 counts × min × mL × h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine, or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

[Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy].

PubMed

Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Regulation of hypnosis in Propofol anesthesia administration based on non-linear control strategy.

PubMed

Ilyas, Muhammad; Khaqan, Ali; Iqbal, Jamshed; Riaz, Raja Ali

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

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.

Quantitative aspects of 1-norepinephrine induced pathologic changes: a study in normal dogs

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

Szakacs, J.E.; Mehlman, B.

1959-08-01

The effects of constant rate intravenous infusions of norepinephrine were studied in 28 normal dogs, sedated with morphine. The range of dose rates in this experiment was from 0.5 to 15 mcg/min/kg. Blood levels of epinephrine and norepinephrine were determined in 12 animals up to 10 hours during constant rate infusions. The heart rate and blood pressure were recorded in frequent intervals. The reflex bradycardia was reversed in the animals by prolonged infusions of one or more mcg/min/kg of norepinephrine. Tachycardia and arrhythmia were regularly present in the animals that developed myocardial lesions. Death occurred due to cardiac arrest, massivemore » cerebral hemorrhage or pulmonary edema in the animals infused with 10 mcg/min/kg for 1/2 to 3 hours, or 5 mcg/min/kg for 6 hours. Post mortem examination was performed on all animals. The tissue changes were described and correlated with dosage rate and blood catecholamine levels. 17 references, 8 figures.« less

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

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.

Fentanyl by continuous subcutaneous infusion for the management of cancer pain: a retrospective study.

PubMed

Watanabe, S; Pereira, J; Hanson, J; Bruera, E

1998-11-01

Twenty-two patients who received fentanyl by continuous subcutaneous infusion for treatment of cancer pain were evaluated retrospectively. No local toxicities were noted. Five patients were switched from transdermal fentanyl due to uncontrolled pain; three achieved stability, accompanied by improvement in visual analogue scores for pain. Seventeen patients were switched from other opioids due to toxicity; 10 achieved stability, with documented improvement in toxicity in seven. The median dose ratio of opioid prior to switchover (mg/day) to fentanyl at stabilization (mg/day) was 85.4 (range 65-112.5) for morphine and 23.0 (range 10.7-29.7) for hydromorphone. Of six stable patients switched from subcutaneous to transdermal fentanyl, four maintained stability. We conclude that fentanyl by continuous subcutaneous infusion is a useful alternative for cancer patients who experience uncontrolled pain while receiving transdermal fentanyl or who experience toxicity on other opioids.

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.

[Prevention of perioperative hypothermia].

PubMed

Horn, Ernst-Peter; Torossian, Alexander

2010-03-01

Inadvertent perioperative hypothermia impairs postoperative outcome in surgical patients due to ischemic myocardial events, wound infections and coagulation disorders. Body core temperature should be assessed 1-2h preoperatively and continuously during surgery. To prevent hypothermia patients and nursing clinical staff should be teached and trained. Preoperatively surgical patients should always be prewarmed by using convective warming devices and active warming should be continued in surgeries longer than 1 hour. Warming of IV fluids is effective if infusion rates are above 1l/h. Core temperature should be measured in the recovery room and active warming should be started when patients are hypothermic or if they feel cold. Georg Thieme Verlag Stuttgart * New York.

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.

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

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.

Influence of the rate of infusion on cyclosporine nephrotoxicity in the rat.

PubMed

Finn, W F; McCormack, A J; Sullivan, B A; Hak, L J; Clark, R L

1989-01-01

The effect of the rate of infusion of single and multiple doses of cyclosporine (CsA) on renal function was evaluated in Sprague-Dawley rats. CsA was dissolved in cremophore (Crem) or Tween 80 (Tween) and infused over consecutive 10-min periods at doses of 10, 20, 30 and 40 mg/kg. CsA-Crem and CsA-Tween produced similar and progressive changes in MAP, RBF, and RVR. By the end of the infusion, the mean values (% of control) of MAP (122 +/- 16% and 131 +/- 22%), RBF (56 +/- 11% and 66 +/- 20%), and RVR (222 +/- 38% and 232 +/- 134%) were significantly different from their respective preinfusion values. Infusion of Crem alone resulted in renal vasodilation at low doses and renal vasoconstriction at high doses. Vasoconstriction was not produced by infusion of Tween alone. In addition, animals were treated with vehicle alone (Gp 1), CsA 10 mg/kg/day by injection (Gp 2), or CsA 20 mg/kg/day by i.v. infusion over 4 hr (Gp 3), and were studied at 1 week. Systemic toxicity was greater with the 4-hr infusion as judged by an increase in MAP. The mean values of MAP were 107 +/- 8 (Gp 1), 101 +/- 13 (Gp 2), and 135 +/- 5 mm Hg (Gp 3; p less than 0.05). However, renal function was less severely affected with the 4-hr infusion. The mean values of CIn were 434 +/- 99 (Gp 1), 298 +/- 101 (Gp 2; p less than 0.05), and 425 +/- 114 microL/min/100 g BW (Gp 3); and the mean values for RBF were 2.72 +/- 0.74 (Gp 1), 2.08 +/- 0.17 (Gp 2; p less than 0.05), and 3.35 +/- 0.61 mL/min/100 g BW (Gp 3), respectively. Microangiograms showed marked abnormalities in the intrarenal perfusion pattern in the rats injected with CsA, 10 mg/kg BW. In rats infused over 4 hr with CsA, 20 mg/kg BW, the microangiographic pattern was normal. These studies demonstrate that the acute hemodynamic effects of CsA are directly related to the rate of infusion. Furthermore, the renal toxicity which follows repetitive injection of CsA can be minimized or avoided by administering CsA as a slow infusion. In addition to the total dose administered, the rate of infusion is an important determinant of nephrotoxicity.

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.

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.

Decreasing the infusion rate reduces the proarrhythmic risk of NS-7: confirming the relevance of short-term variability of repolarisation in predicting drug-induced torsades de pointes

PubMed Central

Detre, Elke; Thomsen, Morten B; Beekman, Jet D; Petersen, Karl-Uwe; Vos, Marc A

2005-01-01

The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. A fast (5 min intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg−1, n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg−1, n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs with chronic, complete AV block (CAVB), an animal model of TdP (n=6). No electrophysiological effects were seen after 0.3 mg kg−1 NS-7. Fast infusion of 3.0 mg kg−1 caused prolongation of repolarisation, for example, heart rate corrected QT interval (QTc): in SR: 6±1%; in CAVB: 10±7%, which was accompanied by TdP in three of six CAVB dogs. No TdP were seen in SR dogs. Slow infusion did not cause TdP in the same CAVB dogs, although NS-7 caused repolarisation to prolong with a similar magnitude (QTc: 12±7%) as in the fast-infusion experiment. Short-term variability (STV) is a novel parameter for the prediction of drug-induced TdP analysing the beat-to-beat variability of repolarisation. STV was only increased after the fast infusion in CAVB dogs (2.6±0.3 versus 6.0±1.4 ms, P<0.05), while there was no increase (2.1±0.2 versus 2.5±1.0 ms) after the slow infusion of NS-7. Peak plasma concentrations attained were lower in slow (0.5±0.1 μg ml−1 after 50 min) than in fast-infusion regimen (2.1±0.4 μg ml−1 after 5 min; P<0.05). The results support the conclusion that limiting peak plasma concentration by decreasing the rate of infusion of NS-7 reduces the proarrhythmic risk despite comparable prolongation in repolarisation parameters. The relevance of STV in predicting drug-induced TdP was confirmed. PMID:15778734

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

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.

Effects of acetic acid or sodium acetate infused into the rumen or abomasum on feeding behavior and metabolic response of cows in the postpartum period.

PubMed

Gualdrón-Duarte, Laura B; Allen, Michael S

2018-03-01

Effects of continuous isomolar infusions of acetic acid (AcA) or sodium acetate (NAc) infused into the rumen (RU) or into the abomasum (AB) on feeding behavior, dry matter intake (DMI), and metabolic response of cows in the early postpartum period were evaluated. Six rumen-cannulated multiparous Holstein cows (11.8 ± 3.9 d in milk; mean ± SD) were utilized in a 6 × 6 Latin square design experiment balanced for carryover effects with a 2 × 3 factorial arrangement of treatments. Treatments were AcA and NAc, with sodium chloride (CON) as a control, infused at a rate of ˜0.75 mol/h (0.5 L/h) into the RU or AB for the first 8 h following feeding, with a rest day between infusion days. Treatment sequences were assigned randomly to cows. Feeding behavior was recorded by a computerized data acquisition system and blood was sampled at 0, 4, and 8 h relative to the start of infusion. We hypothesized that AcA is more hypophagic than NAc, and that infusion into the AB is more hypophagic than infusion into the RU. Dry matter intakes (DMI) for the CON treatments were similar at 6.2 kg/8 h for RU and 6.1 kg/8 h for AB, and the AcA and NAc treatments interacted with site of infusion to affect DMI. The NAc-RU treatment did not reduce DMI (7.0 kg/8 h), whereas AcA-RU (2.6 kg/8 h), AcA-AB (3.7 kg/8 h), and NAc-AB (4.0 kg/8 h) decreased DMI compared with CON. Following infusions of AcA compared with NAc, there was a residual effect on DMI for the remainder of the day, but treatments did not affect DMI during the rest day. Treatments increased plasma acetate and β-hydroxybutyrate concentrations over time (interaction) and decreased plasma insulin concentration compared with CON. Plasma glucose concentration decreased over time after AcA-AB infusion compared with other treatments and CON. Plasma nonesterified fatty acid concentration increased over time for AcA compared with NAc and CON, suggesting an increase in lipolysis to compensate the decrease in DMI. In contrast to the other treatments, NAc-RU did not decrease DMI compared with control but we cannot determine the reason for this from the data available from the current study. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Lack of effect of pancreatic polypeptide in the rate of gastric emptying and gut hormone release during breakfast.

PubMed

Adrian, T E; Greenberg, G R; Fitzpatrick, M L; Bloom, S R

1981-01-01

Bovine pancreatic polypeptide (PP) was infused intravenously in 5 healthy subjects on two separate occasions with mean doses of 1 and 2 pmol kg-1 min-1, respectively, which achieved plasma levels equal to and twice those observed after a normal mixed breakfast. The gastric emptying rate of a carbohydrate-rich breakfast 20 min after the start of each PP infusion was not significantly different from a control infusion of 0.15 M saline. PP is unlikely to be an important physiological modulator of gastric emptying rate in man.

Vascular dilation, tachycardia, and increased inotropy occur sequentially with increasing epinephrine dose rate, plasma and myocardial concentrations, and cAMP

PubMed Central

Maslov, Mikhail Y.; Wei, Abraham E.; Pezone, Matthew J.; Edelman, Elazer R.; Lovich, Mark A.

2015-01-01

Background While epinephrine infusion is widely used in critical care for inotropic support, there is no direct method to detect the onset and measure the magnitude of this response. We hypothesized that surrogate measurements, such as heart rate and vascular tone, may indicate if the plasma and tissue concentrations of epinephrine and cAMP are in a range sufficient to increase myocardial contractility. Methods Cardiovascular responses to epinephrine infusion (0.05–0.5 mcg·kg−1·min−1) were measured in rats using arterial and left ventricular catheters. Epinephrine and cAMP levels were measured using ELISA techniques. Results The lowest dose of epinephrine infusion (0.05 mcg·kg−1·min−1) did not raise plasma epinephrine level and did not lead to cardiovascular response. Incremental increase in epinephrine infusion (0.1 mcg·kg−1·min−1) elevated plasma but not myocardial epinephrine levels, providing vascular, but not cardiac effects. Further increase in the infusion rate (0.2 mcg·kg−1·min−1) raised myocardial tissue epinephrine levels sufficient to increase heart rate but not contractility. Inotropic and lusitropic effects were significant at the infusion rate of 0.3 mcg·kg−1·min−1. Correlation of plasma epinephrine to hemodynamic parameters suggest that as plasma concentration increases, systemic vascular resistance falls (EC50=47 pg/ml), then HR increases (ED50=168 pg/ml), followed by a rise in contractility and lusitropy (ED50=346 pg/ml and ED50=324 pg/ml accordingly). Conclusions The dose response of epinephrine is distinct for vascular tone, HR and contractility. The need for higher doses to see cardiac effects is likely due to the threshold for drug accumulation in tissue. Successful inotropic support with epinephrine cannot be achieved unless the infusion is sufficient to raise the heart rate. PMID:25790776

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.

[Anesthetic management using esmolol for arthroscopic synovectomy in a patient with thyroid storm].

PubMed

Torigoe, Kei; Suzuki, Hiroto; Nakajima, Waka; Takahashi, Minori; Aoyagi, Mitsuo

2010-02-01

We report a case of a 47-year-old woman with past medical history of Graves disease who presented with thyroid storm, a state of physiologic decompensation due to severe thyrotoxicosis, and arthritis purulenta. Antithyroid therapy ameliorated thyrotoxicosis in 4 days, and arthroscopic synovectomy of the right knee was performed. Anesthesia was induced with intravenous propofol. Esmolol, an ultra-short-acting beta blocker listed in national drug tariff of Japan for intraoperative continuous iv infusion in March 2008, was also administered to control heart rate. Then, laryngeal mask airway was inserted and echo-guided femoral nerve block was done with ropivacaine. Anesthesia was maintained with i.v. infusion of propofol and fentanyl. Short episode of supraventricular tachycardia occurred twice, but each tachycardia disappered in about a half minute. The postoperative course was uneventful. Esmolol probably acted to prevent intraoperative tachycardia due to increased beta-adrenergic tone.

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

Organ toxicity and mortality in propofol-sedated rabbits under prolonged mechanical ventilation.

PubMed

Ypsilantis, Petros; Politou, Maria; Mikroulis, Dimitrios; Pitiakoudis, Michail; Lambropoulou, Maria; Tsigalou, Christina; Didilis, Vasilios; Bougioukas, Georgios; Papadopoulos, Nikolaos; Manolas, Constantinos; Simopoulos, Constantinos

2007-07-01

Prolonged administration of propofol at large doses has been implicated in propofol infusion syndrome in intensive care unit patients. In this study we investigated organ toxicity and mortality of propofol sedation at large doses in prolonged mechanically ventilated rabbits and determined the role of propofol's lipid vehicle. Eighteen healthy male rabbits were endotracheally intubated and sedated with propofol 2% (Group P), sevoflurane (Group S) or sevoflurane while receiving Intralipid 10% (Group SI). Sedation lasted 48 h or until death (Group P) or the maximum surviving period of Group P (Groups S and SI). The initial propofol infusion rate (20 mg x kg(-1) x h(-1)) or sevoflurane concentration (1.5%) was adjusted, if needed, to maintain a standard level of sedation. Blood biochemical analysis was performed in serial blood samples and histologic examination in the heart, lungs, liver, gallbladder, kidneys, urinary bladder, and quadriceps femoris muscle at autopsy. The mortality rate was 100% (surviving period, 26-38 h) for Group P, whereas 0% for Groups S and SI. The initial propofol infusion rate had to be increased up to 65.7 +/- 4.6 mg x kg(-1) x h(-1) and sevoflurane concentration up to 4%. Serum liver function indices, lipids and creatine kinase were significantly increased (P < 0.05) in Groups P and SI and lactate was increased only in Group P, whereas amylase was increased in all groups. In Group P, histologic examination revealed myocarditis, pulmonary edema with interstitial pneumonia, hepatitis, steatosis, and focal liver necrosis, cholangitis, gallbladder necrosis, acute tubular necrosis of the kidneys, focal loss of the urinary bladder epithelium, and rhabdomyolysis of skeletal muscles; in Group S, low-grade bronchitis and incipient inflammation of the liver and the kidneys; and in Group SI, low-grade bronchitis, liver steatosis and hepatitis, and incipient inflammation of the gallbladder, kidneys, and urinary bladder. Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofol's lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.

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

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.

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.

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

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

Kawaoka, Tomokazu; Aikata, Hiroshi, E-mail: aikata@hiroshima-u.ac.jp; Takaki, Shintaro

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% atmore » 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.« less

Measurements of evaporated perfluorocarbon during partial liquid ventilation by a zeolite absorber.

PubMed

Proquitté, Hans; Rüdiger, Mario; Wauer, Roland R; Schmalisch, Gerd

2004-01-01

During partial liquid ventilation (PLV) the knowledge of the quantity of exhaled perfluorocarbon (PFC) allows a continuous substitution of the PFC loss to achieve a constant PFC level in the lungs. The aim of our in vitro study was to determine the PFC loss in the mixed expired gas by an absorber and to investigate the effect of the evaporated PFC on ventilatory measurements. To simulate the PFC loss during PLV, a heated flask was rinsed with a constant airflow of 4 L min(-1) and PFC was infused by different speeds (5, 10, 20 mL h(-1)). An absorber filled with PFC selective zeolites was connected with the flask to measure the PFC in the gas. The evaporated PFC volume and the PFC concentration were determined from the weight gain of the absorber measured by an electronic scale. The PFC-dependent volume error of the CO2SMO plus neonatal pneumotachograph was measured by manual movements of a syringe with volumes of 10 and 28 mL with a rate of 30 min(-1). Under steady state conditions there was a strong correlation (r2 = 0.999) between the infusion speed of PFC and the calculated PFC flow rate. The PFC flow rate was slightly underestimated by 4.3% (p < 0.01). However, this bias was independent from PFC infusion rate. The evaporated PFC volume was precisely measured with errors < 1%. The volume error of the CO2SMO-Plus pneumotachograph increased with increasing PFC content for both tidal volumes (p < 0.01). However for PFC flow rates up to 20 mL/h the error of the measured tidal volumes was < 5%. PFC selective zeolites can be used to quantify accurately the evaporated PFC volume during PLV. With increasing PFC concentrations in the exhaled air the measurement errors of ventilatory parameters have to be taken into account.

Successful management of minoxidil toxicosis in a dog.

PubMed

Jordan, Tyler J M; Yaxley, Page E; Culler, Christine A; Balakrishnan, Anusha

2018-01-15

CASE DESCRIPTION A 2-year-old sexually intact female mixed-breed dog was evaluated at an emergency hospital approximately 5 hours after ingestion of an unknown amount of over-the-counter topical hair growth promoter containing 5% minoxidil foam. Vomiting and signs of lethargy were reported by the owner, and physical examination revealed tachycardia and hypotension. No treatments were performed, and the dog was transferred to a veterinary referral hospital for management of suspected minoxidil toxicosis. CLINICAL FINDINGS On arrival at the referral hospital, the dog was tachycardic (heart rate, 200 to 220 beats/min) and hypotensive (systolic arterial blood pressure, 70 mm Hg). Electrocardiography revealed a regular, narrow-complex tachycardia with no evidence of ventricular ectopy. TREATMENT AND OUTCOME Hypotension was effectively managed with a constant rate infusion of dopamine hydrochloride (12.5 μg/kg/min [5.7 μg/lb/min], IV). Once normotensive, the dog remained tachycardic and a constant rate infusion of esmolol hydrochloride (40 μg/kg/min [18.2 μg/lb/min], IV) was initiated for heart rate control. A lipid emulsion was administered IV as a potential antidote for the toxic effects of the lipophilic minoxidil, with an initial bolus of 1.5 mL/kg (0.7 mL/lb) given over 15 minutes followed by a continuous rate infusion at 0.25 mL/kg/min (0.11 mL/lb/min) for 60 minutes. While hospitalized, the dog also received maropitant citrate and ondansetron. Resolution of clinical signs was achieved with treatment, and the dog was discharged from the hospital 36 hours after admission. Four days later, the owner reported that the dog had made a full recovery and had returned to its typical behavior and activity level at home. CLINICAL RELEVANCE To the authors' knowledge, this is the first report of successful clinical management of accidental minoxidil toxicosis in a dog.

Proof of principle: hydration by low-osmolar mannitol-glucose solution alleviates undesirable renal effects of an iso-osmolar contrast medium in rats.

PubMed

Seeliger, Erdmann; Ladwig, Mechthild; Sargsyan, Lilit; Cantow, Kathleen; Persson, Pontus B; Flemming, Bert

2012-04-01

Saline infusion is widely used to prevent contrast media (CM)-induced acute kidney injury, because it fosters diuresis. Osmodiuretics have a stronger diuretic effect than saline, yet previous trials indicate that osmodiuretic mannitol tends to promote rather than to prevent CM-induced acute kidney injury. However, these studies used hypertonic mannitol solutions that will result in rebound volume contraction. We hypothesize that combining the osmodiuretic effects of a nonhypertonic mannitol solution with sustained volume expansion alleviates undesirable renal effects of CM. Forty-four anesthetized rats were studied by 4 protocols. Urine flow rate, urine viscosity, and glomerular filtration rate (GFR) were measured. Intravenous infusions of hydration solutions were initiated 60 minutes before CM administration and continued throughout the observation period. Hydration by a 3.2% mannitol and 3.2% glucose solution infused at 12 mL/kg per hour (Mannit-Gluc regimen) was compared with a standard regimen of isotonic saline at 4 mL/kg per hour (NaCl regimen); greater infusion rates are required for the Mannit-Gluc regimen because of the profound diuretic effect of mannitol. Two CM were studied: iso-osmolar iodixanol (320 mg I/mL) and low-osmolar iopromide (370 mg I/mL), they were administered as 1.5-mL bolus injection into the thoracic aorta. The Mannit-Gluc regimen resulted in higher urine flow rates than the standard NaCl regimen, yet maintained a good volume status. By virtue of its stronger diuretic effect, the Mannit-Gluc regimen greatly diminished the increase in urine viscosity and completely prevented the transient decrease in GFR caused by iodixanol with the NaCl regimen. After iopromide, the differences between the hydration regimens were much less, as iopromide increased urine flow rates much more than iodixanol, thus resulting in a much smaller increase in viscosity than iodixanol and no decrease in GFR even with the NaCl regimen. This proof of principle study shows that a hydration regimen that combines the osmodiuretic effect of a low-osmolar mannitol-glucose solution with sustained volume expansion is effective in reducing high urine viscosity and preventing GFR reduction caused by iso-osmolar iodixanol. For low-osmolar CM, the beneficial effects seem negligible, because these compounds per se exert greater osmodiuretic action.

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.

[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 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.

Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men.

PubMed

Kuebler, Ulrike; von Känel, Roland; Heimgartner, Nadja; Zuccarella-Hackl, Claudia; Stirnimann, Guido; Ehlert, Ulrike; Wirtz, Petra H

2014-11-01

Mental stress reliably induces increases in salivary alpha amylase (sAA), a suggested surrogate marker for sympathetic nervous system (SNS) reactivity. While stress-induced sAA increases correlate with norepinephrine (NE) secretion, a potential mediating role of noradrenergic mechanisms remains unclear. In this study, we investigated for the first time in humans whether a NE-stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in sAA. In a single-blind placebo-controlled within-subjects design, 21 healthy men (29-66 years) took part in three different experimental trials varying in terms of substance infusion with a 1-min first infusion followed by a 15-min second infusion: saline-infusion (trial-1), NE-infusion (5 μg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2-adrenergic receptors (trial-3). Saliva samples were collected immediately before, during, and several times after substance infusion in addition to blood pressure and heart rate readings. Experimental trials significantly differed in sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic-blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective phentolamine application was verified by blood pressure and heart rate infusion reactivity. Salivary cortisol was not affected by NE, either with or without alpha-adrenergic-blockade. We found that NE-infusion stimulates sAA secretion, regardless of co-administered non-selective alpha-adrenergic blockade by phentolamine, suggesting that the mechanism underlying stress-induced sAA increases may involve NE. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

PubMed

Hirata, Yoshinori; Sata, Makoto; Makiuchi, Yuko; Morikane, Keita; Wada, Akihito; Okabe, Nobuhiko; Tomoike, Hitonobu

2009-12-01

During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

A Functional Melanocortin System May Be Required for Chronic CNS-Mediated Antidiabetic and Cardiovascular Actions of Leptin

PubMed Central

da Silva, Alexandre A.; do Carmo, Jussara M.; Freeman, J. Nathan; Tallam, Lakshmi S.; Hall, John E.

2009-01-01

OBJECTIVE We recently showed that leptin has powerful central nervous system (CNS)-mediated antidiabetic and cardiovascular actions. This study tested whether the CNS melanocortin system mediates these actions of leptin in diabetic rats. RESEARCH DESIGN AND METHODS A cannula was placed in the lateral ventricle of Sprague-Dawley rats for intracerebroventricular infusions, and arterial and venous catheters were implanted to measure mean arterial pressure (MAP) and heart rate 24 h/day and for intravenous infusions. After recovery from surgery for 8 days, rats were injected with streptozotocin (STZ), and 5 days later, either saline or the melanocortin 3 and 4 receptor (MC3/4R) antagonist SHU-9119 (1 nmol/h) was infused intracerebroventricularly for 17 days. Seven days after starting the antagonist, leptin (0.62 μg/h) was added to the intracerebroventricular infusion for 10 days. Another group of diabetic rats was infused with the MC3/4R agonist MTII (10 ng/h i.c.v.) for 12 days, followed by 7 days at 50 ng/h. RESULTS Induction of diabetes caused hyperphagia, hyperglycemia, and decreases in heart rate (−76 bpm) and MAP (−7 mmHg). Leptin restored appetite, blood glucose, heart rate, and MAP back to pre-diabetic values in vehicle-treated rats, whereas it had no effect in SHU-9119–treated rats. MTII infusions transiently reduced blood glucose and raised heart rate and MAP, which returned to diabetic values 5–7 days after starting the infusion. CONCLUSIONS Although a functional melanocortin system is necessary for the CNS-mediated antidiabetic and cardiovascular actions of leptin, chronic MC3/4R activation is apparently not sufficient to mimic these actions of leptin that may involve interactions of multiple pathways. PMID:19491210

Effect of changes in fat availability on exercise capacity in McArdle disease.

PubMed

Andersen, Susanne T; Jeppesen, Tina D; Taivassalo, Tanja; Sveen, Marie-Louise; Heinicke, Katja; Haller, Ronald G; Vissing, John

2009-06-01

The major fuel for exercising muscle at low exercise intensities is fat. To investigate the role of fat metabolism in McArdle disease (also known as glycogen storage disease type V), an inborn error of muscle glycogenolysis, by manipulating free fatty acid availability for oxidation during exercise. Randomized, placebo-controlled, crossover trial. Hospitalized care. Ten patients (8 men and 2 women) with McArdle disease. Patients cycled at a constant workload corresponding to 70% of their maximum oxygen consumption. In random order and on separate days, patients received nicotinic acid (a known blocker of lipolysis) to decrease the availability of free fatty acids or 20% Intralipid infusion to increase free fatty acid availability during exercise. Results were compared with placebo (isotonic sodium chloride solution infusion) and glucose infusion trials. Exercise tolerance was assessed by heart rate response to exercise during different infusions. Free fatty acid levels more than tripled by Intralipid infusion and were halved by nicotinic acid administration. Heart rate was significantly higher during exercise in the Intralipid infusion and nicotinic acid trials compared with the placebo and glucose infusion trials, an effect that was observed before and after the patients had experienced the second wind phenomenon. Lipids are an important source of fuel for exercising muscle in McArdle disease, but maximal rates of fat oxidation seem limited and cannot be increased above physiologically normal rates during exercise. This limitation is probably caused by a metabolic bottleneck in the tricarboxylic acid cycle due to impaired glycolytic flux in McArdle disease. Therapies aimed at enhancing fat use in McArdle disease should be combined with interventions targeting expansion of the tricarboxylic acid cycle.

Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: A matched-pair analysis

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

Das, Prajnan; Lin, Edward H.; Bhatia, Sumita

2006-12-01

Purpose: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU). Methods: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002. Results: In each group, 5more » patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively. Conclusion: Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.« less

Inflammatory breast cancer: enhanced local control with hyperfractionated radiotherapy and infusional vincristine, ifosfamide and epirubicin.

PubMed

Gurney, H; Harnett, P; Kefford, R; Boyages, J

1998-06-01

Local control rate for inflammatory breast cancer (IBC) is < 50% with standard chemotherapy-radiotherapy regimen. Nineteen women (age range 40-65, median 50 years) with IBC (18 patients) or with a primary tumour of > 10 cm (one patient) received a novel treatment comprising hyperfractionated radiotherapy (HFRT) sandwiched between two cycles of infusional chemotherapy using vincristine, ifosfamide and epirubicin (VIE). The primary endpoint was local control. VIE was continuously infused for six weeks via a Hickman's line using a Deltec CADD-1 ambulatory pump. Ifosfamide (3 gm/m2) mixed with equi-dose mesna was infused for seven days and alternated every week with an infusion of epirubicin (50 mg/m2) mixed with vincristine (1.5 mg/m2). HFRT consisted of 1.5 Gy twice daily for 34 frct (51 Gy) followed by a boost of 15 Gy in 10 frct. The total treatment time was less than 22 weeks. Median follow-up was 37 months. Local control rate was 58%. Three patients failed to respond initially and five relapsed in the breast at a median time of 36.8 months. Median overall and disease-free survival was 18 and 25.3 months respectively. Toxicity from VIE was minimal (WHO gd 3 emesis--two patients, gd 3 mucositis--one patient, neutropenic sepsis--three patients). Radiotherapy caused moist desquamation in 17/19 patients. Twenty-four central lines were complicated by seven line infections, three thromboses, and one extravasation. The local control rate of 58% with VIE + HFRT appears similar to reported chemoradiotherapy regimen, although the treatment time of 22 weeks is much shorter than other regimens which take up to 12 months. Toxicity is acceptable. Hickman-related complications need to be reduced. The study is ongoing.

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

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.

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles

PubMed Central

Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-01-01

Abstract Background: Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Methods: Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Results: Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P < 0.001), and 48 hours (10 [10] vs 20 [15]; P < 0.001) in neck area. No statistically significant differences were found between the 2 groups in terms of the requirements for rescue analgesics or the occurrence of adverse events. Conclusion: Intravenous ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events. PMID:27930531

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles: A consort compliant article.

PubMed

Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-12-01

Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P < 0.001), and 48 hours (10 [10] vs 20 [15]; P < 0.001) in neck area. No statistically significant differences were found between the 2 groups in terms of the requirements for rescue analgesics or the occurrence of adverse events. Intravenous ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events.

Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

PubMed

Dubinion, John H; da Silva, Alexandre A; Hall, John E

2011-04-01

Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

The effect of short-term hyperammonaemia on milk synthesis in dairy cows.

PubMed

Purdie, Norm G; Trout, Donald R; Cieslar, Scott R L; Madsen, Torben G; Poppi, Dennis P; Cant, John P

2009-02-01

To test the hypothesis that ammonia detoxification in ruminants consumes amino acids to the detriment of milk protein production, we infused four lactating dairy cows with ammonium acetate or sodium acetate in switchback experiments. Plasma ammonia concentrations increased to 411 microm within 1 h of the start of infusion of ammonium acetate at 567 mmol/h. The rate constant for ammonia clearance from plasma was 0 x 054/min and the half-life was 12 x 9 min. Infusion at 567 mmol/h for 1 h followed by 1 h without infusion, repeated four times between am- and pm-milking, caused a decrease in feed intake. Compared with sodium acetate, continuous infusion of ammonium acetate at 360 mmol/h throughout an entire 10-h milking interval increased plasma ammonia concentrations to 193 microm and caused a 20% decrease in milk, protein and lactose production with no effect on percentage composition of milk or the yield of milk fat. Arterial concentrations of glucose and non-esterified fatty acids tended to increase; there was no effect on arterial acetate, beta-hydroxybutyrate or triacylglcerol, and branched-chain amino acids, Lys and Thr decreased. Mammary plasma flow, estimated by assuming 100% uptake/output of Phe+Tyr, was significantly correlated with milk yield. Mammary uptakes of acetate tended to be reduced by hyperammonaemia, but uptakes of other energy metabolites and amino acids were not affected. Thus, while an increase in amino acid consumption during hyperammonaemia was apparent from the drop in circulating concentrations of Leu, Ile, Val, Lys and Thr, there was no evidence to support the hypothesis that milk yield is affected by the lower concentrations. An ammonia-induced depression in feed intake may have caused the decrease in milk synthesis.

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

PubMed

Savage, A P; Adrian, T E; Carolan, G; Chatterjee, V K; Bloom, S R

1987-02-01

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.

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.

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.

[Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marqués de Valdecilla diagnostic and therapeutic protocol].

PubMed

Martín-Láez, Rubén; Vázquez-Barquero, Alfonso

Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marqués de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (R OUT ) >4.5mmHg/ml/min in bolus infusion test; R OUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high-volume cerebrospinal fluid withdrawal. The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

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.).

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.

[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.

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

Glauber, H.; Wallace, P.; Brechtel, G.

We studied the measurement of hepatic glucose output (HGO) with prolonged (3-/sup 3/H)glucose infusion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Over the course of 10.5 h, plasma glucose concentration fell with fasting by one-third, from 234 +/- 21 to 152 +/- 12 mg/dl, and HGO fell from 2.35 +/- 0.18 to 1.36 +/- 0.07 mg . kg-1 . min-1 (P less than .001). In the basal state, HGO and glucose were significantly correlated (r = 0.68, P = .03), and in individual patients, HGO and glucose were closely correlated as both fell with fasting (mean r = 0.79,more » P less than .01). Plasma (3-/sup 3/H)glucose radioactivity approached a steady state only 5-6 h after initiation of the primed continuous infusion, and a 20% overestimate of HGO was demonstrated by not allowing sufficient time for tracer labeling of the glucose pool. Assumption of steady-state instead of non-steady-state kinetics in using Steele's equations to calculate glucose turnover resulted in a 9-24% overestimate of HGO. Stimulation of glycogenolysis by glucagon injection demonstrated no incorporation of (3-/sup 3/H)glucose in hepatic glycogen during the prolonged tracer infusion. In a separate study, plasma glucose was maintained at fasting levels (207 +/- 17 mg/dl) for 8 h with the glucose-clamp technique. Total glucose turnover rates remained constant during this prolonged tracer infusion. However, HGO fell to 30% of the basal value simply by maintaining fasting hyperglycemia in the presence of basal insulin levels.« less

Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study

PubMed Central

Forceville, Xavier; Laviolle, Bruno; Annane, Djillali; Vitoux, Dominique; Bleichner, Gérard; Korach, Jean-Michel; Cantais, Emmanuel; Georges, Hugues; Soubirou, Jean-Louis; Combes, Alain; Bellissant, Eric

2007-01-01

Introduction Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients. Methods A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded. Results Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups. Conclusion Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious toxicity but did not improve the clinical outcome in septic shock patients. Trial Registration = NCT00207844. PMID:17617901

Acute regulation of plasma leptin by isoprenaline in lean and obese fasted subjects.

PubMed

Baynes, K C R; Nicholas, M D; Shojaee-Moradie, F; Umpleby, A M; Giannoulis, M G

2006-07-01

In human obesity, there is some evidence for impaired adrenergic sensitivity with respect to catecholamine-induced lipolysis. The beta-adrenoceptor agonist isoprenaline has been shown to suppress plasma leptin levels in lean humans in vivo. We hypothesized that a reduced adrenergic sensitivity in obese humans would result in impaired suppression of leptin secretion. Eight obese [Ob, body mass index (BMI) = 33.3 kg/m2] and seven lean (Ln, BMI = 21.8 kg/m2) men were studied after an overnight fast. Intravenous isoprenaline infusion was initiated at a rate of 8 ng/kg/min, titrated up to 24 ng/kg/min over 30 min and continued at this rate for a further 120 min with continuous electrocardiogram monitoring. Baseline fasting plasma leptin was higher in obese compared with lean subjects (Ob 12.2 +/- 1.8, Ln 2.6 +/- 0.6 ng/ml, p < 0.05 unpaired t-test). Baseline fasting glycerol as a measure of lipolysis was similar in both groups (Ob 62.9 +/- 7.6, Ln 42.4 +/- 8.9 micromol/l) and increased from baseline to 150 min by equivalent amounts (Ob +66.9%, Ln +81.2%, p = NS). Plasma leptin decreased from baseline to 150 min with similar relative changes in both groups (Ob -29.2%, Ln -27.8%). Obese subjects show a similar lipolytic and leptin response to acute isoprenaline infusion compared with lean subjects. Impaired beta-adrenergic-induced inhibition of leptin secretion does not appear to contribute to hyperleptinaemia in obese human subjects.

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.

A computerized system to evaluate volumetric infusion pumps.

PubMed

Kobayashi, S; Ogata, T

1992-01-01

A computerized system was developed to examine the performance characteristics of infusion pumps. This system collects solution delivered by an infusion pump through an intravenous needle into a collection vessel. Using an inductor-type weight sensor and a semiconductor type of strain-gauge pressure sensor, the weight of the collection vessel and the pressure at the needle were monitored over a specific period (the sampling time), and changes in pressure, flow rate, and volume of fluid were calculated. This system was applied to five volumetric infusion pumps with different pumping mechanisms. Test conditions involved two different solutions, two sizes of needle gauge, and seven flow rates, for a total of 28 measurements per pump. Results showed considerable variation in the infusion pumps' performances based on differences in these indices. Use of an inductance weight sensor as a means to evaluate gravimetric performance appears to be an improvement over conventional methods, which use analytical balances for data generation. The results indicate that this system will be useful in evaluating the performances of commercially available infusion pumps as well as those in development.

The feasibility of inducing mild therapeutic hypothermia after cardiac resuscitation using iced saline infusion via an intraosseous needle.

PubMed

Mader, Timothy J; Walterscheid, Joshua K; Kellogg, Adam R; Lodding, Cynthia C

2010-01-01

This study was done, using a swine model of prolonged ventricular fibrillation out-of-hospital cardiac arrest, to determine the feasibility of inducing therapeutic hypothermia after successful resuscitation by giving an intraosseous infusion of iced saline. This study was IACUC approved. Liter bags of normal saline, after being refrigerated for at least 24h, were placed in an ice filled cooler. Female Yorkshire swine weighing between 27 and 35 kg were sedated and instrumented under general anesthesia. A temperature probe was inserted 10 cm into the esophagus. Ventricular fibrillation was electrically induced and allowed to continue untreated for 10 min. Animals were randomized to one of two resuscitation schemes for the primary study (N=53). One group had central intravenous access for drug delivery and the other had an intraosseous needle inserted into the proximal tibia for drug administration. Animals in which spontaneous circulation was restored were immediately cooled, for this secondary study, by means of a rapid, pump-assisted infusion of 1L of iced saline either through the intraosseous needle (n=8), the central access (n=6), or a peripheral intravenous catheter (n=7) in a systematic, non-randomized fashion. Room, animal, and saline temperatures were recorded at initiation and upon completion of infusion. The data were analyzed descriptively using Stata SE v8.1 for Macintosh. The baseline characteristics of all three groups were mathematically the same. The average ambient room temperature during the experimental sessions was 25.5 degrees C (SD=1.3 degrees C). There were no statistically significant differences between the three groups with regard to saline temperature, rate of infusion, or decrease in core body temperature. The decrease in core temperature for the intraosseous group was 2.8 degrees C (95% CI=1.8, 3.8) over the infusion period. Mild therapeutic hypothermia can be effectively induced in swine after successful resuscitation of prolonged ventricular fibrillation by infusion of iced saline through an IO needle. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

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).

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

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.

Remifentanil for the insertion and removal of long-term central venous access during monitored anesthesia care.

PubMed

Burlacu, Crina L; McKeating, Kevin; McShane, Alan J

2011-06-01

To determine the analgesic efficacy of three different rates of remifentanil infusion in patients undergoing insertion or removal of long-term central venous access devices during monitored anesthesia care and local anesthetic field infiltration. Double-blinded, randomized, controlled study. Operating theatre of an University hospital. 44 unpremedicated, ASA physical status 1 and 2 patients, aged 18-65 years, undergoing insertion or removal of a Port-a-Cath or Hickman catheter. Patients sedated with a propofol target-controlled infusion were randomly allocated to three groups: Group R25 (n = 14), Group R50 (n = 15), and Group R75 (n = 15), to receive remifentanil 0.025, 0.05, and 0.075 μg/kg/min, respectively. Rescue remifentanil 0.5 μg/kg was administered for pain scores > 3. The remifentanil infusion rate was maintained constant unless respiratory and/or cardiovascular unwanted events occurred, whereupon the rate was adjusted in 0.01 μg/kg/min decrements as necessary. Pain scores (primary outcome), sedation, and movement scores (secondary outcomes) were assessed during local anesthetic infiltration of the anterior chest wall and 5 other procedural steps. All infusion rates had equal analgesic efficacy, as shown by comparable pain scores, number of rescue boluses, and number of patients requiring rescue analgesia. Excessive sedation was associated with the highest remifentanil rate such that Group R75 patients were significantly more sedated than Groups R25 or R50 at selective procedural steps (P < 0.05). More Group R75 patients (6/15) required remifentanil rate reduction than did patients from Group R50 (1/15) or Group R25 (0/14), P < 0.01, most commonly because of respiratory depression. For the insertion or removal of long-term central venous access devices, all three remifentanil infusion rates proved to be equally analgesic-efficient. However, the excessive sedation and tendency to respiratory and cardiovascular events associated with the highest remifentanil infusion rate renders such a rate less desirable for this purpose. Copyright © 2011 Elsevier Inc. All rights reserved.

[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.

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…

Cardiopulmonary effects during anaesthesia induced and maintained with propofol in acepromazine pre-medicated donkeys.

PubMed

Naddaf, Hadi; Baniadam, Ali; Rasekh, Abdolrahman; Arasteh, Abdolmajid; Sabiza, Soroush

2015-01-01

To evaluate the cardiopulmonary effects of anaesthesia induced and maintained with propofol in acepromazine pre-medicated donkeys. Prospective experimental study. Six healthy male donkeys weighing 78-144 kg. Donkeys were pre-medicated with intravenous (IV) acepromazine (0.04 mg kg(-1) ). Ten minutes later, anaesthesia was induced with IV propofol (2 mg kg(-1) ) and anaesthesia maintained by continuous IV infusion of the propofol (0.2 mg kg(-1)  minute(-1) ) for 30 minutes. Baseline measurements of physiological parameters, and arterial blood samples were taken before the acepromazine administration, then 5, 15, 30, 45, and 60 minutes after the induction of anaesthesia. Changes from baseline were analysed by anova for repeated measures. When compared with baseline (standing) values, during anaesthesia heart rate increased throughout: significant at 5 (p = 0.001) and 15 (p = 0.015) minutes. Mean arterial blood pressure increased significantly only at 15 minutes (p < 0.001). Respiratory rate and arterial pH did not change significantly. PaO2 was lower throughout anaethesia, but this only reached significance at 15 minutes (p = 0.041). PaCO2 was statistically (but not clinically) significantly reduced at the times of 30 (p = 0.02), 45 (p = 0.01) and 60 (p = 0.04). Rectal temperature decreased significantly at all times of the study. Administration of propofol by the continuous infusion rate for the maintenance of anaesthesia resulted in stable cardiopulmonary effects and could prove to be clinically useful in donkeys. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Adrenergic control of lipolysis in women compared with men

PubMed Central

Bessesen, Daniel H.; Stotz, Sarah; Peelor, Frederick F.; Miller, Benjamin F.; Horton, Tracy J.

2014-01-01

Data suggest women are more sensitive to the lipolytic action of epinephrine compared with men while maintaining similar glucoregulatory effects (Horton et al. J Appl Physiol 107: 200–210, 2009). This study aimed to determine the specific adrenergic receptor(s) that may mediate these sex differences. Lean women (n = 14) and men (n = 16) were studied on 4 nonconsecutive days during the following treatment infusions: saline (S: control), epinephrine [E: mixed β-adrenergic (lipolytic) and α2-adrenergic (antilipolytic) stimulation], epinephrine + phentolamine (E + P: mixed β-adrenergic stimulation only), and terbutaline (T: selective β2-adrenergic stimulation). Tracer infusions of glycerol, palmitate, and glucose were administered to determine systemic lipolysis, free fatty acid (FFA) release, and glucose turnover, respectively. Following basal measurements, substrate and hormone concentrations were measured in all subjects over 90 min of treatment and tracer infusion. Women had greater increases in glycerol and FFA concentrations with all three hormone infusions compared with men (P < 0.01). Glycerol and palmitate rate of appearance (Ra) and rate of disappearance (Rd) per kilogram body weight were greater with E infusion in women compared with men (P < 0.05), whereas no sex differences were observed with other treatments. Glucose concentration and kinetics were not different between sexes with any infusion. In conclusion, these data support the hypothesis that the greater rate of lipolysis in women with infusion of E was likely due to lesser α2 antilipolytic activation. These findings may help explain why women have greater lipolysis and fat oxidation during exercise, a time when epinephrine concentration is elevated. PMID:25190743

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

PubMed Central

Savage, A P; Adrian, T E; Carolan, G; Chatterjee, V K; Bloom, S R

1987-01-01

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology. PMID:3557189

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.

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

Postoperative administration of landiolol hydrochloride for patients with supraventricular arrhythmia: the efficacy of sustained intravenous infusion at a low dose.

PubMed

Wariishi, Seiichiro; Yamashita, Koichi; Nishimori, Hideaki; Fukutomi, Takashi; Yamamoto, Masaki; Radhakrishnan, Geethalakshmi; Sasaguri, Shiro

2009-11-01

The purpose of this study was to investigate the efficacy of landiolol hydrochloride, a short-acting beta(1) blocker, by initiating its administration at a low dose (5 microg kg(-1) min(-1)) in patients with postoperative supraventricular arrhythmia. The efficacy of landiolol was evaluated in 38 patients who, after developing postoperative atrial flutter or fibrillation, with sinus tachycardia and two patients who had a history of paroxysmal atrial fibrillation with frequent atrial extrasystole. The heart rate and blood pressure before and 2 h after the administration of landiolol were compared. A return to the sinus rhythm from supraventricular arrhythmia was noted in 89%. The heart rate was reduced from 137+/-26 bpm (before landiolol administration) to 93+/-18 bpm (2 h after the start of the medication, P<0.01). As an agent to correct an arrhythmic condition, landiolol successfully raised the systolic blood pressure from 108+/-24 mmHg (before medication) to 120+/-19 mmHg (2 h after the medication was started, P<0.05). Continuous intravenous infusion of landiolol at a low dose was found to be effective for postoperative supraventricular arrhythmia.

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.

Immunodeficiencies

PubMed Central

Ballow, M; Notarangelo, L; Grimbacher, B; Cunningham-Rundles, C; Stein, M; Helbert, M; Gathmann, B; Kindle, G; Knight, A K; Ochs, H D; Sullivan, K; Franco, J L

2009-01-01

Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented. PMID:19883420

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.

The Effect of an Amino Acid Infusion on Central Thermoregulatory Control in Humans

PubMed Central

Nakajima, Yasufumi; Takamata, Akira; Matsukawa, Takashi; Sessler, Daniel I.; Kitamura, Yoshihiro; Ueno, Hiroshi; Tanaka, Yoshifumi; Mizobe, Toshiki

2005-01-01

Background Administration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. We thus tested the hypothesis that amino acid infusion increases the thermoregulatory setpoint. Methods Nine male volunteers each participated on four study days in randomized order: 1) intravenous amino acids infused at 4 kJ·kg−1·hr−1 for 2.5 h combined with skin-surface warming; 2) amino acid infusion combined with cutaneous cooling; 3) a saline infusion combined with skin-surface warming; and, 4) saline infusion combined with cutaneous cooling. Results Amino acid infusion increased resting core temperature by 0.3 ± 0.1°C (mean ± SD) and oxygen consumption by 18 ± 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean-skin temperature of 34°C) for active cutaneous vasodilation by 0.3 ± 0.3°C, for sweating by 0.2 ± 0.2°C, for thermoregulatory vasoconstriction by 0.3 ± 0.3°C, and for thermogenesis by 0.4 ± 0.5°C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. Conclusions Amino acid infusion increased the metabolic rate and resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the setpoint increase — even in a cold environment with amble potential to dissipate heat. In subjects with intact thermoregulatory defenses, amino acid-induced hyperthermia appears to result from an elevated setpoint increase rather than increased metabolic rate per se. PMID:15108979

A comparison of the hourly output between the Ambu® Smart-Infuser™ Pain Pump and the On-Q Pump® with Select-A-Flow™ Variable Rate Controller with standard and overfill volumes.

PubMed

Iliev, Peter; Bhalla, Tarun; Tobias, Joseph D

2016-04-01

The Ambu Smart-Infuser Pain Pump and the On-Q Pump with Select-a-Flow Variable Rate Controller are elastomeric devices with a flow regulator that controls the rate of infusion of a local anesthetic agent through a peripheral catheter. As a safety evaluation, we evaluated the infusion characteristics of these two devices when filled with manufacturer recommended standard volumes and when overfilled with a volume 50% in excess of that which is recommended. Nineteen disposable devices from the two manufacturers were used in this study. Nine were filled with 0.9% normal saline according to the respective manufacturers' recommendations (four Ambu pumps were filled with 650 ml and five On-Q pumps were filled with 550 ml) and 10 devices were 150% overfilled (five Ambu pumps were filled with 975 ml and five On-Q pumps were filled with 825 ml). All of the devices were set to infuse at 10 ml · h(-1) at room temperature (21°C) for 12 h. The fluid delivered during each 2-h period was measured using a graduated column. The On-Q pump (in the settings of normal fill and 150% overfill) delivered a significantly higher output per hour than the set rate during the first 8 h, while the Ambu pump delivered a value close to the set rate of 10 ml · h(-1). No significant difference in the hourly delivered output was noted for either device when comparing the normal fill to the 150% overfill groups. This investigation demonstrates that no change in the hourly output occurs with overfilling of these home infusion devices. However, as noted previously, the hourly output from the On-Q device is significantly higher than the set rate during the initial 8 h of infusion which could have potential clinical implications. © 2016 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.

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.

Residue pattern of polycyclic aromatic hydrocarbons during green tea manufacturing and their transfer rates during tea brewing.

PubMed

Gao, Guanwei; Chen, Hongping; Liu, Pingxiang; Hao, Zhenxia; Ma, Guicen; Chai, Yunfeng; Wang, Chen; Lu, Chengyin

2017-06-01

Residues of polycyclic aromatic hydrocarbons (PAHs) in green tea and tea infusion were determined using gas chromatography-tandem mass spectrometry to study their dissipation pattern during green tea processing and infusion. Concentration and evaporation of PAHs during tea processing were the key factors affecting PAH residue content in product intermediates and in green tea. PAH residues in tea leaves increased by 2.4-3.1 times during the manufacture of green tea using the electric heating model. After correction to dry weight, PAH residue concentrations decreased by 33.5-48.4% during green tea processing because of PAH evaporation. Moreover, spreading and drying reduced PAH concentrations. The transfer rates of PAH residues from green tea to infusion varied from 4.6% to 7.2%, and PAH leaching was higher in the first infusion than in the second infusion. These results are useful for assessing exposure to PAHs from green tea and in formulating controls for the maximum residue level of PAHs in green tea.

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.

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.

Comparison of the cardiopulmonary effects of anesthesia maintained by continuous infusion of romifidine, guaifenesin, and ketamine with anesthesia maintained by inhalation of halothane in horses.

PubMed

McMurphy, Rose M; Young, Lesley E; Marlin, David J; Walsh, Karen

2002-12-01

To compare cardiopulmonary responses during anesthesia maintained with halothane and responses during anesthesia maintained by use of a total intravenous anesthetic (TIVA) regimen in horses. 7 healthy adult horses (1 female, 6 geldings). Each horse was anesthetized twice. Romifidine was administered IV, and anesthesia was induced by IV administration of ketamine. Anesthesia was maintained for 75 minutes by administration of halothane (HA) or IV infusion of romifidine, guaifenesin, and ketamine (TIVA). The order for TIVA or HA was randomized. Cardiopulmonary variables were measured 40, 60, and 75 minutes after the start of HA orTIVA. Systolic, diastolic, and mean carotid arterial pressures, velocity time integral, and peak acceleration of aortic blood flow were greater, and systolic, diastolic, and mean pulmonary arterial pressure were lower at all time points for TIVA than for HA. Pre-ejection period was shorter and ejection time was longer for TIVA than for HA. Heart rate was greater for HA at 60 minutes. Minute ventilation and alveolar ventilation were greater and inspiratory time was longer for TIVA than for HA at 75 minutes. The PaCO2 was higher at 60 and 75 minutes for HA than forTIVA. Horses receiving a constant-rate infusion of romifidine, guaifenesin, and ketamine maintained higher arterial blood pressures than when they were administered HA. There was some indication that left ventricular function may be better during TIVA, but influences of preload and afterload on measured variables could account for some of these differences.

Calorigenic effect of glucagon and catecholamines in king penguin chicks.

PubMed

Barre, H; Rouanet, J L

1983-06-01

The calorigenic action of glucagon and catecholamine infusion was evaluated in winter-acclimatized king penguin chicks at 20 and 0 degrees C ambient temperature (Ta). At Ta = 20 degrees C the mean increase in metabolic rate was 0.73 W . kg-1 for epinephrine (80 micrograms . kg-1), 0.42 W . kg-1 for norepinephrine (150 micrograms . kg-1), and 1.16 W . kg-1 for glucagon (0.75 micrograms . kg-1); i.e., respectively 30, 17, and 47% of the control value. The maximum response to glucagon reached 89% over control. At Ta = 0 degrees C, for the same glucagon infusion, the mean increase in specific metabolic rate was 0.84 W . kg-1, 27% of control rate. In the cold, glucagon infusion inhibited shivering and substituted its calorigenic action, resulting in a less apparent effect. In contrast with the negligible effect of catecholamines, glucagon infused at low doses exerted a powerful calorigenic action in young king penguins and could be considered as a possible nonshivering thermogenesis mediator.

Transition rates of selected metals determined in various types of teas (Camellia sinensis L. Kuntze) and herbal/fruit infusions.

PubMed

Schulzki, Grit; Nüßlein, Birgit; Sievers, Hartwig

2017-01-15

Teas and raw materials used as ingredients of herbal and fruit infusions (HFI) were analysed by means of ICP-MS for their content of aluminium, arsenic, cadmium, copper, lead and mercury in the dry product and in the infusion. Samples of tea (Camellia sinensis L. Kuntze) were selected to include different origins, types (black, green), leaf grades (whole leaf, broken, fannings, dust) and manufacturing techniques (orthodox, "crush, tear, curl"). The selected HFI raw materials (chamomile, elderberries, fennel, hibiscus, mate, peppermint, rooibos and rose hip) cover the most important matrices (flower, fruit, seed, herb, leaf) and reflect the economic significance of these HFI materials in trade. Infusions were prepared under standardised conditions representing typical household brewing. Transition rates for the investigated metals vary significantly but are mostly well below 100%. We propose default transition rates for metals to avoid overestimation of exposure levels from tea/HFI consumption. Copyright © 2016. Published by Elsevier Ltd.

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)

Gluconeogenesis, non-essential amino acid synthesis and substrate partitioning in chicken embryos during later development.

PubMed

Hu, Q; Agarwal, U; Bequette, B J

2017-02-01

We aimed to quantify the rate of gluconeogenesis (GNG), non-essential amino-acid (NEAA) synthesis, and substrate partitioning to the Krebs cycle in embryonic (e) day e14 and e19 chicken embryos. An in ovo continuous tracer infusion approach was employed to test the hypotheses that GNG and NEAA synthesis in developing chicken embryo increases from e14 to e19. [ 13 C 6 ]Glucose or [ 13 C 3 ]glycerol was continuously infused (8 h) into the chorio-allantoic compartment of eggs on e14 and e19. Glucose entry rate, Cori cycling, and GNG were higher (P < 0.05) in e19 compared to e14 embryos, presumably to support higher glycogen deposition in liver and muscle. Whereas de novo synthesis of alanine, aspartate, and glutamate via glycolysis and the Krebs cycle was higher (P < 0.01) in e14 embryos, synthesis of these NEAA from glycerol was higher (P < 0.05) in e19 compared to e14 embryos. These patterns of glucose and glycerol utilization suggest a metabolic shift to conserve glucose for glycogen synthesis and an increased utilization of yolk glycerol (from triacylglyceride) after e14. Although the contribution of glycerol to GNG in e19 embryos was higher (P < 0.05) than that in e14 embryos, the contribution of glycerol to GNG (1.3 to 6.0%) was minor. Based on [ 13 C 6 ]glucose tracer kinetics, the activities of both pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) in the liver were higher (P < 0.05) in e19 embryos; whereas the higher (P < 0.01) relative activity of liver PC compared to PDH in e14 embryos suggests a greater anaplerotic flux into the Krebs cycle. In summary, the in ovo continuous tracer infusion approach allowed for a measurement of chicken embryo whole body and liver metabolism over a shorter window of development. This study provided quantitative estimates of the developmental shifts in substrate utilization, GNG, and NEAA synthesis by chicken embryos, as well as qualitative estimates of the activities of enzymes central to the Krebs cycle, glucose, and fatty acid metabolism. © 2016 Poultry Science Association Inc.

Fault Detection and Safety in Closed-Loop Artificial Pancreas Systems

PubMed Central

2014-01-01

Continuous subcutaneous insulin infusion pumps and continuous glucose monitors enable individuals with type 1 diabetes to achieve tighter blood glucose control and are critical components in a closed-loop artificial pancreas. Insulin infusion sets can fail and continuous glucose monitor sensor signals can suffer from a variety of anomalies, including signal dropout and pressure-induced sensor attenuations. In addition to hardware-based failures, software and human-induced errors can cause safety-related problems. Techniques for fault detection, safety analyses, and remote monitoring techniques that have been applied in other industries and applications, such as chemical process plants and commercial aircraft, are discussed and placed in the context of a closed-loop artificial pancreas. PMID:25049365

The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.

PubMed Central

Gregory, P C; Rayner, D V

1987-01-01

1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine. PMID:3656166

The effects of ketamine on the minimum alveolar concentration of isoflurane in cats.

PubMed

Pascoe, Peter J; Ilkiw, Janet E; Craig, Carolyn; Kollias-Baker, Cynthia

2007-01-01

To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine. Prospective, experimental trial. Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg. Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study. The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted. The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.

Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control.

PubMed

Huang, Chunxia; Ng, Olivia Tsz-Wa; Ho, Yuen-Shan; Irwin, Michael Garnet; Chang, Raymond Chuen-Chung; Wong, Gordon Tin-Chun

2016-01-01

Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

2017-02-01

Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

Renal effects of multiple infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution in dogs.

PubMed

Takahashi, T; Iwasaki, K; Malchesky, P S; Harasaki, H; Matsushita, M; Nosé, Y; Rolin, H; Hall, P M

1993-03-01

Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out-dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and CH2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na+ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl-beta-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The results demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.

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.

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

PubMed

Özcan, Behiye; Neggers, Sebastian J C M M; Miller, Anne Reifel; Yang, Hsiu-Chiung; Lucaites, Virginia; Abribat, Thierry; Allas, Soraya; Huisman, Martin; Visser, Jenny A; Themmen, Axel P N; Sijbrands, Eric J G; Delhanty, Patric J D; van der Lely, Aart Jan

2014-06-01

The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10  μg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome. © 2014 European Society of Endocrinology.

Variable use of amiodarone is associated with a greater risk of recurrence of atrial fibrillation in the critically ill.

PubMed

Mitrić, Goran; Udy, Andrew; Bandeshe, Hiran; Clement, Pierre; Boots, Rob

2016-04-02

Atrial fibrillation is a common rhythm disturbance in the general medical-surgical intensive care unit. Amiodarone is a popular drug in this setting but evidence to inform clinical practice remains scarce. We aimed to identify whether variation in the clinical use of amiodarone was associated with recurrent atrial fibrillation. This was a retrospective audit of 177 critically ill patients who developed new-onset atrial fibrillation after admission to a tertiary level medical-surgical trauma intensive care unit. Patterns of amiodarone prescription (including dosage schedule and duration) were assessed in relation to recurrence of atrial fibrillation during the intensive care unit stay. Known recurrence risk factors, such as inotrope administration, cardiac disease indices, Charlson Comorbidity Index, magnesium concentrations, fluid balance, and potassium concentrations, were also included in adjusted analysis using forward stepwise logistic regression modelling. The cohort had a median (interquartile range) age of 69 years (60-75), Acute Physiology and Chronic Health Evalution II score of 22 (17-28) and Charlson Comorbidity Index of 2 (1-4). A bolus dose of amiodarone followed by infusion (P = 0.02), in addition to continuing amiodarone infusion through to discharge from the intensive care unit (P < 0.001), were associated with less recurrent dysrhythmia. Recurrence after successful treatment was associated with ceasing amiodarone while an inotrope infusion continued (P < 0.001), and was more common in patients with a prior history of congestive cardiac failure (P = 0.04), and a diagnosis of systemic inflammatory response syndrome (P = 0.02). Amiodarone should be administered as a bolus dose followed immediately with an infusion when treating atrial fibrillation in the medical-surgical intensive care unit. Consideration should be given to continuing amiodarone infusions in patients on inotropes until they are ceased.

SMARTDIAB: a communication and information technology approach for the intelligent monitoring, management and follow-up of type 1 diabetes patients.

PubMed

Mougiakakou, Stavroula G; Bartsocas, Christos S; Bozas, Evangelos; Chaniotakis, Nikos; Iliopoulou, Dimitra; Kouris, Ioannis; Pavlopoulos, Sotiris; Prountzou, Aikaterini; Skevofilakas, Marios; Tsoukalis, Alexandre; Varotsis, Kostas; Vazeou, Andrianni; Zarkogianni, Konstantia; Nikita, Konstantina S

2010-05-01

SMARTDIAB is a platform designed to support the monitoring, management, and treatment of patients with type 1 diabetes mellitus (T1DM), by combining state-of-the-art approaches in the fields of database (DB) technologies, communications, simulation algorithms, and data mining. SMARTDIAB consists mainly of two units: 1) the patient unit (PU); and 2) the patient management unit (PMU), which communicate with each other for data exchange. The PMU can be accessed by the PU through the internet using devices, such as PCs/laptops with direct internet access or mobile phones via a Wi-Fi/General Packet Radio Service access network. The PU consists of an insulin pump for subcutaneous insulin infusion to the patient and a continuous glucose measurement system. The aforementioned devices running a user-friendly application gather patient's related information and transmit it to the PMU. The PMU consists of a diabetes data management system (DDMS), a decision support system (DSS) that provides risk assessment for long-term diabetes complications, and an insulin infusion advisory system (IIAS), which reside on a Web server. The DDMS can be accessed from both medical personnel and patients, with appropriate security access rights and front-end interfaces. The DDMS, apart from being used for data storage/retrieval, provides also advanced tools for the intelligent processing of the patient's data, supporting the physician in decision making, regarding the patient's treatment. The IIAS is used to close the loop between the insulin pump and the continuous glucose monitoring system, by providing the pump with the appropriate insulin infusion rate in order to keep the patient's glucose levels within predefined limits. The pilot version of the SMARTDIAB has already been implemented, while the platform's evaluation in clinical environment is being in progress.

Evidence for central venous pressure resetting during initial exposure to microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Ludwig, D. A.; Elliott, J. J.; Wade, C. E.

2001-01-01

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

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

Continuous subcutaneous insulin infusion allows tolerance induction and diabetes treatment in a type 1 diabetic child with insulin allergy.

PubMed

Hasselmann, C; Pecquet, C; Bismuth, E; Raverdy, C; Sola-Gazagnes, A; Lobut, J-B; Carel, J-C; Tubiana-Rufi, N

2013-04-01

Insulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin. Three months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA1c 7.6%). In T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the "honeymoon" period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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.

Effects of intravenous delivery systems on infused red blood cells.

PubMed

Gibson, J S; Leff, R D; Roberts, R J

1984-03-01

The effects of various intravenous delivery systems on the integrity of infused red blood cells (RBCs) were studied. Using a factorial design, whole blood and packed RBCs were infused through i.v. delivery systems employing various combinations of i.v. tubing diameter and length, needle gauge, infusion rate (5 and 50 ml/hr), type of infusion pump (piston, diaphragm, or peristaltic operation), and type of blood product. The age and temperature of the blood filter used were held constant. A 5-ml sample of the blood product obtained during each experimental run was analyzed for plasma free-hemoglobin to assess the degree of hemolysis. Osmotic fragility of the RBCs was evaluated by measuring the percentage of hemolysis in the blood products in various concentrations of sodium chloride solution. Type of blood product and i.v. pump were the only variables significantly influencing RBC hemolysis. In both blood products, a greater degree of hemolysis occurred with the peristaltic-type pump than with the other types of pumps. In packed RBCs, the diaphragm-type pump produced greater hemolysis than the piston-type pump, but hemolysis was similar in whole-blood samples. Regardless of the type of pump, more hemolysis occurred in whole blood at the 5-ml/hr infusion rate than at the 50-ml/hr rate, but the converse was true in packed RBCs. Samples of both blood products were less osmotically fragile than their respective controls at sodium chloride concentrations ranging from 0.30 to 0.50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

NASA Technical Reports Server (NTRS)

Kumagai, Kazuhiro; Reid, Ian A.

1994-01-01

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

Continuous thermographic observation may predict extravasation in chemotherapy-treated patients.

PubMed

Oya, Maiko; Murayama, Ryoko; Oe, Makoto; Yabunaka, Koichi; Tanabe, Hidenori; Takahashi, Toshiaki; Matsui, Yuko; Otomo, Eiko; Komiyama, Chieko; Sanada, Hiromi

2017-06-01

Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation. Outpatients undergoing chemotherapy using peripheral intravenous catheters were enrolled in this prospective observational study. We filmed and classified infrared thermography movies of puncture sites during infusion; ultrasonography was also utilized at puncture sites to observe the subcutaneous condition. Multiple logistic regression analysis was performed to examine the association of thermographic patterns with induration or necrosis observed on the next chemotherapy day. Differences in patient characteristics, puncture sites, and infusions were analyzed by Mann-Whitney's U test and Fisher's exact test according to thermographic patterns. Eight patients developed induration among 74 observations in 62 patients. Among six thermographic patterns, a fan-shaped lower temperature area gradually spreading from the puncture site (fan at puncture site) was significantly associated with induration. Ultrasonography revealed that catheters of patients with fan at puncture site remained in the vein at the end of infusion, indicating that the infusion probably leaked from the puncture site. Patients with fan at puncture site had no significant differences in characteristics and infusion conditions compared with those with the other five thermographic patterns. We determined that fan at puncture site was related to induration caused by extravasation. Continuous thermographic observation may enable us to predict adverse events of chemotherapy. Copyright © 2017. Published by Elsevier Ltd.

Pathology in Continuous Infusion Studies in Rodents and Non-Rodents and ITO (Infusion Technology Organisation)-Recommended Protocol for Tissue Sampling and Terminology for Procedure-Related Lesions

PubMed Central

Weber, Klaus; Mowat, Vasanthi; Hartmann, Elke; Razinger, Tanja; Chevalier, Hans-Jörg; Blumbach, Kai; Green, Owen P.; Kaiser, Stefan; Corney, Stephen; Jackson, Ailsa; Casadesus, Agustin

2011-01-01

Many variables may affect the outcome of continuous infusion studies. The results largely depend on the experience of the laboratory performing these studies, the technical equipment used, the choice of blood vessels and hence the surgical technique as well the quality of pathological evaluation. The latter is of major interest due to the fact that the pathologist is not involved until necropsy in most cases, i.e. not dealing with the complicated surgical or in-life procedures of this study type. The technique of tissue sampling during necropsy and the histology processing procedures may influence the tissues presented for evaluation, hence the pathologist may be a source of misinterpretation. Therefore, ITO proposes a tissue sampling procedure and a standard nomenclature for pathological lesions for all sites and tissues in contact with the port-access and/or catheter system. PMID:22272050

[Continuous subcutaneous infusion in palliative care, an undervalued method].

PubMed

van Marum, R J; de Vogel, E M; Zylicz, Z

2002-11-23

Three patients, 2 men aged 55 and 54 years and a woman aged 86 years, were admitted to hospital for treatment of symptoms resulting from terminal disease (pain, agitation, nausea etc.). In all three patients, continuous subcutaneous infusion (CSI) of medication was successfully used to control the symptoms. Compared with intravenous infusion, the technique of CSI is easy to learn and is associated with fewer complications. Its reliability and ease-of-use make it a technique that can be used not only in a hospital setting, but also in general practice and nursing homes. Medication used in palliative care (e.g. morphine, haloperidol, metoclopramide, levomepromazine, midazolam) can often be administered safely by CSI. In palliative care, where goals should be accomplished with minimal burden to the patient, CSI must be considered the technique of choice in patients who are unable to swallow their medication.

Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

PubMed

Fernández-Pajarín, Gustavo; Sesar, Ángel; Ares, Begoña; Castro, Alfonso

2016-10-19

There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

Lipid emulsions – Guidelines on Parenteral Nutrition, Chapter 6

PubMed Central

Adolph, M.; Heller, A. R.; Koch, T.; Koletzko, B.; Kreymann, K. G.; Krohn, K.; Pscheidl, E.; Senkal, M.

2009-01-01

The infusion of lipid emulsions allows a high energy supply, facilitates the prevention of high glucose infusion rates and is indispensable for the supply with essential fatty acids. The administration of lipid emulsions is recommended within ≤7 days after starting PN (parenteral nutrition) to avoid deficiency of essential fatty acids. Low-fat PN with a high glucose intake increases the risk of hyperglycaemia. In parenterally fed patients with a tendency to hyperglycaemia, an increase in the lipid-glucose ratio should be considered. In critically ill patients the glucose infusion should not exceed 50% of energy intake. The use of lipid emulsions with a low phospholipid/triglyceride ratio is recommended and should be provided with the usual PN to prevent depletion of essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic steatosis. Biologically active vitamin E (α-tocopherol) should continuously be administered along with lipid emulsions to reduce lipid peroxidation. Parenteral lipids should provide about 25–40% of the parenteral non-protein energy supply. In certain situations (i.e. critically ill, respiratory insufficiency) a lipid intake of up to 50 or 60% of non-protein energy may be reasonable. The recommended daily dose for parenteral lipids in adults is 0.7–1.3 g triglycerides/kg body weight. Serum triglyceride concentrations should be monitored regularly with dosage reduction at levels >400 mg/dl (>4.6 mmol/l) and interruption of lipid infusion at levels >1000 mg/dl (>11.4 mmol/l). There is little evidence at this time that the choice of different available lipid emulsions affects clinical endpoints. PMID:20049078

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes

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

Shaw, J.H.; Wolfe, R.R.

1988-03-01

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4more » +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC.« less

Vasopressin release induced by water deprivation - Effects of centrally administered saralasin

NASA Technical Reports Server (NTRS)

Keil, L. C.; Dundore, R. L.; Wurpel, J. N. D.; Severs, W. B.; Barbella, Y. R.

1983-01-01

Uncertainty exists as to whether endogenous angiotensin activates brain mechanisms controlling vasopressin (AVP) secretion during dehydration. Various doses of saralasin were injected into a lateral cgrebroventricle (IVT) of conscious, male rats deprived of water for 48 h. The rats were killed at different times. The concentration of AVP in the plasma p(AVP), measured by radioimmunoassay, was unaffected by saralasin. IVT pretreatment with 1-Sar-8-Ile-angiotensin II blocked maximal AVP release by IVT angiotensin, but this pretreatment did not reduce p(AVP) after 24, 48 or 72 hr water deprivation. A 3-hour continuous IVT infusion of CSF or saralasin (10 micrograms/hour) into 48-hour water-deprived rats revealed equivalent p(AVP) concentration and urine volumes. When the infusions were continued for 3 h more with water available, control and saralasin-treated rats: (1) drank at similar rates, (2) excreted similar amounts of urine, and (3) reduced their p(AVP) concentration levels to the same extent. IVT saralasin did not affect p(AVP) concentration of rats dehydrated with hypertonic NaCl. Combined IVT saralasin and atropine reduced p(AVP) concentration of 48-hour water deprived rats about 30 percent (p less than 0.05). It is concluded that redundancy exists for sensing, integrating and releasing vasopressin in dehydrated rats.

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.

Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings.

PubMed

Rush, Eric T; DeHaai, Kristi; Kreikemeier, Rose M; Lutz, Richard E

2012-01-01

The use of bisphosphonates in children to treat low bone mineral density has increased. Safety and efficacy of pamidronate has been previously demonstrated. However, little research has been done on pamidronate infusion in the home health setting for patients with metabolic bone disease. Data were collected via a survey to assess satisfaction and convenience of infusions. Adverse events were measured by collecting calcium levels before and after infusions. Infusion costs were estimated from the standard orders from one home health agency and our infusion center. We found no difference in the rates of hypocalcemia between the two groups. The survey results showed high satisfaction for both groups, with higher scores in the home health group for convenience and stress. Home health infusions showed lower cost and less absenteeism from school and work. Home health-based pamidronate infusion appears to be safe, less expensive, and is associated with high patient satisfaction.

Regulation of branchial V-H(+)-ATPase, Na(+)/K(+)-ATPase and NHE2 in response to acid and base infusions in the Pacific spiny dogfish (Squalus acanthias).

PubMed

Tresguerres, Martin; Katoh, Fumi; Fenton, Heather; Jasinska, Edyta; Goss, Greg G

2005-01-01

To study the mechanisms of branchial acid-base regulation, Pacific spiny dogfish were infused intravenously for 24 h with either HCl (495+/- 79 micromol kg(-1) h(-1)) or NaHCO(3) (981+/-235 micromol kg(-1) h(-1)). Infusion of HCl produced a transient reduction in blood pH. Despite continued infusion of acid, pH returned to normal by 12 h. Infusion of NaHCO(3) resulted in a new steady-state acid-base status at approximately 0.3 pH units higher than the controls. Immunostained serial sections of gill revealed the presence of separate vacuolar proton ATPase (V-H(+)-ATPase)-rich or sodium-potassium ATPase (Na(+)/K(+)-ATPase)-rich cells in all fish examined. A minority of the cells also labeled positive for both transporters. Gill cell membranes prepared from NaHCO(3)-infused fish showed significant increases in both V-H(+)-ATPase abundance (300+/-81%) and activity. In addition, we found that V-H(+)-ATPase subcellular localization was mainly cytoplasmic in control and HCl-infused fish, while NaHCO(3)-infused fish demonstrated a distinctly basolateral staining pattern. Western analysis in gill membranes from HCl-infused fish also revealed increased abundance of Na(+)/H(+) exchanger 2 (213+/-5%) and Na(+)/K(+)-ATPase (315+/-88%) compared to the control.

Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.

PubMed

Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

1985-09-01

The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.

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.

Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast.

PubMed

Seol, Ja Young; Yoon, Ji Young; Jeong, Hee Sun; Joo, Nami; Choi, Soon Young

2016-01-01

Many researchers revealed that collagen contribute to maintaining the skin's elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity.

Effects of noradrenaline on human vagal baroreflexes

NASA Technical Reports Server (NTRS)

Airaksinen, K. E.; Huikuri, H. V.; Huhti, L.; Kuusela, T. A.; Tahvanainen, K. U.; Tulppo, M.; Makikallio, T.; Eckberg, D. L.

2001-01-01

BACKGROUND: Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function. AIM: To understand better the role of NA in cardiovascular homeostasis. METHODS: We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz. RESULTS: The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (+/- SD) baseline level of 17.3+/-6.6 to 34.1+/-20.8 ms/mmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0+/-12.9 to 10.1+/-7.4 during the low NA infusion rate and to 6.2+/-6.2% during the high rate (P < 0.05 and 0.01, respectively). CONCLUSIONS: Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.

Cardiovascular adverse effects of phenytoin.

PubMed

Guldiken, B; Rémi, J; Noachtar, Soheyl

2016-05-01

Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses.

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.

Assessment of right liver graft perfusion effectiveness between one and two-catheter infusion methods.

PubMed

Jung, Bo-Hyun; Hwang, Shin; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Kim, Ki-Hun; Ahn, Chul-Soo; Moon, Deok-Bog; Park, Gil-Chun; Kang, Sung-Hwa; Yoon, Young-In; Lee, Sung-Gyu

2014-05-01

Conventional graft perfusion method using one small-caliber catheter takes a relatively long time for right liver graft perfusion, thus some modification is needed. In this study, we intended to assess the effectiveness of right liver graft perfusion methods through comparison of different infusion catheters. The study consisted of two parts including one bench experiment to obtain data of hydraulic infusion and one clinical trial of 40 cases on graft perfusion with one- versus two-catheter infusion methods. These two graft infusion methods were compared in terms of the perfusion time and washing-out efficiency. At bench experiment, the infusion flow rate and infusion pressure were 3.3 ml/sec and 1.9 cmH20 in one blood transfusion catheter group, and 11.7 ml/sec and 3.1 cmH20 in single transurethral resection of prostate irrigation catheter group, and 6.6 ml/sec and 2.0 cmH20 in two blood transfusion catheters group, respectively. In clinical trial with 40 right liver grafts, two-catheter group had a shorter graft portal perfusion time for the first 2 L of histidine-tryptophan-ketoglutarate (HTK) solution than the conventional one-catheter group (375±25 seconds vs. 662±34 seconds; p=0.001) and a lower rate of incomplete blood washing-out after the initial 2 L portal perfusion (40% vs. 85%; p=0.03). The two-catheter infusion method appears to be more effective than the conventional one-catheter infusion method for right liver graft perfusion at the back table. Large size of right liver grafts seems to be its good indication.

Safety and efficacy of gas-forced infusion (air pump) in coaxial phacoemulsification.

PubMed

Chaudhry, Prashaant; Prakash, Gaurav; Jacob, Soosan; Narasimhan, Smita; Agarwal, Sunita; Agarwal, Amar

2010-12-01

To evaluate the safety and efficacy of gas-forced infusion (air pump) in uncomplicated coaxial phacoemulsification. Dr. Agarwal's Eye Hospital, Chennai, India. Comparative case series. Specular microscopy and optical coherence tomography were used to analyze the endothelium, central macular thickness (CMT), and peripapillary retinal nerve fiber layer (RNFL) thickness before and approximately 1, 7, 30, and 90 days after coaxial phacoemulsification with (infusion group) or without (control group) gas-forced infusion. Surgical time, surge, phaco energy, irrigation fluid volume, surgical ease, complications, and visual gain in the 2 groups were compared. The mean endothelial cell loss was lower in the infusion group than in the control group (6.98% ± 8.46% [SD] versus 10.54% ± 11.24%; P = .045) and the irrigation/aspiration time significantly shorter (54 ± 39 seconds versus 105 ± 84 seconds; P = .0001). The surgery was rated as easier with gas-forced infusion (scale 1 to 10: mean 8.3 ± 2.1 versus 6.6 ± 1.6; P = .00002). However, the amount of irrigating fluid volume was higher in the infusion group (117 ± 37 mL versus 94 ± 41 mL; P = .003). No surge occurred in the infusion group; it occurred a mean of 3.00 ± 4.16 times in the control group (P<.0001). The rate of visual gain, CMT, peripapillary RNFL thickness, phaco time, and amount of phaco energy were comparable in the 2 groups. Gas-forced infusion was safe and effective in controlling surge and increased the safety, ease, and speed of coaxial phacoemulsification. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation.

PubMed

Hoy, Andrew J; Brandon, Amanda E; Turner, Nigel; Watt, Matthew J; Bruce, Clinton R; Cooney, Gregory J; Kraegen, Edward W

2009-07-01

Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding, in vivo skeletal muscle glucose uptake (31%, P < 0.05) and glycogen synthesis rate (38%, P < 0.02) were significantly reduced after 5 h compared with 3 h of lipid infusion. Despite the development of insulin resistance, there was no difference in the phosphorylation state of multiple insulin-signaling intermediates or muscle diacylglyceride and ceramide content over the same time course. However, there was an increase in cumulative exposure to long-chain acyl-CoA (70%) with lipid infusion. Interestingly, although muscle pyruvate dehydrogenase kinase 4 protein content was decreased in hyperinsulinemic glycerol-infused rats, this decrease was blunted in muscle from hyperinsulinemic lipid-infused rats. Decreased pyruvate dehydrogenase complex activity was also observed in lipid- and insulin-infused animals (43%). Overall, these results suggest that acute reductions in muscle glucose metabolism in rats with hyperlipidemia and hyperinsulinemia are more likely a result of substrate competition than a significant early defect in insulin action or signaling.

In-line pressure within a HOTLINE® Fluid Warmer, under various flow conditions.

PubMed

Higashi, Midoriko; Yamaura, Ken; Matsubara, Yukie; Fukudome, Takuya; Hoka, Sumio

2015-04-01

Roller pump infusion devices are widely used for rapid infusion, and may be combined with separate warming devices. There may be instances however, where the pressures generated by the roller pump may not be compatible with the warming device. We assessed a commonly used roller pump in combination with a HOTLINE® Fluid Warmer, and found that it could generate pressures exceeding the HOTLINE® manufacturers specifications. This was of concern because the HOTLINE® manufacturer guideline states that not for use with pressure devices generating over 300 mmHg. Pressure greater than 300 mmHg may compromise the integrity of the HOTLINE® Fluid Warming Set. The aim of this study was to compare in-line pressure within a HOTLINE® Fluid Warmer at different infusion rates of a roller pump using various sizes of intravenous cannulae. The rapid infusion system comprised a 500 mL-normal saline bag, roller pump type infusion device, HOTLINE® Fluid Warmer (blood and fluid warmer system), and six different sizes of intravenous cannulae. In-line pressure was measured proximal to the HOTLINE® (pre-warmer) and proximal to the cannula (post-warmer), at flow rate of 50-160 mL/min. The in-line pressures increased significantly with increasing flow rate. The pre-warmer pressures exceeded 300 mmHg when the flow rate was ≥120 mL/min with 20-gauge, 48 mm length cannula, 130 with 20-gauge, 25 mm cannula, and 160 mL/min with 18-gauge, 48 mm cannula. However, they were <300 mmHg at any flow rates with 18-gauge, 30 mm cannula and 16-gauge cannulae. The post-warmer pressures exceeded 300 mmHg at the flow rate of 140 mL/min with 20-gauge, 48 mm cannula, and 160 mL/min with 20-gauge, 25 mm cannula, while they were <300 mmHg at any flow rates with 18 and 16-gauge cannulae. The in-line pressure within a HOTLINE® could exceed 300 mmHg, depending on the flow rate and size and length of cannula. It is important to pay attention to the size and length of cannulae and flow rate to keep the maximum in-line pressure<300 mmHg when a roller pump type infusion device is used.

Behaviour of Standard Gravity-fed Administration Sets Used for Intravenous Infusion

PubMed Central

Flack, F. C.; Whyte, T. D.

1974-01-01

The major factor influencing drip rate during intravenous infusion using a standard administration set is the variation in the venous pressure of the patient. Creep in the plastic material, though present, is shown to be unimportant. For steady and accurate infusion it is necessary to provide the ordinary gravity-fed administration set with some form of servo-control mechanism. PMID:4412178

Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses.

PubMed

Potter, Joanna J; MacFarlane, Paul D; Love, Emma J; Tremaine, Henry; Taylor, Polly M; Murrell, Joanna C

2016-03-01

To compare sedative and analgesic properties of buprenorphine or morphine for standing procedures combined with a detomidine continuous rate infusion (CRI). Blinded, prospective, randomized clinical pilot study. Ten horses presented for dental or sinus procedures. Horses received 0.02 mg kg(-1) acepromazine intravenously (IV), followed 30 minutes later by detomidine 10 μg kg(-1) IV. Five minutes later, buprenorphine 0.01 mg kg(-1) (n = 6) or morphine 0.1 mg kg(-1) (n = 4) was administered IV. Detomidine was administered by CRI (0.2 μg kg(-1) minute(-1)) and adjusted to maintain appropriate sedation. Heart rate, respiratory frequency, gastrointestinal motility and rectal temperature were measured; pain, ataxia and sedation were scored. Sedation, pain scores and ataxia scores were analysed using a mixed linear model. Detomidine dose and procedure success scores were compared using Wilcoxon's rank sum test. Complications between groups were analysed using Fisher's exact test. Two horses had incomplete data. Weights and ages were not different between groups (p = 0.15 and p = 0.42, respectively). The dose rate for detomidine was not different between groups (0.33 ± 0.02 μg kg(-1) minute(-1) in the buprenorphine group and 0.33 ± 0.05 μg kg(-1) minute(-1), in the morphine group p = 0.89). Intraoperative visual analogue scale scores were greater after buprenorphine than morphine (mean ± SD, buprenorphine 48 ± 4, morphine 40 ± 5, p = 0.0497). Procedure duration was not different between groups (buprenorphine 142 ± 33, morphine 140 ± 12 minutes). All horses treated with buprenorphine experienced complications compared with none in the morphine group (p = 0.0286). At the doses used, buprenorphine produced greater sedation but more post-operative complications than morphine. However, Type I or Type II errors cannot be excluded and larger studies are required to confirm these findings. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Continuous intestinal infusion of levodopa-carbidopa in patients with advanced Parkinson's disease in Spain: Subanalysis by autonomous community.

PubMed

Santos-García, D; Catalán, M J; Puente, V; Valldeoriola, F; Regidor, I; Mir, P; Matías-Arbelo, J; Parra, J C; Grandas, F

2018-01-12

To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation. Significant differences were observed between CAs for several baseline variables: duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score during on time, Unified Parkinson's Disease Rating Scale-III score during both on and off time, presence of≥ 4 motor symptoms, and CIILC dose. Significant differences were observed during follow-up (> 24 months in 9 of the 11 CAs studied) for the percentage of off time and on time without disabling dyskinesia, adverse events frequency, and Clinical Global Impression scores. The rate of CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2 CAs). This study reveals a marked variability between CAs in terms of patient selection and CIILC safety and effectiveness. These results may have been influenced by patients' baseline characteristics, the availability of multidisciplinary teams, and clinical experience. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Successful treatment of young infants presenting neonatal diabetes mellitus with continuous subcutaneous insulin infusion before genetic diagnosis.

PubMed

Rabbone, Ivana; Barbetti, Fabrizio; Marigliano, Marco; Bonfanti, Riccardo; Piccinno, Elvira; Ortolani, Federica; Ignaccolo, Giovanna; Maffeis, Claudio; Confetto, Santino; Cerutti, Franco; Zanfardino, Angela; Iafusco, Dario

2016-08-01

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely. We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment. Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea. During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus.

CHANGES IN LIPID-ENCAPSULATED MICROBUBBLE POPULATION DURING CONTINUOUS INFUSION AND METHODS TO MAINTAIN CONSISTENCY

PubMed Central

KAYA, MEHMET; GREGORY, THOMAS S.; DAYTON, PAUL A.

2009-01-01

Stabilized microbubbles are utilized as ultrasound contrast agents. These micron-sized gas capsules are injected into the bloodstream to provide contrast enhancement during ultrasound imaging. Some contrast imaging strategies, such as destruction-reperfusion, require a continuous injection of microbubbles over several minutes. Most quantitative imaging strategies rely on the ability to administer a consistent dose of contrast agent. Because of the buoyancy of these gas-filled agents, their spatial distribution within a syringe changes over time. The population of microbubbles that is pumped from a horizontal syringe outlet differs from initial population as the microbubbles float to the syringe top. In this manuscript, we study the changes in the population of a contrast agent that is pumped from a syringe due to microbubble floatation. Results are presented in terms of change in concentration and change in mean diameter, as a function of time, suspension medium, and syringe diameter. Data illustrate that the distribution of contrast agents injected from a syringe changes in both concentration and mean diameter over several minutes without mixing. We discuss the application of a mixing system and viscosity agents to keep the contrast solution more evenly distributed in a syringe. These results are significant for researchers utilizing microbubble contrast agents in continuous-infusion applications where it is important to maintain consistent contrast agent delivery rate, or in situations where the injection syringe cannot be mixed immediately prior to administration. PMID:19632760

[Consensus document on continuous subcutaneous insulin infusion (CSII) treatment in paediatrics with type I diabetes].

PubMed

Barrio Castellanos, R; García Cuartero, B; Gómez Gila, A; González Casado, I; Hermoso López, F; Luzuriaga Tomás, C; Oyarzabal Irigoyen, M; Rica Etxebarria, I; Rodríguez Rigual, M; Torres Lacruz, M

2010-05-01

This article reports on the Spanish Position Statement for the Diabetes Pediátric Group for the Spanish Pediatric Endocrinology Society (SEEP) on continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes. The practical issues about their indications, appropriate candidates, feasibility, and limits are outlined. The conclusions are based on the comprehensive review and balanced assessment of the evidence base on the international consensus and consensual answers to these questions for the participants. Copyright 2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress.

PubMed

Schlader, Zachary J; Gagnon, Daniel; Lucas, Rebekah A I; Pearson, James; Crandall, Craig G

2015-02-15

This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of ∼1.8°C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 μg/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 ± 1.9 mmHg (normothermia) to -0.6 ± 1.4 mmHg (P < 0.001), while saline infusion returned CVP to normothermic levels (5.1 ± 1.7 mmHg; P > 0.999). Sweat rate was elevated by heat stress (1.21 ± 0.44 mg·cm(-2)·min(-1)) but remained unchanged during rapid saline infusion (1.26 ± 0.47 mg·cm(-2)·min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 ± 10 to 101 ± 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 ± 7 mmHg to 76 ± 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 ± 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 ± 0.22 vs. 1.41 ± 0.24 mg·cm(-2)·min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress. Copyright © 2015 the American Physiological Society.

Effect of warming and flow rate conditions of blood warmers on red blood cell integrity.

PubMed

Poder, T G; Pruneau, D; Dorval, J; Thibault, L; Fisette, J-F; Bédard, S K; Jacques, A; Beauregard, P

2016-11-01

Fluid warmers are routinely used to reduce the risk of hypothermia and cardiac complications associated with the infusion of cold blood products. However, warming blood products could generate haemolysis. This study was undertaken to compare the impact of temperature of blood warmers on the per cent haemolysis of packed red blood cells (RBCs) heated at different flow rates as well as non-flow conditions. Infusion warmers used were calibrated at 41·5°C ± 0·5°C and 37·5°C ± 0·5°C. Cold RBC units stored at 4°C in AS-3 (n = 30), aged 30-39 days old, were divided into half units before being allocated under two different scenarios (i.e. infusion pump or syringe). Blood warmers were effective to warm cold RBCs to 37·5°C or 41·5°C when used in conjunction with an infusion pump at flow rate up to 600 ml/h. However, when the warmed blood was held in a syringe for various periods of time, such as may occur in neonatal transfusions, the final temperature was below the expected requirements with measurement as low as 33·1°C. Increasing the flow with an infusion pump increased haemolysis in RBCs from 0·2% to up to 2·1% at a flow rate of 600 ml/h regardless of the warming device used (P < 0·05). No relevant increase of haemolysis was observed using a syringe. The use of a blood warmer adjusted to 41·5°C is probably the best choice for reducing the risk of hypothermia for the patient without generating haemolysis. However, we should be cautious with the use of an infusion pump for RBC transfusion, particularly at high flow rates. © 2016 International Society of Blood Transfusion.

Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

PubMed

Maher, Dermot P; Chen, Lucy; Mao, Jianren

2017-02-01

Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied.

A randomized double-blind crossover comparison of continuous and intermittent subcutaneous administration of opioid for cancer pain.

PubMed

Watanabe, Sharon; Pereira, Jose; Tarumi, Yoko; Hanson, John; Bruera, Eduardo

2008-05-01

ABSTRACT Although the preferred route of opioid administration is oral, patients with cancer often require an alternative route. Options include continuous subcutaneous infusion (CSCI) or regularly scheduled intermittent subcutaneous injections (ISCI). CSCI maintains steady drug levels, theoretically avoiding the "bolus effect" of nausea and sedation immediately post-dose, and breakthrough pain prior to the next dose. However, portable infusion pumps can be costly to use. The Edmonton Injector is an inexpensive portable device for ISCI. CSCI and ISCI have not been directly compared. The objective of this trial was to compare CSCI and ISCI of opioid for treatment of cancer pain. Patients were recruited from two tertiary palliative care units. Eligibility criteria included stable cancer pain requiring opioid therapy, need for parenteral route, and normal cognition. Patients were randomly assigned to receive opioid by CSCI by portable pump or ISCI by Edmonton Injector for 48 hours, followed by crossover to the alternative modality for 48 hours. During each phase, placebo was administered by the alternative modality. The study was closed after 12 patients were entered, due to slow accrual. Eleven patients completed the study. There were no differences between CSCI and ISCI in mean visual analogue score (VAS) for pain, nausea or drowsiness; categorical rating score of pain; number of breakthrough opioid doses per day; global rating of treatment effectiveness; or adverse effects. In all cases, patients and investigators expressed no preference for one modality over another. Further research is required to confirm that opioid administration by CSCI and ISCI provide similar analgesic and adverse effects.

Extractability of selected mineral and trace elements in infusions of chamomile.

PubMed

Chizzola, Remigius; Michitsch, Hanneliese; Mitteregger, Ulrike S

2008-09-01

Chamomile flower heads were extracted with boiling water and the elements calcium, potassium, magnesium, zinc and cadmium were recorded in the drug and the resulting infusions. The extractabilities for calcium, magnesium and potassium in the infusions were 19-23%, 47-48% and 65-73%, respectively. Cadmium could be recovered to 15-21% in the infusions and zinc to 23-34%. A longer extraction time gave slightly higher recovery rates for potassium and zinc. The extraction of less plant material gave a slight reduction in the extractability only in the case of cadmium. A single cup of chamomile infusion can only afford a small proportion of the daily requirement of the mineral elements.

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.

Infusion-line pressure as a real-time monitor of convection-enhanced delivery in pre-clinical models.

PubMed

Lam, Miu Fei; Foo, Stacy W L; Thomas, Meghan G; Lind, Christopher R P

2014-01-15

Acute convection-enhanced delivery (CED) is a neurosurgical delivery technique that allows for precise and uniform distribution of an infusate to a brain structure. It remains experimental due to difficulties in ensuring successful delivery. Real-time monitoring is able to provide immediate feedback on cannula placement, infusate distribution, and if the infusion is proceeding as planned or is failing due to reflux or catheter obstruction. Pressure gradient is the driving force behind CED, with the infusion pressure being directly proportional to the flow-rate. The aim of this study was to assess the feasibility of using infusion-line pressure profiling to distinguish in real-time between succeeding and failing CED infusions. To do so we delivered cresyl violet dye at 0.5, 1.0 and 2.0 μl/min via CED in vitro using 0.6% agarose gel and in vivo to the rat striatum. Infusions that failed in agarose gel models could only be differentiated late during the procedures. In the rat in vivo model, the infusion-line profiles of obstructed infusions were not distinctive from those of successful infusions. Intraoperative magnetic resonance imaging (MRI) is used for real-time visualisation of cannula placement and infusate distribution. Particularly for animal pre-clinical work, it would be advantageous to supplement MRI with a cheap, accessible technique to monitor infusions and provide a real-time measure of infusion success or failure. Infusion-line pressure monitoring was of limited value in identifying successful CED with small volume infusions, whilst its utility for large volume infusion remains unknown. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Methods of preventing vinorelbine-induced phlebitis: an experimental study in rabbits.

PubMed

Kohno, Emiko; Murase, Saori; Nishikata, Mayumi; Okamura, Noboru; Matzno, Sumio; Kuwahara, Takashi; Matsuyama, Kenji

2008-07-22

In order to identify methods for preventing phlebitis caused by intravenous administration of vinorelbine (VNR), we established a procedure for estimating the severity of phlebitis in an animal model. Four different factors (administration rate, dilution, flushing, and infusion of fat emulsion) were evaluated for alleviation of phlebitis caused by VNR infusion. VNR was diluted with normal saline to prepare test solutions with concentrations of 0.6 mg/mL or 0.3 mg/mL for infusion into the auricular veins of rabbits. Two days after VNR infusion, the veins were subjected to histopathological examination. VNR did not cause obvious loss of venous endothelial cells, the most sensitive and common feature of phlebitis, but VNR infusion led to inflammatory cell infiltration, edema, and epidermal degeneration. Tissue damage was significantly decreased by shortening the administration time and by diluting the VNR solution for infusion from 0.6 mg/mL to 0.3 mg/mL. However, there was no effect of flushing with normal saline after VNR infusion, while treatment with fat emulsion before and after VNR infusion only had a minimal effect. Rapid infusion and dilution are effective methods of reducing phlebitis caused by the infusion of VNR, but the efficacy of flushing with normal saline or infusion of fat emulsion was not confirmed.

Development and Implementation of a Curriculum Infusion Plan for Alcohol Abuse Education in a College Population

ERIC Educational Resources Information Center

Kenney, Sarah; Grim, Melissa

2015-01-01

Background: College binge drinking continues to be a pervasive issue across campuses nationwide. Though curriculum infusion (CI) has been shown to be an effective strategy to reduce students' negative consequences related to alcohol, information about the process is limited. Purpose: The purpose of this study is to examine the content and process…

What Happens when the Research Ends? Factors Related to the Sustainability of a Technology-Infused Mathematics Curriculum

ERIC Educational Resources Information Center

Fishman, Barry; Penuel, William R.; Hegedus, Stephen; Roschelle, Jeremy

2011-01-01

This study examines factors related to the sustainability of SimCalc Mathworlds (SCMW), a technology-infused mathematics curriculum. We surveyed middle school teachers one year after their participation in a randomized trial where they were introduced to SCMW curriculum, to identify factors related to their continued use of the materials in ways…

Subcutaneous drug infusions: a review of problems and solutions.

PubMed

Mitten, T

2001-02-01

Subcutaneous drug infusion using a portable syringe driver has had a significant impact on patient comfort in palliative care. It permits the continuous delivery of a range of drug therapies, so bypassing problems of dysphagia, weakness and the inability of many patients in the terminal phase to take oral medication. The devices are not problem-free, however. Mechanical problems, reactions at the infusion site and difficulties with the mixing of drugs in the syringe are all widely recognized. This article reviews some general issues with the operation of portable syringe drivers, and discusses a range of potential problems and their solutions.

Quantitative partition of threonine oxidation in pigs: Effect of dietary threonine

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

Ballevre, O.; Cadenhead, A.; Calder, A.G.

1990-10-01

Kinetic aspects of threonine (Thr) metabolism were examined in eight pigs fed hourly with a diet containing either 0.68% (LT group) or 0.81% (HT group) of Thr (wt/wt), corresponding to 10 and 30% Thr excess, respectively, compared with an ideal diet. Primary production (PR) and disposal (DR) rates were obtained for Thr, glycine (Gly), and 2-keto-butyrate (KB) after a 12-h continuous infusion of L-(U-14C)-Thr together with (1-13C)Gly and a 6-h continuous infusion of (1-14C)KB. Transfer of Thr into secondary pools was also monitored, and from these the rates of Thr oxidation through the catabolic pathways of L-Thr 3-dehydrogenase (DR(Thr-Gly)) andmore » threonine dehydratase (DR(Thr-KB)) were estimated. For the LT group the results were (mumol.kg-1.h-1) PR(Thr) 314 +/- 3, PR(Gly) 551 +/- 24, PR(KB) 41 +/- 3, DR(Thr-Gly) 22 +/- 2, and DR(Thr-KB) 7 +/- 1. For the HT group they were PR(Thr) 301 +/- 23, PR(Gly) 598 +/- 55, PR(KB) 39 +/- 4, DR(Thr-Gly) 32 +/- 2, and DR(Thr-KB) 8 +/- 1. The increase in Thr intake (14 mumol.kg-1.h-1, P less than 0.01) induced a commensurate increase in the sum of DR(Thr-Gly) and DR(Thr-KB) (14 mumol.kg-1.h-1, P less than 0.001) when liver was used as the precursor pool. This was mainly due to the increased DR(Thr-Gly) (13 mumol.kg-1.h-1, P less than 0.01); the change in DR(Thr-KB) was not statistically significant. By comparison of intracellular-to-plasma ratios of specific activities (or enrichments) for different tissues with each type of infusion, liver was shown to be the major site of production of Gly and KB from Thr. These data suggest that in fed growing pigs a 30% excess of Thr in the diet does not alter the partition of Thr oxidation, since 80% of Thr oxidation occurs through the L-Thr 3-dehydrogenase pathway for both LT and HT groups.« less

Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.

PubMed

Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

2011-10-24

Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. Copyright © 2011 Elsevier B.V. All rights reserved.

Renal function in sheep during infusion of alkali metal ions into the renal artery.

PubMed Central

Beal, A M; Harrison, F A

1975-01-01

1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

Toxic and essential mineral elements content of black tea leaves and their tea infusions consumed in Iran.

PubMed

Salahinejad, Maryam; Aflaki, Fereydoon

2010-04-01

The metal contents of eleven black tea samples, four cultivated in Iran and seven imported, and their tea infusions were determined. Twelve elements consisting toxic metals (Al, As, Pb, Cr, Cd, and Ni) and essential mineral elements (Fe, Zn, Cu, Mn, Ca, and Mg) were analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). Al, Ca, Mg, and Mn ranged in black tea leaves at mg g(-1) levels, while Cr, Fe, Ni, Cu, Zn were at microg g(-1) levels. Analysis of variance showed no statistically significant differences among most elements determined in cultivated and imported black teas in Iran except for Ni and Cu. The extraction efficiency of each element into tea infusions was evaluated. The solubility of measured metals in infusion extracts varied widely and ranged from 0 to 59.3%. Among the studied elements, Cr, Pb, and Cd showed the lowest rates of solubility and Ni had the highest rates of solubility. The amount of toxic metals and essential mineral elements that one may take up through consumption of black tea infusion was estimated. The amount of realizing each element into tea infusions and acceptable daily intake, for safety consumption of black tea, was compared.

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.

[Using the subcutaneous approach for symptoms control in a health center].

PubMed

Pascual López, L; Portaceli Armiñana, A; Ros Sáez, A

2001-01-01

To describe the use of the subcutaneous tract for symptoms control in patients those are in phase of palliative treatment of their illness. Observational study. Primary care. Patients seen in a health center, in phase of palliative treatment of their illness, that needed for symptoms control the subcutaneous administration of drugs. Most of the patients were in terminal phase (19), the fundamental cause (17 cases) that justified the use of the subcutaneous tract was the difficulty to take drugs by oral tract in the last days of life, attention on death throes. The infusion continuous through injector type travenol, at an infusion speed of 2 ml/h, it was the most common way of drug administration (19 patients). The drugs and initial average dose most used were: morphine 19 patients dose 100 mg/24 h, hyoscine butylbromide (Buscapina), 13 patients, 60 mg/24 h, haloperidol 12 patients, 4 mg/24 h. The patients death was the main cause that justified the retirement of the continuous infusion (17 people sick), happening in its own home. Symptoms control was good or very good in the most of patients (14). The experience on using the subcutaneous tract for symptoms control in our health center is positive, being the fundamental cause for its use symptoms control in the last days of the patients life. The continuous subcutaneous infusion should be used in primary attention, as an usual technique for the symptoms control in patients that are in phase of palliative treatment of their illness.

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.

Paramedic Initiation of Neuroprotective Agent Infusions: Successful Achievement of Target Blood Levels and Attained Level Effect on Clinical Outcomes in the FAST-MAG Pivotal Trial (Field Administration of Stroke Therapy - Magnesium).

PubMed

Shkirkova, Kristina; Starkman, Sidney; Sanossian, Nerses; Eckstein, Marc; Stratton, Samuel; Pratt, Frank; Conwit, Robin; Hamilton, Scott; Sharma, Latisha; Liebeskind, David; Restrepo, Lucas; Valdes-Sueiras, Miguel; Saver, Jeffrey L

2017-07-01

Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective therapy for acute stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome. The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy - Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation. Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death. Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute stroke. © 2017 American Heart Association, Inc.

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.

Apoplastic infusion of sucrose into stem internodes during female flowering does not increase grain yield in maize plants grown under nitrogen-limiting conditions.

PubMed

Peng, Yunfeng; Li, Chunjian; Fritschi, Felix B

2013-08-01

Nitrogen (N) limitation reduces leaf growth and photosynthetic rates of maize (Zea mays), and constrains photosynthate translocation to developing ears. Additionally, the period from about 1 week before to 2 weeks after silking is critical for establishing the reproductive sink capacity necessary to attain maximum yield. To investigate the influence of carbohydrate availability in plants of differing N status, a greenhouse study was performed in which exogenous sucrose (Suc) was infused around the time of silking into maize stems grown under different N regimes. N deficiency significantly reduced leaf area, leaf longevity, leaf chlorophyll content and photosynthetic rate. High N-delayed leaf senescence, particularly of the six uppermost leaves, compared to the other two N treatments. While N application increased ear leaf soluble protein concentration, it did not influence glucose and suc concentrations. Interestingly, ear leaf starch concentration decreased with increasing N application. Infusion of exogenous suc tended to increase non-structural carbohydrate concentrations in the developing ears of all N treatments at silking and 6 days after silking. However, leaf photosynthetic rates were not affected by suc infusion, and suc infusion failed to increase grain yield in any N treatment. The lack of an effect of suc infusion on ear growth and the high ear leaf starch concentration of N-deficient maize, suggest that yield reduction under N deficiency may not be due to insufficient photosynthate availability to the developing ear during silking, and that yield reduction under N deficiency may be determined at an earlier growth stage. Copyright © Physiologia Plantarum 2012.

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

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

Induction Speed Is Not a Determinant of Propofol Pharmacodynamics

PubMed Central

Doufas, Anthony G.; Bakhshandeh, Maryam; Bjorksten, Andrew R.; Shafer, Steven L.; Sessler, Daniel I.

2005-01-01

Summary We used individual pharmacodynamic modeling to demonstrate that different sedation endpoints occur at the same effect site propofol concentration, independent of the infusion rate of propofol. Background Evidence suggests that the rate at which they are infused may influence plasma-effect site equilibration of intravenous anesthetics. We used 5 different rates of propofol administration to test the hypothesis that different sedation endpoints occur at the same effect site propofol concentration, independent of the infusion rate. We concurrently evaluated the automated responsiveness monitor (ARM) against other sedation measures and the propofol effect site concentration. Methods With Human Studies Committee approval, 18 healthy volunteers received 5 consecutive target-controlled propofol infusions. During each infusion the effect site concentration was increased by a rate of 0.1, 0.3, 0.5, 0.7, or 0.9 μg·ml−1·min−1. Bispectral index and ARM were recorded at frequent intervals. The times of syringe drop and loss and recovery of responsiveness were noted. Pharmacokinetic and pharmacodynamic modeling was performed using NONMEM. Results Once the correct rate of plasma-effect site equilibration (ke0) was determined for each individual (ke0 = 0.17 min−1, time-to-peak effect = 2.7 min), the effect site concentrations associated with each clinical measure were not affected by the rate of rise of effect site propofol concentration. ARM correlated with all clinical measures of drug effect. Subjects invariably stopped responding to ARM at lower effect site propofol concentrations than those associated with loss of responsiveness. Conclusions Population-based pharmacokinetics, combined with real-time electroencephalographic measures of drug effect, may provide a means to individualize pharmacodynamic modeling during target-controlled drug delivery. ARM appears useful as an automated measure of sedation and may provide the basis for automated monitoring and titration of sedation for a propofol delivery system. PMID:15505446

Correlation Between Biomechanical Responses of Posterior Sclera and IOP Elevations During Micro Intraocular Volume Change

PubMed Central

Morris, Hugh J.; Tang, Junhua; Cruz Perez, Benjamin; Pan, Xueliang; Hart, Richard T.; Weber, Paul A.; Liu, Jun

2013-01-01

Purpose. This study tested the hypothesis that intraocular pressure (IOP) elevations, induced by controlled increase of intraocular volume, are correlated with the biomechanical responses of the posterior sclera. Methods. Porcine globes were tested within 48 hours postmortem. The first group of globes (n = 11) was infused with 15 μL of phosphate-buffered saline at three different rates to investigate rate-dependent IOP elevations. The second group (n = 16) was first infused at the fast rate and then underwent inflation tests to investigate the relationship between IOP elevations (ΔIOP) and scleral strains. The strains in the superotemporal region of the posterior sclera were measured by ultrasound speckle tracking. Linear regression was used to examine the association between ΔIOP due to micro-volumetric infusion and the scleral strains at a specific inflation pressure. Results. The average ΔIOP was 14.9 ± 4.3 mm Hg for the infusion of 15 μL in 1 second. The ΔIOP was greater for the faster infusion rates but highly correlated across different rates (P < 0.001). A significant negative association was found between the ΔIOP and the tangential strains in both the circumferential (R2 = 0.54, P = 0.003) and meridian (R2 = 0.53, P = 0.002) directions in the posterior sclera. Conclusions. This study showed a substantial increase in IOP, with a large intersubject variance during micro-volumetric change. A stiffer response of the sclera was associated with larger IOP spikes, providing experimental evidence linking corneoscleral biomechanics to IOP fluctuation. In vivo measurement of corneoscleral biomechanics may help better predict the dynamic profile of IOP. PMID:24130185

Distribution of crystalloid fluid changes with the rate of infusion: a population-based study.

PubMed

Hahn, R G; Drobin, D; Zdolsek, J

2016-05-01

Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids. Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects. The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled. The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

In vivo study of flow-rate accuracy of the MedStream Programmable Infusion System.

PubMed

Venugopalan, Ramakrishna; Ginggen, Alec; Bork, Toralf; Anderson, William; Buffen, Elaine

2011-01-01

  Flow-rate accuracy and precision are important parameters to optimizing the efficacy of programmable intrathecal (IT) infusion pump delivery systems. Current programmable IT pumps are accurate within ±14.5% of their programmed infusion rate when assessed under ideal environmental conditions and specific flow-rate settings in vitro. We assessed the flow-rate accuracy of a novel programmable pump system across its entire flow-rate range under typical conditions in sheep (in vivo) and nominal conditions in vitro.   The flow-rate accuracy of the MedStream Programmable Pump was assessed in both the in vivo and in vitro settings. In vivo flow-rate accuracy was assessed in 16 sheep at various flow-rates (producing 90 flow intervals) more than 90 ± 3 days. Pumps were then explanted, re-sterilized and in vitro flow-rate accuracy was assessed at 37°C and 1013 mBar (80 flow intervals).   In vivo (sheep body temperatures 38.1°C-39.8°C), mean ± SD flow-rate error was 9.32% ± 9.27% and mean ± SD leak-rate was 0.028 ± 0.08 mL/day. Following explantation, mean in vitro flow-rate error and leak-rate were -1.05% ± 2.55% and 0.003 ± 0.004 mL/day (37°C, 1013 mBar), respectively.   The MedStream Programmable Pump demonstrated high flow-rate accuracy when tested in vivo and in vitro at normal body temperature and environmental pressure as well as when tested in vivo at variable sheep body temperature. The flow-rate accuracy of the MedStream Programmable Pump across its flow-rate range, compares favorably to the accuracy of current clinically utilized programmable IT infusion pumps reported at specific flow-rate settings and conditions. © 2011 International Neuromodulation Society.

Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis.

PubMed

Leng, G; Brown, C H; Bull, P M; Brown, D; Scullion, S; Currie, J; Blackburn-Munro, R E; Feng, J; Onaka, T; Verbalis, J G; Russell, J A; Ludwig, M

2001-09-01

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Wood, David M.; Archer, John R. H.; Rab, Edmund; Flanagan, Robert J.

2016-01-01

Background Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight‐based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. Methods A 6‐month single‐centre prospective study was undertaken at a UK teaching hospital. After preparation, 5‐ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high‐performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight‐based dose and volume were made for each infusion. Results Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10–20% for 27 (30%) infusions, 20.1–50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of −3.6 mg ml−1 (−6.7 to −2.3) for the first infusion, +0.2 mg ml−1 (−0.9 to +0.4) for the second infusion and −0.3 mg ml−1 (−0.6 to +0.2) for third and fourth infusions. Conclusion There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. PMID:27558662

Air elimination capability in rapid infusion systems.

PubMed

Zoremba, N; Gruenewald, C; Zoremba, M; Rossaint, R; Schaelte, G

2011-11-01

Pressure infusion devices are used in clinical practice to apply large volumes of fluid over a short period of time. Although air infusion is a major complication, they have limited capability to detect and remove air during pressure infusion. In this investigation, we tested the air elimination capabilities of the Fluido(®) (The Surgical Company), Level 1(®) (Level 1 Technologies Inc.) and Ranger(®) (Augustine Medical GmbH) pressure infusion devices. Measurements were undertaken with a crystalloid solution during an infusion flow of 100, 200, 400 and 800 ml.min(-1). Four different volumes of air (25, 50, 100 and 200 ml) were injected as boluses in one experimental setting, or infused continuously over the time needed to perfuse 2 l saline in the other setting. The perfusion fluid was collected in an airtight infusion bag and the amount of air obtained in the bag was measured. The delivered air volume was negligible and would not cause any significant air embolism in all experiments. In our experimental setting, we found, during high flow, an increased amount of uneliminated air in all used devices compared with lower perfusion flows. All tested devices had a good air elimination capability. The use of ultrasonic air detection coupled with an automatic shutoff is a significant safety improvement and can reliably prevent accidental air embolism at rapid flows. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

A Boon for the Diabetic

NASA Technical Reports Server (NTRS)

1987-01-01

Diabetics are no longer concerned with scheduling activities around peaking insulin levels since the use of an external pump from Pacesetter Systems, Inc. used to deliver insulin continuously at a preprogrammed individually adjusted rate. The pump wearer can lead a more normal existence, even participate in sports or travel, and there is an even greater benefit. Research indicates that infusion of "short acting" insulin in tiny amounts over a long period - instead of "long- acting" insulin has helped many diabetics achieve better control of blood sugar levels, thereby minimizing the possibility of complications and, in some cases, even halting the progression of complications.

Orthopaedic wear particle-induced bone loss and exogenous macrophage infiltration is mitigated by local infusion of NF-κB decoy oligodeoxynucleotide.

PubMed

Lin, Tzuhua; Pajarinen, Jukka; Nabeshima, Akira; Córdova, Luis A; Loi, Florence; Gibon, Emmanuel; Lu, Laura; Nathan, Karthik; Jämsen, Eemeli; Yao, Zhenyu; Goodman, Stuart B

2017-11-01

Excessive production of wear particles from total joint replacements induces chronic inflammation, macrophage infiltration, and consequent bone loss (periprosthetic osteolysis). This inflammation and bone remodeling are critically regulated by the transcription factor NF-κB. We previously demonstrated that inhibition of NF-κB signaling by using the decoy oligodeoxynucleotide (ODN) mitigates polyethylene wear particle-induced bone loss using in vitro and in vivo models. However, the mechanisms of NF-κB decoy ODN action, and in particular its impact on systemic macrophage recruitment, remain unknown. In the current study, this systemic macrophage infiltration was examined in our established murine femoral continuous particle infusion model. RAW264.7 murine macrophages expressing a luciferase reporter gene were injected into the systemic circulation. Quantification of bioluminescence showed that NF-κB decoy ODN reduced the homing of these reporter macrophages into the distal femurs exposed to continuous particle delivery. Particle-induced reduction in bone mineral density at the distal diaphysis of the femur was also mitigated by infusion of decoy ODN. Histological staining showed that the decoy ODN infusion decreased osteoclast and macrophage numbers, but had no significant effects on osteoblasts. Local infusion of NF-κB decoy ODN reduced systemic macrophage infiltration and mitigated particle-induced bone loss, thus providing a potential strategy to treat periprosthetic osteolysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3169-3175, 2017. © 2017 Wiley Periodicals, Inc.

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.

Intravenous infusion of amino acids in dogs attenuates hypothermia during anaesthesia and stimulates insulin secretion.

PubMed

Takashima, Satoshi; Shibata, Sanae; Yamada, Kazuto; Ogawa, Mizuho; Nishii, Naohito; Kitagawa, Hitoshi

2016-07-01

To evaluate the effect of intravenous infusion of amino acids on the prevention of hypothermia during anaesthesia in dogs. Randomized experimental trial. Seven healthy Beagle dogs. Four concentrations of amino acids were prepared with a 10% amino acid solution and an acetated Ringer's solution, and dogs were infused with each of the solutions at 1 week intervals. Dogs were infused with amino acid solution at 12 mL kg(-1)  hour(-1) for 60 minutes before and for 60 minutes after induction of anaesthesia. Acetated Ringer's solution was infused at the same rate for the remaining 60 minutes of anaesthesia. The infusion treatments were: 1) A0, nutrient-free acetated Ringer's solution; 2) A6, 0.6 g kg(-1)  hour(-1) ; 3) A9, 0.9 g kg(-1)  hour(-1) ; and 4) A12, 1.2 g kg(-1) hour(-1) . Rectal temperature (RT), heart rate (HR), mean arterial pressure (MAP), blood insulin, glucose, urea nitrogen (BUN) and creatinine concentrations, and time to extubation were measured. Before anaesthesia, RT was not affected by amino acid infusion. RT decreased progressively during anaesthesia and the absolute values of RT from 30 to 120 minutes were significantly higher in A12 than in A0 (p < 0.05). Reductions in HR and MAP during anaesthesia were attenuated by amino acid infusion in a dose-dependent manner. Plasma insulin concentration was significantly higher in A12 than in A0 during amino acid infusion and the increase in insulin concentration was greater during than before anaesthesia. BUN increased during amino acid infusion in a dose- and time-dependent fashion. Time until extubation was shorter in A12 than in A0. Amino acids infused at 1.2 g kg(-1)  hour(-1) in dogs attenuated the decrease in RT, HR, and MAP during anaesthesia, and induced a significant increase in plasma insulin concentration. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Safety of combination therapy with milrinone and esmolol for heart protection during percutaneous coronary intervention in acute myocardial infarction.

PubMed

Poh, Kian-Keong; Xu, Xin; Chan, Mark Y; Lee, Chi-Hang; Tay, Edgar L; Low, Adrian F; Chan, Koo Hui; Sia, Winnie; Tang, Liang-Qiu; Tan, Huay Cheem; Lui, Charles Y; Nguyen, Vincent; Fujise, Kenichi; Huang, Ming-He

2014-05-01

Ischemia/reperfusion injury remains an untreated clinical problem in patients with acute myocardial infarction (AMI) despite significant advances in emergent revascularization through percutaneous coronary intervention (PCI). Pharmacological intervention for infarct size reduction is unavailable. We have identified that the medications milrinone and esmolol, when administered together at the beginning of the reperfusion, significantly decrease infarct size via reducing reperfusion injury in an experimental model. The present study tested the safety of combination therapy of milrinone and esmolol (M + E) in patients with AMI. Sixteen subjects with AMI requiring PCI were consecutively recruited. M + E was intravenously infused simultaneously for 10 min started at 5 min before anticipated angioplasty balloon inflation. Another 16 consecutively recruited AMI patients requiring PCI served as a placebo arm treated per routine clinical protocol. Blood pressure (BP) and heart rate (HR) were monitored continuously during PCI. M + E combination therapy resulted in a trend of non-significant reduction in BP compared with a control group. There was a modest but significant increase in HR at the later phase of M + E infusion compared with a control group. No significant cardiac arrhythmia was induced during M + E infusion. The combination therapy with M + E produces a minimal change in hemodynamics and appears safe as an adjunctive therapy to PCI in AMI patients. Further studies are warranted.

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

Duodenal and ileal glucose infusions differentially alter gastrointestinal peptides, appetite response, and food intake: a tube feeding study.

PubMed

Poppitt, Sally D; Shin, Hyun Sang; McGill, Anne-Thea; Budgett, Stephanie C; Lo, Kim; Pahl, Malcolm; Duxfield, Janice; Lane, Mark; Ingram, John R

2017-09-01

Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies. Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides. Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration. On the day before the intervention (day 0), a 380-cm multilumen tube (1.75-mm diameter) with independent port access to the duodenum and ileum was inserted, and position was confirmed by X-ray. Subsequently (days 1-4), a standardized breakfast meal was followed midmorning by a 90-min infusion of isotonic glucose (15 g, 235 kJ) or saline to the duodenum or ileum. Appetite ratings were assessed with the use of visual analog scales (VASs), blood samples collected, and ad libitum energy intake (EI) measured at lunch, afternoon snack, and dinner. Results: Thirteen participants completed the 4 infusion days. There was a significant effect of nutrient infused and site (treatment × time, P < 0.05) such that glucose-to-ileum altered VAS-rated fullness, satisfaction, and thoughts of food compared with saline-to-ileum (Tukey's post hoc, P < 0.05); decreased ad libitum EI at lunch compared with glucose-to-duodenum [-22%, -988 ± 379 kJ (mean ± SEM), Tukey's post hoc, P < 0.05]; and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) compared with all other treatments (Tukey's post hoc, P < 0.05). Conclusions: Macronutrient delivery to the proximal and distal small intestine elicits different outcomes. Glucose infusion to the ileum increased GLP-1 and PYY secretion, suppressed aspects of VAS-rated appetite, and decreased ad libitum EI at a subsequent meal. Although glucose to the duodenum also suppressed appetite ratings, eating behavior was not altered. This trial was registered at www.anzctr.org.au as ACTRN12612000429853. © 2017 American Society for Nutrition.

Methods of preventing vinorelbine-induced phlebitis: an experimental study in rabbits

PubMed Central

Kohno, Emiko; Murase, Saori; Nishikata, Mayumi; Okamura, Noboru; Matzno, Sumio; Kuwahara, Takashi; Matsuyama, Kenji

2008-01-01

Purpose: In order to identify methods for preventing phlebitis caused by intravenous administration of vinorelbine (VNR), we established a procedure for estimating the severity of phlebitis in an animal model. Methods: Four different factors (administration rate, dilution, flushing, and infusion of fat emulsion) were evaluated for alleviation of phlebitis caused by VNR infusion. VNR was diluted with normal saline to prepare test solutions with concentrations of 0.6 mg/mL or 0.3 mg/mL for infusion into the auricular veins of rabbits. Two days after VNR infusion, the veins were subjected to histopathological examination. Results: VNR did not cause obvious loss of venous endothelial cells, the most sensitive and common feature of phlebitis, but VNR infusion led to inflammatory cell infiltration, edema, and epidermal degeneration. Tissue damage was significantly decreased by shortening the administration time and by diluting the VNR solution for infusion from 0.6 mg/mL to 0.3 mg/mL. However, there was no effect of flushing with normal saline after VNR infusion, while treatment with fat emulsion before and after VNR infusion only had a minimal effect. Conclusion: Rapid infusion and dilution are effective methods of reducing phlebitis caused by the infusion of VNR, but the efficacy of flushing with normal saline or infusion of fat emulsion was not confirmed. PMID:18695742

[Pain control by continuous infusion of morphine using subarachnoid catheter access to the port--a report of a home death case].

PubMed

Kawagoe, Koh; Matsuura, Shinobu

2008-12-01

This is a case of a 50s male with cecal cancer suffering from severe pain caused by osteolytic metastasis to the lumbar vertebra, right iliac bone, and the head of the right femur. The pain was palliated by continuous infusion of morphine using a subarachnoid catheter that had access to the subcutaneous "Port". The maximum dose of morphine used a day was 384 mg, which corresponded to 57,600 mg/day of oral morphine. Sixty eight days after the start of home hospice care, the patient died at home because of diffuse peritonitis caused by intestinal rupture.

Relative Incidence of Phlebitis Caused by Continuous Intravenous Infusion of Cephapirin and Cephalothin

PubMed Central

Lane, A. Z.; Taggart, J. G.; Iles, R. L.

1972-01-01

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy. PMID:4790563

NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced pancreatic plasma extravasation.

PubMed

Maa, J; Grady, E F; Kim, E H; Yoshimi, S K; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-10-01

Substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms regulating this response in the rat pancreas. Anesthetized rats were continuously infused with SP, and plasma extravasation was quantified using Evans blue (EB) dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma extravasation. After 60 min, the NK1-R was desensitized to agonist challenge. Resensitization was first detected at 20 min and increased until full recovery was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase (NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous infusion of SP stimulates plasma extravasation in the rat pancreas via activation of the NK1-R, and these effects are terminated by both desensitization of the NK1-R and the cell-surface protease NEP.

Sustained benefit of continuous subcutaneous insulin infusion on glycaemic control and hypoglycaemia in adults with Type 1 diabetes.

PubMed

Beato-Víbora, P; Yeoh, E; Rogers, H; Hopkins, D; Amiel, S A; Choudhary, P

2015-11-01

To evaluate the sustainability of the benefits of continuous subcutaneous insulin infusion therapy in routine practice in a cohort of adults with diabetes. The clinical records of all adults starting continuous subcutaneous insulin infusion over 12 years at our centre were included in this study. Baseline and mean annual HbA(1c) levels were recorded. The frequency of mild-to-moderate and severe hypoglycaemia and hypoglycaemia awareness were analysed in a subgroup. Adequate data were available from 327 patients, of whom 71% were female. The patients' mean ± sd age was 41 ± 14 years, the mean ± sd (range) follow-up for continuous subcutaneous insulin infusion was 4.3 ± 2.7 (1-12) years. The mean ± sd HbA(1c) concentration fell by 8 ± 5 mmol/mol (0.7 ± 0.5%) at year 1 [to 63 ± 12 mmol/mol from 70 ± 18 mmol/mol (7.9 ± 1.1% from 8.6 ± 1.6%); P < 0.0005], sustained to year 5. In patients with initial poor control, HbA(1c) dropped by 12 ± 11 mmol/mol (1.1 ± 1.0%; P < 0.0005) at year 1, sustained to year 6. The percentage of patients with ≥ 5 mild to moderate hypoglycaemic episodes per week fell from 29 to 12% (n = 163; P = 0.006). In the subgroup (n = 87; follow-up 2.5 ± mean ± sd 1.1 years), the frequency of severe hypoglycaemia fell from 0.6 ± 1.7 episodes per patient per year to 0.3 ± 0.9 (P = 0.047). Of 24 patients with impaired awareness of hypoglycaemia (Gold score ≥ 4), the mean ± sd Gold score improved from 4.9 ± 0.9 to 3.8 ± 1.7 (P = 0.011). Nine people regained awareness. No deterioration in HbA(1c) was seen in the hypoglycaemia-prone groups. The benefits of continuous subcutaneous insulin infusion with regard to improving glycaemic control and reducing hypoglycaemia frequency, along with improvement in hypoglycaemia awareness without deterioration in glycaemic control, can be sustained over several years in clinical practice. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Proceedings of the 2010 AFMS Medical Research Symposium. Volume 3. Enroute Track: Abstracts and Presentations

DTIC Science & Technology

2011-03-15

comparison of proximal tibia, proximal humerus and distal femur infusion rates under high pressure using the EZ-IO Intraosseous device on an adult...contaminated complex musculoskeletal wounds. METHODS: We adapted a previously characterized caprine model. Under anesthesia , complex musculoskeletal...of proximal tibia, proximal humerus and distal femur infusion rates under high pressure using the EZ-IO Intraosseous device on an adult swine model

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion.

PubMed

Feistel, Stephan; Albrecht, Stephanie; Messlinger, Karl

2013-11-20

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.

Haemodynamic effects of vasoactive agents following chronic state of high cardiac output in anaesthetized rats.

PubMed

Guo, Liang; Tabrizchi, Reza

2008-05-31

The arteriovenous fistula model of circulation can produce a high output and low peripheral resistance situation. Here, we have examined the effects of noradrenaline, vasopressin and sodium nitroprusside on cardiac index, mean arterial blood pressure, venous tone, resistance to venous return, arterial resistance, and blood volume in chronically shunted anaesthetized rats. The cardiac index of rats with chronic arteriovenous fistula (AVF) was significantly higher (36.65+/-2.28 ml/min per 100 g; (mean+/-S.E.M.; n=24) in comparison to sham-operated rats (20.04+/-0.86 ml/min per 100 g; mean+/-S.E.M.; n=8). Cardiac index did not significantly change during the infusion of noradrenaline (1.0, 3.0 and 10 microg/kg per min), vasopressin (10, 30, 100 ng/kg per min) or sodium nitroprusside (0.1, 0.3 and 1.0 microg/kg per min) compared to saline infusion in AVF animals. Infusion of noradrenaline significantly increased heart rate, dP/dt, mean circulatory filling pressure (Pmcf) and resistance to venous return without affecting mean arterial blood pressure when compared to saline infusion. Administration of vasopressin significantly increased dP/dt, mean arterial blood pressure, and Pmcf without affecting heart rate, resistance to venous return or arterial resistance compared to saline infusion. Infusion of sodium nitroprusside did not significantly affect any haemodynamic parameter measured when compared to saline infusion. The results indicate that the presence of chronic AVF alters responsiveness of the various segments of the circulatory system to vasoactive agents. Moreover, it produces a major impediment to overall changes that can normally be induced following the infusion of such agents.

Chronic central ghrelin infusion reduces blood pressure and heart rate despite increasing appetite and promoting weight gain in normotensive and hypertensive rats.

PubMed

Freeman, John N; do Carmo, Jussara M; Adi, Ahmad H; da Silva, Alexandre A

2013-04-01

Acute studies showed that ghrelin acts on the central nervous system (CNS) to reduce blood pressure (BP), heart rate (HR) and sympathetic activity. However, the long-term CNS cardiovascular actions of ghrelin are still unclear. We tested whether chronic intracerebroventricular (ICV) infusion of ghrelin causes sustained reductions in BP, HR and whether it alters baroreceptor sensitivity (BRS) and autonomic input to the heart. A cannula was placed in the lateral ventricle of male Sprague-Dawley (SD) rats for ICV infusions via osmotic minipump (0.5 μl/h). BP and HR were measured 24-h/day by telemetry. After 5 days of control measurements, ghrelin (0.21 nmol/h) or saline vehicle were infused ICV for 10 days followed by a 5-day post-treatment period. Chronic ICV ghrelin infusion increased food intake (22±3 to 26±1 g/day) leading to ~50 g body weight gain. BP fell slightly during ghrelin infusion while HR decreased by ~26 bpm. In control animals BP and HR increased modestly. ICV Ghrelin infusion caused a 50% reduction in sympathetic tone to the heart but did not alter BRS. We also tested if the depressor responses to ICV ghrelin infusion were enhanced in spontaneously hypertensive rats (SHR) due to their high basal sympathetic tone. However, we observed similar BP and HR responses compared to normotensive rats. These results indicate that ghrelin, acting via direct actions on the CNS, has a sustained effect to lower HR and a modest impact to reduce BP in normotensive and hypertensive animals despite increasing appetite and body weight. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases.

PubMed

Rong, J; Chunhua, M; Yuan, L; Ning, M; Jinduo, L; Bin, W; Liwei, S

2015-11-01

The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6-month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases.

[Effects of lidocaine on arterial and venous circulation of limbs in man].

PubMed

Edouard, A; Probst, D; Duranteau, J; Tarot, J P; Pussard, E

1991-01-01

The effects of intravenous lidocaine on limb arteries and veins were investigated in a placebo-controlled study. Seven young healthy volunteers, 23 to 28-years-old, were included. Electrocardiogram, arterial pressure and arm and leg blood flows were recorded continuously. Systolic and diastolic blood pressures were measured in the left arm by finger photoplethysmography. Limb blood flow and the limb venous system were studied by venous occlusive plethysmography. The venous parameters studied were venous tone, lowest closing pressure, venous volume at 30 mmHg, and venous distensibility. After an initial bolus of 1.5 mg.kg-1 lidocaine had been given, 30, and then 60, micrograms.kg-1.min-1 were given for one hour each. Plasma noradrenaline and serum lidocaine titres were measured before giving the lidocaine, and at the end of each one hour period. Placebo consisted in a two hour infusion of 0.25 ml.min-1 normal saline. Lidocaine titres were 1.64 +/- 0.40 microgram.ml-1 after one hour, and 2.55 +/- 0.69 microgram.ml-1 after two hours. Lidocaine increased vascular resistances in both the forearm (+81% to +93%) and the calf (+38% to +57%). There was a concomitant increase in mean arterial blood pressure (+21% to +28%) without any change in heart rate. There was a significant dose-dependent increase in plasma noradrenaline levels during the second period of the lidocaine infusion with respect to the preinfusion period and the same period during the placebo infusion. Venous capacitance measured before any infusion had been started was greater in the leg than in the arm.(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.

Effects of vitamin D analog on bladder function and sensory signaling in animal models of cystitis.

PubMed

Shapiro, Bennett; Redman, T Lawton; Zvara, Peter

2013-02-01

To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice. Copyright © 2013 Elsevier 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.

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

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.

Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR.

PubMed

Witte, C; Kunth, M; Rossella, F; Schröder, L

2014-02-28

Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of (129)Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

Intestinal absorption and liver uptake of medium-chain fatty acids in non-anaesthetized pigs.

PubMed

Guillot, E; Vaugelade, P; Lemarchal, P; Rérat, A

1993-03-01

In order to study the rate of intestinal absorption and hepatic uptake of medium-chain fatty acids (MCFA), six growing pigs, mean body weight 65 kg, were fitted with a permanent fistula in the duodenum and with three catheters in the portal vein, carotid artery and hepatic vein respectively. Two electromagnetic flow probes were also set up, one around the portal vein and one around the hepatic artery. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and a nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the three vessels at regular intervals for 12 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentration of non-esterified octanoic and decanoic acids in the portal blood rose sharply after the beginning of each infusion and showed a biphasic time-course with two maximum values, one after 15 min and a later one between 75 and 90 min. Only 65% of octanoic acid infused into the duodenum and 54% of decanoic acid were recovered in the portal flow throughout each experiment. The amounts of non-esterified MCFA taken up per h by the liver were close to those absorbed from the gut via the portal vein within the same periods of time, showing that the liver is the main site of utilization of MCFA in pigs. These results have been discussed with a special emphasis laid on the possible mechanisms of the biphasic time-course of MCFA absorption and the incomplete recovery in the portal blood of the infused fatty acids.

APIC position paper: Safe injection, infusion, and medication vial practices in health care.

PubMed

Dolan, Susan A; Arias, Kathleen Meehan; Felizardo, Gwen; Barnes, Sue; Kraska, Susan; Patrick, Marcia; Bumsted, Amelia

2016-07-01

The transmission of bloodborne viruses and other microbial pathogens to patients during routine health care procedures continues to occur because of the use of improper injection, infusion, medication vial, and point-of-care testing practices by health care personnel. These unsafe practices occur in various clinical settings and result in unacceptable and devastating events for patients. This document updates the Association for Professionals in Infection Control and Epidemiology 2010 position paper on safe injection, infusion, and medication vial practices in health care. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

An intravenous medication safety system: preventing high-risk medication errors at the point of care.

PubMed

Hatcher, Irene; Sullivan, Mark; Hutchinson, James; Thurman, Susan; Gaffney, F Andrew

2004-10-01

Improving medication safety at the point of care--particularly for high-risk drugs--is a major concern of nursing administrators. The medication errors most likely to cause harm are administration errors related to infusion of high-risk medications. An intravenous medication safety system is designed to prevent high-risk infusion medication errors and to capture continuous quality improvement data for best practice improvement. Initial testing with 50 systems in 2 units at Vanderbilt University Medical Center revealed that, even in the presence of a fully mature computerized prescriber order-entry system, the new safety system averted 99 potential infusion errors in 8 months.

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 .).

Impact of needleless connector change frequency on central line-associated bloodstream infection rate.

PubMed

Sandora, Thomas J; Graham, Dionne A; Conway, Margaret; Dodson, Brenda; Potter-Bynoe, Gail; Margossian, Steven P

2014-05-01

Bloodstream infection is the most common pediatric health care-associated infection and is strongly associated with catheter use. These infections greatly increase the cost of hospital stay. To assess the association between needleless connector (NC) change frequency and central line-associated bloodstream infection (CLABSI) rate, we modeled monthly pediatric stem cell transplant (SCT) CLABSI rate in 3 periods: baseline period during which NC were changed every 96 hours regardless of infusate (period 1); trial period in which NC were changed every 24 hours with blood or lipid infusions (period 2); and a return to NC change every 96 hours regardless of infusate (period 3). Data on potential confounders were collected retrospectively. Autocorrelated segmented regression models were used to compare SCT CLABSI rates in each period, adjusting for potential confounders. CLABSI rates were also assessed for a nonequivalent control group (oncology unit) in which NC were changed every 24 hours with blood or lipid use in periods 2 and 3. SCT CLABSI rates were 0.41, 3.56, and 0.03 per 1,000 central line-days in periods 1, 2, and 3, respectively. In multivariable analysis, the CLABSI rate was significantly higher in period 2 compared with both period 1 (P = .01) and period 3 (P = .003). In contrast, CLABSI rates on the oncology unit were not significantly different among periods. In pediatric SCT patients, changing needleless connectors every 24 hours when blood or lipids are infused is associated with increased CLABSI rates. National recommendations regarding NC change frequency should be clarified. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Intermediary Variables and Algorithm Parameters for an Electronic Algorithm for Intravenous Insulin Infusion

PubMed Central

Braithwaite, Susan S.; Godara, Hemant; Song, Julie; Cairns, Bruce A.; Jones, Samuel W.; Umpierrez, Guillermo E.

2009-01-01

Background Algorithms for intravenous insulin infusion may assign the infusion rate (IR) by a two-step process. First, the previous insulin infusion rate (IRprevious) and the rate of change of blood glucose (BG) from the previous iteration of the algorithm are used to estimate the maintenance rate (MR) of insulin infusion. Second, the insulin IR for the next iteration (IRnext) is assigned to be commensurate with the MR and the distance of the current blood glucose (BGcurrent) from target. With use of a specific set of algorithm parameter values, a family of iso-MR curves is created, each giving IR as a function of MR and BG. Method To test the feasibility of estimating MR from the IRprevious and the previous rate of change of BG, historical hyperglycemic data points were used to compute the “maintenance rate cross step next estimate” (MRcsne). Historical cases had been treated with intravenous insulin infusion using a tabular protocol that estimated MR according to column-change rules. The mean IR on historical stable intervals (MRtrue), an estimate of the biologic value of MR, was compared to MRcsne during the hyperglycemic iteration immediately preceding the stable interval. Hypothetically calculated MRcsne-dependent IRnext was compared to IRnext assigned historically. An expanded theory of an algorithm is developed mathematically. Practical recommendations for computerization are proposed. Results The MRtrue determined on each of 30 stable intervals and the MRcsne during the immediately preceding hyperglycemic iteration differed, having medians with interquartile ranges 2.7 (1.2–3.7) and 3.2 (1.5–4.6) units/h, respectively. However, these estimates of MR were strongly correlated (R2 = 0.88). During hyperglycemia at 941 time points the IRnext assigned historically and the hypothetically calculated MRcsne-dependent IRnext differed, having medians with interquartile ranges 4.0 (3.0–6.0) and 4.6 (3.0–6.8) units/h, respectively, but these paired values again were correlated (R2 = 0.87). This article describes a programmable algorithm for intravenous insulin infusion. The fundamental equation of the algorithm gives the relationship among IR; the biologic parameter MR; and two variables expressing an instantaneous rate of change of BG, one of which must be zero at any given point in time and the other positive, negative, or zero, namely the rate of change of BG from below target (rate of ascent) and the rate of change of BG from above target (rate of descent). In addition to user-definable parameters, three special algorithm parameters discoverable in nature are described: the maximum rate of the spontaneous ascent of blood glucose during nonhypoglycemia, the glucose per daily dose of insulin exogenously mediated, and the MR at given patient time points. User-assignable parameters will facilitate adaptation to different patient populations. Conclusions An algorithm is described that estimates MR prior to the attainment of euglycemia and computes MR-dependent values for IRnext. Design features address glycemic variability, promote safety with respect to hypoglycemia, and define a method for specifying glycemic targets that are allowed to differ according to patient condition. PMID:20144334