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.

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.

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.

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.

Prophylactic treatment of local reactions to i.v. vinorelbine: a randomized study.

PubMed

Quant, Eva; Bergman, Bengt

2012-08-01

Local reactions on the site of infusion are common with i.v. vinorelbine treatment. The study aims were to evaluate whether an i.v. saline infusion or steroid injection, or the combination of these measures, could decrease vinorelbine-related local reactions and to study to what extent such reactions actually occur. Patients with lung cancer and planned chemotherapy containing i.v. vinorelbine were randomized in a 2 × 2 factorial design to receive either 4 mg betamethasone or placebo i.v. prior to and either 20 or 250 ml saline infusion following the vinorelbine infusion. Local infusion site signs and symptoms were recorded during and 1 h after the vinorelbine infusion and collected by a study-specific diary 24-48 h following each treatment course. A total of 79 patients were randomized and evaluable. Local infusion site signs, symptoms and reactions occurred in 63% of all patients (49% during vinorelbine monotherapy courses), with local pain being most frequently reported. Pre-treatment with i.v. betamethasone was associated with a reduced risk of local pain (5/38 vs. 20/39; p < 0.001) or any symptoms (14/38 vs. 29/39; p = 0.01) compared with placebo during the 48 h following the vinorelbine infusion. The reduced pain effect was seen both during vinorelbine monotherapy courses and during combination chemotherapy with carboplatin. In contrast, there was no difference between post-treatment infusion with 20 or 250 ml saline with regard to local signs or symptoms. Local infusion site side effects are common with i.v. vinorelbine. Pre-treatment with 4 mg betamethasone i.v. is associated with a reduced risk of local symptoms or reactions, local pain in particular.

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

PubMed

Nelson, K A; Glare, P A; Walsh, D; Groh, E S

1997-05-01

The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

PubMed

Muir, Stacy L; Sheppard, Lance B; Maika-Wilson, Anne; Burgert, James M; Garcia-Blanco, Jose; Johnson, Arthur D; Coyner, Jennifer L

2016-08-01

Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV attempts. The lack of significant difference between the TIO and IV routes relative to hemodynamic measures indicate the TIO route is a viable route for the infusion of 5% albumin in a swine model of Class III hemorrhage. Muir SL , Sheppard LB , Maika-Wilson A , Burgert JM , Garcia-Blanco J , Johnson AD , Coyner JL . A comparison of the effects of intraosseous and intravenous 5% albumin on infusion time and hemodynamic measures in a swine model of hemorrhagic shock. Prehosp Disaster Med. 2016;31(4):436-442.

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.

Pain control in patients with hepatocellular carcinoma treated by percutaneous radiofrequency ablation: comparison of the efficacy of one-shot and continuous intravenous fentanyl delivery.

PubMed

Yokoyama, Koichi; Ikeda, Osamu; Kawanaka, Koichi; Nakasone, Yutaka; Inoue, Seijiro; Tamura, Yoshitaka; Yamashita, Yasuyuki

2014-12-01

Hepatic percutaneous radiofrequency ablation (RFA) is usually performed with the patient under deep intravenous (i.v.) sedation or general anesthesia. Nonetheless, many patients report pain during and/or after the procedure. To perform a prospective study of pain control obtained by the i.v. one-shot delivery and the continuous i.v. infusion of fentanyl in patients with hepatocellular carcinoma (HCC) treated by RFA. Between April 2007 and March 2010, 83 patients with 106 HCCs underwent percutaneous RFA. All HCCs were addressed by computed tomography (CT)-guided percutaneous RFA performed within 5 h of embolization of the tumor vessels with iodized oil and gelatin sponges. Standard anesthesia consisted of 10 mL of 1% lidocaine injected locally. For conscious sedation, group one patients (n = 41) were injected i.v. with 100 µg of fentanyl before and 100 µg of fentanyl 30 min after percutaneous RFA. In group two (n = 42) we delivered fentanyl by continuous i.v. infusion at 100 µg/h during RFA. Upon request, patients in both groups also received 5 mg of diazepam i.v. for pain during the RFA procedure. The severity of pain experienced by all patients was evaluated on a visual analogue scale (VAS) and complications elicited by the anesthesia regimens were recorded. We also assessed the effectiveness of the treatment on sequential follow-up CT and/or magnetic resonance imaging (MRI) at 3-month intervals. Percutaneous RFA was technically successful in all 83 patients. Two patients in group one (4.8%) and one patient in group two (2.4%) manifested residual enhancement 3 months post RFA. There was no significant difference in the local recurrence rate between the two groups. At 4.0 ± 1.8 for group one and 3.4 ± 1.9 for group two, the VAS score was not significantly different. Major fentanyl or diazepam toxicity was recorded in 11 patients (24.4%) in group one and two patients (4.8%) in group two; the difference was statistically significant (P < 0.01). The continuous infusion of fentanyl provided effective and safe analgesia in HCC patients undergoing percutaneous RFA. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

PubMed Central

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

2004-01-01

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

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.

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

PubMed Central

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

2016-01-01

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

High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

PubMed

Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

2016-08-01

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

Optimization of Neuromodulation for Bladder Control in a Rat Cystitis Model.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2016-01-01

In a bladder overactivity model of cystitis induced by intravesical infusion of acetic acid (a.a.), several parameters of spinal nerve stimulation (SNS) were optimized using continuous infusion cystometry. The optimal stimulation was further characterized through measurements of urodynamic function using single-fill cystometry. In anesthetized male rats, a cannula was placed into the bladder dome for saline or 0.3% a.a. infusion and intravesical pressure monitoring. For SNS, two teflon-coated stainless steel electrodes were placed bilaterally under each of the L6 spinal nerves, and current stimulation was controlled independently using two Grass stimulators. Stimulation of 1 Hz or 50 Hz at motor threshold (Tmot ) was ineffective for altering bladder activities, but 10-Hz SNS increased the infused volume (IV) in a stimulation intensity-dependent fashion (P < 0.01, mixed model repeated analysis). Pairwise comparisons of IV differences to each stimulation intensity show that IV during 1 × Tmot stimulation was significantly larger than 0 × Tmot (no stim, P = 0.001), while the IV during 2 × Tmot stimulation was significantly larger than other intensities tested (P < 0.01). The mean IV (±SEM) during 0 × Tmot (no stim), 0.5 × Tmot , 1 × Tmot , and 2 × Tmot were 0.23 ± 0.04 mL, 0.25 ± 0.03 mL, 0.26 ± 0.03 mL, and 0.40 ± 0.04 mL, respectively. In single-fill cystometry, 10-Hz SNS at 1 × Tmot and 2 × Tmot stimulation increased the IV, or voiding duration and threshold pressure. SNS did not produce significant effects on basal pressure and micturition pressure. SNS significantly attenuates hypersensitive micturition reflex; 10 Hz and high-intensity stimulation are mostly effective. Acute peripheral nerve activation increases the functional bladder capacity, which may be via mechanisms on the afferent arm of the bladder micturition reflex. © 2015 International Neuromodulation Society.

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.

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

PubMed

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

2017-01-01

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

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.

Implementing smart infusion pumps with dose-error reduction software: real-world experiences.

PubMed

Heron, Claire

2017-04-27

Intravenous (IV) drug administration, especially with 'smart pumps', is complex and susceptible to errors. Although errors can occur at any stage of the IV medication process, most errors occur during reconstitution and administration. Dose-error reduction software (DERS) loaded on to infusion pumps incorporates a drug library with predefined upper and lower drug dose limits and infusion rates, which can reduce IV infusion errors. Although this is an important advance for patient safety at the point of care, uptake is still relatively low. This article discuses the challenges and benefits of implementing DERS in clinical practice as experienced by three UK trusts.

IV treatment at home

MedlinePlus

... venous catheter - home; Port - home; PICC line - home; Infusion therapy - home; Home health care - IV treatment ... is given quickly, all at once. A slow infusion, which means the medicine is given slowly over ...

Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

PubMed

Cilio, Maria Roberta; Bianchi, Roberto; Balestri, Martina; Onofri, Alfredo; Giovannini, Simona; Di Capua, Matteo; Vigevano, Federico

2009-09-01

To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

Use of continuous ambulatory infusions of concentrated subcutaneous (s.q.) hydromorphone versus intravenous (i.v.) morphine: cost implications for palliative care.

PubMed

Fudin, J; Smith, H S; Toledo-Binette, C S; Kenney, E; Yu, A B; Boutin, R

2000-01-01

Health care practitioners are increasingly under pressure to curtail spending while trying to deliver excellent patient care. These issues are also affecting palliative care, particularly now that palliative care programs are expanding. A comparison of cost-effectiveness and feasibility of using continuous subcutaneous (s.q.) ambulatory infusion of hydromorphone versus intravenous (i.v.) ambulatory morphine is illustrated in this study. With the high doses of morphine required in chronic cancer pain, the use of subcutaneous morphine is not feasible due to the volume of solution required to be delivered. Hydromorphone can be prepared in concentrated solutions enabling it to be delivered by the subcutaneous route. Morphine stability data are available. However, hydromorphone stability has only been verified for seven days; thus, stability data were needed post-seven days. Concentrations of 10 mg/ml, 20 mg/ml, 50 mg/ml, and 100 mg/ml, in 0.9 percent normal saline or dextrose 5 percent water, were analyzed via high-performance liquid chromatography (HPLC) at seven and 28 days. Cost comparisons of supplies and associated costs with subcutaneous versus intravenous solutions were obtained. Hydromorphone was found to be stable for 28 days in both dilutants. Cost analysis of a hydromorphone 28-day supply resulted in substantial savings over the equivalent costs of morphine infusions.

Predisposing factors to phlebitis in patients with peripheral intravenous catheters: a descriptive study.

PubMed

Uslusoy, Esin; Mete, Samiye

2008-04-01

The purpose of this study was to investigate the predisposing factors in the development of phlebitis in peripheral intravenous (IV) catheterization sites in patients treated with a variety of IV infusion solutions and drugs. Systematic observation of 568 IV sites inserted for fluid infusion and drug administration in 355 patients in the Department of General Surgery of a University Hospital in Turkey. A data collection tool was based on standards established by the Infusion Nurses Society. Patients' infusion sites were monitored every 24 h during treatment and for 48 h after discontinuation of the IV. In contrast to the usual findings in the literature, the authors found that infusion through an infusion pump and insertion of catheters in the veins around the elbow increased the risk of phlebitis. Also, the number of times infusions were started led to an increased rate of phlebitis. However, conflicting results were obtained about the relation between phlebitis, gender, and catheter size. Phlebitis causes sepsis, pain, additional diagnostic investigations, and treatments, and may lead to increased duration of hospitalization, patient's stress level, and financial burden, as well as increasing staff workload. Advanced practice nurses need to be aware of the factors that increase the likelihood of phlebitis and take appropriate measures to prevent it.

In-flight demonstration of the Space Station Freedom Health Maintenance Facility fluid therapy system (E300/E05)

NASA Technical Reports Server (NTRS)

Lloyd, Charles W.

1993-01-01

The Space Station Freedom (SSF) Health Maintenance Facility (HMF) will provide medical care for crew members for up to 10 days. An integral part of the required medical care consists of providing intravenous infusion of fluids, electrolyte solutions, and nutrients to sustain an ill or injured crew member. In terrestrial health care facilities, intravenous solutions are normally stored in large quantities. However, due to the station's weight and volume constraints, an adequate supply of the required solutions cannot be carried onboard SSF. By formulating medical fluids onboard from concentrates and station water as needed, the Fluid Therapy System (FTS) eliminates weight and volume concerns regarding intravenous fluids. The first full-system demonstration of FTS is continuous microgravity will be conducted in Spacelab-Japan (SL-J). The FTS evaluation consists of two functional objectives and an in-flight demonstration of intravenous administration of fluids. The first is to make and store sterile water and IV solutions onboard the spacecraft. If intravenous fluids are to be produced in SSF, successful sterilization of water and reconstituting of IV solutions must be achieved. The second objective is to repeat the verification of the FTS infusion pump, which had been performed in Spacelab Life Sciences - 1 (SLS-1). during SLS-1, the FTS IV pump was operated in continuous microgravity for the first time. The pump functioned successfully, and valuable knowledge on its performance in continuous microgravity was obtained. Finally, the technique of starting an IF in microgravity will be demonstrated. The IV technique requires modifications in microgravity, such as use of restraints for equipment and crew members involved.

The effect of propofol infusion with topical epinephrine on cochlear blood flow and hearing: An experimental study.

PubMed

Jang, Chul Ho; Cho, Yong Beom; Lee, Jun Sik; Kim, Geun Hyung; Jung, Won-Kyo; Pak, Sok Cheon

2016-12-01

Propofol is the most commonly used intravenous (IV) anesthetic agent and is associated with hypotension upon induction of anesthesia. Intravenous propofol infusion has several properties that may be beneficial to patients undergoing middle ear surgery. Topical application of concentrated epinephrine is a valuable tool for achieving hemostasis in the middle ear and during mastoid surgery. The purpose of the present study was to determine the effects of propofol infusion with topical epinephrine on cochlear blood flow (CBF) and hearing in rats. Twenty one male Sprague-Dawley rats were divided into three groups. The rate of intravenous infusion of propofol was 4-6 ml/kg/hour. The first group (control group, n = 7) was given IV infusion of phosphate buffered saline (PBS) with topical application of PBS in the round window. In study group A (n = 7), the effect of topical phosphate buffered saline with IV infusion of propofol on CBF and hearing was evaluated. In study group B (n = 7), additional effects of topical epinephrine with IV infusion of propofol on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and the mean arterial blood pressure (MAP) were measured and analyzed. Additionally, hearing test using auditory brainstem response (ABR) was performed in both groups. In both groups, infusion of propofol induced a time-dependent decrease in MAP. Approximately 30 min after the start of the propofol infusion, the CBF started to decrease slowly. The decrease in CBF was significantly greater in the study group compared to the control group. The threshold was elevated in the study group relative to the control group. During middle ear surgery, use of IV infusion of propofol with topical epinephrine cotton ball or cottonoid application is not recommended. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

PubMed Central

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

2017-01-01

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

[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.

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.

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

PubMed Central

2013-01-01

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

The shortened infusion time of intravenous ibuprofen, part 2: a multicenter, open-label, surgical surveillance trial to evaluate safety.

PubMed

Gan, Tong J; Candiotti, Keith; Turan, Alparslan; Buvanendran, Asokumar; Philip, Beverly K; Viscusi, Eugene R; Soghomonyan, Suren; Bergese, Sergio D

2015-02-01

The literature and clinical data support the use of intravenous (IV) infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. According to current guidelines, IV ibuprofen can be administered via a slow IV infusion performed during a 30-minute period. Although recent studies indicate that more rapid infusions may yield additional benefits for patients, the safety of such an approach needs further evaluation. The main purpose of this study was to determine the safety of single and multiple doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction of anesthesia and after the surgical procedure for the treatment of postoperative pain. This was a Phase IV, multicenter, open-label, clinical surveillance study. It was conducted at 21 hospitals in the United States, and 300 adult hospitalized patients undergoing surgery were enrolled. The exclusion criteria for the study were: inadequate IV access; hypersensitivity to any component of IV ibuprofen, aspirin, or related products; and any active, clinically significant bleeding. Also excluded were patients who had taken NSAIDs <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female patients; and patients in the perioperative period of coronary artery bypass graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10 minutes preoperatively. Vital signs, adverse events, and pain scores were assessed. Approximately 22% (65 of 300) of patients reported adverse events (serious and nonserious). The most common adverse event was infusion site pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious adverse events, 8 of which occurred during the first 6 hours. All serious events reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%) discontinued the study drug due to an adverse event (1 patient discontinued the study because of infusion site pain, and 1 patient withdrew due to a hypersensitivity reaction after drug administration). Our study found that IV ibuprofen infused over 5 to 10 minutes at induction of anesthesia is a safe administration option for surgical patients. ClinicalTrials.gov identifier: NCT01334957. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Concomitant Intravenous Nitroglycerin With Intracoronary Delivery of AAV1.SERCA2a Enhances Gene Transfer in Porcine Hearts

PubMed Central

Karakikes, Ioannis; Hadri, Lahouaria; Rapti, Kleopatra; Ladage, Dennis; Ishikawa, Kiyotake; Tilemann, Lisa; Yi, Geng-Hua; Morel, Charlotte; Gwathmey, Judith K; Zsebo, Krisztina; Weber, Thomas; Kawase, Yoshiaki; Hajjar, Roger J

2012-01-01

SERCA2a gene therapy improves contractile and energetic function of failing hearts and has been shown to be associated with benefits in clinical outcomes, symptoms, functional status, biomarkers, and cardiac structure in a phase 2 clinical trial. In an effort to enhance the efficiency and homogeneity of gene uptake in cardiac tissue, we examined the effects of nitroglycerin (NTG) in a porcine model following AAV1.SERCA2a gene delivery. Three groups of Göttingen minipigs were assessed: (i) group A: control intracoronary (IC) AAV1.SERCA2a (n = 6); (ii) group B: a single bolus IC injection of NTG (50 µg) immediately before administration of intravenous (IV) AAV1.SERCA2a (n = 6); and (iii) group C: continuous IV NTG (1 µg/kg/minute) during the 10 minutes of AAV1.SERCA2a infusion (n = 6). We found that simultaneous IV infusion of NTG and AAV1.SERCA2a resulted in increased viral transduction efficiency, both in terms of messenger RNA (mRNA) as well as SERCA2a protein levels in the whole left ventricle (LV) compared to control animals. On the other hand, IC NTG pretreatment did not result in enhanced gene transfer efficiency, mRNA or protein levels when compared to control animals. Importantly, the transgene expression was restricted to the heart tissue. In conclusion, we have demonstrated that IV infusion of NTG significantly improves cardiac gene transfer efficiency in porcine hearts. PMID:22215018

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

PubMed

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

2012-05-01

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

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

PubMed

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

2010-01-01

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

Multiple Intravenous Infusions Phase 1b

PubMed Central

Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

2012-01-01

Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all issues are known in advance, and the frequency of errors is too low to be observed in the time allotted and with the limited sample of observations. Conclusions The administration of multiple IV infusions to a single patient is a complex task with many potential associated patient safety risks. Improvements to infusion and infusion-related technology, education standards, clinical best practice guidelines, hospital policies, and unit work practices are required to reduce the risk potential. This report makes several recommendations to Ontario hospitals so that they can develop an awareness of the issues highlighted in this report and minimize some of the risks. Further investigation of mitigating strategies is required and will be undertaken in Phase 2 of this research. Plain Language Summary Patients, particularly in critical care environments, often require multiple intravenous (IV) medications via large volumetric or syringe infusion pumps. The infusion of multiple IV medications is not without risk; unintended errors during these complex procedures have resulted in patient harm. However, the range of associated risks and the factors contributing to these risks are not well understood. Health Quality Ontario’s Ontario Health Technology Advisory Committee commissioned the Health Technology Safety Research Team at the University Health Network to conduct a multi-phase study to identify and mitigate the risks associated with multiple IV infusions. Some of the questions addressed by the team were as follows: What is needed to reduce the risk of errors for individuals who are receiving a lot of medications? What strategies work best? The initial report, Multiple Intravenous Infusions Phase 1a: Situation Scan Summary Report, summarizes the interim findings based on a literature review, an incident database review, and a technology scan. The Health Technology Safety Research Team worked in close collaboration with the Institute for Safe Medication Practices Canada on an exploratory study to understand the risks associated with multiple IV infusions and the degree to which nurses are educated to help mitigate them. The current report, Multiple Intravenous Infusions Phase 1b: Practice and Training Scan, presents the findings of a field study of 12 hospital clinical units across Ontario, as well as 13 interviews with educators from baccalaureate-level nursing degree programs and postgraduate Critical Care Nursing Certificate programs. It makes 9 recommendations that emphasize best practices for the administration of multiple IV infusions and pertain to secondary infusions, line identification, line set-up and removal, and administering IV bolus medications. The Health Technology Safety Research Team has also produced an associated report for hospitals entitled Mitigating the Risks Associated With Multiple IV Infusions: Recommendations Based on a Field Study of Twelve Ontario Hospitals, which highlights the 9 interim recommendations and provides a brief rationale for each one. PMID:23074426

Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats.

PubMed

Radford, Kennett D; Park, Thomas Y; Lee, Bong Hyo; Moran, Sean; Osborne, Lisa A; Choi, Kwang H

2017-02-01

Clinicians administer subanesthetic intravenous (IV) ketamine infusions for treatment of refractory depression, chronic pain, and post-traumatic stress disorder in humans. However, ketamine is administered via the subcutaneous (SC) or intraperitoneal (IP) routes to rodents in most pre-clinical research, which may limit translational application. The present study characterized the dose-response of a subanesthetic IV ketamine bolus (2 and 5mg/kg) and 1-h infusion (5, 10, and 20mg/kg/h) on dissociative stereotypy, locomotion, sensorimotor gating, and thermal nociception in male Sprague-Dawley rats. The secondary aim was to measure ketamine and norketamine plasma concentrations following IV ketamine bolus at 1, 20, and 50min and at the conclusion of the 1-h infusion using liquid chromatography/mass spectrometry. The results showed that ketamine bolus and infusions produced dose-dependent dissociative stereotypy. Bolus (2 and 5mg/kg) and 20mg/kg/h infusion increased locomotor activity while 5mg/kg/h infusion decreased locomotor activity. Both 10 and 20mg/kg/h infusions reduced the acoustic startle reflex, while 5mg/kg bolus and 20mg/kg/h infusion impaired pre-pulse inhibition. Ketamine 5mg/kg bolus and the 10 and 20mg/kg/h infusions induced significant and prolonged antinociception to the hotplate test. Plasma concentrations of ketamine decreased quickly after bolus while norketamine levels increased from 1 to 20min and plateaued from 20 to 50min. The peak ketamine plasma concentrations [ng/ml] were similar between 5mg/kg bolus [4100] vs. 20mg/kg/h infusion [3900], and 2mg/kg bolus [1700] vs. 10mg/kg/h infusion [1500]. These results support the findings from previous ketamine injection studies and further validate the feasibility of administering subanesthetic doses of IV ketamine infusion to rats for neuropharmacological studies. Published by Elsevier Inc.

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.

0.9% sodium chloride injection with and without heparin for maintaining peripheral indwelling intermittent-infusion devices in infants.

PubMed

Nelson, T J; Graves, S M

1998-03-15

The use of 0.9% sodium chloride injection with and without heparin sodium for maintaining peripheral indwelling intermittent-infusion devices (PIIIDs) in infants was studied. In this double-blind study, children up to one year of age who had a 24-gauge PIIID through which a continuous i.v. infusion was no longer running were randomly assigned to have their PIIID capped with 0.9% sodium chloride injection with or without heparin sodium 10 units/mL. PIIIDs were capped every eight hours if no medications were administered; otherwise, they were capped after each dose of an i.v. drug. The heparin group had 26 patients with 28 evaluable PIIIDs, and the 0.9% sodium chloride injection group had 32 patients with 46 evaluable PIIIDs. The two groups did not differ significantly in variables assessing the duration of PIIID use, reasons for removal of PIIIDs, mean number of cappings, irritant potential of administered drugs, or severity of medication-related irritation. There was no significant difference between 0.9% sodium chloride injection with and without heparin sodium 10 units/mL in maintaining 24-gauge PIIIDs in children younger than one year.

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

Intraosseous anesthesia in hemodynamic studies in children with cardiopathy.

PubMed

Aliman, Ana Cristina; Piccioni, Marilde de Albuquerque; Piccioni, João Luiz; Oliva, José Luiz; Auler Júnior, José Otávio Costa

2011-01-01

Intraosseous (IO) access has been used with good results in emergency situations, when venous access is not available for fluids and drugs infusion. The objective of this study was to evaluate IO a useful technique for anesthesia and fluids infusion during hemodynamic studies and when peripheral intravascular access is unobtainable. The setting was an university hospital hemodynamics unit, and the subjects were twenty one infants with congenital heart disease enrolled for elective hemodynamic study diagnosis. This study compared the effectiveness of IO access in relation to IV access for infusion of anesthetics agents (ketamine, midazolam, and fentanyl) and fluids during hemodynamic studies. The anesthetic induction time, procedure duration, anesthesia recovery time, adequate hydration, and IV and IO puncture complications were compared between groups. The puncture time was significantly smaller in IO group (3.6 min) that in IV group (9.6 min). The anesthetic onset time (56.3 second) for the IV group was faster than IO group (71.3 second). No significant difference between groups were found in relation to hydration (IV group, 315.5 mL vs IO group, 293.2 mL), and anesthesia recovery time (IO group, 65.2 min vs IV group, 55.0 min). The puncture site was reevaluated after 7 and 15 days without signs of infection or other complications. Results showed superiority for IO infusion when considering the puncture time of the procedure. Due to its easy manipulation and efficiency, hydration and anesthesia by IO access was satisfactory for hemodynamic studies without the necessity of other infusion access. Copyright © 2011 Elsevier Editora Ltda. All rights reserved.

Effect of Intravenous Infusion Solutions on Bioelectrical Impedance Spectroscopy.

PubMed

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

2017-05-01

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

Comparative effects of rapid bolus administration of aqueous amiodarone versus 10-minute cordarone I.v. infusion on mean arterial blood pressure in conscious dogs.

PubMed

Somberg, John Charin; Cvetanovic, Ivana; Ranade, Vasant; Molnar, Janos

2004-09-01

This study was designed to test the hypothesis that rapid bolus administration of an aqueous formulation of intravenous amiodarone causes less hypotension than a 10-minute infusion of the standard formulation, Cordarone IV. Hypotension was the most common adverse event reported with Cordarone IV. The hypotension was not dose related, but related to the rate of infusion. Therefore, product labeling calls Cordarone and its generic formulations to be administered over 10 minutes. Cordarone IV contains polysorbate 80 and benzyl alcohol, each causes hypotension. A new aqueous formulation of amiodarone (Amio-Aqueous) does not contain these agents and therefore may cause less hypotension. Six conscious beagle dogs were instrumented with a telemetric device for blood pressure monitoring. The study was conducted on 5 days. On the first 2 days, a 10-min infusion or a bolus of D(5)W was administered (placebo). Over the following 3 days, the dogs received (in randomized order, one per day) a 10-min infusion of 2.5 mg/kg Cordarone IV and boluses of 2.5 mg/kg and 5.0 mg/kg Amio-Aqueous injected over 2 to 5 sec. The dogs were monitored for 2 hrs after dosing. Compared to placebo, boluses of aqueous amiodarone produced no significant changes in the mean arterial blood pressure (MABP). In contrast, Cordarone infusion produced significant decreases in MABP that lasted for at least 2 hrs (p < 0.001). Amio-Aqueous had significantly better hemodynamic profile permitting rapid intravenous administration. This is a significant advantage over the standard formulation, because Cordarone cannot be administered by rapid bolus due to excipient-related hypotension.

Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I.

PubMed

Skottner, A; Clark, R G; Fryklund, L; Robinson, I C

1989-05-01

A new mutant GH-deficient dwarf rat has been used to study the effects of iv infusions of human GH (hGH) and recombinant human insulin-like growth factor I (hIGF-I). This animal has only about 5% of normal pituitary GH content, low circulating GH levels, and no regular GH surges. The defect seems to be specific for GH. Infusions of hIGF-I at 180 micrograms/day for 9 days elevated serum IGF-I concentrations significantly over those in the saline-infused controls (713 +/- 20 ng/ml vs. 395 +/- 31 ng/ml); hGH infusions did not raise IGF-I levels significantly (435 +/- 20 ng/ml). Gel filtration of serum samples showed that the high-dose hIGF-I infusions increased free IGF concentrations, without apparently altering the pattern of IGF-I binding whereas hGH infusions increased the amount of high mol wt IGF-I binding protein. Neither IGF-I nor hGH infusions affected the small amounts of rat GH present in the dwarf rat pituitary glands. Continuous iv infusions of hGH (200 mU/day for 9 days) stimulated body wt gain (2.1 +/- 0.2 g/day) and bone growth (96 +/- 9 microns/day) significantly compared to saline-infused dwarf rats (1.2 +/- 0.3 g/day and 43 +/- 3 microns/day). Infusions of hIGF-I at 180 micrograms/day produced a body wt gain (2.1 +/- 0.5 g/day) similar to that seen in the hGH-infused group but a significantly smaller stimulation of bone growth (63 +/- 3 microns/day). Infusion of a 5-fold lower dose of hIGF-I (36 micrograms/day for 9 days) had no effect on body wt or bone growth. Food intake was unaffected by either hGH or hIGF-I infusions. The pattern of tissue growth was affected differentially by hGH and IGF-I infusions that produced the same overall body wt gain. hGH induced a relatively proportional growth in most of the organs studied, whereas hIGF-I infusion at 180 micrograms/day stimulated a disproportionately greater growth of the kidney, adrenals, and spleen. In some of the animals, tissues were extracted for RIA of IGF-I; the amounts of IGF-I in the liver were similar in control, hGH, or IGF-I-infused animals, whereas kidney and adrenals from IGF-I infused animals contained larger amounts of immunoreactive IGF-I than did those tissues from hGH-treated rats. Thus, both hGH and hIGF-I can promote growth in the mutant dwarf rat, but they differ both quantitatively and qualitatively in their pattern of actions.

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

Three insulation methods to minimize intravenous fluid administration set heat loss.

PubMed

Piek, Richardt; Stein, Christopher

2013-01-01

To assess the effect of three methods for insulating an intravenous (IV) fluid administration set on the temperature of warmed fluid delivered rapidly in a cold environment. The three chosen techniques for insulation of the IV fluid administration set involved enclosing the tubing of the set in 1) a cotton conforming bandage, 2) a reflective emergency blanket, and 3) a combination of technique 2 followed by technique 1. Intravenous fluid warmed to 44°C was infused through a 20-drop/mL 180-cm-long fluid administration set in a controlled environmental temperature of 5°C. Temperatures in the IV fluid bag, the distal end of the fluid administration set, and the environment were continuously measured with resistance thermosensors. Twenty repetitions were performed in four conditions, namely, a control condition (with no insulation) and the three different insulation methods described above. One-way analysis of variance was used to assess the mean difference in temperature between the IV fluid bag and the distal fluid administration set under the four conditions. In the control condition, a mean of 5.28°C was lost between the IV fluid bag and the distal end of the fluid administration set. There was a significant difference found between the four conditions (p < 0.001). A mean of 3.53°C was lost between the IV fluid bag and the distal end of the fluid administration set for both the bandage and reflective emergency blanket, and a mean of 3.06°C was lost when the two methods were combined. Using inexpensive and readily available materials to insulate a fluid administration set can result in a reduction of heat loss in rapidly infused, warmed IV fluid in a cold environment.

List of Error-Prone Abbreviations, Symbols, and Dose Designations

MedlinePlus

... unit dose (e.g., diltiazem 125 mg IV infusion “UD” misin- terpreted as meaning to give the entire infusion as a unit [bolus] dose) Use “as directed” ... Names Intended Meaning Misinterpretation Correction “Nitro” drip nitroglycerin infusion Mistaken as sodium nitroprusside infusion Use complete drug ...

Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp

PubMed Central

Erickson, Dana; Miles, John M.; Bowers, Cyril Y.

2011-01-01

To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E2; women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E2/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E2 and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E2/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain. PMID:21467302

Subcutaneous infusion of human C1 inhibitor in swine.

PubMed

Jiang, Haixiang; Zhang, Hua-Mei; Frank, Michael M

2010-09-01

Hereditary angioedema afflicts patients with unpredictable episodes of swelling that can be life threatening. Treatments approved by the Food and Drug Administration for routine prophylaxis include danazol given orally and the nanofiltered human C1 esterase inhibitor, CINRYZE, which is approved for intravenous administration. Approved for the treatment of acute attacks are the C1 esterase inhibitor, Berinert, given intravenously, and the kallikrein inhibitor, KALBITOR, given subcutaneously. C1 inhibitor has generally been non-toxic and neither pro-inflammatory nor pro-fibrotic, suggesting that it may be suitable for subcutaneous infusion. The current study used a swine model to compare blood levels of human C1 inhibitor following intravenous and subcutaneous infusion, and the effect of infusion route on heart and skin pathology. Levels of C1 inhibitor achieved with SC infusion compared favorably with levels achieved after IV infusion and were relatively more stable than those after IV infusion. Neither cardiac nor skin toxicity was observed. Copyright 2010 Elsevier Inc. All rights reserved.

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.

Intravenous magnesium sulfate for vaso-occlusive episodes in sickle cell disease.

PubMed

Goldman, Ran D; Mounstephen, William; Kirby-Allen, Melanie; Friedman, Jeremy N

2013-12-01

Vaso-occlusive episodes (VOEs) are the most common complication of sickle cell disease in children. Treatment with magnesium seems to improve cellular hydration and may result in reduced vaso-occlusion. This study aimed to determine if intravenous (IV) magnesium sulfate (MgSO4) reduces length of stay (LOS) in hospital, pain scores, and cumulative analgesia when compared with placebo. Randomized, double-blind, placebo-controlled trial in children aged 4 to 18 years requiring admission to hospital with a sickle cell disease VOE requiring IV analgesia. Participating children received IV MgSO4 (100 mg/kg) every 8 hours or placebo in addition to standard therapy. We used a t test or Mann-Whitney test (continuous variables), Fisher's exact test, or χ2 test (frequencies). P values were considered significant if <.05, and 95% confidence intervals were calculated for the difference between groups. One hundred six children were randomly assigned to the study, and 104 were included. Fifty-one (49%) received MgSO4. Children's mean age was 12.4 years (range: 4-18 years; SD: 3.8 years), and 56 (54%) were females. There was no significant difference in the primary outcome measure, LOS in hospital, with a mean of 132.6 and 117.7 hours in the MgSO4 and placebo groups, respectively (P = .41). There was no significant difference between groups for the secondary outcomes of mean pain scores (4.9 ± 2.6 vs 4.8 ± 2.6, respectively; P = .92) or analgesic requirements (continuous morphine infusion [P = .928], boluses of IV morphine [P = .82], acetaminophen [P = .34], ibuprofen [P = .15], naproxen [P = .10]). Only minor adverse events were recorded in both groups. Pain at the infusion site was more common in the MgSO4 group. IV MgSO4 was well tolerated but had no effect on the LOS in hospital, pain scores, or cumulative analgesia use in admitted children with a VOE.

Management of exaggerated gag reflex in dental patients using intravenous sedation with dexmedetomidine.

PubMed

Reshetnikov, Aleksei P; Kasatkin, Anton A; Urakov, Aleksandr L; Baimurzin, Dmitrii Y

2017-01-01

Pharmacological sedation is one of the effective ways of prevention of gag reflex development in patients experiencing anxiety and fright before dental treatment. We are reporting a case where we could successfully eliminate exaggerated gag reflex (intravenous [IV] Gagging Severity Index) in a dental patient using IV sedation with dexmedetomidine. IV administration of dexmedetomidine provided elimination of gag reflex at a depth of sedation for the patient with the Richmond Agitation-Sedation Scale score of -2 and -1. The patient received dexmedetomidine 1.0 μg/kg for 10 min and then a continuous infusion of dexmedetomidine 0.4 μg/kg/h. The use of dexmedetomidine for sedation may be an alternative to other pharmacological agents in patients with dental anxiety accompanied by exaggerated gag reflex.

Integrating technology to improve medication administration.

PubMed

Prusch, Amanda E; Suess, Tina M; Paoletti, Richard D; Olin, Stephen T; Watts, Starann D

2011-05-01

The development, implementation, and evaluation of an i.v. interoperability program to advance medication safety at the bedside are described. I.V. interoperability integrates intelligent infusion devices (IIDs), the bar-code-assisted medication administration system, and the electronic medication administration record system into a bar-code-driven workflow that populates provider-ordered, pharmacist-validated infusion parameters on IIDs. The purpose of this project was to improve medication safety through the integration of these technologies and decrease the potential for error during i.v. medication administration. Four key phases were essential to developing and implementing i.v. interoperability: (a) preparation, (b) i.v. interoperability pilot, (c) preliminary validation, and (d) expansion. The establishment of pharmacy involvement in i.v. interoperability resulted in two additional safety checks: pharmacist infusion rate oversight and nurse independent validation of the autoprogrammed rate. After instituting i.v. interoperability, monthly compliance to the telemetry drug library increased to a mean ± S.D. of 72.1% ± 2.1% from 56.5% ± 1.5%, and the medical-surgical nursing unit's drug library monthly compliance rate increased to 58.6% ± 2.9% from 34.1% ± 2.6% (p < 0.001 for both comparisons). The number of manual pump edits decreased with both telemetry and medical-surgical drug libraries, demonstrating a reduction from 56.9 ± 12.8 to 14.2 ± 3.9 and from 61.2 ± 15.4 to 14.7 ± 3.8, respectively (p < 0.001 for both comparisons). Through the integration and incorporation of pharmacist oversight for rate changes, the telemetry and medical-surgical patient care areas demonstrated a 32% reduction in reported monthly errors involving i.v. administration of heparin. By integrating two stand-alone technologies, i.v. interoperability was implemented to improve medication administration. Medication errors were reduced, nursing workflow was simplified, and pharmacists became involved in checking infusion rates of i.v. medications.

Significant air embolism: A possibility even with collapsible intravenous fluid containers when used with rapid infuser system

PubMed Central

Pant, Deepanjali; Narani, Krishan Kumar; Sood, Jayashree

2010-01-01

Significant venous air embolism may develop acutely during the perioperative period due to a number of causes such as during head and neck surgery, spinal surgery, improper central venous and haemodialysis catheter handling, etc. The current trend of using self collapsible intravenous (IV) infusion bags instead of the conventional glass or plastic bottles has several advantages, one of thaem being protection against air embolism. We present a 56-year-old man undergoing kidney transplantation, who developed a near fatal venous air embolism during volume resuscitation with normal saline in collapsible IV bags used with rapid infuser system. To our knowledge, this problem with collapsible infusion bags has not been reported earlier. PMID:20532073

REINFORCING EFFECTS OF NICOTINE AND NON-NICOTINE COMPONENTS OF CIGARETTE SMOKE

PubMed Central

Rose, Jed E.; Salley, Al; Behm, Frederique M.; Bates, James E.; Westman, Eric C.

2014-01-01

We assessed the reinforcing effects of nicotine and non-nicotine components of cigarette smoke, by presenting a concurrent choice paradigm in which participants had access to intravenous (IV) nicotine infusions vs. saline (placebo) infusions and puffs from denicotinized (“denic”) cigarettes vs. air (sham puffs). We also measured the effects on self-administration of prior satiation with each component. Sixteen smokers participated in 7 sessions, consisting of: 1) a baseline smoking assessment, which was used to tailor the nicotine dose per infusion to that of puffs from subjects’ preferred brands of cigarettes; 2) two sessions in which participants were trained to discriminate IV nicotine vs. saline infusions and denic smoke vs. sham (air) puffs; and 3) four sessions assessing choice behavior after different satiation conditions. Results showed that subjects self-administered more puffs of denic smoke than any other alternative, including IV nicotine. IV nicotine, however, was preferred over IV saline and sham puffs. Preference for denic smoke vs. IV nicotine was highly correlated with subjective ratings of “comfort” associated with the two alternatives. Satiation with smoke diminished the number of denic puffs taken during choice periods, while prior administration of nicotine did not affect the number of puffs taken. Smoking withdrawal symptoms were alleviated both by nicotine administration and by denic smoke. These results show that in established smokers, non-nicotine aspects of cigarette smoking have potent reinforcing effects. While current smoking cessation pharmacotherapies primarily address the nicotine component of cigarette addiction, future cessation strategies should also be designed to target non-nicotine factors. PMID:20358364

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.

In vivo evidence for the involvement of tachykinin NK3 receptors in the hexamethonium-resistant inhibitory transmission in the rat colon.

PubMed

Lecci, A; Giuliani, S; Tramontana, M; Meini, S; De Giorgio, R; Maggi, C A

1996-05-01

In urethane-anaesthetized rats, moderate colonic distention (0.5 ml) induced reflex rhythmic contractions (5 mm Hg amplitude and 1.1 cycles/min frequency). Senktide (1-10 nmol/kg, i.v.), a tachykinin NK3 receptor selective agonist, transiently suppressed distension-induced contractions. SR 142,801 (1-10 mumol/kg i.v.), a non-peptide tachykinin NK3 receptor antagonist, had no effect on distension-induced contractions but prevented the inhibitory effect of senktide. Infusion of N-omega-nitro-1-arginine methyl esther hydrochloride (L-NAME, 20 mumol/ml/h, i.v) increased the amplitude of colonic contractions and decreased the inhibitory effect of senktide. Hexamethonium (15 mumol/ml/h, i.v.) or atropine (1 mumol/ml/h, i.v.) inhibited the distension-induced contractions. In hexamethonium- or atropine-treated rats, senktide (10 nmol/kg) transiently and selectively enhanced the amplitude of contractions. Also SR 142,801 (10 mumol/kg), but not its inactive enantiomer SR 142,806, increased both amplitude and frequency of contractions. During continuous infusion of L-NAME and hexamethonium or atropine both frequency and amplitude of distension-induced colonic contractions were higher than when in hexamethonium or atropine only. Senktide (10 nmol/kg) had no effect and SR 142,801 (10 mumol/kg) produced a slight enhancement of colonic contractions. Infusion of sodium nitroprusside (3 mumol/ml/h, i.v.) decreased amplitude and frequency of distension-induced contractions. SR 142,801 had no effect in the presence of the nitric oxide (NO) donor. We conclude that tachykinins acting through NK3 receptors exert at least four different actions on colonic motility activated by distension: 1) a hexamethonium-resistant, NO-dependent, suppressant effect on contractions; 2) a hexamethonium-sensitive, NO-independent inhibitory effect on the amplitude of contractions; 3) a hexamethonium-resistant, NO-independent inhibitory effect on the amplitude of contractions and 4) a hexamethonium resistant and L-NAME-sensitive excitatory effect on amplitude of contractions. The prevalent inhibitory effect evoked in normal conditions along with the excitatory activity induced by SR 142,801 on hexamethonium-resistant colonic motility indicates that tachykinins, acting through neuronal NK3 receptors, activate NO-dependent and NO-independent inhibitory neurotransmission in the rat colon.

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.

Magnesium sulphate has beneficial effects as an adjuvant during general anaesthesia for Caesarean section.

PubMed

Lee, D H; Kwon, I C

2009-12-01

The use of low concentrations of volatile anaesthetics with avoidance of opioids may induce intraoperative awareness and adverse haemodynamic responses during Caesarean section. Magnesium is well known to reduce anaesthetic requirements and to block noxious stimuli. We investigated whether i.v. magnesium sulphate modulates anaesthetic depth and analgesic efficacy during Caesarean section. Seventy-two patients undergoing Caesarean section were randomly assigned to receive i.v. saline (control group) or magnesium sulphate 30 mg kg(-1) bolus+10 mg kg(-1) h(-1) continuous infusion (Mg 30 group) or 45 mg kg(-1) bolus+15 mg kg(-1) h(-1) continuous infusion (Mg 45 group) after induction. Bispectral index (BIS) value, mean arterial pressure (MAP), and midazolam, fentanyl, and atracurium consumptions were recorded. BIS values [mean (sd)] at 7.5 and 10 min after surgery and before delivery in the control [64 (9), 66 (8), 67 (8), P<0.001] and the Mg 30 groups [62 (8), P<0.01; 64 (7), 63 (9), P<0.001] were higher than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. MAP was greater in the control group (P<0.05) than in the Mg 30 and Mg 45 groups during the pre-delivery period. The magnesium groups required less midazolam (P<0.05), fentanyl (Mg 30, P<0.05; Mg 45, P<0.01), and atracurium (P<0.001) vs the control group. Preoperative i.v. magnesium sulphate attenuated BIS and arterial pressure increases during the pre-delivery period. Magnesium sulphate can be recommended as an adjuvant during general anaesthesia for Caesarean section to avoid perioperative awareness and pressor response resulting from inadequate anaesthesia, analgesia, or both.

Safety and efficacy of intravenous hypotonic 0.225% sodium chloride infusion for the treatment of hypernatremia in critically ill patients.

PubMed

Dickerson, Roland N; Maish, George O; Weinberg, Jordan A; Croce, Martin A; Minard, Gayle; Brown, Rex O

2013-06-01

The purpose of this study was to evaluate the safety and efficacy of central venous administration of a hypotonic 0.225% sodium chloride (one-quarter normal saline [¼ NS]) infusion for critically ill patients with hypernatremia. Critically ill, adult patients with traumatic injuries and hypernatremia (serum sodium [Na] >150 mEq/L) who were given ¼ NS were retrospectively studied. Serum sodium, fluid balance, free water intake, sodium intake, and plasma free hemoglobin concentration (fHgb) were assessed. Twenty patients (age, 50 ± 18 years; Injury Severity Score, 29 ± 12) were evaluated. The ¼ NS infusion was given at 1.5 ± 1.0 L/d for 4.6 ± 1.6 days. Serum sodium concentration decreased from 156 ± 4 to 143 ± 6 mEq/L (P < .001) over 3-7 days. Total sodium intake was decreased from 210 ± 153 to 156 ± 112 mEq/d (P < .05). Daily net fluid balance was not significantly increased. Plasma fHgb increased from 4.9 ± 5.4 mg/dL preinfusion to 8.9 ± 7.4 mg/dL after 2.6 ± 1.3 days of continuous intravenous (IV) ¼ NS in 10 patients (P = .055). An additional 10 patients had a plasma fHgb of 10.2 ± 9.0 mg/dL during the infusion. Hematocrit and hemoglobin decreased (26% ± 3% to 24% ± 2%, P < .001 and 9.1 ± 1.1 to 8.2 ± 0.8 g/dL, P < .001, respectively). Although IV ¼ NS was effective for decreasing serum sodium concentration, evidence for minor hemolysis warrants further research to establish its safety before its routine use can be recommended.

Increasing LH Pulsatility in Women With Hypothalamic Amenorrhoea Using Intravenous Infusion of Kisspeptin-54

PubMed Central

Jayasena, Channa N.; Abbara, Ali; Veldhuis, Johannes D.; Comninos, Alexander N.; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M. K.; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A.; Bloom, Stephen R.

2014-01-01

Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P < .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA. PMID:24517142

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.

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)

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

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

Hegarty, T.J.; Thornton, A.F.; Diaz, R.F.

1990-08-01

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe,more » continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.« less

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

PubMed

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

2018-06-01

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

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

[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.

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine.

PubMed

Lou, Wenhui; Xia, Ying; Xiang, Peng; Zhang, Liangqing; Yu, Xiangyou; Lim, Sam; Xu, Mo; Zhao, Lina; Rydholm, Hans; Traxler, Barry; Qin, Xinyu

2018-04-20

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control. ClinicalTrials.gov identifier NCT02157376.

The Arg389Gly beta1-adrenoceptor polymorphism does not affect cardiac effects of exercise after parasympathetic inhibition by atropine.

PubMed

Leineweber, Kirsten; Bruck, Heike; Temme, Thomas; Heusch, Gerd; Philipp, Thomas; Brodde, Otto-Erich

2006-01-01

In vitro, Arg389Gly beta1-adrenoceptor (AR) polymorphism exhibits decreased beta-AR signalling. In vivo, beta1-AR-mediated cardiac effects of exercise showed no genotype-dependent differences in Arg389 vs. Gly389 beta1-AR subjects. We studied in 16 male subjects homozygous Arg389 or Gly389 beta1-AR, whether blockade of parasympathetic activity might unmask genotype-dependence of exercise effects. Subjects were infused with atropine (10 microg/kg i.v. loading dose followed by continuous i.v. infusion of 0.15 microg/kg/min throughout exercise-time); 20 min after start of atropine bicycle-exercise in supine position (25, 50, 75 and 100 W for 5 min each) was performed and heart rate, contractility, blood pressure, plasma noradrenaline and plasma-renin activity were assessed. Exercise-evoked increases in all but one parameters were not different between Arg389 and Gly389 beta1-AR subjects; only plasma noradrenaline increased slightly more in Gly389 vs. Arg389 beta1-AR subjects. It appears to be unlikely that lack of Arg389Gly beta1-AR genotype-dependence of exercise-effects can be explained by influences of parasympathetic activity.

Studies on reproductive toxicity of iloprost in rats, rabbits and monkeys.

PubMed

Battenfeld, R; Schuh, W; Schöbel, C

1995-08-01

A reproduction toxicological test program was performed with the carbaprostacyclin derivative iloprost, an analogue to the endogenous prostacyclin PGI2, in order to detect possible effects on fertility and reproductive performance, on preimplantational, embryonal and fetal development, on delivery as well as on lactation and postpartum development. While in humans iloprost is administered as an i.v. infusion for 6 h/day, it was administered i.v. to rats, rabbits and monkeys by continuous infusion with a subcutaneously implanted pump. No influence on mating or reproductive parameters was found after treatment of male or female rats during the premating phase up to day 7 post coitum (p.c.). Embryonal and fetal development were not remarkably impaired in rabbits or monkeys after treatment throughout the period of organogenesis. The only remarkable observations in the embryotoxicity and peri-/postnatal studies in the rat were defects on the digits (reductions of phalangeal structures) in single individuals. These malformations were interpreted as resulting from a compound-related hypotonia with subsequent change in the regional blood flow and the consequence of temporary impairments of placental blood supply leading to hypoxia in the affected structures.

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

PubMed

Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-10-01

To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter multinational study.

Intravenous nicorandil versus adenosine for fractional flow reserve measurement: a crossover, randomized study.

PubMed

Nishi, Takeshi; Kitahara, Hideki; Fujimoto, Yoshihide; Nakayama, Takashi; Nagashima, Kengo; Hanaoka, Hideki; Kobayashi, Yoshio

2018-06-01

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.

Sodium ferric gluconate (SFG) in complex with sucrose for IV infusion: bioequivalence of a new generic product with the branded product in healthy volunteers.

PubMed

Baribeault, David

2011-08-01

Parenteral sodium ferric gluconate in complex (Ferrlecit [branded SFG]) is used to treat patients with iron deficiency anemia undergoing chronic hemodialysis and receiving supplemental epoetin. This comparative pharmacokinetic study (GeneraMedix, Inc., Study 17909) evaluates whether the recently approved generic product Nulecit (generic SFG) and the branded product Ferrlecit (branded SFG) are bioequivalent. In this open-label study, 240 healthy volunteers in a fasting state were assigned randomly to a single 10-min intravenous (IV) infusion of 125 mg of generic or branded SFG. Total and transferrin-bound iron concentrations were determined for the 36-h period after infusion and corrected for pretreatment levels. Maximum concentration (Cmax) and area under the concentration-time curve of 0 to 36 h (AUC[0-36]) were compared between the two products. Demonstration of bioequivalence required that the 90% confidence intervals of each parameter evaluated for generic SFG were within 80% to 125% of the corresponding values for branded SFG. Uncorrected and baseline-corrected mean serum concentrations of total serum iron during the 36-h assessment period were similar for generic and branded SFG. For total serum iron, the geometric mean ratios of corrected Cmax and AUC[0-36] were 100%. For transferrin-bound iron, the geometric mean ratios were 87% for corrected Cmax and 92% for corrected AUC[0-36]. All associated 90% confidence intervals were within the range of 80% to 125%. A new generic SFG in complex for IV infusion is bioequivalent to the branded SFG in complex for IV infusion. The generic SFG is AB rated by the FDA and considered therapeutically equivalent to the branded product.

Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy.

PubMed

Caritis, Steve; Zhao, Yang; Chen, Hui-Jun; Venkataramanan, Raman

2016-07-01

Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P < .01). The PUQE score prior to patch placement was 7.6 ± 2.4. Scores were significantly (P < .001) reduced within 1 day of patch placement and stayed significantly reduced during the ensuing 6 days of patch placement. The patch was removed on the seventh day and PUQE scores increased significantly on the third day after patch removal. No serious side effects were reported either during IV administration or patch placement. Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was administered as a patch, benefit likewise was seen within 1 day suggesting rapid absorption of the medication transdermally. The beneficial effect of transdermal granisetron on the PUQE score persisted for the entire 7 days during which the patch was in place. In this small cohort, the granisetron patch appeared to be efficacious in reducing the symptoms of nausea and vomiting. The patch provides another option for treating this disorder and may be particularly useful in women who cannot tolerate oral medications. Copyright © 2016 Elsevier Inc. All rights reserved.

Theophylline prevents the inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Salvatore, T; Giunta, R; Torella, R

1988-06-01

This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3-10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 micrograms/min) and glucose disappearance rates were reduced (P less than 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucose-induced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.

Primary Intravenous Set Consumption Across 3 Branded Infusion Pumps

PubMed Central

Hedlund, Nancy; Sarangpur, Shishir; Kayler, Shannon; O'Brien, Kathy

2017-01-01

This retrospective study of 6426 hip replacement, coronary artery bypass graft, and colectomy surgeries across 23 US hospitals found that intravenous (IV) set designs that can be interchanged for use both in gravity-fed and automated pump delivery systems are replaced less frequently than IV sets designed for use primarily by one delivery method. Semistructured interviews with nurses highlighted the impact of set design on nursing workflow when moving between gravity-fed and pump-based administration. Use of interchangeable, single-design IV sets across gravity and automated infusions minimizes disruptions to closed systems, may reduce nurses being distracted from patients' clinical needs when replacing sets, and may yield supply cost savings. PMID:28682999

[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.

Intravenous fluid temperature management by infrared thermometer.

PubMed

Lapostolle, Frédéric; Catineau, Jean; Le Toumelin, Philippe; Proust, Clément; Garrigue, Bruno; Galinski, Michel; Adnet, Frédéric

2006-03-01

The management of intravenous (IV) fluid temperature is a daily challenge in critical care, anesthesiology, and emergency medicine. Infusion of IV fluids at the right temperature partly influences clinical outcomes of critically ill patients. Nowadays, intravenous fluid temperature is poorly managed, as no suitable device is routinely available. Infrared (IR) thermometers have been recently developed for industrial, personal, or medical purposes. The aim of this study was to evaluate the accuracy of an IR thermometer in measuring temperature of warmed and cooled infusion fluids in fluid bags. This study compared temperatures simultaneously recorded by an infrared thermometer and a temperature sensor. Temperatures of warmed (41 degrees C) and cooled (4 degrees C) infusion fluids in fluid bags were recorded by 2 independent operators every minute until IV bags' temperature reached ambient temperature. The relation curve was established with 576 measures. Temperature measures performed with an IR thermometer were perfectly linear and perfectly correlated with the reference method (R(2) = 0.995, P < 10(-5)). Infrared thermometers are efficient to measure IV fluid bag temperature in the range of temperatures used in clinical practice. As these devices are easy to use and inexpensive, they could be largely used in critical care, anesthesiology, or emergency medicine.

Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

PubMed Central

Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

2014-01-01

We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S

PubMed Central

Watson, Catherine E.; Weissbach, Nicole; Kjems, Lise; Ayalasomayajula, Surya; Zhang, Yiming; Chang, Ih; Navab, Mohamad; Hama, Susan; Hough, Greg; Reddy, Srinivasa T.; Soffer, Daniel; Rader, Daniel J.; Fogelman, Alan M.; Schecter, Alison

2011-01-01

L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models. PMID:21068008

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.

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.

Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data.

PubMed

Carreras, E; Cahn, J Y; Puozzo, C; Kröger, N; Sanz, G; Buzyn, A; Bacigalupo, A; Vernant, J P

2010-07-01

This study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg) was administered every six hours during four consecutive days. Clonazepam (0.025 to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least 12 hours prior to i.v. Bu dosing and continued until 24 hours after the last dose. Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis. Through population PK analysis, a 10% average increase (coefficient of variation, RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with clonazepam as compared to phenytoin, which was considered as not being clinically relevant. The suspected induction on Bu metabolism by phenytoin should have resulted in the opposite effect. The patient efficacy and safety profiles were comparable between the two cohorts.

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

PubMed

Kamijo, Y; Hayashi, I; Soma, K; Ohwada, T; Majima, M

2001-11-21

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Semi-elective intraosseous infusion after failed intravenous access in pediatric anesthesia.

PubMed

Neuhaus, Diego; Weiss, Markus; Engelhardt, Thomas; Henze, Georg; Giest, Judith; Strauss, Jochen; Eich, Christoph

2010-02-01

Intraosseous (IO) infusion is a well-established intervention to obtain vascular access in pediatric emergency medicine but is rarely used in routine pediatric anesthesia. In this observational study, we report on a series of 14 children in whom semi-elective IO infusion was performed under inhalational anesthesia after peripheral intravenous (IV) access had failed. Patient and case characteristics, technical details, and estimated timings of IO infusion as well as associated complications were reviewed. Data are median and range. IO infusion was successfully established in fourteen children [age: 0.1-6.00 years (median 0.72 years); weight: 3.5-12.0 kg (median 7.0 kg)]. The majority suffered from chronic cardiac, metabolic, or dysmorphic abnormalities. Estimated time taken from inhalational induction of anesthesia until insertion of an intraosseous needle was 26.5 min (15-65 min). The proximal tibia was cannulated in all patients. The automated EZIO IO system was used in eight patients and the manual COOK system in six patients. Drugs administered included hypnotics, opioids, neuromuscular blocking agents and reversals, cardiovascular drugs, antibiotics, and IV fluids. The IO cannulas were removed either in the operating theatre (n = 5), in the recovery room (n = 5), or in the ward (n = 4), after 73 min (19-225 min) in situ. There were no significant complications except one accidental postoperative dislocation. IO access represents a quick and reliable alternative for pediatric patients with prolonged difficult or failed IV access after inhalational induction of anesthesia.

Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats.

PubMed

Rubio-Beltrán, Eloísa; Labastida-Ramírez, Alejandro; Hernández-Abreu, Oswaldo; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2017-10-05

Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T 9 --T 12 ) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I 1 and I 2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and 2mg/kg⋅min hexamethonium) received i.v. continuous infusions of methoxamine (20μg/kg⋅min) followed by physiological saline (0.02ml/min), moxonidine (1, 3, 10 or 30μg/kg⋅min) or agmatine (1000 or 3000μg/kg⋅min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T 9 -T 12 ) produced frequency-dependent vasodepressor responses which were: (i) unchanged during saline infusion; and (ii) inhibited during the above infusions of moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by 3μg/kg⋅min moxonidine or 3000μg/kg⋅min agmatine (which failed to inhibit the vasodepressor responses by α-CGRP; 0.1-1µg/kg) was: (i) unaltered after saline (1ml/kg), rauwolscine (300μg/kg; α 2 -adrenoceptor antagonist) or BU224 (300μg/kg; imidazoline I 2 receptor antagonist); and (ii) reversed after AGN 192403 (3000μg/kg; imidazoline I 1 receptor antagonist). This reversion was relatively more pronounced after AGN 192403 plus rauwolscine. These blocking doses of antagonists lacked any effects on the electrically-induced vasodepressor responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic outflow by moxonidine and agmatine is mainly mediated by prejunctional imidazoline I 1 receptors on perivascular sensory nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

[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.

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

PubMed

Harding, Andrew D

2012-01-01

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

The effect of a pre-anesthetic infusion of amino acids on body temperature, venous blood pH, glucose, creatinine, and lactate of healthy dogs during anesthesia.

PubMed

Clark-Price, Stuart C; Dossin, Olivier; Ngwenyama, Thandeka R; O'Brien, Mauria A; McMichael, Maureen; Schaeffer, David J

2015-05-01

To evaluate the effect of preanesthetic, intravenous (IV) amino acids on body temperature of anesthetized healthy dogs. Randomized, experimental, crossover study. Eight mixed-breed dogs approximately 2 years of age weighing 20.7 ± 2.1 kg. Dogs received 10% amino acid solution (AA) or 0.9% saline (SA) IV at 5 mL kg(-1) over 60 minutes. Body temperature (BT) was recorded at 5 minute intervals during infusions. Dogs were then anesthetized with sevoflurane for 90 minutes. BT was recorded at 5 minute intervals during anesthesia. Jugular blood samples were analyzed for pH, glucose, creatinine, and lactate concentrations at baseline, after infusion, after anesthesia and after 24 hours. BT at conclusion of infusion decreased -0.34 ± 0.42 °C in group AA and -0.40 ± 0.38 °C in group SA and was not different between groups (p = 0.072). BT decreased 2.72 ± 0.37 °C in group AA and 2.88 ± 0.26 °C in group SA after anesthesia and was different between groups (p < 0.05). Creatinine in group AA was increased immediately after infusion (p < 0.0001) and at 24 hours (p < 0.0001). There were no differences between groups for other parameters. Values for both groups were never outside the clinical reference ranges. In healthy dogs, preanesthetic IV infusion of amino acids attenuated heat loss compared to controls, however, the amount attenuated may not be clinically useful. Further studies are warranted to determine if nutrient-induced thermogenesis is beneficial to dogs undergoing anesthesia. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

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.

Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

1988-01-01

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

Incidence of phlebitis associated with the use of peripheral IV catheter and following catheter removal

PubMed Central

Urbanetto, Janete de Souza; Peixoto, Cibelle Grassmann; May, Tássia Amanda

2016-01-01

ABSTRACT Objective: to investigate the incidence of phlebitis and its association with risk factors when using peripheral IV catheters (PIC) and following their removal - (post-infusion phlebitis) in hospitalized adults. Method: a cohort study of 171 patients using PIC, totaling 361 punctures. Sociodemographic variables and variables associated with the catheter were collected. Descriptive and analytical statistical analyses were performed. Results: average patient age was 56.96 and 51.5% of the sample population was male. The incidence of phlebitis was 1.25% while using PIC, and 1.38% post-infusion. The incidence of phlebitis while using PIC was associated with the length of time the catheter remained in place, whereas post-infusion phlebitis was associated with puncture in the forearm. Ceftriaxone, Clarithromycin and Oxacillin are associated with post-infusion phlebitis. Conclusions: this study made it possible to investigate the association between risk factors and phlebitis during catheter use and following its removal. The frequency of post-infusion phlebitis was larger than the incidence of phlebitis with the catheter in place, with Phlebitis Grade III and II being the most frequently found in each of these situations, respectively. Aspects related to post-infusion phlebitis can be explained, given the limited number of studies addressing this theme from this perspective. PMID:27508916

IGF-1 as a Drug for Preterm Infants: A Step-Wise Clinical Development.

PubMed

Hellstrom, Ann; Ley, David; Hallberg, Boubou; Lofqvist, Chatarina; Hansen-Pupp, Ingrid; Ramenghi, Luca A; Borg, Jan; Smith, Lois E H; Hard, Anna-Lena

2017-01-01

Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 µg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included. IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 µg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days. The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

PubMed Central

Chiam, Elizabeth; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-01-01

Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP –0.15 mmHg, SBP +1.44 mmHg, DBP −–0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). Conclusions I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting. PMID:26606263

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial.

PubMed

Chiam, Elizabeth; Weinberg, Laurence; Bailey, Michael; McNicol, Larry; Bellomo, Rinaldo

2016-04-01

The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting. © 2015 The British Pharmacological Society.

The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

PubMed

Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

2007-12-01

Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of <2 mg/mL amiodarone were established to reduce the risk of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

Postoperative analgesic efficacy of single-shot and continuous transversus abdominis plane block after laparoscopic cholecystectomy: A randomized controlled clinical trial.

PubMed

Choi, Yun-Mi; Byeon, Gyeong-Jo; Park, Soon-Ji; Ok, Young-Min; Shin, Sang-Wook; Yang, Kwangho

2017-06-01

To compare the analgesic efficacy of ultrasound-guided single-shot and continuous transversus abdominis plane (TAP) block to that of IV-PCA in patients undergoing laparoscopic cholecystectomy. Prospective randomized controlled trial. Post-anesthesia care unit and General ward. 108 American Society of Anesthesiologist (ASA) physical status I-II patients undergoing laparoscopic cholecystectomy. Group A received IV-PCA; group B received both ultrasound-guided single-shot TAP block with 0.2% ropivacaine (20mL) and IV-PCA; and group C received continuous TAP block using an ultrasound-guidance-inserted indwelling catheter. In group C, infusion of 0.2% ropivacaine at a basal rate of 3mL/h, bolus dose of 4mL, and a lockout interval of 30min was maintained for 48h postoperatively. The primary outcome was evaluated analgesic efficacy using the numeric rating scale (NRS) for 48h postoperatively. Other outcomes included the number of patients requiring additional analgesics, patient satisfaction with postoperative pain control, and incidence of postoperative adverse events. Compared to other groups, group C had higher deep abdominal NRS at 1h postoperatively (P<0.05), and lower incidence of postoperative urinary retention (P<0.05). There were no significant intergroup differences in the number of patients requiring additional analgesics, and patient satisfaction with postoperative pain control. Compared to IV-PCA with or without single-shot TAP block, ultrasound-guided continuous TAP block provided similar analgesia in somatic pain and less analgesia in visceral pain. Moreover, the latter resulted in a lower incidence of postoperative urinary retention. Copyright © 2017 Elsevier Inc. All rights reserved.

Anesthetic management with sevoflurane combined with alfaxalone-medetomidine constant rate infusion in a Thoroughbred racehorse undergoing a long-time orthopedic surgery

PubMed Central

WAKUNO, Ai; MAEDA, Tatsuya; KODAIRA, Kazumichi; KIKUCHI, Takuya; OHTA, Minoru

2017-01-01

ABSTRACT A three-year old Thoroughbred racehorse was anesthetized with sevoflurane and oxygen inhalation anesthesia combined with constant rate infusion (CRI) of alfaxalone-medetomidine for internal fixation of a third metacarpal bone fracture. After premedication with intravenous (IV) injections of medetomidine (6.0 µg/kg IV), butorphanol (25 µg/kg IV), and midazolam (20 µg/kg IV), anesthesia was induced with 5% guaifenesin (500 ml/head IV) followed immediately by alfaxalone (1.0 mg/kg IV). Anesthesia was maintained with sevoflurane and CRIs of alfaxalone (1.0 mg/kg/hr) and medetomidine (3.0 µg/kg/hr). The total surgical time was 180 min, and the total inhalation anesthesia time was 230 min. The average end-tidal sevoflurane concentration during surgery was 1.8%. The mean arterial blood pressure was maintained above 70 mmHg throughout anesthesia, and the recovery time was 65 min. In conclusion, this anesthetic technique may be clinically applicable for Thoroughbred racehorses undergoing a long-time orthopedic surgery. PMID:28955163

A randomized controlled trial of the effect of intrapartum intravenous fluid management on breastfed newborn weight loss.

PubMed

Watson, Jo; Hodnett, Ellen; Armson, B Anthony; Davies, Barbara; Watt-Watson, Judy

2012-01-01

To determine the effect of conservative versus usual intrapartum intravenous (IV) fluid management for low-risk women receiving epidural analgesia on weight loss in breastfed newborns. A randomized controlled trial. A tertiary perinatal center in a large urban setting. Women experiencing uncomplicated pregnancies who planned to have epidural analgesia and to breastfeed. Healthy pregnant women were randomized to receive an IV epidural preload volume of <500 mLs continuing at an hourly rate of 75-100 mL/h (conservative care) or an epidural preload volume of ≥500 mLs and an hourly rate >125 mL/h (usual care). The primary study outcome was breastfed newborn weight loss >7% prior to hospital discharge. Secondary study outcomes included breastfeeding exclusivity, referral to outpatient breastfeeding clinic support, and delayed discharge. Other outcomes were admission to the neonatal intensive care unit and cord blood pH <7.25. Two hundred women participated (100 in the conservative care and 100 in the usual care groups). Forty-eight of 100 infants in the usual care group and 44 of the 100 infants in the conservative care group lost >7% of their birth weight prior to discharge, p < 0.52 RR 0.92 [0.68-1.24]. A policy of restricted IV fluids did not affect newborn weight loss. Women and their care providers should be reassured that the volumes of IV fluid <2500 mLs are unlikely to have a clinically meaningful effect on breastfed newborn weight loss >7%. Exploratory analyses suggest that breastfed newborn weight loss increases when intrapartum volumes infused are >2500 mLs. Care providers are encouraged to consider volumes of IV fluid infused intrapartum as a factor that may have contributed to early newborn weight loss in the first 48 h of life. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Attenuation of acute lung injury with propofol in endotoxemia.

PubMed

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

2005-03-01

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

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.

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.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

PubMed

Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

2018-05-08

Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.

Efficacy and safety of an intravenous C1-inhibitor concentrate for long-term prophylaxis in hereditary angioedema

PubMed Central

Craig, Timothy; Shapiro, Ralph; Vegh, Arthur; Baker, James W.; Bernstein, Jonathan A.; Busse, Paula; Magerl, Markus; Martinez-Saguer, Inmaculada; Riedl, Marc A.; Lumry, William; Williams-Herman, Debora; Edelman, Jonathan; Feuersenger, Henrike; Machnig, Thomas

2017-01-01

Background: The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis. Objective: This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP). Methods: The international registry (2010–2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason. Results: The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500–3000 IU), with a median time interval between infusion and a subsequent pnfC1-INH–treated attack of 72.0 hours (range, 0.0–166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INH–treated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port). Conclusion: In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration. PMID:28381322

[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.

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

PubMed

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

2013-06-01

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

Continuous-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

Evaluation of insulin secretion and action in New World camelids.

PubMed

Firshman, Anna M; Cebra, Christopher K; Schanbacher, Barbara J; Seaquist, Elizabeth R

2013-01-01

To measure and compare insulin secretion and sensitivity in healthy alpacas and llamas via glucose clamping techniques. 8 llamas and 8 alpacas. Hyperinsulinemic euglycemic clamping (HEC) and hyperglycemic clamping (HGC) were performed on each camelid in a crossover design with a minimum 48-hour washout period between clamping procedures. The HEC technique was performed to measure insulin sensitivity. Insulin was infused IV at 6 mU/min/kg for 4 hours, and an IV infusion of glucose was adjusted to maintain blood glucose concentration at 150 mg/dL. Concentrations of blood glucose and plasma insulin were determined throughout. The HGC technique was performed to assess insulin secretion in response to exogenous glucose infusion. An IV infusion of glucose was administered to maintain blood glucose concentration at 320 mg/dL for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. Alpacas and llamas were not significantly different with respect to whole-body insulin sensitivity during HEC or in pancreatic β-cell response during HGC. Alpacas and llamas had markedly lower insulin sensitivity during HEC and markedly lower pancreatic β-cell response during HGC, in comparison with many other species. New World camelids had lower glucose-induced insulin secretion and marked insulin resistance in comparison with other species. This likely contributes to the disorders of fat and glucose metabolism that are common to camelids.

Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

PubMed

Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

2016-06-01

Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

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.

Prescribing Patterns of Intravenous Golimumab for Rheumatoid Arthritis.

PubMed

Brady, Brenna L; Tkacz, Joseph P; Lofland, Jennifer; Meyer, Roxanne; Bolge, Susan C

2015-09-01

The use of intravenous golimumab (GLM-IV), in combination with methotrexate, was approved by the US Food and Drug Administration in July 2013 for the treatment of moderate to severe, active rheumatoid arthritis (RA). GLM-IV is available in 50-mg vials, and the prescribing information specifies a dosing regimen of 2 mg/kg at 0 and 4 weeks and then every 8 weeks thereafter. The purpose of this study was to examine the patterns of prescribing and administration of GLM-IV, including the demographic, clinical, and utilization characteristics of patients with RA newly treated with GLM-IV. Rheumatology practices across the continental United States were solicited for a chart-review study. Inclusion criteria were: (1) diagnosis of RA; (2) current treatment with GLM-IV; (3) age ≥18 years; and (4) lack of pregnancy (in female patients). Physicians were offered a monetary incentive for each eligible chart provided. An electronic case-report form was developed to aid in the chart data extraction and included fields for demographic characteristics, available comorbid diagnoses, prior RA treatments, and doses and dates of GLM-IV administration. A total of 117 eligible patient charts from 15 rheumatologist practices were reviewed. The patient sample was predominantly female (81.2%), with a mean (SD) age of 55.4 (14.5) years. A total of 55.6% of patients had evidence of biologic treatment before receiving GLM-IV, and 53% had at least 1 comorbid condition. In total, 300 individual GLM-IV infusions from this sample were reviewed. Due to the relatively recent approval of GLM-IV use by the US Food and Drug Administration, the majority of patients in this sample (69.2%) had received only between 2 and 4 infusions at the time of the review. For infusion records with valid dose data, the mean number of administered vials was 3.6 (0.8) (total dose, 180 mg); the majority of patients received a dose consistent with the prescribed dose of 2 mg/kg. Combination therapy with methotrexate was observed in the charts of a minority of patients (27.4%). The mean interval between induction and the first follow-up infusion was 32.9 (11.4) days, with a mean maintenance interval of 56.5 (13.3) days. This analysis provides an early glimpse of the patterns of prescribing GLM-IV. Overall, patients appeared to have been receiving GLM-IV in accordance with Food and Drug Administration labeling; although the rate of prescribing methotrexate was low, dosages and administration intervals were within the expected ranges. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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)

Non-invasive, multi-modal sensing of skin stretch and bioimpedance for detecting infiltration during intravenous therapy.

PubMed

Jambulingam, Jambu A; McCrory, Russell; West, Leanne; Inan, Omer T

2016-08-01

Intravenous infiltration is a condition wherein an infused solution leaks inadvertently into soft tissue surrounding a hypodermic needle site. This occurrence affects approximately 6.5% of patients in hospitals worldwide, and can lead to severe tissue damage if not treated immediately. The methods currently used by medical staff to detect an infiltration are subjective and can potentially be prone to error. Infiltration is an even larger concern in pediatric patients, who have smaller veins than adults and have more difficulty in communicating pain or other discomfort associated with the infiltration with medical staff. For these reasons, automatic IV infiltration detection could potentially reduce the risk associated with this damaging condition. This paper proposes a novel proof-of-concept system that uses non-invasive sensing in conjunction with a low-power embedded computing platform to deliver continuous infiltration monitoring around the IV catheter site. This kind of system could be able to detect an infiltration by non-invasively monitoring for known symptoms: swelling of soft tissue and increased skin firmness; these symptoms can be sensed by measuring skin stretch and local bioimpedance. Moreover, the low-power design and wireless capabilities can potentially enable continuous wear. The proposed automatic IV infiltration detection system could significantly improve the number of infiltrations identified and treated on time.

[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.

Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel Treatment for Gynecologic Cancer.

PubMed

Jeerakornpassawat, Dhammapoj; Suprasert, Prapaporn

2017-10-01

The aim of this study was to assess intravenous hydrocortisone (HCT) added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated hypersensitivity reactions (HSRs). Paclitaxel naives scheduled for 6 cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50 mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean age, body mass index, and paclitaxel dose. The 44 DXM controls underwent 213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles. Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10 to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who erroneously received no HCT. Hypersensitivity reaction symptoms were facial flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension (1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases, symptoms mitigated and infusion successfully restarted for the remaining dose. Adding HCT to routine DXM prophylaxis significantly decreased paclitaxel HSR frequency.

Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder.

PubMed

Molosh, Andre I; Johnson, Philip L; Fitz, Stephanie D; Dimicco, Joseph A; Herman, James P; Shekhar, Anantha

2010-05-01

Panic disorder is a severe anxiety disorder characterized by recurrent panic attacks that can be consistently provoked with intravenous (i.v.) infusions of hypertonic (0.5 M) sodium lactate (NaLac), yet the mechanism/CNS site by which this stimulus triggers panic attacks is unclear. Chronic inhibition of GABAergic synthesis in the dorsomedial hypothalamus/perifornical region (DMH/PeF) of rats induces a vulnerability to panic-like responses after i.v. infusion of 0.5 M NaLac, providing an animal model of panic disorder. Using this panic model, we previously showed that inhibiting the anterior third ventricle region (A3Vr; containing the organum vasculosum lamina terminalis, the median preoptic nucleus, and anteroventral periventricular nucleus) attenuates cardiorespiratory and behavioral responses elicited by i.v. infusions of NaLac. In this study, we show that i.v. infusions of 0.5 M NaLac or sodium chloride, but not iso-osmolar D-mannitol, increased 'anxiety' (decreased social interaction) behaviors, heart rate, and blood pressure responses. Using whole-cell patch-clamp preparations, we also show that bath applications of NaLac (positive control), but not lactic acid (lactate stimulus) or D-mannitol (osmolar stimulus), increases the firing rates of neurons in the A3Vr, which are retrogradely labeled from the DMH/PeF and which are most likely glutamatergic based on a separate study using retrograde tracing from the DMH/PeF in combination with in situ hybridization for vesicular glutamate transporter 2. These data show that hypertonic sodium, but not hyper-osmolarity or changes in lactate, is the key stimulus that provokes panic attacks in panic disorder, and is consistent with human studies.

Development of effective prophylaxis against intraoperative carcinoid crisis.

PubMed

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

2016-08-01

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

Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study.

PubMed

Perez, E A; Scudder, S A; Meyers, F A; Tanaka, M S; Paradise, C; Gandara, D R

1991-02-01

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.

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.

A mathematical model describing the glycemic response of diabetic patients to meal and i.v. infusion of insulin.

PubMed

Fabietti, P G; Calabrese, G; Iorio, M; Bistoni, S; Brunetti, P; Sarti, E; Benedetti, M M

2001-10-01

Nine type 1 diabetic patients were studied for 24 hours. During this period they were given three calibrated meals. The glycemia was feedback-controlled by means of an artificial pancreas. The blood concentration of glucose and the infusion speed of the insulin were measured every minute. The experimental data referring to each of the three meals were used to estimate the parameters of a mathematical model suitable for describing the glycemic response of diabetic patients at meals and at the i.v. infusion of exogenous insulin. From the estimate a marked dispersion of the parameters was found, both interindividual and intraindividual. Nevertheless the models thus obtained seem to be usable for the synthesis of a feedback controller, especially in view of creating a portable artificial pancreas that now seems possible owing to the realization (so far experimental) of sufficiently reliable glucose concentration sensors.

Effect of infusion of equine plasma or 6% hydroxyethyl starch (600/0.75) solution on plasma colloid osmotic pressure in healthy horses.

PubMed

McKenzie, Erica C; Esser, Melissa M; McNitt, Sarah E; Payton, Mark E

2016-07-01

OBJECTIVE To compare the effects of equivalent volumes of equine plasma and 6% hydroxyethyl starch (600/0.75) solution (hetastarch) administered IV on plasma colloid osmotic pressure (pCOP) and commonly monitored clinicopathologic variables in horses. ANIMALS 6 healthy mares. PROCEDURES In a randomized, crossover study, horses were administered hetastarch or plasma (both 10 mL/kg, IV) 18 months apart. The pCOP and variables of interest were measured before (baseline), immediately after, and at intervals up to 96 or 120 hours after infusion. Prothrombin and activated partial thromboplastin times were measured before and at 2 and 8 hours after each infusion. RESULTS Prior to hetastarch and plasma infusions, mean ± SEM pCOP was 19.4 ± 0.5 mm Hg and 19.4 ± 0.8 mm Hg, respectively. In general, hetastarch and plasma infusions comparably increased pCOP from baseline for 48 hours, with maximum increases of 2.0 and 2.3 mm Hg, respectively. Mean Hct and hemoglobin, total protein, and albumin concentrations were decreased for a period of 72, 96, or 120 hours after hetastarch infusion with maximum decrements of 8.8%, 3.2 g/dL, 1.2 g/dL, and 0.6 g/dL, respectively. Plasma infusion decreased (albeit not always significantly) hemoglobin concentration and Hct for 20 and 24 hours (maximum changes of 1.5 g/dL and 6.6%, respectively) and increased total solids concentration (maximum change of 0.6 g/dL) for 48 hours. Platelet count and coagulation times were minimally affected. CONCLUSIONS AND CLINICAL RELEVANCE Overall, the hetastarch and plasma infusions comparably increased pCOP in healthy horses for up to 48 hours. Hetastarch induced greater, more persistent perturbations in clinicopathologic variables.

PM101: intravenous amiodarone formulation changes can improve medication safety.

PubMed

Souney, Paul F; Cooper, Warren D; Cushing, Daniel J

2010-03-01

Intravenous amiodarone (A-IV) is used to manage ventricular and atrial arrhythmias. The current formulation uses polysorbate 80 and benzyl alcohol to maintain amiodarone in solution, and these co-solvents are linked with clinically-important adverse events and pharmaceutical incompatibilities. PM101 is a recently FDA-approved intravenous formulation of amiodarone that uses a cyclodextrin to solubilize amiodarone. This review describes the clinical and pharmaceutical development of formulations of amiodarone for intravenous administration. The medical and pharmaceutical literature was searched for papers discussing A-IV, PM101 and their formulation components. Relevant literature was identified starting from 1948 to the present. The reader will learn about the important medical and pharmaceutical issues complicating A-IV administration, including an understanding of related hypotension and compatibility with commonly used infusion materials and how these issues may impact drug safety. PM101 has been developed to address several of these important issues. PM101 is a new formulation of A-IV that is stable in commonly used infusion materials and avoids co-solvent related toxicities.

Vented spikes improve delivery from intravenous bags with no air headspace.

PubMed

Galush, William J; Horst, Travis A

2015-07-01

Flexible plastic bags are the container of choice for most intravenous (i.v.) infusions. Under certain circumstances, however, the air-liquid interface present in these i.v. bags can lead to physical instability of protein biopharmaceuticals, resulting in product aggregation. In principle, the air headspace present in the bags can be removed to increase drug stability, but experiments described here show that this can result in incomplete draining of solution from the bag using gravity delivery, or generation of negative pressure in the bag when an infusion pump is used. It is expected that these issues could lead to incomplete delivery of medication to patients or pump-related problems, respectively. However, here it is shown that contrary to the standard pharmacy practice of using nonvented spikes with i.v. bags, the use of vented spikes with i.v. bags that lack air headspace allows complete delivery of the dose solution without impacting the physical stability of a protein-based drug. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effects of nitric oxide synthase inhibitor on cochlear blood flow.

PubMed

Hoshijima, Hideaki; Makimoto, Kazuo; Noi, Osamu; Ohinata, Yoshimitsu; Takenaka, Hiroshi

2002-09-01

We observed in rats the changes in cochlear blood flow (CoBF) and cutaneous blood flow of the abdominal wall (AbBF) after the administration of the NO synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME). Ten minutes after i.v. infusion of L-NAME (0.2, 1, 5, 10 mg/kg), L-arginine, which is a substrate of NO, was infused (100 mg/kg) i.v. Employing a laser Doppler flowmeter, the changes in blood flow were recorded from the basal turn of the right cochlea or the abdominal wall and blood pressure (BP) was recorded from the left femoral artery simultaneously. Vascular conductance (VC) was calculated from CoBF/mean BP (cochlear VC) or AbBF/mean BP (abdominal VC). The findings in rats generally agreed with those in guinea pigs [Brechtelsbauer et al., Hear. Res. 77 (1994) 38-42]. Intravenous infusion of L-NAME produced a dose-dependent depression of cochlear VC at 0.2 mg/kg (-18.9), 1 mg/kg (-37.9%), 5 mg/kg (-45.8%) and 10 mg/kg (-48.3%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% in VC) with no significance compared to CoBF (5 mg/kg). Infusion of L-arginine partially reversed the CoBF decrease caused by L-NAME. The group of 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery with L-arginine, while the 10 mg/kg group showed the smallest. The decrease in AbBF did not recover substantially with L-arginine, the degree being less than that of each group in the CoBF experiment. It was suggested that the NO/soluble guanylate cyclase/cGMP system is more active in the cochlear microcirculation. With the round window (RW) application of 1% L-NAME (2 microl), cochlear VC was decreased by 21.6%, which was closest to that of the 0.2 mg/kg group of L-NAME i.v. infusion. The cochlear VC depression after local application of L-NAME did not show any recovery (-0.3%) by RW application of 5% L-arginine (2 microl) 25 min after L-NAME application; a slight gradual increase was observed when a higher concentration (20%) of L-arginine was applied to the RW. We propose that i.v. infusions of L-NAME and L-arginine primarily affect the precapillary arteriole of the spiral modiolar artery which effectively regulates microcirculation as a resistance vessel, and that RW application affects the vessels of the lateral wall, not the spiral modiolar artery because of the difficulty of substance diffusion.

Is continuous infusion of imipenem always the best choice?

PubMed

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

2017-03-01

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

The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men.

PubMed

Xiao, Changting; Giacca, Adria; Lewis, Gary F

2009-11-01

Prolonged elevation of plasma nonesterified fatty acids (NEFA) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. Studies in rodents suggest that inflammation may play a role in this "lipotoxicity." We studied the effects of sodium salicylate, an anti-inflammatory agent, on lipid-induced alterations in β-cell function and insulin sensitivity in six overweight and obese nondiabetic men. Each subject underwent four separate studies, 4-6 wk apart, in random order: 1) SAL, 1-wk placebo followed by intravenous (iv) infusion of saline for 48 h; 2) IH, 1-wk placebo followed by iv infusion of intralipid plus heparin for 48 h to raise plasma NEFA approximately twofold; 3) IH + SS, 1-wk sodium salicylate (4.5 g/day) followed by 48-h IH infusion; and 4) SS, 1-wk oral sodium salicylate followed by 48-h saline infusion. After 48-h saline or lipid infusion, insulin secretion and sensitivity were assessed by hyperglycemic clamp and euglycemic hyperinsulinemic clamp, respectively, in sequential order. Insulin sensitivity was reduced by lipid infusion (IH = 67% of SAL) and was not improved by salicylate (IH + SS = 56% of SAL). Lipid infusion also reduced the disposition index (P < 0.05), which was not prevented by sodium salicylate. Salicylate reduced insulin clearance. These data suggest that oral sodium salicylate at this dose impairs insulin clearance but does not ameliorate lipid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men.

The relationship of muscle perfusion and metabolism with cardiovascular variables before and after detomidine injection during propofol-ketamine anaesthesia in horses.

PubMed

Edner, Anna; Nyman, Görel; Essén-Gustavsson, Birgitta

2002-10-01

To study in horses (1) the relationship between cardiovascular variables and muscle perfusion during propofol-ketamine anaesthesia, (2) the physiological effects of a single intravenous (IV) detomidine injection, (3) the metabolic response of muscle to anaesthesia, and (4) the effects of propofol-ketamine infusion on respiratory function. Prospective experimental study. Seven standardbred trotters, 5-12 years old, 416-581 kg. Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg -1 ) and maintained with a continuous IV infusion of propofol (0.15 mg kg -1 minute -1 ) and ketamine (0.05 mg kg -1 minute -1 ) with horses positioned in left lateral recumbency. After 1 hour, detomidine (0.01 mg kg -1 ) was administered IV and 40-50 minutes later anaesthesia was discontinued. Cardiovascular and respiratory variables (heart rate, cardiac output, systemic and pulmonary artery blood pressures, respiratory rate, tidal volume, and inspiratory and expiratory O 2 and CO 2 ) and muscle temperature were measured at pre-determined times. Peripheral perfusion was measured continuously in the gluteal muscles and skin using laser Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal muscles were analysed for glycogen, creatine phosphate, creatine, adenine nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for PO 2 , PCO 2 , pH, oxygen saturation and HCO 3 . Mixed venous blood was analysed for PO 2 , PCO 2 , pH, oxygen saturation, HCO 3 , cortisol, lactate, uric acid, hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase, electrolytes, total protein, haemoglobin, haematocrit and white blood cell count. Circulatory function was preserved during propofol-ketamine anaesthesia. Detomidine caused profound hypertension and bradycardia and decreased cardiac output and muscle perfusion. Ten minutes after detomidine injection muscle perfusion had recovered to pre-injection levels, although heart rate and cardiac output had not. No difference in indices of muscle metabolism was found between dependent and independent muscles. Anaerobic muscle metabolism, indicated by decreased muscle and creatine phosphate levels was evident after anaesthesia. Muscle perfusion was closely related to cardiac output but not arterial blood pressure. Total intravenous anaesthesia with propofol-ketamine deserves further study despite its respiratory depression effects, as the combination preserves cardiovascular function. Decreases in high-energy phosphate stores during recovery show that muscle is vulnerable after anaesthesia. Continued research is required to clarify the course of muscle metabolic events during recovery. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Excretory, secretory, and tissue residues after label and extra-label administration of flunixin meglumine to saline or lipopolysaccharide-exposed dairy cows

USDA-ARS?s Scientific Manuscript database

Twenty lactating dairy cattle were intravenously infused with either lipopolysaccharide (n = 10) or sterile saline (n = 10). Five cattle in each group received 3 doses of flunixin meglumine administered by either IV infusion or IM injection at 24 h intervals. Milk, urine, and tissues were collected....

Augmentation of neurally evoked cholinergic bronchoconstrictor responses by prejunctional NK2 receptors in the guinea-pig.

PubMed

Hey, J A; Danko, G; del Prado, M; Chapman, R W

1996-02-01

1. We examined the effect of exogenously administered tachykinins, neurokinin A (NKA), substance P (SP) and neurokinin B (NKB) on neurally mediated cholinergic bronchoconstrictor responses in guinea-pigs. 2. Electrical stimulation of regions in the dorsal medulla oblongata produced a cholinergic bronchospasm that was not affected by depletion of endogenous tachykinins with capsaicin pretreatment (50 mg kg-1, s.c., 1 week earlier) or by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon (3 mg kg-1, i.v.). 3. Infusion of NKA (0.03-0.1 microgram kg-1 min-1), SP (1 microgram kg-1 min-1) or NKB (1 microgram kg-1 min-1) potentiated the bronchoconstrictor response to electrical stimulation of the dorsal medulla. The doses of tachykinins tested were subthreshold for direct activation of airway smooth muscle, because they were devoid of direct bronchoconstrictor effects. The relative rank order potency for augmentation of centrally induced bronchospasm was NKA > NKB approximately SP, suggesting activation of the NK2 receptor subtype. 4. Infusion of NKA, SP and NKB had no effect on bronchoconstrictor responses to i.v. methacholine (1 microgram kg-1) indicating that a prejunctional neural mechanism of action was responsible for the effects on CNS stimulation-induced bronchospasm. 5. Potentiation of the bronchoconstrictor response to dorsal medullary stimulation produced by infusion of NKA was blocked by pretreatment with the NK2 antagonist SR 48968 (1 mg kg-1, i.v.) but not by the NK1 antagoinst CP 96,345 (1 mg kg-1, i.v.). 6. The potentiation of CNS-induced bronchospasm produced by infusion of SP was partially inhibited by CP 96,345 (1 mg kg-1, i.v.) but not by SR 48968 (1 mg kg-1, i.v.). Treatment with combined SR 48968 (1 mg kg-1, i.v.) and CP 96,345 (1 mg kg-1, i.v.) completely blocked the SP-induced potentiation of CNS-stimulated bronchospasm. 7. These results identify an important modulatory role for NK2 receptors, located at prejunctional sites on parasympathetic nerves, on cholinergic bronchoconstrictor responses in guinea-pigs. 8. It is proposed that substances that release tachykinins from airway sensory nerves, e.g. inflammatory mediators or irritants, may induce hyperresponsiveness of cholinergic bronchomotor responses by activation of NK2-receptors on parasympathetic airway nerves. Furthermore, these studies indicate that endogenous tachykinins are not involved in the maintenance of basal cholinergic bronchomotor tone in the intact guinea-pig.

[Effect of nonsteroidal antiinflammatory drugs on colonic lipoxygenase and cyclooxygenase activities from patients with colonic neoplasia].

PubMed

Di Girolamo, G; Franchi, A; De Los Santos, A R; Martí, M L; Farina, M; Fernández de Gimeno, M A

2001-01-01

Lysine clonixinate (LC) is a nonsteroidal anti-inflammatory drug (NSAID) with good gastrointestinal tolerance. Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 (COX-2) and production of 5 hydroxy-eicosatetraeonic acid (5-HETE) and slightly affected levels of cyclooxygenase 1 (COX-1) in in vitro studies carried out on human tissues. This study deals with the in vivo effect of the drug on human colon segments. Experiment 1: Five patients about to undergo hemicholectomy due to colon neoplasia were treated preoperatively with a continuous infusion of LC, to achieve a steady-state concentration between 4 and 6 mg/ml. Human colon segments from the five patients and from another five control patients receiving no treatment with [14C]-arachidonic acid were incubated. Human colon segments treated with LC showed significant inhibition of PGE2, the only prostaglandin (PG) synthesised by the tissue, as well as of 5-HETE. Experiment 2: Fifteen patients received an i.v. bolus of LC 100 mg (n1 = 5); LC 200 mg (n2 = 5) or indomethacin (INDO) 50 mg (n3 = 5). Both doses of LC showed greater inhibition of PGE2 synthesis than the INDO bolus. Both NSAIDs studied proved to have different effects on the production of 5-HETE; while treatment with LC elicited significant inhibition, levels with INDO remained unchanged. Western blotting analysis showed expression of both COX isoforms in colon segments, COX-2 levels being 20% higher. Both types of in vivo studies conducted continuous infusion and i.v. bolus, revealed that LC exerted significant inhibition of basal synthesis of PGE2 and 5-HETE.

Role of 5-HT7 receptors in the inhibition of the vasodepressor sensory CGRPergic outflow in pithed rats.

PubMed

Cuesta, Cristina; García-Pedraza, José Ángel; García, Mónica; Villalón, Carlos M; Morán, Asunción

2014-10-01

The role of calcitonin gene-related peptide (CGRP) in the modulation of vascular tone has been widely documented. Indeed, electrical stimulation of the perivascular sensory outflow in pithed rats induces vasodepressor responses by activation of CGRP receptors. This study investigated the role of 5-HT7 receptors in the inhibition of the rat vasodepressor sensory outflow. Male Wistar pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by physiological saline or AS-19 (a 5-HT7 receptor agonist). Then, electrical stimulation of the spinal cord resulted in frequency-dependent decreases in DBP. The infusions of AS-19, as compared to those of saline, inhibited the vasodepressor responses induced by electrical stimulation without affecting those to i.v. bolus injections of exogenous α-CGRP. This inhibition by AS-19 was abolished by the antagonists pimozide (5-HT7) or sulfisoxazole (ETA), but not by indomethacin (COX1/2) or losartan (AT1), at doses that did not affect per se the electrically-induced vasodepressor responses. Interestingly, glibenclamide (an ATP-dependent K(+) channel blocker) attenuated these vasodepressor responses. The present results suggest that AS-19-induced inhibition of the rat vasodepressor sensory CGRPergic outflow is mainly mediated by 5-HT7 receptors via endothelin release, with the possible involvement of ATP-dependent K(+) channels. Copyright © 2014 Elsevier Inc. All rights reserved.

Case report: efficacy and tolerability of ketamine in opioid-refractory cancer pain.

PubMed

Amin, Priya; Roeland, Eric; Atayee, Rabia

2014-09-01

A 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, "patient pain free and resting comfortably." Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.

Safety and Efficacy of Once-Daily Intravenous Busulfan in Allogeneic Transplantation: A Matched-Pair Analysis.

PubMed

Kako, Shinichi; Fujiwara, Shinichiro; Sato, Miki; Kimura, Shun-Ichi; Nakasone, Hideki; Ohashi, Kazuteru; Kawakita, Toshiro; Maeda, Tetsuo; Morishita, Takanobu; Suzuki, Ritsuro; Fukuda, Takahiro; Ichinohe, Tatsuo; Kurata, Mio; Atsuta, Yoshiko; Kanda, Yoshinobu

2018-04-19

Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P = .94), disease-free survival (51.6% versus 50.8%, P = .73), relapse rate (28.5% versus 26.2%, P = .94), nonrelapse mortality (19.9% versus 23.0%, P = .71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P = .001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P = .04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis.

PubMed

Sepah, Yasir Jamal; Sadiq, Mohammad Ali; Chu, David S; Dacey, Mark; Gallemore, Ron; Dayani, Pouya; Hanout, Mostafa; Hassan, Muhammad; Afridi, Rubbia; Agarwal, Aniruddha; Halim, Muhammad Sohail; Do, Diana V; Nguyen, Quan Dong

2017-11-01

To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Randomized, controlled, multicenter clinical trial. STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

Intravenous Carbamazepine for Adults With Seizures.

PubMed

Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

2018-03-01

To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

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.

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

PubMed

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

2013-05-01

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

Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy.

PubMed

Na, H-S; Lee, J-H; Hwang, J-Y; Ryu, J-H; Han, S-H; Jeon, Y-T; Do, S-H

2010-03-01

In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

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.

[Evaluation of combination chemotherapy with oral S-1 administration followed by docetaxel by superselective intra-arterial infusion for patients with oral squamous cell carcinomas].

PubMed

Nagai, Hirokazu; Takamaru, Natsumi; Ohe, Go; Uchida, Daisuke; Tamatani, Tetsuya; Fujisawa, Kenji; Iwamoto, Seiji; Miyamoto, Youji

2011-05-01

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel (DOC) treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study (9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m(2) per day for 14 days, and DOC 40-50mg/m(2) by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade II a, 4 cases Grade II b, 1 case Grade IV a, and 4 cases Grade IV c. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.

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

PubMed

Kawabata, Yoshinori

2012-01-01

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

Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double-blind randomized trial.

PubMed

Boucher, Marc; Nimrod, Carl A; Tawagi, Georges F; Meeker, Tracy A; Rennicks White, Ruth E; Varin, Jocelyn

2004-05-01

To compare the efficacy of a single 100 micro g intramuscular (IM) carbetocin injection, a long-acting oxytocin agonist, to a 2-hour 10 IU oxytocin intravenous (IV) infusion, in reducing the incidence and severity of postpartum hemorrhage (PPH) in women at risk for this condition. A randomized, double-blind, placebo-controlled study was conducted at 2 hospital centres, including 160 women with at least 1 risk factor for PPH. Eighty-three women received 100 microg carbetocin IM and an IV placebo immediately after placental delivery, while 77 women received placebo IM and oxytocin IV infusion. Complete blood count was collected at entry and 24 hours postpartum. All outcome measures, including the need for additional uterotonic agents or uterine massage, blood loss, and drop in hemoglobin and hematocrit, were analyzed using chi-square, Fisher exact, and Student t tests. Population profile and risk factors for PPH were similar for each group. No significant difference was observed in the number of women requiring additional uterotonic medication (12 in each group). However, in the carbetocin group, 36 of the 83 women (43.4%) required at least 1 uterine massage compared to 48 of the 77 women (62.3%) in the oxytocin group (P <.02). Overall, uterotonic intervention was clinically indicated in 37 of the women (44.6%) receiving carbetocin compared to 49 of the women (63.6%) given an IV oxytocin infusion (P <.02). There were no differences in laboratory PPH indicators between the 2 groups.

Effects of intravenous tryptophan infusion on thermoregulation in steers exposed to acute heat stress.

PubMed

Sutoh, Madoka; Kasuya, Etsuko; Yayou, Ken-Ichi

2018-05-01

This study was conducted to investigate the effect of tryptophan (TRP) supply on the thermoregulatory responses via brain serotonin (5-HT) in cattle. In period 1, 12 Holstein steers were kept under a constant room temperature (22°C) and were administered the intravenous (i.v.) infusion of saline or TRP (38.5 mg/kg/2 h). Changes in rectal temperature (RT), 5-HT concentration in the cerebrospinal fluid (CSF), and other factors involved in thermoregulation were measured. In period 2, the steers received the same treatments as in period 1; however, the room temperature was elevated from 22°C to 33°C during i.v. infusion and maintained at 33°C for 3 h. 5-HT concentration in CSF increased following TRP infusion in both periods, and RT significantly decreased following TRP infusion only in period 2. The effect of TRP on respiration rate and plasma prolactin and total triiodothyronine concentrations was not significant. These results suggest that increase in TRP supply can attenuate increase in RT in response to acute heat stress through the increase in brain 5-HT, followed by presumable increase in evaporative heat loss from the skin surface in cattle. It is possible that the increase in peripheral blood TRP metabolites could also participate in the hypothermic effect of TRP. © 2018 Japanese Society of Animal Science.

Bioavailability of the antiemetic metopimazine given as a microenema

PubMed Central

HERRSTEDT, JØRN; JØRGENSEN, MORTEN; ANGELO, HELLE RIIS; RASSING, MARGRETHE RØMER; MØLLER-SONNERGAARD, JØRN; DOMBERNOWSKY, PER

1996-01-01

The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration. PMID:8799530

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.

Propylene Glycol-Related Delirium After Esmolol Infusion.

PubMed

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

2014-07-01

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

Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols.

PubMed

Tran, Tara T T; Pease, Anthony; Wood, Anna J; Zajac, Jeffrey D; Mårtensson, Johan; Bellomo, Rinaldo; Ekinci, Elif I I

2017-01-01

Diabetic ketoacidosis (DKA) is an endocrine emergency with associated risk of morbidity and mortality. Despite this, DKA management lacks strong evidence due to the absence of large randomised controlled trials (RCTs). To review existing studies investigating inpatient DKA management in adults, focusing on intravenous (IV) fluids; insulin administration; potassium, bicarbonate, and phosphate replacement; and DKA management protocols and impact of DKA resolution rates on outcomes. Ovid Medline searches were conducted with limits "all adult" and published between "1973 to current" applied. National consensus statements were also reviewed. Eligibility was determined by two reviewers' assessment of title, abstract, and availability. A total of 85 eligible articles published between 1973 and 2016 were reviewed. The salient findings were (i) Crystalloids are favoured over colloids though evidence is lacking. The preferred crystalloid and hydration rates remain contentious. (ii) IV infusion of regular human insulin is preferred over the subcutaneous route or rapid acting insulin analogues. Administering an initial IV insulin bolus before low-dose insulin infusions obviates the need for supplemental insulin. Consensus-statements recommend fixed weight-based over "sliding scale" insulin infusions although evidence is weak. (iii) Potassium replacement is imperative although no trials compare replacement rates. (iv) Bicarbonate replacement offers no benefit in DKA with pH > 6.9. In severe metabolic acidosis with pH < 6.9, there is lack of both data and consensus regarding bicarbonate administration. (v) There is no evidence that phosphate replacement offers outcome benefits. Guidelines consider replacement appropriate in patients with cardiac dysfunction, anaemia, respiratory depression, or phosphate levels <0.32 mmol/L. (vi) Upon resolution of DKA, subcutaneous insulin is recommended with IV insulin infusions ceased with an overlap of 1-2 h. (vii) DKA resolution rates are often used as end points in studies, despite a lack of evidence that rapid resolution improves outcome. (viii) Implementation of DKA protocols lacks strong evidence for adherence but may lead to improved clinical outcomes. There are major deficiencies in evidence for optimal management of DKA. Current practice is guided by weak evidence and consensus opinion. All aspects of DKA management require RCTs to affirm or redirect management and formulate consensus evidence-based practice to improve patient outcomes.

Evaluation of total intravenous anesthesia with propofol-guaifenesin-medetomidine and alfaxalone-guaifenesin-medetomidine in Thoroughbred horses undergoing castration.

PubMed

Aoki, Motoki; Wakuno, Ai; Kushiro, Asuka; Mae, Naomi; Kakizaki, Masashi; Nagata, Shun-Ichi; Ohta, Minoru

2017-12-22

Anesthetic and cardiorespiratory effects of total intravenous anesthesia (TIVA) technique using propofol-guaifenesin-medetomidine (PGM) and alfaxalone-guaifenesin-medetomidine (AGM) were preliminarily evaluated in Thoroughbred horses undergoing castration. Twelve male Thoroughbred horses were assigned randomly into two groups. After premedication with intravenous (IV) administrations of medetomidine (5.0 µg/kg) and butorphanol (0.02 mg/kg), anesthesia was induced with guaifenesin (10 mg/kg IV), followed by either propofol (2.0 mg/kg IV) (group PGM: n=6) or alfaxalone (1.0 mg/kg IV) (group AGM: n=6). Surgical anesthesia was maintained for 60 min at a constant infusion of either propofol (3.0 mg/kg/hr) (group PGM) or alfaxalone (1.5 mg/kg/hr) (group AGM), in combination with guaifenesin (80 mg/kg/hr) and medetomidine (3.0 µg/kg/hr). Responses to surgical stimuli, cardiorespiratory values, and induction and recovery characteristics were recorded throughout anesthesia. During anesthesia induction, one horse paddled in group PGM. All horses from group AGM were maintained at adequate anesthetic depth for castration. In group PGM, 3 horses showed increased cremaster muscle tension and one showed slight movement requiring additional IV propofol to maintain surgical anesthesia. No horse exhibited apnea, although arterial oxygen tension decreased in group AGM to less than 60 mmHg. Recovery quality was good to excellent in both groups. In conclusion, TIVA using PGM and AGM infusion was available for 60 min anesthesia in Thoroughbred horses. TIVA techniques using PGM and AGM infusion provided clinically acceptable general anesthesia with mild cardiorespiratory depression. However, inspired air should be supplemented with oxygen to prevent hypoxemia during anesthesia.

Evaluation of total intravenous anesthesia with propofol-guaifenesin-medetomidine and alfaxalone-guaifenesin-medetomidine in Thoroughbred horses undergoing castration

PubMed Central

AOKI, Motoki; WAKUNO, Ai; KUSHIRO, Asuka; MAE, Naomi; KAKIZAKI, Masashi; NAGATA, Shun-ichi; OHTA, Minoru

2017-01-01

Anesthetic and cardiorespiratory effects of total intravenous anesthesia (TIVA) technique using propofol-guaifenesin-medetomidine (PGM) and alfaxalone-guaifenesin-medetomidine (AGM) were preliminarily evaluated in Thoroughbred horses undergoing castration. Twelve male Thoroughbred horses were assigned randomly into two groups. After premedication with intravenous (IV) administrations of medetomidine (5.0 µg/kg) and butorphanol (0.02 mg/kg), anesthesia was induced with guaifenesin (10 mg/kg IV), followed by either propofol (2.0 mg/kg IV) (group PGM: n=6) or alfaxalone (1.0 mg/kg IV) (group AGM: n=6). Surgical anesthesia was maintained for 60 min at a constant infusion of either propofol (3.0 mg/kg/hr) (group PGM) or alfaxalone (1.5 mg/kg/hr) (group AGM), in combination with guaifenesin (80 mg/kg/hr) and medetomidine (3.0 µg/kg/hr). Responses to surgical stimuli, cardiorespiratory values, and induction and recovery characteristics were recorded throughout anesthesia. During anesthesia induction, one horse paddled in group PGM. All horses from group AGM were maintained at adequate anesthetic depth for castration. In group PGM, 3 horses showed increased cremaster muscle tension and one showed slight movement requiring additional IV propofol to maintain surgical anesthesia. No horse exhibited apnea, although arterial oxygen tension decreased in group AGM to less than 60 mmHg. Recovery quality was good to excellent in both groups. In conclusion, TIVA using PGM and AGM infusion was available for 60 min anesthesia in Thoroughbred horses. TIVA techniques using PGM and AGM infusion provided clinically acceptable general anesthesia with mild cardiorespiratory depression. However, inspired air should be supplemented with oxygen to prevent hypoxemia during anesthesia. PMID:29057764

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

PubMed

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

1995-05-01

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

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

PubMed

Mayer, Kenneth H; Seaton, Kelly E; Huang, Yunda; Grunenberg, Nicole; Isaacs, Abby; Allen, Mary; Ledgerwood, Julie E; Frank, Ian; Sobieszczyk, Magdalena E; Baden, Lindsey R; Rodriguez, Benigno; Van Tieu, Hong; Tomaras, Georgia D; Deal, Aaron; Goodman, Derrick; Bailer, Robert T; Ferrari, Guido; Jensen, Ryan; Hural, John; Graham, Barney S; Mascola, John R; Corey, Lawrence; Montefiori, David C

2017-11-01

VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Clinical Trials Registration: NCT02165267.

Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.

PubMed

Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L

2014-05-01

The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Fosaprepitant-induced Phlebitis: A Focus on Patients receiving Doxorubicin/Cyclophosphamide therapy

PubMed Central

Leal, A. D.; Kadakia, K. C.; Looker, S.; Hilger, C.; Sorgatz, K.; Anderson, K.; Jacobson, A.; Grendahl, D.; Seisler, D.; Hobday, T.; Loprinzi, C. L.

2014-01-01

Purpose The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. Methods A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Results Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7% (n=34), while the incidence of aprepitant-associated ISAEs was 2.3% (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were: infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5) and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. Conclusions The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy is significant and appreciably higher than what has been previously reported. PMID:24402411

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

Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy.

PubMed

Bonnefoy, Francis; Daoui, Anna; Valmary-Degano, Séverine; Toussirot, Eric; Saas, Philippe; Perruche, Sylvain

2016-08-11

Apoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy. The effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen. The number and functions of antigen-presenting cells (APC), regulatory CD4(+) T cells (Treg), and circulating anti-collagen auto-antibodies were analyzed in CIA mice. Treatment of arthritic mice with i.v. apoptotic cell infusion significantly reduced the arthritis clinical score. This therapeutic approach modified T cell responses against the collagen auto-antigen with selective induction of collagen-specific Treg. In addition, we observed that APC from apoptotic-cell-treated animals were resistant to toll-like receptor ligand activation and favored ex vivo Treg induction, indicating APC reprogramming. Apoptotic cell injection-induced arthritis modulation was dependent on transforming growth factor (TGF)-β, as neutralizing anti-TGF-β antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy. Overall, our data demonstrate that apoptotic-cell-based therapy is efficient in treating ongoing CIA, compatible with current RA treatments, and needs to be evaluated in humans in the treatment of RA.

Effects of fenoldopam on renal blood flow in hypertensive chronic kidney disease.

PubMed

Rovella, Valentina; Ferrannini, Michele; Tesauro, Manfredi; Marrone, Giulia; Busca, Andrea; Sorge, Roberto; Manca di Villahermosa, Simone; Casasco, Maurizio; Di Daniele, Nicola; Noce, Annalisa

2018-05-15

The synthetic drug fenoldopam mesylate (FM) may have a renoprotective role, and a "renal dose" of 0.1 µg/kg/min intravenous (IV) infusion of FM has been reported as able to increase renal blood flow without affecting systemic blood pressure. But conclusive data are still lacking. We aimed to investigate by color-Doppler ultrasonography the effects of IV administration of FM at this dosage in hypertensive chronic kidney disease (CKD) patients, and verify whether it may induce any systemic hemodynamic alteration. In 60 hypertensive CKD patients, we measured by duplex Doppler ultrasonography, at baseline and during infusion of 0.1 µg/kg/min of FM, the systolic and diastolic flow velocity (sampled at the renal hilum, intermediate section and origin of both renal arteries) and the intra-parenchymal renal resistive index (RRI) sampled on interlobular arteries of both kidneys. Patients were divided into four subgroups (I-IV) according to classification of National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-DOQI). Infusion of 0.1 µg/kg/min FM significantly decreased the RRI (0.73 ± 0.05 vs. 0.65 ± 0.06; p < 0.0001) and increased the systolic and diastolic flow velocities in all renal artery tracts examined. No single episode of systemic hypotension was observed. Very low-dose FM may significantly increase renal blood flow and exert a renal protective effect in hypertensive CKD patients. Infusion of FM at such low dosage appears also to be quite safe, even in CKD and hypertensive patients.

Radiofrequency ablation during continuous saline infusion can extend ablation margins

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2018-01-01

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

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

Roy, Sumit; Laerum, Frode; Brosstad, Frank

Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, themore » mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution.« less

L-carnitine reduces susceptibility to bupivacaine-induced cardiotoxicity: an experimental study in rats.

PubMed

Wong, Gail K; Pehora, Carolyne; Crawford, Mark W

2017-03-01

The primary aim of this study was to evaluate the effect of acute administration of L-carnitine 100 mg·kg -1 iv on susceptibility to bupivacaine-induced cardiotoxicity in rats. In the first of two experiments, L-carnitine 100 mg·kg -1 iv (n = 10) or saline iv (n = 10) was administered to anesthetized and mechanically ventilated Sprague-Dawley rats following which an infusion of bupivacaine 2.0 mg·kg -1 ·min -1 iv was given until asystole occurred. The primary outcome was the probability of survival. Secondary outcomes included times to asystole, first dysrhythmia, and to 50% reductions in heart rate (HR) and mean arterial pressure (MAP). To determine whether the same dose of L-carnitine is effective in treating established bupivacaine cardiotoxicity, we also conducted a second experiment in which bupivacaine 20 mg·kg -1 iv was infused over 20 sec. Animals (n = 10 per group) received one of four iv treatments: 30% lipid emulsion 4.0 mL·kg -1 , L-carnitine 100 mg·kg -1 , 30% lipid emulsion plus L-carnitine, or saline. The primary outcome was the return of spontaneous circulation (ROSC) during resuscitation. In the first study, L-carnitine 100 mg·kg -1 increased the probability of survival during bupivacaine infusion (hazard ratio, 12.0; 95% confidence interval, 3.5 to 41.5; P < 0.001). In L-carnitine-treated animals, the times to asystole, first dysrhythmia, and to 50% reductions in HR and MAP increased by 33% (P < 0.001), 65% (P < 0.001), 71% (P < 0.001), and 63% (P < 0.001), respectively. In the second study, no animal in the control or L-carnitine alone groups achieved ROSC when compared with the lipid emulsion groups (P < 0.01). These findings suggest that acute administration of L-carnitine 100 mg·kg -1 decreases susceptibility to bupivacaine cardiotoxicity, but is ineffective during resuscitation from bupivacaine-induced cardiac arrest.

Clinical Pharmacokinetics of Sulfobutylether-β-Cyclodextrin in Patients With Varying Degrees of Renal Impairment.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Luke, David R; Cammarata, Sue K

2018-03-26

Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms including methicillin-resistant S aureus and fluoroquinolone-susceptible and -resistant Gram-negative organisms. The intravenous formulation of delafloxacin contains the excipient sulfobutylether-β-cyclodextrin (SBECD), which is eliminated by renal filtration. This study examined the pharmacokinetics and safety of SBECD after single intravenous (IV) infusions in subjects with renal impairment. The study was an open-label, parallel-group, crossover study in subjects with normal renal function or mild, moderate, or severe renal impairment, and those with end-stage renal disease undergoing hemodialysis. Subjects received 300 mg delafloxacin IV or placebo IV, containing 2400 mg SBECD, in 2 periods separated by ≥14-day washouts. SBECD total clearance decreased with decreasing renal function, with a corresponding increase in area under the concentration-time curve (AUC 0-∞ ). After IV delafloxacin 300 mg administration, SBECD mean total clearance was 6.28 and 1.24 L/h, mean AUC 0-∞ was 387 and 2130 h·μg/mL, and mean renal clearance was 5.36 and 1.14 L/h in normal and severe renal subjects, respectively. Similar values were obtained after IV placebo administration. In subjects with end-stage renal disease, delafloxacin 300 mg IV produced mean SBECD AUC 0-48 values of 2715 and 7861 h·μg/mL when dosed before and after hemodialysis, respectively. Total SBECD clearance exhibited linear relationships to estimated glomerular filtration rate and creatinine clearance. Single doses of IV delafloxacin 300 mg and IV placebo were well tolerated in all groups. In conclusion, decreasing renal function causes reduced SBECD clearance and increased exposures, but SBECD continues to exhibit a good safety and tolerability profile in IV formulations. © 2018, The American College of Clinical Pharmacology.

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

[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.

Post-infectious new daily persistent headache may respond to intravenous methylprednisolone.

PubMed

Prakash, Sanjay; Shah, Nilima D

2010-02-01

New daily persistent headache (NDPH) is a subtype of chronic daily headache (CDH) that starts acutely and continues as a daily headache from the onset.It is considered as one of the most treatment refractory of all headache syndromes. The pathophysiology is largely unknown. Viral infections, extracranial surgery, and stressful life events are considered as triggers for the onset of NDPH. A few patients may have the onset of their symptoms during an infection. Here we report nine patients with NDPH like headache. All of them had a history suggestive of extracranial infections a few weeks prior to the onset of headache. All patients received intravenous methylprednisolone (IV MPS) for 5 days. Intravenous MPS was followed by Oral steroids for 2-3 weeks in six patients.The relief of headache started between the second and fifth days of infusion in all patients. The steady improvement in headache continued and seven patients experienced almost complete improvement within 2 weeks. Two other patients showed complete improvement between 6 and 8 weeks after initiation of IV MPS therapy. We conclude that NDPH-like headache may occur as a post infectious process following a recent infection. We also speculate on the possible mechanisms of headache in our patients.

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

PubMed

Ledgerwood, J E; Coates, E E; Yamshchikov, G; Saunders, J G; Holman, L; Enama, M E; DeZure, A; Lynch, R M; Gordon, I; Plummer, S; Hendel, C S; Pegu, A; Conan-Cibotti, M; Sitar, S; Bailer, R T; Narpala, S; McDermott, A; Louder, M; O'Dell, S; Mohan, S; Pandey, J P; Schwartz, R M; Hu, Z; Koup, R A; Capparelli, E; Mascola, J R; Graham, B S

2015-12-01

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 μg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 μg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies. © 2015 British Society for Immunology.

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

PubMed

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

2013-03-01

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

Non-effect of hexamethonium, a ganglionic blocker, on the response of ileal apolipoprotein A-IV mRNA following a massive small bowel resection in rats.

PubMed

Sonoyama, K; Fujiwara, R; Kasai, T

2000-06-01

An intravenous infusion of hexamethonium, a ganglionic blocker, did not affect the increase in the apolipoprotein A-IV mRNA level in the residual ileum following a massive small bowel resection in unrestrained conscious rats. The result suggests that upregulation of the apolipoprotein A-IV gene in the residual ileum is not mediated by a neural pathway, including the nicotinic synapse route.

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.

Career Education. Administrators and Counselors Implementation Model. Module IV--Planning. (4.1) Develop Plans for Curriculum Preparation and Infusion.

ERIC Educational Resources Information Center

Thompson, John A.; Chock, Mona K.O.

Part of a 13-volume series designed to be used as a group inservice or a self-learning system to train school administrators and counselors for their role in career education, this first section (4.1) of module 4 (Planning) is designed to assist principals and other school administrators to develop plans for curriculum preparation and infusion of…

Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

PubMed

Tadros, Elizabeth M; Frank, Nicholas; De Witte, Fiamma Gomez; Boston, Raymond C

2013-07-01

To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). 6 healthy adult mares and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.

Improved arterial blood oxygenation following intravenous infusion of cold supersaturated dissolved oxygen solution.

PubMed

Grady, Daniel J; Gentile, Michael A; Riggs, John H; Cheifetz, Ira M

2014-01-01

One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer's lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model.

Improved Arterial Blood Oxygenation Following Intravenous Infusion of Cold Supersaturated Dissolved Oxygen Solution

PubMed Central

Grady, Daniel J; Gentile, Michael A; Riggs, John H; Cheifetz, Ira M

2014-01-01

BACKGROUND One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. METHODS Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer’s lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. RESULTS Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. CONCLUSIONS A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model. PMID:25249764

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs.

PubMed

Jakob, S; Mosenthin, R; Thaela, M J; Weström, B R; Rehfeld, J F; Olsen, O; Karlsson, S; Ahrén, B; Ohlsson, A; Karlsson, B W; Pierzynowski, S G

2000-01-01

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered. Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and alpha-amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.v. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.

[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.

Propylene glycol accumulation in critically ill patients receiving continuous intravenous lorazepam infusions.

PubMed

Horinek, Erica L; Kiser, Tyree H; Fish, Douglas N; MacLaren, Robert

2009-12-01

Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24-48 hours after continuous-infusion lorazepam was initiated and every 3-5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r(2) > or = 0.77; p < 0.001). Independent correlation analyses showed that these 2 variables were so strongly associated with propylene glycol concentration (r(2) > or = 0.71; p < 0.001) that they alone predicted propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol-associated adverse effects were not observed. The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol-associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with a once-yearly IV infusion of zoledronic acid (Reclast) 5 mg: two cases and review of the literature.

PubMed

Katz, Joseph; Ordoveza, Patrisha A

2014-09-01

The use of a once-yearly IV infusion of 5 mg zoledronic acid has become more common, as the drug is being reported as safe, with few to minimal adverse reactions. This one-time annual administration has a favorable outcome for patients with osteoporosis and spares the burden of taking daily oral bisphosphonates. The present literature search found 10 well-documented cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with annual administration of 5 mg zoledronic acid for the treatment of osteoporosis. Two new cases are also described, with underlying risk factors similar to previous reports. These include prior dental surgical procedures, the presence of diabetes, autoimmune conditions, past use of bisphosphonate and steroids, and concomitant immunosuppression. Although the reported incidence of BRONJ related to once-a-year IV administered zoledronic acid is low, it may be plausible. Both medical and dental clinicians should be aware of its manifestation.

Infiltration and extravasation.

PubMed

Hadaway, Lynn

2007-08-01

The Infusion Nurses Society's national standards of practice require that a nurse who administers IV medication or fluid know its adverse effects and appropriate interventions to take before starting the infusion. A serious complication is the inadvertent administration of a solution or medication into the tissue surrounding the IV catheter--when it is a nonvesicant solution or medication, it is called infiltration; when it is a vesicant medication, it is called extravasation. Both infiltration and extravasation can have serious consequences: the patient may need surgical intervention resulting in large scars, experience limitation of function, or even require amputation. Another long-term effect is complex regional pain syndrome, a neurologic syndrome that requires long-term pain management. These outcomes can be prevented by using appropriate nursing interventions during IV catheter insertion and early recognition and intervention upon the first signs and symptoms of infiltration and extravasation. Nursing interventions include early recognition, prevention, and treatment (including the controversial use of antidotes, and heat and cold therapy). Steps to manage infiltration and extravasation are presented.

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.

Clevidipine for severe hypertension in patients with renal dysfunction: A VELOCITY trial analysis

PubMed Central

PEACOCK, W FRANK; VARON, JOSEPH; EBRAHIMI, RAMIN; DUNBAR, LALA; POLLACK, CHARLES V

2011-01-01

Introduction. Acute and severe hypertension is common, especially in patients with renal dysfunction (RD). Clevidipine is a rapidly acting (t½∼1 min) intravenous (IV) dihydropyridine calcium-channel blocker metabolized by blood and tissue esterases and may be useful in patients with RD. The purpose of this analysis was to assess the safety and efficacy of clevidipine in patients with RD. Methods. VELOCITY, a multicenter open-label study of severe hypertension, enrolled 126 patients with persistent systolic blood pressure (SBP) >180 mmHg. Investigators pre-specified a SBP initial target range (ITR) for each patient to be achieved within 30 min. Blood pressure monitoring was by cuff. Clevidipine was infused via peripheral IV at 2 mg/h for at least 3 min, then doubled every 3 min as needed to a maximum of 32 mg/h (non-weightbased treat-to-target protocol). Per protocol, clevidipine was continued for at least 18 h (96 h maximum). RD was diagnosed and reported as an end-organ injury by the investigator and was defined as requiring dialysis or an initial creatinine >2.0 mg/dl. Primary endpoints were the percentage of patients within the ITR by 30 min and the percentage below the ITR after 3 min of clevidipine infusion. Results. Of the 24 patients with moderate to severe RD, most (13/24) were dialysis dependent. Forty-six percent were male, with mean age 51 >14 years; 63% were black and 96% had a hypertension history. Median time to achieve the ITR was 8.5 min. Almost 90% of patients reached the ITR in 30 min without evidence of overshoot and were maintained on clevidipine through 18 h. Most patients (88%) transitioned to oral antihypertensive therapy within 6 h of clevidipine termination. Conclusions. This report is the first demonstrating that clevidipine is safe and effective in RD complicated by severe hypertension. Prolonged infusion maintained blood pressure within a target range and allowed successful transition to oral therapy. PMID:21091269

Cardiovascular effects of fentanyl in conscious rats.

PubMed

Baechtold, F; Cavadas, C; Gasser, D; Markert, M; Grouzmann, E; Peterson, K L; Waeber, B; Feihl, F

2001-10-01

The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in the rat is widely used in shock research. For ethical reasons, narcotic analgesics are often administered in this model, with the potential risk of confounding effects. In conscious non-septic rats, we investigated the cardiovascular effects of a continuous i.v. infusion of fentanyl (20 microg/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen commonly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl group), or fluid loading alone (Control). All endpoints were assessed after 24 h of infusion. At that time, Control animals had mild respiratory alkalosis, which was essentially abolished by fentanyl. Analgesia mildly elevated the plasma norepinephrine levels [median (interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-676), P=0.045] but was devoid of any effect on blood pressure, heart rate, cardiac output (mean +/-SD: Control 388+/-61 ml/kg per min, Fentanyl 382+/-62 ml/kg per min, P=0.87) and indices of left ventricular function derived from high-fidelity recordings of left ventricular pressure (dP/dtmax: Control 11782+/-2324 mmHg/s, Fentanyl 12107+/-2816 mmHg/s, P=0.77). In ex vivo experiments carried out immediately after animal sacrifice, no differences were noted between the Control and Fentanyl groups in the sensitivity of endothelium-intact aortic rings to norepinephrine-induced vasoconstriction (-logEC50: Control 8.78+/-0.28, Fentanyl 8.83+/-0.26, P=0.52) or acetylcholine-induced vasodilatation (-logEC50: Control 7.00+/-0.37, Fentanyl 7.06+/-0.26+/-0.53, P=0.75). In conclusion, the present data provide no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious catheterized rats undergoing CLP or other painful procedures.

Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations.

PubMed

Cooney, Lewis; McBride, Antonia; Lilley, Andrew; Sinha, Ian; Johnson, Trevor N; Hawcutt, Daniel B

2017-04-01

To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those <10 mg/L, and adverse effects occurred in 57%. Therapeutic drug monitoring (TDM) data correlated well with PBPK model. PBPK modelling of a 5 mg/kg iv loading dose (≤18yr) shows a mean C max of 8.99 mg/L (5th-95th centiles 5.5-13.7 mg/L), with 70.3% of subjects <10 mg/L, 29.4% achieving 10-20 mg/L, and 0.1% > 20 mg/L. For an aminophylline infusion (0-12 y) of 1.0  mg/kg/h, the mean steady state infusion concentration was 16.4 mg/L, (5th-95th centiles 5.3-32 mg/L), with 26.8% having a serum concentration >20 mg/L. For 12-18yr receiving 0.5  mg/kg/h infusion, the mean steady state infusion concentration was 9.37 mg/L (5th-95th centiles 3.4-18 mg/L), with 59.8% having a serum concentration <10 mg/L. PBPK software modelling correlates well with clinical data. Current aminophylline iv loading dosage recommendations achieve levels <10 mg/l in 70% of children. Routine TDM may need altering as low risk of toxicity (>20 mg/l). Copyright © 2017 Elsevier Ltd. All rights reserved.

Intraosseous vascular access in the treatment of chemical warfare casualties assessed by advanced simulation: proposed alteration of treatment protocol.

PubMed

Vardi, Amir; Berkenstadt, Haim; Levin, Inbal; Bentencur, Ariel; Ziv, Amitai

2004-06-01

Current treatment protocols for chemical warfare casualties assume no IV access during the early treatment stages. Time constraints in mass casualty scenarios, impaired manual dexterity of medical personnel wearing protective gear, and victims' complex clinical presentations render standard IV access techniques impractical. A newly developed spring-driven, trigger-operated intraosseous infusion device may offer an effective solution. Sophisticated simulators were developed and used to mimic scenarios of chemical warfare casualties for assessing the feasibility of intraosseous infusion delivery. We evaluated the clinical performance of medical teams in full protective gear. The success rate in intraosseous insertion, time to completion of treatment goals, and outcome were measured in a simulated setting. Medical teams from major hospitals in Israel, designated for emergency response in a real chemical warfare mass casualty scenario, were trained in a simulated setting. All 94 participating physicians were supplied with conventional treatment modalities: only the 64 study group physicians received intraosseous devices. The simulated survival rate was 73.4% for the study group and 3.3% for the controls (P < 0.001). Treatment goals were achieved within 3.5 min (range, 1-9 min) in the study group and within >10 min for controls (P < 0.001), and the complication rate for intraosseous use was 13.8%. Personnel satisfaction with the intraosseous device was unanimous and high. New-generation intraosseous infusions have great potential value in the early treatment stages of chemical warfare casualties. In a chemical warfare mass casualty scenario, the protective gear worn by medical personnel, the time constraints, and the casualties' medical condition impose limitations on the establishment of IV access during early treatment of the victims. A spring-driven, trigger-operated intraosseous infusion delivery system may offer an effective solution.

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol (KMP-TIVA) in horses undergoing surgery

PubMed Central

UMAR, Mohammed Ahmed; FUKUI, Sho; KAWASE, Kodai; ITAMI, Takaharu; YAMASHITA, Kazuto

2014-01-01

Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25 µg/kg/hr). The horses were anesthetized for 175 ± 14 min (range from 160 to 197 min). Propofol infusion rates ranged from 0.13 to 0.17 mg/kg/min, and plasma concentration (Cpl) of propofol ranged from 11.4 to 13.3 µg/ml during surgery. Cardiovascular measurements during surgery remained within clinically acceptable ranges in the horses (heart rate: 33 to 37 beats/min, mean arterial blood pressure: 111 to 119 mmHg, cardiac index: 48 to 53 ml/kg/min, stroke volume: 650 to 800 ml/beat and systemic vascular resistance: 311 to 398 dynes/sec/cm5). The propofol Cpl declined rapidly after the cessation of propofol infusion and was significantly lower at 10 min (4.5 ± 1.5 µg/ml), extubation (4.0 ± 1.2 µg/ml) and standing (2.4 ± 0.9 µg/ml) compared with the Cpl at the end of propofol administration (11.4 ± 2.7 µg/ml). All the horses recovered uneventfully and stood at 74 ± 28 min after the cessation of anesthesia. KMP-TIVA provided satisfactory quality and control of anesthesia with minimum cardiovascular depression in horses undergoing surgery. PMID:25409552

Effects of dexamethasone and nimesulide on bisphosphonate-related osteonecrosis of the jaw: An experimental study.

PubMed

Oliveira, Camila Carvalho de; Barros Silva, Paulo Goberlânio de; Ferreira, Antonio Ernando Carlos; Gonçalves, Romélia Pinheiro; Sousa, Fabrício Bitu de; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes

2017-11-01

To evaluate the effects of dexamethasone (DEX) and nimesulide (NIM) on Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) in rats. BRONJ was induced by zoledronic acid (ZA) infusion (0.2mg/kg) in Wistar rats (n=8), followed by extraction of the left lower first molar (BRONJ groups). Control groups (n=40) received saline (IV). For eight weeks, DEX (0.04, 0.4, 4mg/kg) or saline (SAL) were administered by gavage 24h before each infusion of ZA or saline (IV), or NIM (10.3mg/kg) was administered 24h and 12h before each infusion of ZA or saline (IV). The haematological analyses were conducted weekly. After euthanasia (day 70), the jaws were submitted to radiographic and microscopic analysis. Kidney, liver, spleen and stomach were analysed histopathologically. The BRONJ groups showed a higher radiolucent area compared with the control groups (p<0.05). Histomorphometric analysis revealed healing and new bone formation in the control groups, while the BRONJ groups exhibited devitalized bone with bacterial colonies and inflammatory infiltrate. The BRONJ-DEX 0.4 and 4mg/kg groups had a greater number of bacterial colonies (p<0.05) and an increased polymorphonuclear cell count compared to the saline-BRONJ group, while the BRONJ-NIM group had a lower polymorphonuclear count (p<0.05). The BRONJ groups had leucocytosis, which was reduced by DEX administration. Treatments with DEX with or without ZA caused white pulp atrophy. Thus, DEX or NIM therapy was not effective in preventing radiographic and histopathologic events associated with BRONJ. Treatment with DEX attenuated leucocytosis post-infusion with ZA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of sustained effects of levosimendan and dobutamine on left ventricular systolic functions by using novel tissue Doppler derived indices in patients with advanced heart failure.

PubMed

Oner, Ender; Erturk, Mehmet; Birant, Ali; Kurtar Mansıroglu, Aslı; Akturk, Ibrahim Faruk; Karakurt, Huseyin; Yalcin, Ahmet Arif; Uzun, Fatih; Somuncu, Mustafa Umut; Yildirim, Aydin

2015-01-01

Previous studies comparing levosimendan vs. dobutamine have revealed that levosimendan is better in relieving symptoms. Echocardiographic studies have been done using second measurements immediately following a dobutamine infusion or while it was still being administered. The aim of our study was assessment of sustained effects of 24 h levosimendan and dobutamine infusions on left ventricular systolic functions. A total of 61 patients with acutely decompensated heart failure with New York Heart Association (NYHA) class III or IV symptoms were randomized to receive either levosimendan or dobutamine 2:1 in an open label fashion. Before and 5 days after the initiation of infusions, functional class was assessed, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fraction (LVEF), mitral inflow peak E and A wave velocity, and E/A ratios were measured; using tissue Doppler imaging, isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), early (E') and late (A') diastolic velocities, and E'/A' and E/E' ratios were measured. The NYHA class improved in both groups, but improvements were prominent in the levosimendan group. NT-proBNP levels were significantly reduced in the levosimendan group. Improvements in LVEF and diastolic indices were significant in the levosimendan group. Tissue Doppler-derived systolic indices of IVV and IVA increased significantly in the levosimendan group. Improvements in left ventricular systolic and diastolic functions continue after a levosimendan infusion.

Plasma and erythrocyte uptake of omega-3 fatty acids from an intravenous fish oil based lipid emulsion in patients with advanced oesophagogastric cancer.

PubMed

Eltweri, A M; Thomas, A L; Fisk, H L; Arshad, A; Calder, P C; Dennison, A R; Bowrey, D J

2017-06-01

It has been demonstrated that short term intravenous (IV) administration of omega-3 polyunsaturated fatty acids (PUFAs) is more effective than oral supplementation at promoting incorporation of the bioactive omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma, blood cells and tissues. The effect of repeated short term IV infusion of omega-3 PUFAs was investigated in patients with advanced oesophagogastric cancer during palliative chemotherapy. Patients with advanced oesophagogastric cancer (n = 21) were recruited into a phase II pilot clinical trial. All patients were scheduled for an intravenous infusion of Omegaven ® (fish oil supplement containing EPA and DHA) at a rate of 2 ml/kg body weight for 4 h once a week for up to six months. Blood samples were collected to assess omega-3 PUFA uptake into plasma non-esterified fatty acids (NEFAs) and phosphatidylcholine (PC) and into red blood cell (RBC) membranes. Fatty acid profiles were analysed by gas chromatography. Twenty patients received at least one Omegaven ® treatment and were included in the analysis. Each infusion of omega-3 PUFAs resulted in increased EPA and DHA in plasma NEFAs, but there was little effect on PUFAs within plasma PC during the infusions. However, with repeated weekly infusion of omega-3 PUFAs, the EPA content of plasma PC and of RBC membranes increased. Repeated weekly omega-3 PUFA infusion is effective in enriching plasma PC and RBC membranes in EPA in patients with advanced oesophagogastric cancer receiving palliative chemotherapy. Clinical Trials.Gov NCT01870791. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Syringe Pump Performance Maintained with IV Filter Use During Low Flow Rate Delivery for Pediatric Patients.

PubMed

Chau, Destiny F; Vasilopoulos, Terrie; Schoepf, Miriam; Zhang, Christina; Fahy, Brenda G

2016-09-01

Complex surgical and critically ill pediatric patients rely on syringe infusion pumps for precise delivery of IV medications. Low flow rates and in-line IV filter use may affect drug delivery. To determine the effects of an in-line filter to remove air and/or contaminants on syringe pump performance at low flow rates, we compared the measured rates with the programmed flow rates with and without in-line IV filters. Standardized IV infusion assemblies with and without IV filters (filter and control groups) attached to a 10-mL syringe were primed and then loaded onto a syringe pump and connected to a 16-gauge, 16-cm single-lumen catheter. The catheter was suspended in a normal saline fluid column to simulate the back pressure from central venous circulation. The delivered infusate was measured by gravimetric methods at predetermined time intervals, and flow rate was calculated. Experimental trials for initial programmed rates of 1.0, 0.8, 0.6, and 0.4 mL/h were performed in control and filter groups. For each trial, the flow rate was changed to double the initial flow rate and was then returned to the initial flow rate to analyze pump performance for titration of rates often required during medication administration. These conditions (initial rate, doubling of initial rate, and return to initial rate) were analyzed separately for steady-state flow rate and time to steady state, whereas their average was used for percent deviation analysis. Differences between control and filter groups were assessed using Student t tests with adjustment for multiplicity (using n = 3 replications per group). Mean time from 0 to initial flow (startup delay) was <1 minute in both groups with no statistical difference between groups (P = 1.0). The average time to reach steady-state flow after infusion startup or rate changes was not statistically different between the groups (range, 0.8-5.5 minutes), for any flow rate or part of the trial (initial rate, doubling of initial rate, and return to initial rate), although the study was underpowered to detect small time differences. Overall, the mean steady-state flow rate for each trial was below the programmed flow rate with negative mean percent deviations for each trial. In the 1.0-mL/h initial rate trial, the steady-state flow rate attained was lower in the filter than the control group for the initial rate (P = 0.04) and doubling of initial rate (P = 0.04) with a trend during the return to initial rate (P = 0.06), although this same effect was not observed when doubling the initial rate trials of 0.8 or 0.6 mL/h or any other rate trials compared with the control group. With low flow rates used in complex surgical and pediatric critically ill patients, the addition of IV filters did not confer statistically significant changes in startup delay, flow variability, or time to reach steady-state flow of medications administered by syringe infusion pumps. The overall flow rate was lower than programmed flow rate with or without a filter.

Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion.

PubMed

Rackow, E C; Mecher, C; Astiz, M E; Griffel, M; Falk, J L; Weil, M H

1989-05-01

Twenty consecutive patients with severe sepsis were randomized to fluid challenge with 5% albumin or 10% low MW hydroxyethyl starch (pentastarch) solutions. Fluid challenge was administered iv as 250 ml of test colloid every 15 min until the pulmonary artery wedge pressure (WP) was greater than or equal to 15 mm Hg or a maximum dose of 2000 ml was infused. Hemodynamic, respiratory, and coagulation profiles were measured before and after fluid infusion. The amount of colloid required to achieve a WP of 15 mm Hg was comparable between groups. Both colloid infusions resulted in similar increases in cardiac output, stroke output, and stroke work. The effect of fluid infusion with pentastarch on coagulation was not significantly different from albumin, although pentastarch was associated with a 45% decrease in factor VIII:c. We conclude that pentastarch is equivalent to albumin for fluid resuscitation of patients with severe sepsis.

The effect of low molecular weight dextran on haemodynamics and respiratory function during endotoxin-induced shock.

PubMed Central

Christenson, J T; al-Sarraf, A; Abu-Saleh, R

1992-01-01

The effects of low molecular weight dextran (LMWD) infusion, on gas exchange and haemodynamics were evaluated in sheep during endotoxin shock. The infusion of LMWD was started after signs of shock and lung injury were evident. After a stabilization period 10 micrograms kg-1 E. Coli endotoxin was infused i.v.. Endotoxin infusion resulted in an marked increase in pulmonary artery pressure (PAP) and decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2l). After 3 h MAP, PaO2, DO2l and compliance improved significantly in LMWD treated animals. The PAP had also decreased significantly in the LMWD-treated animals, but remained high in the controls (P less than 0.01). It was concluded that LMWD infusion improves haemodynamics and gas-exchange in sheep during endotoxin shock. PMID:1373624

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.

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.

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.

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.

Pharmacokinetics of three formulations of ondansetron hydrochloride in healthy volunteers: 24-mg oral tablet, rectal suppository, and i.v. infusion.

PubMed

VanDenBerg, C M; Kazmi, Y; Stewart, J; Weidler, D J; Tenjarla, S N; Ward, E S; Jann, M W

2000-06-01

The absolute bioavailability and pharmacokinetics of three formulations of ondansetron hydrochloride 24 mg--an oral tablet, an intravenous solution, and an extemporaneous rectal suppository--were studied. Twelve healthy, nonsmoking volunteers (six men and six women) were given ondansetron in a study with a three-way cross-over design. All subjects received each dosage form on the same day in the following order: oral tablet, rectal suppository, and intravenous infusion. Administrations were separated by one week. Blood sampling times varied, depending on the administration route. Mean absolute bioavailability for the oral tablet and the rectal suppository differed significantly. Absorption of ondansetron was prolonged when it was administered as the rectal suppository. Absolute bioavailability for the 24-mg tablet was similar to that for other tablet strengths in previous studies. All subjects completed the study without significant adverse effects. Absorption of ondansetron from the rectal suppository was prolonged compared with the oral tablet and the i.v. infusion. Bioavailability for the 24-mg suppository formulation was considerably lower than for the 24-mg tablet.

Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report.

PubMed

Chinn, Matthew; Colella, M Riccardo

2017-01-01

A 57-year-old woman was found at home by paramedics to be hypoglycemic with altered mental status. She had multiple attempts at IV access and eventually a 22G IV was established and D50 was infused into her right forearm. Extravasation of the dextrose was noted after approximately 12 g of the medication was infused. She was given a dose of glucagon intramuscularly and her mental status improved. Shortly after her arrival to the emergency department, she was noted to have findings of compartment syndrome of her forearm at the site of the dextrose extravasation. She was evaluated by plastic surgery and taken to the operating room for emergent fasciotomy. She recovered well from the operation. D50 is well known to cause phlebitis and local skin necrosis as a complication. This case illustrates the danger of compartment syndrome after D50 extravasation. It is the first documented case of prehospital dextrose extravasation leading to compartment syndrome. There may be safer alternatives to D50 administration and providers must be acutely aware to monitor for D50 infusion complications.

Intravenous infusion of prostaglandin E2 for management of premature rupture of membranes.

PubMed

Thiery, M; Parewijck, W; Martens, G

1982-01-01

In term with premature rupture of the membranes (PROM) and an unripe cervix who have no contraindications for prostaglandin (PG) administration and vaginal delivery, intravenous (I.V.) infusion of titrated PGE2 is highly effective. In healthy gravidas with dito fetus this treatment appeared perinatally safe and was well tolerated by the mother. To enhance its safety margin and procedure must be conducted under toco-cardiographic control.

Intravenous Milrinone Infusion Improves Congestive Heart Failure Caused by Diastolic Dysfunction

PubMed Central

Albrecht, Carlos A.; Giesler, Gregory M.; Kar, Biswajit; Hariharan, Ramesh; Delgado, Reynolds M.

2005-01-01

Although there have been significant advances in the medical treatment of heart failure patients with impaired systolic function, very little is known about the diagnosis and treatment of diastolic dysfunction. We report the cases of 3 patients in New York Heart Association functional class IV who had echocardiographically documented diastolic dysfunction as the main cause of heart failure. All 3 patients received medical therapy with long-term milrinone infusion. PMID:16107121

Extracorporeal Membrane Oxygenation in Drug Overdose: A Clinical Case Series

PubMed Central

Vignesh, C.; Kumar, Madhan; Venkataraman, Ramesh; Rajagopal, Senthilkumar; Ramakrishnan, Nagarajan; Abraham, Babu K.

2018-01-01

Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy. We report three patients with cardiovascular medication overdose presenting with profound cardiovascular instability refractory to medical therapy. Venoarterial extracorporeal membrane oxygenation support (VA ECMO) was initiated to provide hemodynamic support. Despite the occurrence of device-associated complications, the outcome was good and all patients survived. VA ECMO may be considered in patients with severe refractory shock due to cardiotoxic medication overdose. PMID:29531453

Extracorporeal Membrane Oxygenation in Drug Overdose: A Clinical Case Series.

PubMed

Vignesh, C; Kumar, Madhan; Venkataraman, Ramesh; Rajagopal, Senthilkumar; Ramakrishnan, Nagarajan; Abraham, Babu K

2018-02-01

Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy. We report three patients with cardiovascular medication overdose presenting with profound cardiovascular instability refractory to medical therapy. Venoarterial extracorporeal membrane oxygenation support (VA ECMO) was initiated to provide hemodynamic support. Despite the occurrence of device-associated complications, the outcome was good and all patients survived. VA ECMO may be considered in patients with severe refractory shock due to cardiotoxic medication overdose.

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

[The effect of bombesin and its analogs on the secretion of gastric juice and its content of pepsin and hydrochloric acid].

PubMed

Barashkova, G M; Klimov, P K; Kuranova, I L; Churkina, S I; Filonova, E B

1990-07-01

I.V. Infusion of bombesine after eating raw meat inhibited for 30-60 min the secretion of gastric juice and hydrochloric acid in dogs. Within 90-120 min of simultaneous infusion of pentagastrin and bombesine, the amount of secreted juice and its acidity decreased and then the secretion of gastric parietal cells increased. Simultaneous infusion of histamine and bombesine increased the response of gastric parietal cells during the whole experiment as compared with the histamine effect alone. Microapplication of bombesine into cerebral structures also decreased the secretory response of the parietal cells.

A Phase II Study of Cetuximab (Erbitux®) plus FOLFIRI for Irinotecan and Oxaliplatin-refractory Metastatic Colorectal Cancer

PubMed Central

Koo, Dong Hoe; Lee, Jae-Lyun; Kim, Tae Won; Chang, Heung Moon; Ryu, Min-Hee; Lee, Sung Sook; Kim, Min Kyoung; Sym, Sun Jin; Lee, Jung Shin

2007-01-01

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens. PMID:17923763

PM101: a cyclodextrin-based intravenous formulation of amiodarone devoid of adverse hemodynamic effects.

PubMed

Cushing, Daniel J; Kowey, Peter R; Cooper, Warren D; Massey, Bill W; Gralinski, Michael R; Lipicky, Raymond J

2009-04-01

Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.

Continuous subcutaneous levetiracetam in the management of seizures at the end of life: a case report.

PubMed

Wells, Geoffrey Howard; Mason, Louise D; Foreman, Emma; Chambers, John

2016-03-01

We report the case of a man who developed seizures on a background of recurrent metastatic squamous cell carcinoma with intracranial involvement. Initial seizure control with enteral levetiracetam was achieved, and when enteral and intravenous (i.v.) access was no longer available, a continuous subcutaneous infusion (CSCI) of levetiracetam successfully controlled his seizures without the need for sedating anticonvulsants. As a result, end-of-life care was able to be given with the patient retaining the ability to communicate with his family and healthcare staff. This report adds to the sparse but growing evidence base for the use of subcutaneous levetiracetam to manage seizures in palliative and end-of-life care. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Face-to-face instruction combined with online resources improves retention of clinical skills among undergraduate nursing students.

PubMed

Terry, Victoria R; Terry, Peter C; Moloney, Clint; Bowtell, Les

2018-02-01

There is growing evidence that online resources used to develop clinical skills among students in the healthcare professions can produce equivalent learning outcomes to traditional face-to-face training methods. Whether clinical competence is retained equally well for online and face-to-face training methods is not yet established. The objective of the study was to compare retention of competence in using an IV infusion pump among nursing students trained in its use using three different protocols. A quasi-experimental design was used. The study was conducted in the School of Nursing and Midwifery at a regional university in Queensland, Australia. Participants were 102 first year nursing students (female=89, male=13) enrolled in a medications course, ranging in age from 18 to 44years. Three groups of participants were trained in the use of an IV infusion pump and competence was assessed following a 26-week period of no access to the pump. Group 1 participants (ONL; n=34) were trained online using an Intravenous Pump Emulator (IVPE); Group 2 participants (ONC; n=38) were trained on campus using an actual IV pump in a traditional face-to-face setting; Group 3 participants (ONL+ONC; n=30) were trained both on campus using the actual IV pump and online using the IVPE. As hypothesised, no significant differences in learning outcomes, measured by assessment scores out of 80 points, were found between the ONL (M=68.7±5.9) and ONC (M=65.5±11.5; p>0.05) groups. The ONL+ONC group recorded the highest mean assessment score (M=70.0±5.0) and completed the assessment task significantly faster (p<0.001) than the other two groups. This study suggests that nursing students retained clinical competence in preparing and administrating IV infusions better when face-to-face and online learning were combined. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

PubMed

Tawfic, Qutaiba A; Faris, Ali S; Kausalya, Rajini

2014-02-01

Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

PubMed

Nguyen, Natalie L; Kome, Anne M; Lowe, Denise K; Coyne, Patrick; Hawks, Kelly G

2015-01-01

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

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.

Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

PubMed

Aleman, M; Williams, D C; Guedes, A; Madigan, J E

2015-01-01

An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

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

PubMed

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

2011-05-01

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

Evaluation of the Cardiovascular and Subjective Effects of Rivastigmine In Combination With Methamphetamine in Methamphetamine-Dependent Human Volunteers

PubMed Central

De La Garza, R.; Shoptaw, S.; Newton, T. F.

2008-01-01

Acetylcholine (ACh) has been implicated in the reinforcing and locomotor activating effects produced by methamphetamine. Of interest, recent data suggest that acetylcholinesterase (AChE) inhibitors attenuate methamphetamine-seeking behavior in rats. We conducted this study in order to determine the safety (adverse events, mood changes, cardiovascular effects) and preliminary efficacy (subjective effects) of the AChE inhibitor rivastigmine when tested in combination with methamphetamine. Twenty-three non-treatment seeking methamphetamine-dependent participants resided in an inpatient unit at UCLA for two-weeks, and completed this double-blind, between-subjects, placebo-controlled study. Prior to randomization to study drug, infusions of saline (day 4; o mg) and methamphetamine (day 5; 30 mg, IV) were given to all participants at 11:30 a.m. in single-blinded fashion. On day 7 and continuing through day 11, participants were randomized to receive oral placebo (0 mg, N=7) or rivastigmine (1.5 mg, N=7; 3 mg, N=9). On day 11, the subjects received saline and methamphetamine infusions again (randomized to either 11:30 a.m. or 2:30 p.m.), under double-blind conditions. The data analyses compared across-study measures of adverse events and mood, and a post-randomization analysis of cardiovascular and subjective effects (on Day 11). The data reveal that rivastigmine was not associated with increased adverse events or alterations in mood. As expected, acute methamphetamine exposure (30 mg, IV) increased heart rate and blood pressure, as well as several positive subjective effects, ARCI ratings, and reported monetary value (p<0.05). The data indicated that rivastigmine, at 3 mg, significantly attenuated methamphetamine-induced increases in diastolic blood pressure, and self-reports of “anxious” and “desire” (p<0.05). Taken together, the findings in the current report suggest that pharmacological manipulations that enhance brain ACh warrant continued investigation as potential treatments for methamphetamine addiction. PMID:18248689

The effects of L-carnitine on spinal cord ischemia/reperfusion injury in rabbits.

PubMed

Tetik, O; Yagdi, T; Islamoglu, F; Calkavur, T; Posacioglu, H; Atay, Y; Ayik, F; Canpolat, L; Yuksel, M

2002-02-01

Paraplegia after distal aortic aneurysm repair remains a persistent clinical problem. We hypothesized that the tolerance of the spinal cord to an ischemic period could be improved with hypothermic Ringer's Lactate containing L-Carnitine. Twenty-eight New Zealand white rabbits were used as spinal cord ischemia models. We separated rabbits into four equal groups and clamped each animal's abdominal aorta distal to the left renal artery. We occluded the aortas above the iliac bifurcation for 30 minutes. In group I, the infrarenal aorta was clamped without infusing any solution. In group II, Ringer's Lactate solution was infused at + 25degrees C for 3 minutes at a rate of 5 ml/min into the isolated aortic segments immediately after cross-clamping and the last 3 minutes of ischemia. In group III, Ringer's Lactate solution at +3 degrees C was given in the same method as that of group II. In group IV, Ringer's Lactate solution at +3 degrees C plus 100 mg/kg of L-carnitine was infused using the same technique. We assessed the neurological status of the hind limbs 24 and 48 hours after operation according to Tarlov's criteria. All animals were sacrificed and spinal cords were harvested for histological analyses. The neurological status in groups III and IV was significantly superior to that of groups I and II. All the animals in group I had complete hind-limb paraplegia. Complete hind-limb paraplegia occurred in 5 rabbits in group II. Two of the 7 animals in group III had spastic paraplegia, and none at all in group IV. Histological analysis of the cross-clamped segments of the rabbits with paraplegia in group I, II and III revealed changes consistent with ischemic injury, while findings were normal for the normal animals in group III and IV. In this model, the infusion of hypothermic Ringer's Lactate contained L-carnitine provided sufficient spinal cord protection against ischemia. Clinically, this may be a useful adjunct for prevention of paraplegia during surgery of the descending aorta.

Time Savings with Rituximab Subcutaneous Injection versus Rituximab Intravenous Infusion: A Time and Motion Study in Eight Countries

PubMed Central

De Cock, Erwin; Kritikou, Persefoni; Sandoval, Mariana; Tao, Sunning; Wiesner, Christof; Carella, Angelo Michele; Ngoh, Charles; Waterboer, Tim

2016-01-01

Background Rituximab is a standard treatment for non-Hodgkin lymphoma. The SABRINA trial (NCT01200758) showed that a subcutaneous (SC) rituximab formulation did not compromise efficacy or safety compared with intravenous (IV) infusion. We aimed to quantify active healthcare professional (HCP) time and patient chair time for rituximab SC and IV, including potential time savings. Methods This non-interventional time and motion study was run in eight countries and 30 day oncology units. Rituximab SC data were collected alongside the MabCute trial (NCT01461928); IV data were collected per routine real-world practice. Trained observers recorded active HCP time for pre-specified tasks (stopwatch) and chair time (time of day). A random intercept model was used to analyze active HCP time (by task and for all tasks combined) in the treatment room and drug preparation area, drug administration duration, chair time and patient treatment room time by country and/or across countries. Active HCP and chair time were extrapolated to a patient’s first year of treatment (11 rituximab sessions). Results Mean active HCP time was 35.0 and 23.7 minutes for IV and SC process, respectively (-32%, p <0.0001). By country, relative reduction in time was 27–58%. Absolute reduction in extrapolated active HCP time (first year of treatment) was 1.1–5.2 hours. Mean chair time was 262.1 minutes for IV, including 180.9 minutes infusion duration, vs. 67.3 minutes for SC, including 8.3 minutes SC injection administration (-74%, p <0.0001). By country, relative reduction was 53–91%. Absolute reduction in extrapolated chair time for the first year of treatment was 3.1–5.5 eight-hour days. Conclusions Compared with rituximab IV, rituximab SC was associated with reduced chair time and active HCP time. The latter could be invested in other activities, whereas the former may lead to more available appointments, reducing waiting lists and increasing the efficiency of day oncology units. Trial Registration ClinicalTrials.gov NCT01200758 PMID:27362533

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.

Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

2015-11-01

Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

Opioid neurotoxicity: neuropathologic effects in rats of different fentanyl congeners and the effects of hexamethonium-induced normotension.

PubMed

Kofke, W A; Garman, R H; Janosky, J; Rose, M E

1996-07-01

We tested the hypotheses that convulsant doses of opioids would produce limbic system damage exacerbated by hexamethonium. Ventilated paralyzed rats received intravenous (IV) isovolumic infusion of fentanyl loading dose (LD) 1000 micrograms/kg, maintenance dose (MD) 40 micrograms.kg-1.min-1 (n = 10), sufentanil LD 400 micrograms/kg, MD 13.3 micrograms.kg-1.min-1 (n = 10), alfentanil LD 1500 micrograms/kg, MD 150 micrograms.kg-1.min-1 (n = 10), or 0.9% saline control LD 4 mliter/kg, MD 4 mliter.kg-1.h-1 (n = 10), with O2/N2 30%/70% during opioid infusion and O2/N2O in controls during saline infusion. Hexamethonium (LD 20 mg/kg, MD 40-120 mg.kg-1.h-1) was given IV during opioid infusion to half of the rats. Cerebral perfusion-fixation with formalin was performed 24 h later, followed by histopathologic assessment. None of the control rats showed any histologic abnormalities. Overall summed neuropathologic severity was worse in opioid treated groups (P = 0.01). Lesions occurred primarily in cortical regions and limbic system structures. When arterial blood pressure was controlled to a lower level with hexamethonium (147 vs 100 mm Hg), rats had less severe lesions (P = 0.02). These data indicate that fentanyl, sufentanil, and alfentanil all can produce histopathologic evidence of brain injury in rats mitigated by hexamethonium.

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

Daily Palonosetron Is Superior to Ondansetron in the Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting in Patients With Acute Myelogenous Leukemia

PubMed Central

Mattiuzzi, Gloria N.; Cortes, Jorge E.; Blamble, Deborah A.; Bekele, B. Nebiyou; Xiao, Lianchun; Cabanillas, Maria; Borthakur, Gautam; O’Brien, Susan; Kantarjian, Hagop

2014-01-01

BACKGROUND Nausea and vomiting in patients with acute myelogenous leukemia (AML) can be from various causes, including the use of high-dose cytarabine. METHODS The authors compared 2 schedules of palonosetron versus ondansetron in the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with AML receiving high-dose cytarabine. Patients were randomized to: 1) ondansetron, 8 mg intravenously (IV), followed by 24 mg continuous infusion 30 minutes before high-dose cytarabine and until 12 hours after the high-dose cytarabine infusion ended; 2) palonosetron, 0.25 mg IV 30 minutes before chemotherapy, daily from Day 1 of high-dose cytarabine up to Day 5; or 3) palonosetron, 0.25 mg IV 30 minutes before high-dose cytarabine on Days 1, 3, and 5. RESULTS Forty-seven patients on ondansetron and 48 patients on each of the palonosetron arms were evaluable for efficacy. Patients in the palonosetron arms achieved higher complete response rates (no emetic episodes plus no rescue medication), but the difference was not statistically significant (ondansetron, 21%; palonosetron on Days 1–5, 31%; palonosetron on Days 1, 3, and 5, 35%; P = .32). Greater than 77% of patients in each arm were free of nausea on Day 1; however, on Days 2 through 5, the proportion of patients without nausea declined similarly in all 3 groups. On Days 6 and 7, significantly more patients receiving palonosetron on Days 1 to 5 were free of nausea (P = .001 and P = .0247, respectively). CONCLUSIONS The daily assessments of emesis did not show significant differences between the study arms. Patients receiving palonosetron on Days 1 to 5 had significantly less severe nausea and experienced significantly less impact of CINV on daily activities on Days 6 and 7. PMID:21218459

Cocaine self-administration punished by i.v. histamine in rat models of high and low drug abuse vulnerability: Effects of saccharin preference, impulsivity, and sex

PubMed Central

Holtz, Nathan A.; Anker, Justin J.; Regier, Paul S.; Claxton, Alex; Carroll, Marilyn E.

2015-01-01

A key feature of substance use disorders is continued drug consumption despite aversive consequences. This has been modeled in the animal laboratory by pairing drug self-administration with electric shock, thereby punishing drug intake (Deroche-Gamonet et al. 2004). In the present experiments, we examined the effects of punishment on i.v. cocaine self-administration by adding histamine to the cocaine solution in three different animal models of high and low vulnerability to drug abuse: rats selectively bred for high (HiS) and low (LoS) saccharin consumption, rats selected for high (HiI) and low (LoI) impulsivity, and sex differences. Animals were allowed to self-administer cocaine (0.4 mg/kg/infusion) to establish a baseline of operant responding. Histamine (4.0 mg/kg/infusion) was then added directly into the cocaine solution and its consequent effects on self-administration were compared to baseline. The histamine + cocaine solution was then replaced with a cocaine-only solution, and the rats' operant responding was again measured and compared to baseline. Concurrent histamine exposure was effective in reducing cocaine consumption in all groups of rats; however, LoS and female rats took longer to return to baseline levels of cocaine consumption after histamine was removed compared to HiS and male rats. These data suggest the reduction of drug self-administration by aversive consequences may differ in groups that vary in drug use vulnerability, and these results may inform pharmacological strategies that enhance the negative aspects of drug consumption. PMID:23948673

Distribution and chloramphenicol in the bovine genital tract and pharmacokinetic studies of florfenicol in cattle

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

Bretzlaff, K.N.

1986-01-01

The objectives were to investigate selected aspects of the distribution of chloramphenicol (CAP) in the bovine genital tract and to conduct preliminary pharmacologic studies with florfenicol (FLO), a fluorinated analogue of thiamphenicol, in cattle. After 8 hours' continuous intravenous (IV) infusion of CAP to 7 postpartum cows, steady state plasma-to-genital tissue ratios of CAP were approximately 3. After intrauterine infusion of 20 mg CAP/kg to 3 postpartum cows, approximately 40% of the dose was absorbed into the bloodstream. Tissue concentrations were high at 8 hour postdosing in tissues lining the uterine lumen but were below desired therapeutic concentrations in themore » myometrium of 2 of the cows. Eighty cows with retained fetal membranes (RFM) were assigned to receive on the following treatments: (1) removal of membranes only; (2) removal plus CAP; (3) nonremoval; (4) nonremoval plus CAP. CAP treatment consisted of 5 g administered IU twice daily for 3 days. The majority of cows in all groups acquired endometritis, although CAP reduced the prevalence and severity of the disease. A quantitative assay for FLO in plasma was developed and validated on a high performance liquid chromatographic (HPLC) system. The pharmacokinetics of FLO determined after IV administration of 50 mg FLO/kg to 5 cows were best described by a three-compartment model. FLO was approximately 18% bound to plasma proteins as determined by equilibrium dialysis and ultrafiltration. In an in vitro system, 5, 125, or 1000 ug/ml of CAP had no effect on neutrophils from 6 cows.« less

Venipuncture and intravenous infusion access during zero-gravity flight

NASA Technical Reports Server (NTRS)

Krupa, Debra T.; Gosbee, John; Billica, Roger; Bechtle, Perry; Creager, Gerald J.; Boyce, Joey B.

1991-01-01

The purpose of this experiment is to establish the difficulty associated with securing an intravenous (IV) catheter in place in microgravity flight and the techniques applicable in training the Crew Medical Officer (CMO) for Space Station Freedom, as well as aiding in the selection of appropriate hardware and supplies for the Health Maintenance Facility (HMF). The objectives are the following: (1) to determine the difficulties associated with venipuncture in a microgravity environment; (2) to evaluate the various methods of securing an IV catheter and attached tubing for infusion with regard to the unique environment; (3) to evaluate the various materials available for securing an intravenous catheter in place; and (4) to evaluate the fluid therapy administration system when functioning in a complete system. The inflight test procedures and other aspects of the KC-135 parabolic flight test to simulate microgravity are presented.

Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification

PubMed Central

Ferrer, Miguel D.; Ketteler, Markus; Tur, Fernando; Tur, Eva; Isern, Bernat; Salcedo, Carolina; Joubert, Pieter H.; Behets, Geert J.; Neven, Ellen; D’Haese, Patrick C.

2018-01-01

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60–70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans. PMID:29742152

Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.

PubMed

Seckl, J R; Johnson, M; Shakespear, C; Lightman, S L

1988-05-01

The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.

Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

PubMed Central

Guo, Honglei; Li, Hongmei; Ling, Lilu

2016-01-01

Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo. PMID:27721575

Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

PubMed

Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

2016-04-01

Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

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.

Recombinant human hyaluronidase-enabled subcutaneous pediatric rehydration.

PubMed

Allen, Coburn H; Etzwiler, Lisa S; Miller, Melissa K; Maher, George; Mace, Sharon; Hostetler, Mark A; Smith, Sharon R; Reinhardt, Neil; Hahn, Barry; Harb, George

2009-11-01

The Increased Flow Utilizing Subcutaneously-Enabled (INFUSE)-Pediatric Rehydration Study was designed to assess efficacy, safety, and clinical utility of recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration in children 2 months to 10 years of age. Patients with mild/moderate dehydration requiring parenteral treatment in US emergency departments were eligible for this phase IV, multicenter, single-arm study. They received subcutaneous injection of 1 mL rHuPH20 (150 U), followed by subcutaneous infusion of 20 mL/kg isotonic fluid over the first hour. Subcutaneous rehydration was continued as needed for up to 72 hours. Rehydration was deemed successful if it was attributed by the investigator primarily to subcutaneous fluid infusion and the child was discharged without requiring an alternative method of rehydration. Efficacy was evaluated in 51 patients (mean age: 1.9 years; mean weight: 11.2 kg). Initial subcutaneous catheter placement was achieved with 1 attempt for 46/51 (90.2%) of patients. Rehydration was successful for 43/51 (84.3%) of patients. Five patients (9.8%) were hospitalized but deemed to be rehydrated primarily through subcutaneous therapy, for a total of 48/51 (94.1%) of patients. No treatment-related systemic adverse events were reported, but 1 serious adverse event occurred (cellulitis at infusion site). Investigators found the procedure easy to perform for 96% of patients (49/51 patients), and 90% of parents (43/48 parents) were satisfied or very satisfied. rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.

Medication-related osteonecrosis of the jaws from once per year intravenous zoledronic acid (Reclast): report of 4 cases.

PubMed

Lee, Cameron Y S; Suzuki, Jon B

2015-04-01

Osteonecrosis of the jaws is a commonly reported side effect with patients prescribed oral antiresorptive medications to treat osteoporosis and osteopenia. Oral antiresorptive agents are considered as the standard of care for the prevention and treatment of women with postmenopausal osteoporosis. Because of patient's noncompliance of the antiresorptive medications, which may require once-weekly or once-monthly oral ingestion, a new once a year intravenous (IV) infusion of zoledronic acid was recently introduced in the management of osteoporosis. Reports of medication-related osteonecrosis of the jaw (MRONJ) have been reported in patients with cancer treated with multiple doses of IV zoledronic acid. However, there is a paucity of reports occurring with the once-yearly infusion of zoledronic acid (Reclast) for the management of osteoporosis. In this article, we report 4 cases of patients who had a history of long-term oral antiresorptive therapy and now were taking the once-yearly IV zoledronic acid (Reclast) and soon developed MRONJ after completing surgery of the maxilla and mandible.

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.

Initial Experience with IV Ketamine Infusion for Treatment of Post Sternotomy Pain in a Patient with a Total Artificial Heart.

PubMed

Maher, Dermot P; Loyferman, Rusty; Yumul, Roya; Louy, Charles

2015-01-01

The implantation of total artificial hearts (TAH) via midline sternotomy for the treatment of severe biventricular cardiac dysfunction is associated with complex postoperative pain management. Ketamaine increases blood pressure by raising sympathetic outflow and cardiac output; however, ketamine is a direct vasodilator on isolated arterial tissues. In the setting of a TAH with a mechanically fixed cardiac output, a ketamine infusion for postoperative pain control has the potential to decrease blood pressure due to direct arterial vasodilation. We present the initial experience with a ketamine infusion in a patient with a TAH with minimal observed decreases in blood pressure and significantly improved postoperative pain.

Costs of subcutaneous and intravenous administration of trastuzumab for patients with HER2-positive breast cancer.

PubMed

Olsen, Jens; Jensen, Kenneth Forsstrøm; Olesen, Daniel Sloth; Knoop, Ann

2018-05-01

Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.) formulation. The objective of this study was to estimate the costs of administration of iv. and sc. trastuzumab treatment. Via interviews, we identified all the activities associated with iv. and sc. administration. The outcome was time estimates. To estimate the administration costs, the time estimates were valued by average gross wages.  The iv. administration takes longer time as infusion time is longer (25 or 85 min). The iv. administration is associated with higher cost for 17 cycles; €971 (€1858 vs €887). sc. administration is associated with lower administration costs. Switching patients from iv. to sc. would make it possible to treat more patients without increasing the personnel resources.

Effect of intravenous or oral sodium chlorate administration on the fecal shedding of Escherichia coli in sheep

USDA-ARS?s Scientific Manuscript database

The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 +/- 2.5 kg) were administered 150 mg NaClO3 per kg BW by gavage or i.v. infusion in a cross-over design with sal...

A Pilot Chemical and Physical Stability Study of Extemporaneously Compounded Levetiracetam Intravenous Solution.

PubMed

Raphael, Chenzira D; Zhao, Fang; Hughes, Susan E; Juba, Katherine M

2015-01-01

Levetiracetam is a commonly used antiepileptic medication for tumor-related epilepsy. However, the 100 mL intravenous (IV) infusion volume can be burdensome to imminently dying hospice patients. A reduced infusion volume would improve patient tolerability. The purpose of this study was to evaluate the stability of 1000 mg/25 mL (40 mg/mL) levetiracetam IV solution in sodium chloride 0.9%. We prepared levetiracetam 40 mg/mL IV solution and added it to polyvinyl chloride (PVC) bags, polyolefin bags, and polypropylene syringes. Triplicate samples of each product were stored at refrigeration (2-8°C) and analyzed on days 0, 1, 4, 7, and 14. Samples were subjected to visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis. Over the 2-week storage period, there was no significant change in visual appearance or pH for any of the stability samples. The HPLC results confirmed that all stability samples retained 94.2-101.3% of initial drug concentration and no degradation products or leachable material from the packaging materials were observed. We conclude that levetiracetam 1000 mg/25 mL IV solution in sodium chloride 0.9% is physically and chemically stable for up to 14 days under refrigeration in polypropylene syringes, PVC bags, and polyolefin bags.

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

The role of tachykinin NK1 and NK2 receptors in atropine-resistant colonic propulsion in anaesthetized guinea-pigs.

PubMed

Lecci, A; Giuliani, S; Tramontana, M; Giorgio, R D; Maggi, C A

1998-05-01

1. The role of endogenous tachykinins on guinea-pig colonic propulsion was investigated by using potent and selective tachykinin NK1 and NK2 receptor antagonists. Colonic propulsion and contractions were determined by means of a balloon-catheter device, inserted into the rectum of guanethidine (68 micromol kg(-1), s.c., 18 and 2 h before)-pretreated, urethane-anaesthetized guinea-pigs. Propulsion of the device (dynamic model) was determined by measuring the length of the catheter expelled during 60 min filling of the balloon (flow rate 5 microl min(-1)). 2. In control conditions the tachykinin NK1 receptor antagonist SR 140333 (1 micromol kg(-1), i.v.) did not affect either colonic propulsion or the amplitude of contractions. The tachykinin NK2 receptor antagonists MEN 10627 and MEN 11420 (1 micromol kg(-1), i.v.) increased colonic propulsion at 10 min (+120% and 150%, respectively) but at 60 min the effect was significant only for MEN 10627 (+84%). SR 48968 (1 micromol kg(-1), i.v.) did not significantly enhance the colonic propulsion. None of these tachykinin NK2 receptor antagonists modified the amplitude of colonic contractions. In contrast, both atropine (6 micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)) and hexamethonium (55 micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished propulsion (81% and 87% inhibition, respectively) and decreased the amplitude of contractions (68% inhibition for either treatment). 3. In atropine-treated animals (6 micromol kg(-1), i.v., plus infusion of 1.8 micromol h(-1)), apamin (30 nmol kg(-1), i.v.) restored colonic propulsion (+416%) and increased the amplitude of contractions (+367% as compared to atropine alone). Hexamethonium (55 micromol kg(-1), i.v., plus infusion of 17 micromol h(-1)) abolished the apamin-induced, atropine-resistant colonic propulsion (97% inhibition) and reduced the amplitude of the atropine-resistant contractions (52% inhibition). 4. The apamin-induced, atropine-resistant colonic propulsion was inhibited by SR 140333 (-69% at 1 micromol kg(-1)), SR 48968 (-78% at 1 micromol kg(-1)), MEN 11420 (-59% at 1 micromol kg(-1)) and MEN 10627 (-50% at 1 micromol kg(-1)), although the latter effect was not statistically significant. The combined administration of SR 140,333 and MEN 10,627 (1 micromol kg(-1) for each antagonist) almost completely abolished colonic propulsion (90% inhibition). The amplitude of colonic contractions was also reduced by SR 140333 (-42%), SR 48968 (-29%), MEN 11420 (-45%) but not by MEN 10627 (-16%). The combined administration of SR 140333 and MEN 10,627 reduced the amplitude of contractions by 47%. SR 140603 (1 micromol kg(-1), i.v.), the less potent enantiomer of SR 140333, was inactive. 5. In control animals, apamin (30 nmol kg(-1), i.v.) enhanced colonic propulsion (+84%) and increased the amplitude of contractions (+68%), as compared to the vehicle. Hexamethonium (55 micromol kg(-1), i.v. plus infusion of 17 micromol h(-1)) inhibited propulsion (86% inhibition) and decreased the amplitude of contractions (49% inhibition). SR 140333, SR 48968, MEN 11420, MEN 10627, or the coadministration of SR 140333 and MEN 10627 had no effect. 6. In a separate series of experiments, the mean amplitude of colonic contractions was also recorded under isovolumetric conditions through the balloon-catheter device kept in place at 75 mm from the anal sphincter (static model). In control conditions, neither SR 140333 nor MEN 11420 modified the amplitude of contractions. In atropine-pretreated guinea-pigs, SR 140333 and MEN 11420 (0.1-1 micromol kg(-1)) dose-dependently decreased the amplitude of contractions. In apamin- and atropine-pretreated animals, only the highest (1 micromol kg(-1)) dose of SR 140333 or MEN 11420 significantly decreased the amplitude of contractions. The inhibitory potency of atropine (0.3-1 micromol kg(-1)) was similar in apamin-pretreated animals and in controls. 7. It was concluded that, in anaesthetized guinea-pigs, endogenous tachykinins, acting through both NK(1) and NK(2) receptors, act as non-cholinergic excitatory neurotransmitters in promoting an apamin-evoked reflex propulsive activity of the distal colon.

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.

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

PubMed

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

2013-04-01

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

Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall

PubMed Central

Young, Kymberly; Drevets, Wayne C.; Schulkin, Jay; Erickson, Kristine

2011-01-01

The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n=66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n=33) or high-dose (0.45 mg/kg IV; n=33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = 0.04), increased the percent of categorical (nonspecific) memories recalled, and slowed response times for categorical memories (p <0.001), compared to placebo performance (p < 0.001). Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories. PMID:21942435

Measurement of net whole-body transcapillary fluid transport and effective vascular compliance in humans

NASA Technical Reports Server (NTRS)

Watenpaugh, D. E.; Gaffney, F. A.; Schneider, S. M. (Principal Investigator)

1998-01-01

BACKGROUND: Net whole-body transcapillary fluid transport (TFT) between the circulation and the interstitial (extravascular) space may be calculated as: IV - deltaPV - UV - IL, where IV=infused or ingested volume (when applicable), deltaPV = change in plasma volume, UV=urine volume, and IL=insensible loss. RESULTS: Infusion of 30 mL/kg isotonic saline over 25 minutes increased supine TFT from a basal capillary reabsorption of -106+/-24 mL/h (mean+/-SE) to a net filtration of 1,229+/-124 mL/h. One hour after infusion, reabsorption of -236+/-102 mL/h was seen, and control reabsorption levels returned by 3 hours. Four hours of 30 mm Hg lower body negative pressure (LBNP) elicited no net TFT, probably because of upper body reabsorptive compensation for lower body capillary filtration. When ingestion of 1 L of isotonic saline accompanied LBNP, filtration of 145+/-10 mL/h occurred. Reabsorption of extravascular fluid into the circulation always followed LBNP. CONCLUSION: Application of this technique could aid understanding of physiologic conditions, experimental interventions, disease states, and therapies that cause or are influenced by fluid shifts between intravascular and interstitial compartments.

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

Cardiac T1 mapping in congenital heart disease: bolus vs. infusion protocols for measurements of myocardial extracellular volume fraction.

PubMed

Al-Wakeel-Marquard, Nadya; Rastin, Sanaz; Muench, Frédéric; O H-Ici, Darach; Yilmaz, Sevim; Berger, Felix; Kuehne, Titus; Messroghli, Daniel R

2017-12-01

Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD). Healthy controls (n = 17; median age 24.0 years) and patients with CHD (n = 19; 25.0 years) were prospectively enrolled. Using modified Look-Locker inversion recovery T1 mapping before, 15 min after bolus injection, and during constant infusion of gadolinium-DOTA, T1 values were obtained for blood pool and myocardium of the left ventricle (LV), the interventricular septum (IVS), and the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation. ECV of LV, IVS and RV by bolus-only and bolus-infusion correlated significantly in CHD patients (r = 0.94, 0.95, and 0.74; p < 0.01, respectively) and healthy controls (r = 0.96, 0.89, and 0.64; p < 0.05, respectively). Bland-Altman plots revealed no significant bias between the techniques for any of the analyzed regions. ECV of LV and RV myocardium measured by bolus-only T1 mapping agrees well with bolus-infusion measurements in patients with CHD. The use of a bolus-only approach facilitates the integration of ECV measurements into existing CMR imaging protocols, allowing for assessment of diffuse myocardial fibrosis in CHD in clinical routine.

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

PubMed

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

1992-03-15

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

Influence of detomidine and xylazine on spleen dimensions and on splenic response to epinephrine infusion in healthy adult horses.

PubMed

Deniau, Valérie; Depecker, Marianne; Bizon-Mercier, Céline; Couroucé-Malblanc, Anne

2013-07-01

To compare the changes in splenic length and thickness and in packed cell volume (PCV) following detomidine or xylazine administration and subsequent epinephrine infusion. Spleen relaxation occurs following xylazine or detomidine administration and interferes with subsequent splenic contractile response to epinephrine. Randomized non-blinded crossover experimental study. 6 healthy adult mares. The mares received an intravenous (IV) epinephrine infusion (1 μg kg(-1 ) minute(-1) over 5 minutes) one hour after IV administration of detomidine (0.01 mg kg(-1) ), xylazine (0.5 mg kg(-1) ) or no drug (control), with a withdrawal period of at least 7 days between experiments. The splenic length measured in two different axes, the splenic thickness, and the PCV were measured prior to sedation (T0), 30 minutes later, and at 5-minute intervals from the start of the epinephrine infusion (T1) until T1 + 40 minutes. Changes from base-line and between treatments were compared using a two-way anova for repeated measures. Significance was set at p < 0.05. Splenic length was significantly increased and PCV was significantly decreased after detomidine administration compared to baseline. Epinephrine infusion resulted in a significant decrease in splenic length and thickness, and a significant increase in PCV, irrespective of prior treatment with detomidine or xylazine. Detomidine administration was followed by a sonographically detectable increase of splenic length. Neither detomidine nor xylazine interfered with the ability of the spleen to contract following subsequent administration of an epinephrine infusion given one hour later. Previous sedation with alpha-2 agonists does not preclude the efficiency of epinephrine as a medical treatment of left dorsal displacement of the large colon, but further investigations are required with other drug doses and different time intervals between administrations. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Intravenous Dexmedetomidine Infusion Compared with that of Fentanyl in Patients Undergoing Arthroscopic Shoulder Surgery under General Anesthesia.

PubMed

Abdel Hamid, Mona Hossam Eldin

2017-01-01

Anesthesia for arthroscopic shoulder surgery is challenging due to the need for oligaemic surgical field as well as a good postoperative recovery profile. The present study was prospective, randomized to evaluate the efficacy of dexmdetomidine infusion compared to that of fentanyl in patients undergoing arthroscopic shoulder surgery under general anesthesia. A total of 60 patients aged from thirty to fifty years, American Society of Anesthesiologists Class I/II of either sex for arthroscopic shoulder surgery, were included. The patients were divided into two groups of 30 patients each. Group I received dexmedetomidine loading 1 μg/kg over 10 min followed by maintenance 0.5 μg/kg/h and Group II Fentanyl loading 1 μg/kg followed by maintenance 0.5 μg/kg/h. Hemodynamic readings (Heart rate HR, and mean arterial blood pressure MAP) were recorded after the start of the study drug infusion (T1), after intubation (T2), then every 15 minutes till the end of surgery (T15, T30, T45, T60, T75, T90). In the PACU, MAP, and HR were recorded on arrival, after 30 min, 1 hr, and 2 hrs (R0, R30, R1 hr, R2 hr) Postoperative analgesia was assessed by visual analogue scale (VAS), Modified Observers's Assessment of Alertness and Sedation OAA/S was recorded on arrival to PACU. This study showed that in the dexmedatomidine group there was statistically significant decrease of MAP and HR after drug infusion up to two hours in the recovery period, more sedation, better control of pain and surgeon satisfaction. Iv infusion of dexamedatomidine may be an attractive option during arthroscopic shoulder surgery as it provided a better hypotensive anesthesia by lowering MAP and HR which leads to better surgical field and surgeon satisfaction than iv infusion fentanyl along with a better postoperative VAS.

Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series.

PubMed

Lauritsen, Clinton; Mazuera, Santiago; Lipton, Richard B; Ashina, Sait

2016-12-01

Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting. Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion. The study sample had a median age of 36.5 years (range 29-54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12-0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects. IV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine.

An estimate of the cost of administering intravenous biological agents in Spanish day hospitals

PubMed Central

Nolla, Joan Miquel; Martín, Esperanza; Llamas, Pilar; Manero, Javier; Rodríguez de la Serna, Arturo; Fernández-Miera, Manuel Francisco; Rodríguez, Mercedes; López, José Manuel; Ivanova, Alexandra; Aragón, Belén

2017-01-01

Objective To estimate the unit costs of administering intravenous (IV) biological agents in day hospitals (DHs) in the Spanish National Health System. Patients and methods Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48), rituximab (n=38), abatacept (n=41), or tocilizumab (n=61). The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1) structural costs, 2) material costs, and 3) staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM). In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM). All costs were expressed in euros for the reference year 2014. Results The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM) and €29.70 per infusion (SD ±11.42; PIM). The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated between €3.48 and €20.34 per patient and DH. In terms of the care process, the average difference between the shortest and the longest time taken by different hospitals to administer an IV biological therapy was 113 minutes. Conclusion The average total cost of infusion was less than that normally used in models of economic evaluation coming from secondary sources. This cost is even less when the staff costs are imputed according to the PIM. A high degree of variability was observed between different DHs in the cost of the consumables, in the structure-related costs, and in those of the care process. PMID:28356746

Drug-indiced aseptic meningitis: development of subacute sclerosing panencephalitis following repeated intraventricular infusion therapy with interferon alpha/beta.

PubMed

Imataka, George; Nakagawa, Eiji; Yamanouchi, Hideo; Arisaka, Osamu

2011-12-01

Interferon (IFN)-α was reported to be effective in longterm intrathecal treatment of subacute sclerosing panencephalitis (SSPE). However, the side effects related with longterm use of IFN-α/β are unclear. We evaluated the therapeutic effects of IFN-α/β in a 13-years-old patient with SSPE. The cerebrospinal fluid (CSF) measles antibody titer was 64 × NT/128×HI, IgG-index was 4.5, and the SSPE diagnosis was based on electroencephalography (Jabbour-stage II on admission). With Inosiplex (INP) given orally, IFN-α (3 × 10(6) units) was infused intraventricularly twice-a-week for 1-year. Resultantly, CSF cell count was elevated (2502/3), total protein and glucose levels were normal; however, DIAM occurred repeatedly. Consequently, reduced IFN-α (5 × 10(5) units) with hydrocorton was administered at 2-months interval for 19 months, during which, DIAM occurred four times. Therefore, IFN-β (3 × 10(6) units; twice-a-week) therapy was started and continued for 3 years. Although the symptoms were improved considerably, DIAM recurred after 15-months therapy and CSF cell counts were also elevated (2121/3). Since SSPE progressed to Jabbour-stage IV, indicated by irreversible consciousness disorder, IFN therapy was discontinued and INP monotherapy was followed for another 3 years. We, therefore, concluded that the longterm intraventricular IFN-α/β infusion therapy of SSPE involved the potential risk of DIAM with serious irreversible neurological sequelae and should be monitored carefully.

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

PubMed

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

1993-08-01

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

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

PubMed

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

2018-05-22

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

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.

Predictive value of lidocaine for treatment success of oxcarbazepine in patients with neuropathic pain syndrome.

PubMed

Schipper, Sivan; Gantenbein, Andreas R; Maurer, Konrad; Alon, Eli; Sándor, Peter S

2013-06-01

Pharmacotherapy in patients with neuropathic pain syndromes (NPS) can be associated with long periods of trial and error before reaching satisfactory analgesia. The aim of this study was to investigate whether a short intravenous (i.v.) infusion of lidocaine may have a predictive value for the efficacy of oxcarbazepine. In total, 16 consecutive patients with NPS were studied in a prospective, uncontrolled, open-label study design. Each patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term oral oxcarbazepine treatment (900-1,500 mg/day). During an observation period of 28 days, treatment response was documented by a questionnaire including the average daily pain score documented on a numeric rating scale (NRS). A total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine treatment due to side effects. In an interim analysis predictive value of the lidocaine infusion was low with a Kendall's tau correlation coefficient of 0.29 and coefficient of determination R(2) of 0.119 (95% confidence interval -0.29 to 0.72). As a consequence of this low correlation, the study was discontinued for ethical reasons. In conclusion, lidocaine infusion has a low predictive value for effectiveness of oxcarbazepine-if at all.

Rapid Resolution of Grief with IV Infusion of Ketamine: A Unique Phenomenological Experience

PubMed Central

Gowda, Mahesh Ramanna; Srinivasa, Preethi; Kumbar, Prabha S.; Ramalingaiah, Vinay Hosagavi; Muthyalappa, Chandrashekar; Durgoji, Sumit

2016-01-01

Ketamine, a primarily FDA-approved anaesthetic agent is also used as recreational drug. Based on preclinical findings and later the clinical observations it is noted to have rapid antidepressant effect due to its mechanisms related to NMDA antagonism. In spite of established evidence of ketamine being effective in depression with significant role in treatment resistant cases as well, there was absolute dearth of literature regarding its utility in grief-related disorders. In this context we present a case of 28-year-old graduate male who presented to us in complicated grief following death of his wife due to obstetric complications. With the patient and immediate family members consenting for use of ketamine as off-label use, patient had single IV infusion of ketamine following which he had unique phenomenological experience ultimately resolving his grief in few minutes. Through this case we highlight the enormous therapeutic promise of ketamine in complicated grief. PMID:27011405

Dipeptidyl peptidase IV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes.

PubMed

Wiedeman, Paul E; Trevillyan, James M

2003-04-01

Glucagon-like peptide-1 (GLP-1 (7-36) amide) is a gut hormone released from L-cells in the small intestine in response to the ingestion of nutrients and enhances the glucose-dependent secretion of insulin from pancreatic beta-cells. In type 2 diabetic patients, the continuous infusion of GLP-1 (7-36) amide decreases plasma glucose and hemoglobin A1c concentrations and improves beta-cell function. Hormone action is rapidly terminated by the N-terminal cleavage of GLP-1 at Ala2 by the aminopeptidase, dipeptidyl peptidase IV (DPPIV). The short in vivo half-life of GLP-1 (< 3 min) poses challenges to the development of exogenous GLP-1-based therapy. The inhibition of endogenous GLP-1 degradation by reducing DPPIV activity is an alternative strategy for improving the incretin action of GLP-1 in vivo. This review summarizes recent advances in the design of potent and selective small molecule inhibitors of DPPIV and the potential challenges to the development of DPPIV inhibitors for the treatment of impaired glucose tolerance and type 2 diabetes.

A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.

PubMed

Spandorfer, Philip R; Mace, Sharon E; Okada, Pamela J; Simon, Harold K; Allen, Coburn H; Spiro, David M; Friend, Keith; Harb, George; Lebel, Francois

2012-11-01

Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children. This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration. The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire. 148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P < 0.0001). All IV failures occurred in patients aged <3 years; rHFSC rescue was successful in all patients in whom it was attempted. Both treatments were well tolerated. Clinicians rated fluid administration as easy to perform in 94.5% (69 of 73) of the rHFSC group versus 65.3% (49 of 75) of the IV group (P < 0.001). Parents/caregivers were satisfied or very satisfied with fluid administration in 94.5% (69 of 73) of rHFSC-treated patients and 73.3% (55 of 75) of IV-treated patients. In mild to moderately dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration. Additional benefits of rHFSC included time and success of line placement, ease of use, and satisfaction. SC hydration facilitated with recombinant human hyaluronidase represents a reasonable addition to the treatment options for children who have mild to moderate dehydration, especially those with difficult IV access. ClinicalTrials.gov identifier: NCT00773175. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

The effects of sub-anesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine dependent research volunteers

PubMed Central

Dakwar, Elias; Levin, Frances; Foltin, Richard W.; Nunes, Edward V.; Hart, Carl L.

2014-01-01

Background Cocaine dependence involves problematic neuroadaptations that may be responsive to modulation of glutamatergic circuits. This investigation examined the effects of sub-anesthetic ketamine infusions on motivation for quitting cocaine and on cue-induced craving in cocaine dependent participants, 24 hours post-infusion. Methods Eight volunteers with active DSM-IV cocaine dependence not seeking treatment or abstinence were entered into this crossover, double-blind trial. Three 52 minute intravenous infusions were administered: ketamine (0.41 mg/kg or 0.71 mg/kg) or lorazepam 2 mg, counterbalanced into three orderings in which ketamine 0.41 mg/kg always preceded the 0.71 mg/kg dose. Infusions were separated by 48 hours, and assessments occurred at baseline and at 24 hours post-infusion. Outcomes were change between post-infusion and pre-infusion values for 1) motivation to quit cocaine scores using the University of Rhode Island Change Assessment (URICA), and 2) sums of visual analogue scale (VAS) craving ratings administered during cue exposure. Results Compared to the active control lorazepam, a single ketamine infusion (0.41 mg/kg) led to a mean 3.9 points gain in URICA (p=0.012), which corresponds to an approximately 60% increase over preceding values. There was a reduction of comparable magnitude in cue-induced craving (p=0.012). A subsequent ketamine infusion (0.71 mg/kg) led to further reductions in cue-induced craving compared to the control. Infusions were well tolerated. Conclusions Sub-anesthetic ketamine demonstrated promising effects on motivation to quit cocaine and on cue-induced craving, 24 hours post-infusion. Research is needed to expand on these preliminary results, and to evaluate the efficacy of this intervention in clinical settings. PMID:24035344

Drug‐specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions

PubMed Central

Hvas, Christian L.; Dahlerup, Jens F.

2017-01-01

Aims Intravenous (IV) iron infusions have been associated with hypophosphataemia (HP) and hypersensitivity reactions (HSRs). No studies have compared the side effects of ferric carboxymaltose (FCM) with those of isomaltoside 1000 (ISM). This study aimed to describe the occurrence of HP and HSRs following the administration of either FCM or ISM. Methods Data on 231 outpatients treated with IV iron infusions, between November 2011 and April 2014, were collected. During that period, the department made a switch from FCM to ISM and then back to FCM. Of the 231 patients, 39 received both FCM and ISM during the period. The prevalences of HP and HSRs were compared between the two drugs. Results We found more HP events when FCM was given (64 vs. 9; P < 0.01). In contrast, more patients had mild HSRs when ISM was given (2.5% vs. 10.7%; P < 0.01). A comparison of the two drugs in the subpopulation who received both drug types (n = 39) revealed a difference in phosphate decrease (P < 0.01), with the most marked decrease occurring with FCM. Nine patients who had HSRs were exposed to both drugs. No potential HSR crossover between the two drugs was found. Conclusion We found a higher risk of HP with FCM administration when compared to ISM administration. Conversely, we found a higher risk of mild HSRs with ISM administration when compared to FCM administration. The impacts of the two types of side effects should be considered when choosing an IV iron drug. PMID:27859495

Drug-specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions.

PubMed

Bager, Palle; Hvas, Christian L; Dahlerup, Jens F

2017-05-01

Intravenous (IV) iron infusions have been associated with hypophosphataemia (HP) and hypersensitivity reactions (HSRs). No studies have compared the side effects of ferric carboxymaltose (FCM) with those of isomaltoside 1000 (ISM). This study aimed to describe the occurrence of HP and HSRs following the administration of either FCM or ISM. Data on 231 outpatients treated with IV iron infusions, between November 2011 and April 2014, were collected. During that period, the department made a switch from FCM to ISM and then back to FCM. Of the 231 patients, 39 received both FCM and ISM during the period. The prevalences of HP and HSRs were compared between the two drugs. We found more HP events when FCM was given (64 vs. 9; P < 0.01). In contrast, more patients had mild HSRs when ISM was given (2.5% vs. 10.7%; P < 0.01). A comparison of the two drugs in the subpopulation who received both drug types (n = 39) revealed a difference in phosphate decrease (P < 0.01), with the most marked decrease occurring with FCM. Nine patients who had HSRs were exposed to both drugs. No potential HSR crossover between the two drugs was found. We found a higher risk of HP with FCM administration when compared to ISM administration. Conversely, we found a higher risk of mild HSRs with ISM administration when compared to FCM administration. The impacts of the two types of side effects should be considered when choosing an IV iron drug. © 2016 The British Pharmacological Society.

Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation.

PubMed

Nielsen, Torben K; Højgaard, Martin; Andersen, Jon T; Poulsen, Henrik E; Lykkesfeldt, Jens; Mikines, Kári J

2015-04-01

Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. ± 0.40), volume of distribution 0.19 L/kg (S.D. ±0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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.

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.

Introducing iron isomaltoside 1000 (Monofer®)-development rationale and clinical experience.

PubMed

Kalra, Philip A

2011-06-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anaemia necessitating treatment with intravenous (IV) iron. Several studies demonstrate that oral iron is insufficient in these patients and that IV supplementation is a more effective treatment. Until now, use of available parenteral iron preparations has been limited by dosing schedules and the need, in some cases, for a test dose, and despite the availability of a range of different IV iron compounds, there is still a need for improved compounds. The new IV iron, iron isomaltoside 1000 Monofer®, is composed of iron and chemically modified isomalto-oligosaccharides which have a mean molecular weight of 1000 Da and consist predominantly of 3-5 glucose units. In contrast to dextrans, the carbohydrate isomaltoside 1000 is a linear and unbranched structure with theoretically a low immunological potential. Hence, a test dose is not necessary. Iron isomaltoside 1000 contains strongly bound iron within the iron-isomaltoside formulation, which enables a controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity. This allows flexible dosing including high and rapid dosing securing convenient iron therapy for a wide range of patients. The development of Monofer® has been enthusiastically acknowledged by clinicians, and in 2009, there has been fast approval by European authorities via a decentralized registration procedure. This new IV iron is currently being marketed in several European countries. This article describes the development rationale and summarizes the clinical data assessing the use of iron isomaltoside 1000 administered without a test dose by either repeated bolus injections or fast high single iron infusions [defined as total dose infusion (TDI)] to patients suffering from CKD. Since CKD is associated with a high prevalence of cardiovascular disease, data from a small trial applying high single doses of iron isomatoside 1000 in patients with chronic heart failure (CHF) are also reviewed. Collectively, the available data demonstrate adequate efficacy and a good safety profile of iron isomaltoside 1000 in CKD and CHF patients even when administered without a test dose and as single rapid high-dose infusions.

Connecting Research and Practice: An Experience Report on Research Infusion with SAVE

NASA Technical Reports Server (NTRS)

Lindvall, Mikael; Stratton, William C.; Sibol, Deane E.; Ackermann, Christopher; Reid, W. Mark; Ganesan, Dharmalingam; McComas, David; Bartholomew, Maureen; Godfrey, Sally

2009-01-01

NASA systems need to be highly dependable to avoid catastrophic mission failures. This calls for rigorous engineering processes including meticulous validation and verification. However, NASA systems are often highly distributed and overwhelmingly complex, making the software portion of these systems challenging to understand, maintain, change, reuse, and test. NASA's systems are long-lived and the software maintenance process typically constitutes 60-80% of the total cost of the entire lifecycle. Thus, in addition to the technical challenges of ensuring high life-time quality of NASA's systems, the post-development phase also presents a significant financial burden. Some of NASA's software-related challenges could potentially be addressed by some of the many powerful technologies that are being developed in software research laboratories. Many of these research technologies seek to facilitate maintenance and evolution by for example architecting, designing and modeling for quality, flexibility, and reuse. Other technologies attempt to detect and remove defects and other quality issues by various forms of automated defect detection, architecture analysis, and various forms of sophisticated simulation and testing. However promising, most such research technologies nevertheless do not make the transition from the research lab to the software lab. One reason the transition from research to practice seldom occurs is that research infusion and technology transfer is difficult. For example, factors related to the technology are sometimes overshadowed by other types of factors such as reluctance to change and therefore prohibits the technology from sticking. Successful infusion might also take very long time. One famous study showed that the discrepancy between the conception of the idea and its practical use was 18 years plus or minus three. Nevertheless, infusing new technology is possible. We have found that it takes special circumstances for such research infusion to succeed: 1) there must be evidence that the technology works in the practitioner's particular domain, 2) there must be a potential for great improvements and enhanced competitive edge for the practitioner, 3) the practitioner has to have strong individual curiosity and continuous interest in trying out new technologies, 4) the practitioner has to have support on multiple levels (i.e. from the researchers, from management, from sponsors etc), and 5) to remain infused, the new technology has to be integrated into the practitioner's processes so that it becomes a natural part of the daily work. NASA IV&V's Research Infusion initiative sponsored by NASA's Office of Safety & Mission Assurance (OSMA) through the Software Assurance Research Program (SARP), strives to overcome some of the problems related to research infusion.

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

PubMed

Kajiura, Akira; Nagata, Osamu; Sanui, Masamitsu

2018-04-27

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

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

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

Lubienski, Andreas; Duex, Markus; Lubienski, Katrin

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

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

PubMed Central

2014-01-01

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

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

PubMed

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy published by Wiley Periodicals, Inc. on behalf of Pharmacotherapy Publications, Inc.

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.

Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route.

PubMed

Chou, Ting-Chao; Dong, Huajin; Zhang, Xiuguo; Tong, William P; Danishefsky, Samuel J

2005-10-15

Epothilones, 16-membered macrolides isolated from a myxobacterium in soil, exert their antitumor effect, like Taxol, by induction of microtubule polymerization and microtubule stabilization. They are effective against tumor cells that are resistant to Taxol or vinblastine. We recently designed, via molecular editing and total synthesis, a new class of epothilones represented by 26-trifluoro-(E)-9,10-dehydro-12,13-desoxy-epothilone B (Fludelone), which has emerged as a lead candidate for clinical development. Treatment of nude mice bearing MX-1 human mammary carcinoma xenografts (as large as 3.4% body weight) with Fludelone (6-hour i.v. infusion, 25 mg/kg, q3d x 5, q3d x 4) led to complete disappearance and de facto "cure" (i.e., remission without a relapse for over 15% of the average life span of 2 years). The toxicities induced by bolus i.v. injection could be avoided through prolonged i.v. infusion, which allowed for a 10-fold increase in maximal tolerated dose. Complete remission of MX-1 xenografts was achieved with only one third of this maximal tolerated dose. Parallel studies with Taxol and Fludelone [20 mg/kg, 6-hour i.v. infusion (q2d x 4) x3] against HCT-116 human colon carcinoma xenografts revealed that both drugs achieved tumor remission; however, all Taxol-treated mice relapsed in approximately 1.3 months, whereas the Fludelone-treated mice were cured without any relapse for over 7 months. Furthermore, tumor remission was achieved by Fludelone against SK-OV-3 (ovary), PC-3 (prostate), and the Taxol-resistant CCRF-CEM/Taxol (leukemia) xenograft tumors. Most remarkably, p.o. administration of Fludelone (30 mg/kg, q2d x 7, q2d x 9, q2d x 5) against MX-1 xenografts achieved a nonrelapsing cure for as long as 8.4 months. The above results indicate that Fludelone is a highly promising compound for cancer chemotherapeutics.

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

PubMed

Vullo, Cecilia; Carluccio, Augusto; Robbe, Domenico; Meligrana, Marina; Petrucci, Linda; Catone, Giuseppe

2017-10-11

In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO 2 ) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction.

PubMed

Palazzuoli, Alberto; Pellegrini, Marco; Franci, Beatrice; Beltrami, Matteo; Ruocco, Gaetano; Gonnelli, Stefano; Angelini, Gianni D; Nuti, Ranuccio

2015-02-01

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR (p = 0.01), creatinine (p = 0.02) and BNP levels (p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period (p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administration.

Mechanisms of Selective Induction of Gastric Mucosal Eicosanoids in Response to Potentially Noxious Stimuli

DTIC Science & Technology

1991-04-30

the proposed source of leukotrienes. Lidocaine (2.2 mg/kg iv bolus followed by 66 /ig/kg/min iv Infusion) was used to inhibit sensory afferents... Lidocaine significantly inhibited LTC4 generation following acid or bile, but had no effect on PGE2 synthesis after bile. Thus, the release of LTĈ...viil Effect of Inhibition of Sensory Afferent Nerves by Lidocaine on Gastric Emptying and Mucosal Eicosanoid Generation After Exposure of the

Inadvertent venous air embolism during cesarean section: collapsible intravenous fluid bags without self-sealing outlet have risks. Case report.

PubMed

Bakan, Mefkur; Topuz, Ufuk; Esen, Asim; Basaranoglu, Gokcen; Ozturk, Erdogan

2013-01-01

The anesthesiologist must be aware of the causes, diagnosis and treatment of venous air embolism and adopt the practice patterns to prevent its occurrence. Although venous air embolism is a known complication of cesarean section, we describe an unusual inattention that causes iatrogenic near fatal venous air embolism during a cesarean section under spinal anesthesia. One of the reasons for using self-collapsible intravenous (IV) infusion bags instead of conventional glass or plastic bottles is to take precaution against air embolism. We also demonstrated the risk of air embolism for two kinds of plastic collapsible intravenous fluid bags: polyvinyl chloride (PVC) and polypropylene-based. Fluid bags without self-sealing outlets pose a risk for air embolism if the closed system is broken down, while the flexibility of the bag limits the amount of air entry. PVC-based bags, which have more flexibility, have significantly less risk of air entry when IV administration set is disconnected from the outlet. Using a pressure bag for rapid infusion can be dangerous without checking and emptying all air from the IV bag. 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Inadvertent venous air embolism during cesarean section: Collapsible intravenous fluid bags without self-sealing outlet have risks. Case report.

PubMed

Bakan, Mefkur; Topuz, Ufuk; Esen, Asim; Basaranoglu, Gokcen; Ozturk, Erdogan

2013-01-01

The anesthesiologist must be aware of the causes, diagnosis and treatment of venous air embolism and adopt the practice patterns to prevent its occurrence. Although venous air embolism is a known complication of cesarean section, we describe an unusual inattention that causes iatrogenic near fatal venous air embolism during a cesarean section under spinal anesthesia. One of the reasons for using self-collapsible intravenous (IV) infusion bags instead of conventional glass or plastic bottles is to take precaution against air embolism. We also demonstrated the risk of air embolism for two kinds of plastic collapsible intravenous fluid bags: polyvinyl chloride (PVC) and polypropylene-based. Fluid bags without self-sealing outlets pose a risk for air embolism if the closed system is broken down, while the flexibility of the bag limits the amount of air entry. PVC-based bags, which have more flexibility, have significantly less risk of air entry when IV administration set is disconnected from the outlet. Using a pressure bag for rapid infusion can be dangerous without checking and emptying all air from the IV bag. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

A case of severe Pembrolizumab-induced neutropenia.

PubMed

Ariane, Barbacki; Maliha, Peter G; Hudson, Marie; Small, David

2018-06-08

Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.

A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

PubMed

Loubani, Osama M; Green, Robert S

2015-06-01

The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs. Copyright © 2015 Elsevier Inc. All rights reserved.

Carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery.

PubMed

El Behery, Manal M; El Sayed, Gamal Abbas; El Hameed, Azza A Abd; Soliman, Badeea S; Abdelsalam, Walid A; Bahaa, Abeer

2016-01-01

To assess and compare the effectiveness and safety of single IV polus dose of carbetocin, versus IV oxytocin infusion in the prevention of PPH in obese nulliparous women undergoing emergency Cesarean Delivery. A double-blinded randomized-controlled trial was conducted on 180 pregnant women with BMI >30. Women were randomized to receive either oxytocin or carbetocin during C.S. The primary outcome measure was major primary PPH >1000 ml within 24 h of delivery as per the definition of PPH by the World Health Organization Secondary outcome measures were hemoglobin and hematocrit changes pre- and post-delivery, use of further ecobolics, uterine tone 2 and 12-h postpartum and adverse effects. A significant difference in the amount of estimated blood loss or the incidence of primary postpartum haemorrhage (>1000 ml) in both groups. Haemoglobin levels before and 24-h postpartum was similar. None from the carbetocin group versus 71.5% in oxytocin group needed additional utrotonics (p < 0.01). The uterine contractility was better in the carbetocin group at 2, and 12-h postpartum (p < 0.05). A single 100-µg IV carbetocin is more effective than IV oxytocin infusion for maintaining adequate uterine tone and preventing postpartum bleeding in obese nulliparous women undergoing emergency cesarean delivery, both has similar safety profile and minor hemodynamic effect.

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.

Contribution of propionate to glucose synthesis in sheep

PubMed Central

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

1967-01-01

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

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

PubMed

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

2015-01-01

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

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.

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.

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.

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

PubMed

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

1998-09-01

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

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.

Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

PubMed

Moran-Muñoz, Rafael; Valverde, Alexander; Ibancovichi, J A; Acevedo-Arcique, Carlos M; Recillas-Morales, Sergio; Sanchez-Aparicio, Pedro; Osorio-Avalos, Jorge; Chavez-Monteagudo, Julio Raul

2017-07-01

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 μg/kg BW per min] at 1.4% end-tidal of sevoflurane (FE SEV ); T2-Dexmedetomidine (loading dose 2 μg/kg BW, IV, and CRI of 2 μg/kg BW per hour) and FE SEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FE SEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant ( P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant ( P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Effects of lorcaserin (Belviq®) on nicotine- and food-maintained responding in non-human primates.

PubMed

Jacobs, David S; Barkin, Claire E; Kohut, Michelle R; Bergman, Jack; Kohut, Stephen J

2017-12-01

Accumulating evidence suggests that the FDA-approved serotonin 5-HT 2C receptor agonist, lorcaserin (Belviq ® ), may be a promising candidate for the management of substance use disorders, including nicotine addiction. The present study was conducted to determine the efficacy and selectivity of acute or continuous lorcaserin treatment for decreasing the reinforcing effects of nicotine in a primate species. Adult rhesus monkeys (n=4) with a history of nicotine self-administration (>2years) responded for injections of nicotine (0.32-100μg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement during daily 100-min sessions. When responding was stable, lorcaserin was administered either as an acute pretreatment (0.1-1.0mg/kg, IM) or by continuous infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also monitored immediately following experimental sessions. Results indicate that acute lorcaserin pretreatment produced significant and dose-dependent decreases in nicotine-maintained responding across a >100-fold range of self-administered nicotine doses. Continuous lorcaserin treatment decreased intake of 10μg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding was only moderately decreased in 3 of 4 subjects after acute administration and unaffected in all subjects during continuous treatment. Daily activity also was significantly decreased-to ≤50% of control values-following experimental sessions in which acute lorcaserin was administered. These data indicate that lorcaserin reduces IV self-administration of nicotine at a dose that decreases motoric activity but less consistently disrupts food-maintained responding. Further research into lorcaserin's potential utility for the management of nicotine dependence is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Needleless connectors substantially reduce flow of crystalloid and red blood cells during rapid infusion.

PubMed

Lehn, Robert A; Gross, Jeffrey B; McIsaac, Joseph H; Gipson, Keith E

2015-04-01

Although needleless connectors (NC) are frequently used in the perioperative setting, the potential of modern NCs to slow delivery of IV fluids has not been thoroughly studied. We examined flow characteristics of 5 NC models during pressurized delivery of crystalloid and banked red blood cells from a Level 1 warmer through various IV catheters. Crystalloid flow rates were reduced by 29% to 85% from control in catheters >18 gauge, while red blood cell flow reductions ranged from 22% to 76% in these catheters (all P < 0.0050). We suggest that practitioners consider eliminating NCs when large IV catheters are inserted for rapid fluid administration.

Pharmacokinetics of heparin and related polysaccharides

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

Boneu, B.; Dol, F.; Caranobe, C.

1989-01-01

The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activitymore » present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where /sup 125/I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses.« less

Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial

PubMed Central

Mathew, Sanjay J.; Murrough, James W.; Rot, Marije aan het; Collins, Katherine A.; Reich, David L.; Charney, Dennis S.

2013-01-01

The N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-dose intravenous (i.v.) ketamine; (2) test the efficacy of the glutamate-modulating agent riluzole in preventing post-ketamine relapse ; and (3) examine whether pretreatment with lamotrigine would attenuate ketamine’s psychotomimetic effects and enhance its antidepressant activity. Twenty-six medication-free patients received open-label i.v. ketamine (0.5 mg/kg over 40 min). Two hours prior to infusion, patients were randomized to lamotrigine (300 mg) or placebo. Seventeen patients (65%) met response criterion (≥50% reduction from baseline on the Montgomery–Asberg Depression Rating Scale) 24 h following ketamine. Lamotrigine failed to attenuate the mild, transient side-effects associated with ketamine and did not enhance its antidepressant effects. Fourteen patients (54%) met response criterion 72 h following ketamine and proceeded to participate in a 32-d, randomized, double-blind, placebo-controlled, flexible-dose continuation trial of riluzole (100–200 mg/d). The main outcome measure was time-to-relapse. An interim analysis found no significant differences in time-to-relapse between riluzole and placebo groups [log-rank χ2 = 0.17, d.f. = 1, p = 0.68], with 80% of patients relapsing on riluzole vs. 50% on placebo. The trial was thus stopped for futility. This pilot study showed that a sub-anaesthetic dose of i.v. ketamine is well-tolerated in TRD, and may have rapid and sustained antidepressant properties. Riluzole did not prevent relapse in the first month following ketamine. Further investigation of relapse prevention strategies post-ketamine is necessary. PMID:19288975

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

PubMed

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

2017-01-01

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

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. 

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

PubMed

Argyrakopoulou, Georgia; Kontrafouri, Paraskevi; Eleftheriadou, Ioanna; Kokkinos, Alexander; Arapostathi, Christina; Kyriaki, Despoina; Perrea, Despoina; Revenas, Constantinos; Katsilambros, Nicholas; Tentolouris, Nicholas

2018-06-11

The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion. © Georg Thieme Verlag KG Stuttgart · New York.

Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

PubMed

Evans, W S; Anderson, S M; Hull, L T; Azimi, P P; Bowers, C Y; Veldhuis, J D

2001-02-01

How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs. placebo to modulate basal, pulsatile, entropic, and 24-h rhythmic GH secretion driven by a continuous iv infusion of recombinant human GHRH-(1--44)-amide vs. saline in nine healthy postmenopausal women. Volunteers underwent concurrent blood sampling every 10 min for 24 h on four occasions in a prospectively randomized, single blind, within-subject cross-over design (placebo/saline, placebo/GHRH, estradiol/saline, estradiol/GHRH). Intensively sampled serum GH concentrations were quantitated by ultrasensitive chemiluminescence assay. Basal, pulsatile, entropic (feedback-sensitive), and 24-h rhythmic modes of GH secretion were appraised by deconvolution analysis, the approximate entropy (ApEn) statistic, and cosine regression, respectively. ANOVA revealed that continuous iv infusion of GHRH in the estrogen-withdrawn (control) milieu 1) amplified individual basal (P = 0.00011) and pulsatile (P < 10(-13)) GH secretion rates by 12- and 11-fold, respectively; 2) augmented GH secretory burst mass and amplitude each by 10-fold (P < 10(-11)), without altering GH secretory burst frequency, duration, or half-life; 3) increased the disorderliness (ApEn) of GH release patterns (P = 0.0000002); 4) elevated the mesor (cosine mean) and amplitude of the 24-h rhythm in serum GH concentrations by nearly 30-fold (both P < 10(-12)); 5) induced a phase advance in the clocktime of the GH zenith (P = 0.021); and 6) evoked a new 24-h rhythm in GH secretory burst mass with a maximum at 0018 h GH (P < 10(-3)), while damping the mesor of the 24-h rhythm in GH interpulse intervals (P < 0.025). Estradiol supplementation alone 1) increased the 24-h mean and integrated serum GH concentration (P = 0.047); 2) augmented GH secretory burst mass (P: = 0.025) without influencing pulse frequency, duration, half-life, or basal secretion; 2) stimulated more irregular patterns of GH release (higher ApEn; P = 0.012); and 3) elevated the 24-h rhythmic GH mesor (P = 0.0005), but not amplitude. Notably, combined stimulation of the GH axis with GHRH-(1--44)-amide and estradiol exerted no further effect beyond that evoked by GHRH alone, except for normalizing the acrophase of 24-h GH rhythmic release and elevating the postinfusion plasma insulin-like growth factor I concentration (P = 0.016). Unexpectedly, the two GHRH-infused serum GH concentration profiles monitored after placebo and estradiol pretreatment showed strongly nonrandom synchrony with a 20- to 30-min lag (P < 0.001). In summary, the present clinical investigations unmask a 3-fold (pulsatile, entropic, and daily rhythmic) similitude between the neuroregulatory actions of estradiol and GHRH in healthy postmenopausal women. However, GHRH infusion was multifold more effectual than estradiol, and only GHRH elevated nonpulsatile (basal) GH secretion, shifted the GH acrophase, and synchronized GH profiles. Given the nonadditive nature of the joint effects of estradiol and GHRH on pulsatile and entropic GH release, we hypothesize that estrogen amplifies GH secretion in part by enhancing endogenous GHRH release or actions. In addition, the distinctive ability of GHRH (but not estradiol) to increase basal (nonpulsatile) GH secretion, shift the GH acrophase and synchronize GH output patterns identifies certain divergent hypothalamo-pituitary actions of these two major GH secretagogues.

Piracetam Attenuates LPS-Induced Neuroinflammation and Cognitive Impairment in Rats.

PubMed

Tripathi, Alok; Paliwal, Pankaj; Krishnamurthy, Sairam

2017-11-01

The present study was performed to investigate the effect of piracetam on neuroinflammation induced by lipopolysaccharide (LPS) and resulting changes in cognitive behavior. Neuroinflammation was induced by a single dose of LPS solution infused into each of the lateral cerebral ventricles in concentrations of 1 μg/μl, at a rate of 1 μl/min over a 5-min period, with a 5-min waiting period between the two infusions. Piracetam in doses of 50, 100, and 200 mg/kg i.p. was administered 30 min before LPS infusion and continued for 9 days. On ninth day, the behavioral test for memory and anxiety was done followed by blood collection and microdissection of the hippocampus (HIP) and prefrontal cortex brain regions. Piracetam attenuated the LPS-induced decrease in coping strategy to novel environment indicating anxiolytic activity. It also reversed the LPS-induced changes in the known arm and novel arm entries in the Y-maze test indicating amelioration of spatial memory impairment. Further, piracetam moderated LPS-induced decrease in the mitochondrial complex enzyme activities (I, II, IV, and V) and mitochondrial membrane potential. It ameliorated changes in hippocampal lipid peroxidation and nitrite levels including the activity of superoxide dismutase. Piracetam region specifically ameliorated LPS-induced increase in the level of IL-6 in HIP indicating anti-neuroinflammatory effect. Further, piracetam reduced HIP Aβ (1-40) and increased blood Aβ level suggesting efflux of Aβ from HIP to blood. Therefore, the present study indicates preclinical evidence for the use of piracetam in the treatment of neuroinflammatory disorders.

Intraosseous infusions: a review for the anesthesiologist with a focus on pediatric use.

PubMed

Tobias, Joseph D; Ross, Allison Kinder

2010-02-01

Intraosseous (IO) access is used most frequently for emergency care of critically ill infants and children when IV access cannot be rapidly achieved. Despite its efficacy in such situations, applications outside of the emergency room or resuscitation scenario have been limited. Furthermore, although the technique is emphasized in the teaching of those caring for critically ill infants and children in the emergency room or critical care setting, there is limited emphasis on its potential use in the perioperative setting. When peripheral venous access cannot be achieved in the operating room, alternative means of securing vascular access such as central line placement or surgical cutdown are generally successful; however, these techniques may be time consuming. Anyone providing anesthesia care for infants and children may want to become facile with the use of IO infusions for selected indications. We present the history of IO infusions, review the anatomy of the bone marrow space, discuss the potential role of IO infusions in the perioperative period, and analyze its adverse effect profile.

Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)

PubMed Central

Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael

2014-01-01

Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study

PubMed Central

Churilov, Leonid

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting. PMID:29659631

Sorption of amiodarone to polyvinyl chloride infusion bags and administration sets.

PubMed

Weir, S J; Myers, V A; Bengtson, K D; Ueda, C T

1985-12-01

The loss of amiodarone from i.v. admixtures to flexible polyvinyl chloride (PVC) infusion bags and i.v. administration sets was studied. Admixtures containing amiodarone hydrochloride 600 micrograms/mL and either 5% dextrose injection or 0.9% sodium chloride injection were stored at room temperature in glass bottles (both with and without contact of the drug solution with the rubber bottle closure), in flexible PVC bags, or in rigid PVC bottles. After 120 hours, the contents of each flexible PVC bag were emptied and replaced by methanol, which was allowed to remain in the bag for an additional 120 hours and was then analyzed for amiodarone content. To determine availability of amiodarone after infusion through a 1.8-m PVC i.v. administration set, solutions stored in glass containers were run through the set at 0.5 mL/min for 90 minutes. Samples of drug solutions were collected at appropriate intervals and analyzed by a stability-indicating high-performance liquid chromatography (HPLC) assay. Admixtures containing 0.9% sodium chloride injection were not stable; visual incompatibility was evident after 24 hours of storage in glass bottles, and no further testing was performed. In admixtures containing 5% dextrose injection that were stored in 50-mL flexible PVC bags, 60% of the initial amiodarone concentration remained after 120 hours; approximately half of the lost drug was recovered with the methanol. In effluent collected from the PVC administration set, 82% of the initial amiodarone concentration remained. Amiodarone concentrations did not decrease appreciably, after storage in glass or rigid PVC bottles, indicating that drug loss was probably affected by the plasticizer, di-2-ethylhexyl phthalate.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study.

PubMed

Chiam, Elizabeth; Bellomo, Rinaldo; Churilov, Leonid; Weinberg, Laurence

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.

[Comparison of effects on the oxidant/antioxidant system of sevoflurane, desflurane and propofol infusion during general anesthesia].

PubMed

Erbas, Mesut; Demiraran, Yavuz; Yildirim, Hayriye Ak; Sezen, Gulbin; Iskender, Abdulkadir; Karagoz, Ibrahim; Kandis, Hayati

2015-01-01

Desflurane and sevoflurane are frequently used for maintenance of anesthesia and studies have shown that these anesthetics cause a variety of changes to the oxidative stress and antioxidative defense mechanisms. This study aims to compare the effects of sevoflurane, desflurane and propofol infusion anesthesia on the oxidant and antioxidant systems of patients undergoing laparoscopic cholecystectomy. 45 patients between 18 and 50 years with planned laparoscopic cholecystectomy under general anesthetic were included in the study. Patients were divided into three groups on the way to surgery: propofol (group P, n=15), sevoflurane (group S, n=15) and desflurane (group D, n=15). All groups were given hypnotic 2mg/kg propofol IV, 1mcg/kg fentanyl IV and 0.1mg/kg vecuronium IV for induction. For maintenance of anesthesia group S were ventilated with 2% sevoflurane, group D cases were given 6% desflurane and group P were given propofol infusions of 12mg/kg/h for the first 10minutes, 9mg/kg/h for the second 10minutes and 6mg/kg/h after that. Before induction and after the operation venous blood samples were taken to evaluate the levels of glutation peroxidase, total oxidants and antioxidants. The 45 patients included in the study were 22 male and 23 female patients. The demographic characteristics of the groups were similar. In the postoperative period we observed that while sevoflurane and propofol increased antioxidants by a statistically significant level, desflurane increased the total oxidants level by a significant amount compared to levels before the operation. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

21 CFR 870.1800 - Withdrawal-infusion pump.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

PubMed

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

1971-04-01

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

Improving efficiency and value in health care. Intravenous iron management for anaemia associated with chronic kidney disease: linking treatment to an outpatient clinic, optimizing service provision and patient choice.

PubMed

Bhandari, Sunil; Naudeer, Sarah

2008-12-01

The National Service Framework advocates correction of anaemia in patients with chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV) supplementation replenishes and maintains iron stores. In Yorkshire numerous peripheral clinics exist to reduce travel for patients, but patients must travel to the main unit for IV iron therapy. Therefore an outpatient service in tandem with a routine clinic for administration of IV CosmoFer was created. To evaluate the feasibility and benefits of IV iron therapy in the outpatient clinic during active patient review for CKD patients. A cross-sectional study of patients attending for total dose IV iron (n = 57) at a peripheral clinic. Iron was administered and monitored according to protocol by one of the clinic nurses with medical staff available in the adjoining room. Haemoglobin, ferritin and renal function were recorded pre-infusion and after 4-6 months. Results are given as medians/means +/- standard error. A total of 76 IV infusions were carried out with no reported side effects or haemodynamic instability. Haemoglobin (median 10.9 vs. 11.3 g dL(-1), P = NS), creatinine and estimated glomerular filtration rate (eGFR) over the 6-month period remained stable. Serum ferritin rose significantly [80.9 +/- 6.2 vs. 186.4 +/- 18.2 g L(-1) (P < 0.001)]. Hospital time saved 380 day case bed hours, doctor hours saved 76 hours, and patient hours saved 3 hours/patient. Cost savings for TDI CosmoFer in peripheral clinic versus in centre therapy and versus sucrose, respectively, for 76 treatments was pound 5749.40 and pound 46,320.80 respectively. We have demonstrated, in a resource-limited service, the feasibility and cost-effectiveness of a management care pathway for patients with CKD, in a peripheral clinic, to receive total dose IV CosmoFer without disruption of a functioning renal clinic.

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

PubMed

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

2013-06-15

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

Effects of parenteral fish oil on plasma nonesterified fatty acids and systemic inflammatory mediators in dogs following ovariohysterectomy.

PubMed

Tsuruta, Kaoru; Backus, Robert C; DeClue, Amy E; Fritsche, Kevin L; Mann, Fred A

2017-09-01

To evaluate the effects of intravenous (IV) infusion of fish oil (FO) emulsion following ovariohysterectomy (OVH) on inflammatory mediators and plasma omega-3 nonesterified fatty acids (NEFA) concentrations in dogs. Prospective clinical study. University teaching hospital. Twenty-nine privately owned dogs undergoing routine OVH. Postoperative 3-hour IV infusion of saline (n = 9), FO (Omegaven, n = 10), or soybean oil (SO, intralipid, n = 10) emulsion and blood collected before, 5 and 24 hours following OVH for plasma NEFA and RBC membrane fatty acids (FAs) concentrations, leukocyte cytokine production capacity, and C-reactive protein (CRP) measurement. Plasma omega-3 NEFA, eicosapentaenoic acid, docosahexaenoic acid, and total long-chain omega-3 FA significantly increased shortly after FO infusion (8.8 ± 3.3 μM, 13.6 ± 5.6 μM, and 25.1 ± 9.6 μM, respectively) compared to SO (0.7 ± 0.9, 2.3 ± 1.8, and 4.2 ± 3.0 μM, respectively) and saline infusion (1.6 ± 2.5, 2.6 ± 3.1, and 5.9 ± 6.4 μM, respectively). Plasma CRP concentration significantly increased after OVH, but with no significant group differences. A weak negative correlation occurred between post-OVH CRP and postinfusion total long-chain omega-3 FA concentrations (r 2 = 0.21, P = 0.014). Stimulated leukocyte interleukin (IL) 6 production capacity increased (P = 0.001) after OVH in all groups; SO infusion resulted in reduced leukocyte IL-6 production capacity (1048.1 ± 277.7 pg/mL) compared to FO (1299.9 ± 302.1 pg/mL, P = 0.048) and saline infusions (1499.0 ± 363.1 pg/mL, P = 0.01). No significant group difference was observed in leukocyte IL-10 and tumor necrosis factor α production capacities. Postoperative administration of FO emulsion increases plasma omega-3 NEFA concentrations promptly, but does not significantly attenuate CRP production or leukocyte cytokine production capacity. FO infusion at the dosage used in the present study can be safely used in dogs, but it was not clearly beneficial in decreasing post-OVH indices of inflammation. © Veterinary Emergency and Critical Care Society 2017.

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins.

PubMed

Tebot, I; Bonnet, J-M; Paquet, C; Ayoub, J-Y; Da Silva, S M; Louzier, V; Cirio, A

2012-04-01

To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.

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

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.

PubMed

Creaven, P J; Rustum, Y M; Petrelli, N J; Meropol, N J; Raghavan, D; Rodriguez-Bigas, M; Levine, E G; Frank, C; Udvary-Nagy, S; Proefrock, A

1994-01-01

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.

Sign-tracking (autoshaping) in rats: a comparison of cocaine and food as unconditioned stimuli.

PubMed

Kearns, David N; Weiss, Stanley J

2004-11-01

A series of experiments was performed to determine whether sign-tracking would occur in rats with intravenous (i.v.) cocaine as the unconditioned stimulus. In Experiment 1, a retractable lever paired with food produced strong sign-tracking, but a lever paired with one of three doses of i.v. cocaine did not elicit any approach or contact behavior. Experiment 2 demonstrated that doses of cocaine that did not elicit sign-tracking would function as a positive reinforcer for a lever contact operant. In Experiment 3, an artificial consummatory response was added to make the cocaine reinforcement episode more behaviorally comparable to that occasioned by food. Although the rats readily performed this response when it was required to receive cocaine infusions, they still did not contact a lever that signaled the availability of these infusions. It appears that cocaine is different from other positive reinforcers (e.g., food, water, warmth, or intracranial stimulation) in that it will not produce sign-tracking in rats.

[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.

Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia.

PubMed

Ryu, J-H; Kang, M-H; Park, K-S; Do, S-H

2008-03-01

This randomized, double-blind, prospective study was undertaken to evaluate the effects of magnesium sulphate on anaesthetic requirements and postoperative analgesia in patients undergoing total i.v. anaesthesia (TIVA). Fifty patients who underwent gynaecological surgery were randomly divided into two groups. Before induction of anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and then 15 mg kg(-1) h(-1) i.v. by continuous infusion. The control group (Group S) received the same amount of isotonic saline. TIVA (propofol+remifentanil) was administered under bispectral index monitoring during anaesthesia induction and maintenance. Rocuronium was administered before orotracheal intubation and during surgery when the train-of-four count was 2 or more. After operation, patient-controlled analgesia with a solution of ketorolac and morphine was used and the consumption of this solution was recorded. Pain scores at rest and upon movement were evaluated 30 min, 4, 24, and 48 h after surgery. Patients in Group M required less rocuronium than those in Group S [mean (SD) 0.44 (0.09) vs 0.35 (0.07) microg kg(-1) min(-1), P<0.05]. The total amounts of propofol and remifentanil administered were similar in the two groups. Postoperative pain scores, cumulative analgesic consumption, and shivering incidents were significantly lower in Group M (P<0.05). Mean arterial pressure just after intubation and during the immediate postoperative period was also significantly lower in Group M (P<0.05). I.v. magnesium sulphate during TIVA reduced rocuronium requirement and improved the quality of postoperative analgesia.

[A case report of the combination therapy with S-1 plus CDDP intraperitoneal chemotherapy for CY positive cancer patient].

PubMed

Ishii, Yasushi; Iwasaki, Yoshiki; Ohashi, Manabu; Iwanaga, Tomohiro; Ohinata, Ryouki; Takahashi, Keiichi; Matsumoto, Hiroshi; Yamaguchi, Tatsurou; Nakano, Daisuke

2011-11-01

A male patient in his 50s underwent distal gastrectomy for gastric cancer. In operation, there was no peritoneal dissemination. But peritoneal lavage cytology revealed positive peritoneal dissemination. Thus, we set an intraperitoneal infuser port to this patient. On specimen, a type-3 tumor was located in the gastric lesser of antrum to angle. Microscopic examination of specimens revealed a signet ring cell carcinoma and poorly differentiated adenocarcinoma under serosa, and positive of lymph node metastasis. The diagnosis was pT4N2M1P0CY1H0, Stage IV( Japanese classification of gastric carcinoma The 14 Edition). CDDP was administered through the infuser port (on day 7, a first dose of 60 mg/m2 and 30 mg/m2 for second) combined with oral administration of S-1 (100 mg/body) for two weeks, with one week of drug withdrawal. This chemotherapy was repeated for 11 courses. After that, peritoneal lavage cytology became negative. S-1 oral administration was continued for four years, and this patient has been well for five years and six months after the surgery. Therefore, it is suggested that intraperitoneal chemotherapy with cisplatin is an effective treatment for microscopical peritoneal dissemination.

Comparison between carbachol iontophoresis and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

PubMed

Wendt, Mark; He, Lin; Glasser, Adrian

2013-10-01

Rhesus monkeys are an animal model for human accommodation and presbyopia and consistent and repeatable methods are needed to stimulate and measure accommodation in anesthetized rhesus monkeys. Accommodation has typically been pharmacologically stimulated with topical pilocarpine or carbachol iontophoresis. Intravenous (i.v.) pilocarpine has recently been shown to produce more natural, rapid and reproducible accommodative responses compared to topical pilocarpine. Here, i.v. pilocarpine was compared to carbachol iontophoresis stimulated accommodation. Experiments were performed under anaesthesia on five previously iridectomized monkeys aged 10-16 years. In three monkeys, accommodation was stimulated with carbachol iontophoresis in five successive experiments and refraction measured with a Hartinger coincidence refractometer. In separate experiments, accommodation was stimulated using a 5 mg/kg bolus of i.v. pilocarpine given over 30 s followed by a continuous infusion of 20 mg/kg/hr for 5.5 min in three successive experiments with the same monkeys as well as in single experiments with two additional monkeys. Refraction was measured continuously using photorefraction with baseline and accommodated refraction also measured with the Hartinger. In subsequent i.v. pilocarpine experiments with each monkey, accommodative changes in lens equatorial diameter were measured in real-time with video-image analysis. Maximum accommodation of three monkeys with carbachol iontophoresis (five repeats) was (mean ± SD; range) 14.0 ± 3.5; 9.9-20.3 D and with i.v. pilocarpine stimulation (three repeats) was 11.1 ± 1.1; 9.9-13.0 D. The average of the standard deviations of maximum accommodation from each monkey was 0.8 ± 0.3 D from carbachol iontophoresis and 0.3 ± 0.2 from i.v. pilocarpine. The average latency to the start of the response after carbachol iontophoresis was 2.5 ± 3.9; 0.0-12.0 min with a time constant of 12.7 ± 9.5; 2.3-29.2 min. The average latency after i.v. pilocarpine was 0.31 ± 0.03; 0.25-0.34 min with a time constant of 0.19 ± 0.07; 0.11-0.31 s. During i.v. pilocarpine stimulated accommodation in five monkeys, lens diameters decreased by 0.54 ± 0.09; 0.42-0.64 mm with a rate of change of 0.052 ± 0.002; 0.050-0.055 mm/D. Accommodative responses with i.v. pilocarpine were more rapid, consistent and stable than those with carbachol iontophoresis. The accommodative decrease in lens diameter with i.v. pilocarpine as a function of age was consistent with previous results using constant topical pilocarpine. Intravenous pilocarpine stimulated accommodation is safe, more consistent and more rapid than carbachol iontophoresis and it requires no contact with or obstruction of the eye thus allowing continuous and uninterrupted refraction and ocular biometry measurements. Copyright © 2013 Elsevier Ltd. All rights reserved.

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...

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

PubMed

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

2017-01-01

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

Real-time hemodynamic response and mitochondrial function changes with intracarotid mannitol injection

PubMed Central

Joshi, Shailendra; Singh-Moon, Rajinder; Wang, Mei; Bruce, Jeffrey N.; Bigio, Irving J.; Mayevsky, Avraham

2014-01-01

Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug delivery. The purpose of this study was to understand the time course of hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in order to optimize the delivery of drugs for treating brain tumors. Principal results We compared hemodynamic response, EEG changes, and mitochondrial function as judged by relative changes in tissue NADH concentrations, after intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our rabbit IC drug delivery model. We observed significantly greater, though transient, hyperemic response to IC infusion of mannitol compared to normal saline. Infusion of mannitol also resulted in a greater increase in tissue NADH concentrations relative to the baseline. These hemodynamic, and metabolic changes returned to baseline within 5 min of mannitol injection. Conclusion Significant, though transient, changes in blood flow and brain metabolism occur with IA mannitol infusion. The observed transient hyperemia would suggest that intravenous (IV) chemotherapy should be administered either just before, or concurrent with IA mannitol injections. On the other hand, IA chemotherapy should be delayed until the peak hyperemic response has subsided. PMID:24440631

Identification of Risk Factors for Intravenous Infiltration among Hospitalized Children: A Retrospective Study

PubMed Central

2016-01-01

This retrospective study was aimed to identify risk factors of intravenous (IV) infiltration for hospitalized children. The participants were 1,174 children admitted to a general hospital, who received peripheral intravenous injection therapy at least once, and had complete records. Data were analyzed with frequency and percentage or mean and standard deviation were calculated, and odds ratio (OR) from univariate and multiple logistic regressions. The number and % of infiltrations were 92 and 7.8%, respectively. IV infiltration risk factors were lower limb (OR = 1.72), phenytoin (OR = 11.03), 10% dextrose (OR = 6.55), steroids (OR = 6.21), vancomycin (OR = 4.10), high-concentration electrolytes (OR = 3.49), and ampicillin/sulbactam combination (OR = 3.37). Nurses working at children’s hospitals should consider the risk of IV infiltration for children receiving IV infusion therapy and make a preventive effort to identify IV infiltration in high-risk children at an early stage. PMID:27351488

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…

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

PubMed

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

2016-07-01

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

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

PubMed

Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

2015-04-15

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog.

PubMed Central

McAuliffe, S. J.; Moors, J. A.; Snow, H. M.; Wayne, M.; Jessup, R.

1993-01-01

1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin. PMID:8485629

Effect of low-dose atropine administration on dobutamine dose requirement in horses anesthetized with detomidine and halothane.

PubMed

Weil, A B; Keegan, R D; Greene, S A

1997-12-01

To determine whether a low dose of atropine is associated with decreased requirement for cardiovascular supportive treatment in horses given detomidine prior to maintenance of general anesthesia with halothane. 3 groups of 10 healthy horses. Detomidine (20 micrograms/kg of body weight, i.m.) was administered to all 30 horses. Then, 10 horses received atropine (0.006 mg/kg, i.v.) 1 hour after detomidine administration, 10 horses received atropine (0.012 mg/kg, i.m.) at the time of detomidine administration, and 10 horses served as a control group. Heart rate was measured prior to detomidine administration and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mm of Hg was recorded. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and arterial blood gas tensions were measured at fixed intervals. Mean heart rate was higher among horses receiving atropine i.v. or i.m., compared with that in control horses. Horses that received atropine i.v. had higher systemic arterial blood pressure and required a lower dobutamine infusion rate than did horses of the other groups. Detomidine-treated, halothane-anesthetized horses given atropine i.v. required less dobutamine, compared with horses receiving or not receiving atropine i.m. Complications, such as colic and dysrhythmias, from use of higher doses of atropine, were not observed at this lower dose of atropine. i.v. administration of a low dose of atropine prior to induction of general anesthesia may result in improved blood pressure in horses that have received detomidine before anesthesia with halothane.

The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

PubMed

Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

2008-08-01

Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was <5% relative to total plasma concentration, but CSF drug exposure was approximately 30% of plasma free drug exposure, which was calculated from published plasma protein binding values. The IV administration of erlotinib was well tolerated. Erlotinib and its active metabolite OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

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.

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects

PubMed Central

Gosmanov, Aidar R.; Smiley, Dawn D.; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. PMID:22483976

Comparison of Morphine, Morphine-Lidocaine, and Morphine-Lidocaine-Ketamine Infusions in Dogs Using an Incision-Induced Pain Model.

PubMed

Chiavaccini, Ludovica; Claude, Andrew K; Meyer, Robert E

We aimed to compare antinociceptive effects of IV infusions of morphine (M), morphine-lidocaine (ML), or morphine-lidocaine-ketamine (MLK) combined, in a mild-to-moderate pain model in dogs. Eighteen adult hounds were heavily sedated with IV morphine (0.2 mg/kg) and dexmedetomidine to undergo thoracic skin incisions. After reversal, dogs were randomly assigned to receive loading doses of lidocaine and ketamine (MLK), lidocaine and saline (ML), or equivalent volume of saline (M), followed by 18 hr constant infusions of morphine (0.12 mg/kg/hr), lidocaine (3 mg/kg/hr) and ketamine (0.6 mg/kg/hr); morphine (0.12 mg/kg/hr) and lidocaine (3 mg/kg/hr); or morphine (0.12 mg/kg/hr), respectively. Pain was assessed with Short Form Glasgow Composite Measure Pain Scale and mechanical nociception with von Frey filaments (VFFS). Data were analyzed with linear mixed model on ranks. Independently of treatment, Short Form Glasgow Composite Measure Pain Scale was significantly higher than baseline for 24 hr (p < .0001), while VFFS was significantly lower than baseline for 48 hr post-recovery (p < .0001), with no difference between MLK and M groups. The ML group recorded significantly lower VFFS (p = .02) than the M group for the entire study. In conclusion, there was no significant analgesic difference between MLK and M alone.

Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder

PubMed Central

Verrico, Christopher D.; Newton, Thomas F.; Mahoney, James J.; Thompson-Lake, Daisy G. Y.

2016-01-01

Background: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. Methods: The current report describes results from a double-blind, placebo-controlled study in which participants (n=14–17/group) were randomized to huperzine A (0.4 or 0.8mg) or placebo. Participants received randomized infusions of cocaine (0 and 40mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. Results: Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4mg of huperzine A significantly attenuated cocaine-induced increases of “Any Drug Effect,” “High,” “Stimulated,” “Willing to Pay,” and “Bad Effects” (all P>.05). Conclusions: The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder. PMID:26364275

Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

PubMed

Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

2014-04-01

Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

Effect of a polyethylene-lined administration set on the availability of diazepam injection.

PubMed

Hancock, B G; Black, C D

1985-02-01

Delivery of diazepam through a polyethylene-lined i.v. administration set and through a polyvinyl chloride (PVC) set was compared. Diazepam was prepared in concentrations of 50 mg/500 mL and 100 mg/500 mL in 0.9% sodium chloride injection and 5% dextrose injection in glass containers. Diazepam concentrations were measured by high-performance liquid chromatography at 0 through 5 hours in samples collected simultaneously from the glass solution containers and from the distal ends of a PVC administration set and a polyethylene-lined (non-PVC) set. Flow rates of 50 and 100 mL/hr were tested. For the non-PVC sets, diazepam concentration in the infusate was not significantly different from concentration in the glass container at any sampling time. The overall percentage of diazepam recovered was 100.7 +/- 6.8%. For the PVC sets, diazepam concentration in the infusate was less than in the container at all sampling times, and the overall percentage of diazepam recovered was 65.4 +/- 13.3% (significantly different from delivery for the non-PVC sets). Delivery through the non-PVC sets was not affected by flow rate, type of solution, or concentration of diazepam. For infusion periods of up to five hours, delivery of diazepam through polyethylene-lined i.v. administration sets was superior to delivery through polyvinyl chloride sets.

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Endoscopic and histological outcomes.

PubMed

Pérez-Merino, E M; Usón-Casaús, J M; Duque-Carrasco, J; Zaragoza-Bayle, C; Mariñas-Pardo, L; Hermida-Prieto, M; Vilafranca-Compte, M; Barrera-Chacón, R; Gualtieri, M

2015-12-01

Systemic administration of mesenchymal stem cells (MSCs) has been shown to be safe and efficacious in humans with Crohn's disease. The aim of this study was to evaluate the safety of an intravenous (IV) infusion of adipose tissue-derived mesenchymal stem cells (ASCs) and to assess macroscopic and histological effects in the digestive tract of dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received a single ASC infusion (2 × 10(6) cells/kg bodyweight). Full digestive endoscopic evaluation was performed pre-treatment and between 90 and 120 days post-treatment with mucosal changes being assessed using a fit-for-purpose endoscopic scale. Endoscopic biopsies from each digestive section were evaluated histologically according to the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group criteria. The pre- and post-treatment canine IBD endoscopic index (CIBDEI) and histological score (HS) were calculated and compared using the Wilcoxon test. Remission was defined as a reduction of >75% of the CIBDEI and HS compared with pre-treatment. No acute reactions to ASC infusion or side effects were reported in any dog. Significant differences between pre- and post-treatment were found in both the CIBDEI (P = 0.004) and HS (P = 0.004). Endoscopic remission occurred in 4/11 dogs with the remaining dogs showing decreased CIBDEI (44.8% to 73.3%). Histological remission was not achieved in any dog, with an average reduction of the pre-treatment HS of 27.2%. In conclusion, a single IV infusion of allogeneic ASCs improved gastrointestinal lesions as assessed macroscopically and slightly reduced gastrointestinal inflammation as evaluated by histopathology in dogs with IBD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

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.

Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants.

PubMed

Ohlsson, Arne; Walia, Rajneesh; Shah, Sachin S

2015-02-18

Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects. To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor, placebo or no intervention for closing a patent ductus arteriosus in preterm, low birth weight, or preterm and low birth weight infants. We searched The Cochrane Library, MEDLINE, EMBASE, Clincialtrials.gov, Controlled-trials.com, and www.abstracts2view.com/pas in May 2014. Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants. Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We included 33 studies enrolling 2190 infants.Two studies compared intravenous (iv) ibuprofen versus placebo (270 infants). In one study (134 infants) ibuprofen reduced the incidence of failure to close a PDA (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.51 to 0.99; risk difference (RD) -0.18, 95% CI -0.35 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 100). In one study (136 infants), ibuprofen reduced the composite outcome of infant mortality, infants who dropped out, or infants who required rescue treatment (RR 0.58, 95% CI 0.38 to 0.89; RD -0.22, 95% CI -0.38 to -0.06; NNTB 5, 95% CI 3 to 17). One study (64 infants) compared oral ibuprofen with placebo and noted a significant reduction in failure to close a PDA (RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4).Twenty-one studies (1102 infants) reported failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 1.00, 95% CI 0.84 to 1.20; I(2) = 0%; typical RD 0.00, 95% CI -0.05 to 0.05; I(2) = 0%). The risk of developing necrotising enterocolitis (NEC) was reduced for ibuprofen (16 studies, 948 infants; typical RR 0.64, 95% CI 0.45 to 0.93; typical RD -0.05, 95% CI -0.08 to -0.01; NNTB 20, 95% CI 13 to 100; I(2) = 0% for both RR and RD). The duration of ventilatory support was reduced with ibuprofen (oral or iv) compared with iv or oral indomethacin (six studies, 471 infants; mean difference (MD) -2.4 days, 95% CI -3.7 to -1.0; I(2) = 19%).Eight studies (272 infants) reported on failure rates for PDA closure in a subgroup of the above studies comparing oral ibuprofen with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 0.96, 95% CI 0.73 to 1.27; typical RD -0.01, 95% CI -0.12 to 0.09). The risk of NEC was reduced with oral ibuprofen compared with indomethacin (oral or iv) (seven studies, 249 infants; typical RR 0.41, 95% CI 0.23 to 0.73; typical RD -0.13, 95% CI -0.22 to -0.05; NNTB 8, 95% CI 5 to 20; I(2) = 0% for both RR and RD). There was a decreased risk of failure to close a PDA with oral ibuprofen compared with iv ibuprofen (four studies, 304 infants; typical RR 0.41, 95% CI 0.27 to 0.64; typical RD -0.21, 95% CI -0.31 to -0.12; NNTB 5, 95% CI 3 to 8). Transient renal insufficiency was less common in infants who received ibuprofen compared with indomethacin. High dose versus standard dose of iv ibuprofen, early versus expectant administration of iv ibuprofen, echocardiographically guided iv ibuprofen treatment vs. standard iv ibuprofen treatment and continuous infusion of ibuprofen vs. intermittent boluses of ibuprofen and long-term follow-up were studied in too few trials to draw any conclusions. Ibuprofen is as effective as indomethacin in closing a PDA and currently appears to be the drug of choice. Ibuprofen reduces the risk of NEC and transient renal insufficiency. Oro-gastric administration of ibuprofen appears as effective as iv administration. To make further recommendations, studies are needed to assess the effectiveness of high-dose versus standard-dose ibuprofen, early versus expectant administration of ibuprofen, echocardiographically guided versus standard iv ibuprofen, and continuous infusion versus intermittent boluses of ibuprofen. Studies are lacking evaluating the effect of ibuprofen on longer-term outcomes in infants with PDA.

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

Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions.

PubMed

Wong, Anselm; Graudins, Andis

2016-01-01

Adverse reactions to intravenous (IV) acetylcysteine treatment in paracetamol overdose, are common. Previous studies suggest the incidence and severity of non-allergic anaphylactic reactions (NAARs) are influenced by the rate of acetylcysteine infusion. We compared the incidence of adverse drug events of a two-bag IV acetylcysteine regimen with that of the traditional three-bag regimen. This was a retrospective analysis of patients presenting with paracetamol overdose requiring treatment with acetylcysteine to three emergency departments. We prospectively identified all presentations where IV acetylcysteine was administered using a 20 h, two-bag regimen (200 mg/kg over 4 h followed by 100 mg/kg over 16 h) from February 2014 to June 2015. We compared this to an historical cohort treated with the 21 h three-bag IV regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h and 100 mg/kg over 16 h) from October 2009 to October 2013. Medical and nursing notes were searched retrospectively for entries suggesting the presence of an adverse reaction. The primary outcome was incidence of NAARs and gastrointestinal reactions in each group. 389 presentations were treated with the three-bag regimen and 210 presentations received the two-bag regimen. NAARs were recorded more commonly with the three-bag acetylcysteine regimen than the two-bag regimen (10% vs 4.3%, p = 0.02, OR 2.5, 95% CI 1.1-5.8). There was no difference in reports of gastrointestinal reactions between cohorts (three-bag 39% vs two-bag 41%, p = 0.38, OR 1.17 95% CI (0.83-1.65)). The incidence of NAARs was significantly reduced by combining the first two bags of the traditional three-bag regimen and infusing these over 4 h at 50 mg/kg/hr. Simplifying the administration of acetylcysteine may have other benefits such as better utilisation of nursing time and reduced infusion administration errors. A two-bag 20 h acetylcysteine regimen was well tolerated and resulted in significantly fewer and milder NAARs than the standard three-bag regimen.

[Two Kinds of HLA-mismatched Allogeneic Hematopoictic Stem Cell Transplantation for Treatment of Hematologic Malignancies].

PubMed

Li, Wei-Da; Gao, Zhi-Yong; Yu, Xin-Jian; Lu, Da-Yu; Lu, Dao-Pei

2016-04-01

To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance. A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used. All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%). These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

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.

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.

The haemodynamic effects of bolus versus slower infusion of intravenous crystalloid in healthy volunteers.

PubMed

Ukor, Ida F; Hilton, Andrew K; Bailey, Michael J; Bellomo, Rinaldo

2017-10-01

This pilot study aimed to characterise the haemodynamic effect of 1L of IV normal saline (NS) administered as a rapid versus slow infusion on cardiac output (CO), heart rate (HR), systemic blood pressures, and carotid blood flow in six healthy volunteers. Six healthy male volunteers aged 18-65years were randomized to receive 1L NS given over 30min or 120min. On a subsequent study session the alternate fluid regimen was administered. Haemodynamic data was gathered using a non-invasive finger arterial pressure monitor (Nexfin®), echocardiography and carotid duplex sonography. Time to micturition and urine volume was also assessed. Compared to baseline, rapid infusion of 1L of saline over 30min produced a fall in Nexfin®-measured CO by 0.62L/min (p<0.001), whereas there was a marginal but significant increase during infusion of 1L NS over 120min of 0.02L/min (p<0.001). This effect was mirrored by changes in HR and blood pressure (BP) (p<0.001). There were no significant changes in carotid blood flow, time to micturition, or urine volume produced. Slower infusion of 1L NS in healthy male volunteers produced a greater increase in CO, HR and BP than rapid infusion. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Venous damage prevention by defibrotide in vinorelbine-treated patients.

PubMed

Mare, M; Maisano, R; Caristi, N; Adamo, V; Altavilla, G; Carboni, R; Munaò, S; La Torre, F

2003-09-01

The aim of our study was to evaluate the incidence of venous toxicity induced by vinorelbine administration in patients who received a preventive therapy with defibrotide. From July 1996 to July 2002 we treated 203 patients with vinorelbine, 51 with vinorelbine alone and 152 with vinorelbine in combination with other drugs via peripheral vein infusion. Of the 203 patients, 123 were male and 80 female with a median age of 67 years (range 18 to 82 years), and 118 were chemotherapy-naive. Defibrotide was delivered i.v. at a dose of 400 mg in 250 ml normal saline. After infusion of 125 ml over about 15 min, vinorelbine mixed with 10 ml normal saline was delivered as quick brief repeated pulses over 5 min through the plastic tube, followed by infusion of the remaining defibrotide. The specific Rittenberg scale was used to assess venous irritation episodes. Among a total of 1336 vinorelbine infusions, with a median of five infusions per patient, the incidence of venous irritation episodes graded according to Rittenberg scale was 1.1% (15), of which 0.6% (8) were grade 2 and 0.5% (7) grade 1. Globally, 15 patients (7.3%) developed venous toxicity after a median of 3 infusions (range 1-14), but no patient had more than one event. Our findings support the use of defibrotide as an effective, safe and low-cost means for preventing vinorelbine-related venous damage.

Medical resource utilization for administration of trastuzumab in a New Zealand oncology outpatient setting: a time and motion study

PubMed Central

North, Richard T; Harvey, Vernon J; Cox, Levonne C; Ryan, Stuart N

2015-01-01

Background In New Zealand, trastuzumab is standard therapy for human epidermal growth factor receptor-2 (HER2)-positive early and metastatic breast cancer. Given the requirement for ongoing adjuvant or maintenance treatment and intravenous (IV) delivery, such a regimen consumes considerable health care resources. The development of a subcutaneous (SC) trastuzumab formulation with a short administration time offers the potential to reduce hospital expenditure. The aim of this study was to determine medical resource utilization associated with administration of trastuzumab SC injection via handheld syringe vs trastuzumab IV infusion in patients with HER2-positive breast cancer in New Zealand. Methods This noninterventional, descriptive study was conducted at the outpatient oncology centers at Auckland City and Tauranga Hospitals. Trained observers recorded times associated with health care professional (HCP) tasks and consumables use associated with preparation and administration of trastuzumab IV or SC in women with early or metastatic breast cancer. The cost for each formulation was calculated as the mean cost of HCP time (based on Pharmaceutical Management Agency hourly rates) plus the mean cost of consumables used. Results Use of trastuzumab SC vs IV reduced mean chair time by 36.95 minutes and total nurse time by 6.12 minutes; there was a 20.45-minute reduction in pharmacist time when the SC formulation was used. After adding consumable costs, the overall estimated saving with trastuzumab SC vs IV was $76.94 (New Zealand dollars) per patient per cycle. Conclusions Compared with trastuzumab IV infusion, administration of trastuzumab via SC injection reduced time spent in the clinic and decreased HCP resources and consumables needed to administer treatment. These reductions could contribute to a decrease in health care costs and an improvement in the efficiency of HER2-positive breast cancer treatment delivery. PMID:26251623

Comparison of dexmedetomidine and midazolam for monitored anesthesia care combined with tramadol via patient-controlled analgesia in endoscopic nasal surgery: A prospective, randomized, double-blind, clinical study

PubMed Central

Karaaslan, Kazim; Yilmaz, Fahrettin; Gulcu, Nebahat; Colak, Cemil; Sereflican, Murat; Kocoglu, Hasan

2007-01-01

Abstract Background Monitored anesthesia care (MAC) may be applied for septoplasty or endoscopic sinus surgery in which an adequate sedation and analgesia without respiratory depression are desired for comfort of both the patient and the surgeon. Several combinations with different agents have been used for this purpose in these patients. However, analgesic properties for these agents have not been reported. Objective The aim of this study was to investigate the analgesic and sedative effects of dexmedetomidine or midazolam infusion combined with tramadol that was used via patient-controlled analgesia (PCA), and to document the effects of these drugs on early cognitive functions. Methods This prospective, randomized, double-blind, clinical study enrolled patients undergoing septoplasty or endoscopic sinus surgery at the Abant Izzet Baysal University Hospital, Bolu, Turkey, between February and September 2006. Patients were randomly allocated in a 1:1 ratio into 1 of 2 groups: the dexmedetomidine group (group D) patients received IV dexmedetomidine 1 μg/kg for 10 minutes followed by continuous infusion of 0.5 μg/kg · h−1; and the midazolam group (group M) patients were administered a loading dose of IV midazolam 40 μg/kg for 10 minutes followed by infusion at the rate of 50 μg/kg · h−1. A 1-minute bolus dose of IV tramadol (1.5 mg/kg) was administered in both groups 10 minutes after the administration of the primary drug, and continued via infusion using a PCA device. After baseline measurements, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), oxygen saturation, and rate of respiration were recorded after the loading dose of study drug, after the bolus tramadol dose, at 10-minute intervals during the operation, and twice in the recovery rooms; 5 minutes after arrival and 5 minutes before discharge. Verbal rating score (VRS) and Ramsay sedation score were determined at baseline (after surgery was started), every 10 minutes thereafter until the end of the operation, and 2 times during recovery. All patients were assessed with the Wechsler Memory Scale-Revised at baseline (preoperatively) and 4 hours after the operation. Results Seventy patients were enrolled in the study and randomly assigned to 1 of 2 groups: group D (sex, male/female, 23/12; mean [SEM] age, 32.53 [2.07] years; mean [SEM] weight, 73.03 [2.41] kg) or group M (sex, male/female, 21/14; mean [SEM] age, 34.43 [1.83] years; mean [SEM] weight, 67.90 [2.32] kg). All hemodynamic parameters (SAP, DAP, MAP, HR) were significantly higher in group M compared with group D from the onset of the surgery to discharge time (P < 0.05). Pain and sedation scores were similar in both groups, but the amount of PCA-administered rescue tramadol was significantly higher in group M (P = 0.001). A higher, though not statistically significant, prevalence of adverse events (ie, hypotension, bradycardia, and perioperative nausea and vomiting) were observed in group D. Postoperative logical verbal memory and digit span values were significantly higher in group D when compared with group M (P < 0.05). Postoperative digit span and visual reproduction scores were significantly higher than preoperative values in group D (P < 0.05). Postoperative personality functioning scores were significantly higher than preoperative values in group M (P < 0.05). Conclusions Based on VRS, Ramsay sedation scores, and surgeon and anesthesiologist satisfaction scores, dexmedetomidine or midazolam combined with tramadol PCA provided adequate analgesia and sedation in these adult patients undergoing septoplasty or endoscopic sinus surgery with MAC. A significantly larger amount of rescue tramadol was used by group M, suggesting that a better analgesic effect was achieved with dexmedetomidine. PMID:24678121

Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy.

PubMed

Nikolaidis, Lazaros A; Elahi, Dariush; Shen, You-Tang; Shannon, Richard P

2005-12-01

We have shown previously that the glucagon-like peptide-1 (GLP-1)-(7-36) amide increases myocardial glucose uptake and improves left ventricular (LV) and systemic hemodynamics in both conscious dogs with pacing-induced dilated cardiomyopathy (DCM) and humans with LV systolic dysfunction after acute myocardial infarction. However, GLP-1-(7-36) is rapidly degraded in the plasma to GLP-1-(9-36) by dipeptidyl peptidase IV (DPP IV), raising the issue of which peptide is the active moiety. By way of methodology, we compared the efficacy of a 48-h continuous intravenous infusion of GLP-1-(7-36) (1.5 pmol.kg(-1).min(-1)) to GLP-1-(9-36) (1.5 pmol.kg(-1).min(-1)) in 28 conscious, chronically instrumented dogs with pacing-induced DCM by measuring LV function and transmyocardial substrate uptake under basal and insulin-stimulated conditions using hyperinsulinemic-euglycemic clamps. As a result, dogs with DCM demonstrated myocardial insulin resistance under basal and insulin-stimulated conditions. Both GLP-1-(7-36) and GLP-1-(9-36) significantly reduced (P < 0.01) LV end-diastolic pressure [GLP-1-(7-36), 28 +/- 1 to 15 +/- 2 mmHg; GLP-1-(9-36), 29 +/- 2 to 16 +/- 1 mmHg] and significantly increased (P < 0.01) the first derivative of LV pressure [GLP-1-(7-36), 1,315 +/- 81 to 2,195 +/- 102 mmHg/s; GLP-1-(9-36), 1,336 +/- 77 to 2,208 +/- 68 mmHg] and cardiac output [GLP-1-(7-36), 1.5 +/- 0.1 to 1.9 +/- 0.1 l/min; GLP-1-(9-36), 2.0 +/- 0.1 to 2.4 +/- 0.05 l/min], whereas an equivolume infusion of saline had no effect. Both peptides increased myocardial glucose uptake but without a significant increase in plasma insulin. During the GLP-1-(9-36) infusion, negligible active (NH2-terminal) peptide was measured in the plasma. In conclusion, in DCM, GLP-1-(9-36) mimics the effects of GLP-1-(7-36) in stimulating myocardial glucose uptake and improving LV and systemic hemodynamics through insulinomimetic as opposed to insulinotropic effects. These data suggest that GLP-1-(9-36) amide is an active peptide.

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

Docetaxel in combination with epirubicin in metastatic breast cancer: pharmacokinetic interactions.

PubMed

Ceruti, M; Tagini, V; Recalenda, V; Arpicco, S; Cattel, L; Airoldi, M; Bumma, C

1999-01-01

Epirubicin (75 mg/m2) and docetaxel (75 mg/m2) were administered to 16 patients affected by metastatic breast cancer following two different schedules: (1) docetaxel as infusion administered 1 h after epirubicin administration (schedule A); and (2) docetaxel as infusion immediately (10 min) after the end of epirubicin i.v. bolus administration (schedule B). Experimental non-compartmental analyses such as AUC and Css, were affected very little by the drug combination, irrespective of whether the administration of docetaxel was immediately after the epirubicin bolus (10 min) or delayed (1 h). However, serum levels showed evidence of transient drug interaction: in schedule A, docetaxel infusion was associated with a transient increase of plasma epirubicin in correspondence with Cssmax of docetaxel. Bi-compartmental analysis showed a significant difference in epirubicin clearance between protocols A and B. It is suggested that polysorbate 80, used in minimal amounts to formulate docetaxel, may interfere with epirubicin plasma level.

Benefits of smart pumps for automated changeovers of vasoactive drug infusion pumps: a quasi-experimental study.

PubMed

Cour, M; Hernu, R; Bénet, T; Robert, J M; Regad, D; Chabert, B; Malatray, A; Conrozier, S; Serra, P; Lassaigne, M; Vanhems, P; Argaud, L

2013-11-01

Manual changeover of vasoactive drug infusion pumps (CVIP) frequently lead to haemodynamic instability. Some of the newest smart pumps allow automated CVIP. The aim of this study was to compare automated CVIP with manual 'Quick Change' relays. We performed a prospective, quasi-experimental study, in a university-affiliated intensive care unit (ICU). All adult patients receiving continuous i.v. infusion of vasoactive drugs were included. CVIP were successively performed manually (Phase 1) and automatically (Phase 2) during two 6-month periods. The primary endpoint was the frequency of haemodynamic incidents related to the relays, which were defined as variations of mean arterial pressure >15 mm Hg or heart rate >15 bpm. The secondary endpoints were the nursing time dedicated to relays and the number of interruptions in care because of CVIP. A multivariate mixed effects logistic regression was fitted for analytic analysis. We studied 1329 relays (Phase 1: 681, Phase 2: 648) from 133 patients (Phase 1: 63, Phase 2: 70). Incidents related to CVIP decreased from 137 (20%) in Phase 1 to 73 (11%) in Phase 2 (P<0.001). Automated relays were independently associated with a 49% risk reduction of CVIP-induced incidents (adjusted OR=0.51, 95% confidence interval 0.34-0.77, P=0.001). Time dedicated to the relays and the number of interruptions in care to manage CVIP were also significantly reduced with automated relays vs manual relays (P=0.001). These results demonstrate the benefits of automated CVIP using smart pumps in limiting the frequency of haemodynamic incidents related to relays and in reducing the nursing workload.

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...

Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI.

PubMed

Doran, Jesse A; Sajjad, Waseem; Schneider, Marabel D; Gupta, Rohit; Mackin, Maria L; Schwartz, Ronald G

2017-06-01

Aminophylline shortages led us to compare intravenous (IV) aminophylline with IV and oral (PO) caffeine during routine pharmacologic stress testing with SPECT MPI. We measured presence, duration, and reversal of adverse symptoms and cardiac events following regadenoson administration in consecutive patients randomized to IV aminophylline (100 mg administered over 30-60 seconds), IV caffeine citrate (60 mg infused over 3-5 minutes), or PO caffeine as coffee or diet cola. Of 241 patients, 152 (63%) received regadenoson reversal intervention. Complete (CR), predominant (PRE), or partial (PR) reversal was observed in 99%. CR by IV aminophylline (87%), IV caffeine (87%), and PO caffeine (78%) were similar (P = NS). Time to CR (162 ± 12.6 seconds, mean ± SD) was similar in treatment arms. PO caffeine was inferior to IV aminophylline for CR + PRE. IV aminophylline and IV caffeine provide rapid, safe reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine appeared similarly effective for CR but not for the combined CR + PRE. Our results suggest PO caffeine may be an effective initial strategy for reversal of regadenoson, but IV aminophylline or IV caffeine should be available to optimize symptom reversal as needed.

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…

Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment--a clinical report.

PubMed

Lawson, Sarah L; Brady, William; Mahmoud, Ahmed

2013-05-01

Treatment for significant hypoglycemia includes administration of dextrose containing agents, including 50% dextrose (D50%W) intravenously. Significant extravasation of D50%W can lead to complications, including skin and soft tissue injury, loss of limb, or death. The aim of this case report, using an interdisciplinary team approach, explores extravasation protocols as well as literature review, is to provide information about the proper use of hyaluronidase in patients with D50%W extravasations. A 46-year-old African American man presented to the emergency department (ED) after blood glucose level was initially 13 mg/dL. Emergency medical service established a large bore intravenous (IV) line in the right antecubital vein and administered a total of 50 g of D50%W. Upon arrival to the ED, the patient's level of consciousness had significantly improved. After arrival to the ED, the patient started complaining of pain in his right arm, near the site of the IV line insertion. On inspection, the IV site was grossly infiltrated. Hospital protocols for hyperosmolar infiltration were used. Extravasation is a common medical complication of infused medications and needs to be properly identified and treated. The multitude of skills from nursing, medicine, and pharmacy ensures that extravasation is managed appropriately and effectively to ensure safety to patients. Recognition, communication, and awareness of the institutional guidelines on how to treat infiltration and extravasation should be encouraged in all ED and intensive care unit medical personnel who deal with a variety of infusions and IV medications that have serious implications if not treated correctly.

Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

PubMed

Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D

2015-02-01

The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

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.

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

PubMed

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

2015-11-01

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

Evaluation of total-dose iron sucrose infusions in patients with iron deficiency anemia.

PubMed

Wall, Geoffrey C; Pauly, Rebecca A

2008-01-15

The safety and efficacy of a total-dose iron sucrose infusion protocol used in a large, tertiary care teaching hospital were studied. Nondialysis-dependent patients ages 18 years or older who received > or =250 mg of iron sucrose as a single i.v. infusion between January 2005 and January 2007 were eligible for study inclusion. The protocol for total-dose iron sucrose infusion was the same for all patients. The total dose of iron sucrose for each patient was calculated using an equation that included the desired hemoglobin (Hb) value, observed Hb level, ideal body weight, and sex. The calculated dose was divided into portions, rounded to the nearest 250 mg, and administered over four hours every other day. Outcomes measured included Hb, transferrin saturation, and serum ferritin values. A total of 26 patients met the inclusion criteria. The mean +/- S.D. Hb concentration before total-dose iron sucrose infusion was 9.37 +/- 0.9 g/dL, and the mean +/- S.D. corpuscular volume was 75 +/- 7.1 mum(3). The mean +/- S.D. postinfusion Hb concentration for 19 patients for whom follow-up Hb levels were available was 11.4 +/- 1.2 g/dL, significantly higher than the 9.45 +/- 0.8 g/dL measured before the first infusion (p = 0.03). No significant adverse effects were reported in 47 of 49 infusions, with 2 patients experiencing mild nausea. A treatment protocol consisting of alternate-day total-dose iron sucrose infusions was well tolerated and appeared to be effective in improving Hb concentrations in patients with iron deficiency anemia and without chronic kidney disease.

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.

Effects of L-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys.

PubMed

Kohut, Stephen J; Bergman, Jack; Blough, Bruce E

2016-03-01

Monoamine releasers with prominent dopaminergic actions, e.g., D-methamphetamine (D-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, D-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. The L-isomer of methamphetamine (L-MA), unlike D-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether L-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Separate groups (N = 4-5) of rhesus monkeys were studied to determine whether L-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. L-MA, like D-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10-day treatments with continuously infused L-MA (0.032-0.32 mg/kg/h, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. These results indicate that L-MA both shares discriminative stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. L-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder.

Effects of l-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys

PubMed Central

Kohut, Stephen J.; Bergman, Jack; Blough, Bruce E.

2015-01-01

Rationale Monoamine releasers with prominent dopaminergic actions, e.g., d-methamphetamine (d-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, d-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. Objectives The l-isomer of methamphetamine (l-MA), unlike d-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether l-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Methods Separate groups (N=4-5) of rhesus monkeys were studied to determine whether l-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and, (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. Results l-MA, like d-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10 day treatments with continuously infused l-MA (0.032-0.32 mg/kg/hr, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. Conclusions These results indicate that l-MA both shares discriminative-stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. l-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder. PMID:26713332

Use of Epinephrine in Patients with Drug-Induced Anaphylaxis: An Analysis of the Beijing Pharmacovigilance Database

PubMed Central

Wang, Tiansheng; Ma, Xiang; Xing, Yan; Sun, Shusen; Zhang, Hua; Stürmer, Til; Wang, Bin; Li, Xiaotong; Tang, Huilin; Jiao, Ligong; Zhai, Suodi

2017-01-01

Background Few studies assessing the use of epinephrine in drug-induced anaphylaxis (DIA) in the hospital setting are available. We utilized the Beijing Pharmacovigilance Database (BPD) to evaluate the appropriateness of epinephrine for DIA management. Methods DIA cases collected in the BPD from January 2004 to December 2014 were adjudicated and analyzed for demographics, causative drugs, clinical signs, outcomes, initial treatment, route, dosing, and cardiovascular adverse events (CAE) of epinephrine. Results DIA was primarily caused by antibiotics (38.4%), radiocontrast agents (11.9%), traditional Chinese medicine injections (10.9%), and chemotherapeutic drugs (10.3%). Only 708 (59.5%) patients received epinephrine treatment. Patients who received epinephrine were more likely to experience wheezing (p < 0.001) and respiratory arrest (p < 0.001). Among 518 patients with a complete record of the epinephrine administration route, the percentage of patients receiving it by intramuscular (IM) injection, subcutaneous (SC) injection, intravenous (IV) bolus injection, or IV continuous infusion was 16.9, 31.5, 43.5, and 8.1%, respectively. Among the 427 patients with a record of both the administration route and the dosing, an overdose was more likely with IV bolus (94.1%) in contrast to IM injection (56.6%; p < 0.001) or SC injection (43.7%; p < 0.001). Among the patients analyzed for CAE (n = 349), 17 patients accounted for 19 CAE, and 13 (76.5%) of these patients were overdosed with epinephrine. Conclusion Underuse, inappropriate IV bolus use, and overdosing were the 3 major problems with epinephrine use in DIA in China. Educational training for health care professionals on the appropriate use of epinephrine in managing anaphylactic reactions is suggested. PMID:28505618

Site of Action of Antidiuretic Hormone on Mammalian Nephrons.

DTIC Science & Technology

1981-01-01

techniques. Na and K concen- trations were determined by flamirne photometry and Cl by coulombmetric titration. 3ILO 14C- inulin and "Na were...of Cr in sequential Slop-flow samples. The appearance of 14C- inulin deriv ed from the posl-stop-Ilow IV infusion signalled the appearance of fresh

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.

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

PubMed

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

2007-01-01

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

Continuous subcutaneous infusion of 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.

The effect of adhesion molecule blockade on pulmonary reperfusion injury.

PubMed

Levine, Adrian J; Parkes, Karen; Rooney, Stephen J; Bonser, Robert S

2002-04-01

Selectins are the molecules involved in the initial adhesion of the activated neutrophil on pulmonary endothelium. We investigated the efficacy of selectin blockade in a selective (monoclonal antibody RMP-1) and nonselective (Fucoidin) manner in pulmonary reperfusion injury. Groups of six rat lungs were flushed with University of Wisconsin solution then stored at 4 degrees C for 4 hours. They then underwent sanguinous reperfusion for 30 minutes during which functional measures (gas exchange, pulmonary artery pressure, and airway pressure) of lung performance were made. After reperfusion we estimated their capillary filtration coefficient (Kfc units g/cm water/minute/g wet lung tissue) using a gravimetric technique. Four groups were studied: group I had no reperfusion, group II had 30 minutes of reperfusion, group III had infusion of 20 mg/kg Fucoidin before reperfusion, and group IV had infusion of 20 microg/mL RMP-1 before reperfusion. Reperfusion injury was found between groups I and II by an increase in capillary filtration coefficient (1.048 +/- 0.316 to 3.063 +/- 0.466, p < 0.01). Groups III and IV had a significantly lower Kfc than group II (0.967 +/- 0.134 and 1.205 +/- 0.164, respectively, p < 0.01). There was no significant functional difference between groups II, III, and IV. Reperfusion-induced hyperpermeability was ameliorated by selective (RMP-1) and nonselective (Fucoidin) selectin blockade.

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.

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

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans

PubMed Central

Sidani, Reem M.; Garcia, Anna E.; Antoun, Joseph; Isbell, James M.; Abumrad, Naji N.

2016-01-01

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These “isoglycemic clamps” enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

Should in-line filters be used in peripheral intravenous catheters to prevent infusion-related phlebitis? A systematic review of randomized controlled trials.

PubMed

Niël-Weise, Barbara S; Stijnen, Theo; van den Broek, Peterhans J

2010-06-01

In this systematic review, we assessed the effect of in-line filters on infusion-related phlebitis associated with peripheral IV catheters. The study was designed as a systematic review and meta-analysis of randomized controlled trials. We used MEDLINE and the Cochrane Controlled Trial Register up to August 10, 2009. Two reviewers independently assessed trial quality and extracted data. Data on phlebitis were combined when appropriate, using a random-effects model. The impact of the risk of phlebitis in the control group (baseline risk) on the effect of in-line filters was studied by using meta-regression based on the bivariate meta-analysis model. The quality of the evidence was determined by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. Eleven trials (1633 peripheral catheters) were included in this review to compare the effect of in-line filters on the incidence of phlebitis in hospitalized patients. Baseline risks across trials ranged from 23% to 96%. Meta-analysis of all trials showed that in-line filters reduced the risk of infusion-related phlebitis (relative risk, 0.66; 95% confidence interval, 0.43-1.00). This benefit, however, is very uncertain, because the trials had serious methodological shortcomings and meta-analysis revealed marked unexplained statistical heterogeneity (P < 0.0000, I(2) = 90.4%). The estimated benefit did not depend on baseline risk. In-line filters in peripheral IV catheters cannot be recommended routinely, because evidence of their benefit is uncertain.

Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions of unexplained aetiology.

PubMed

Yamada, H; Kishida, T; Kobayashi, N; Kato, E H; Hoshi, N; Fujimoto, S

1998-09-01

The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, +16, +20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk category of first trimester abortions.

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.

Zoledronic acid infusion for lumbar interbody fusion in osteoporosis.

PubMed

Tu, Chao-Wei; Huang, Kuo-Feng; Hsu, Hsien-Ta; Li, Hung-Yu; Yang, Stephen Shei-Dei; Chen, Yi-Chu

2014-11-01

Clinical outcomes of intravenous (IV) infusion of zoledronic acid (ZOL) for lumbar interbody fusion surgery (LIFS) remain unknown. We investigated the efficacy of IV ZOL on clinical outcome and bone fusion after LIFS. We retrospectively analyzed 64 patients with both degenerative lumbar spondylolisthesis and osteoporosis who underwent LIFS from January 2007 to April 2010. All patients were followed up for 2 y. Thirty-two were treated with an IV infusion of ZOL 3 d after surgery and a second injection 1 y later, and the other 32 patients did not receive ZOL. Preoperatively and every 3 mo postoperatively, oswestry disability index questionnaire and visual analog scale (VAS) scores for back and leg were compared. Preoperative and final postoperative follow-up to evaluate for subsequent compression fractures were also performed. Pedicle screw loosening, cage subsidence, and fusion rate were documented 2 y after surgery. At 2-y follow-up, a solid fusion was achieved in 75% of the ZOL group and only 56% of the control group. At final follow up, the incidence of final subsequent vertebral compression fractures (19% of the ZOL group and 51% of the control group, P = 0.006), pedicle screw loosening (18% of the ZOL group and 45% of the control group, P = 0.03), and cage subsidence >2 mm (28% of the ZOL group and only 54% of the control group, P = 0.04) were significantly lower in the ZOL group than in the control group. The ZOL group demonstrated improvement in VAS (for leg pain VAS, 2/10 for the ZOL group and 5/10 for the control group; for back pain VAS, 2/10 for the ZOL group and 6/10 for the control group) and oswestry disability index scores (7/25 for the ZOL group and 16/25 for the control group). ZOL treatment has beneficial effects on instrumented LIFS both radiographic and clinically. Thus, ZOL treatment can be recommended for osteoporosis patients undergoing LIFS. Copyright © 2014 Elsevier Inc. All rights reserved.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

PubMed

Greene, Stephen J; Epstein, Stephen E; Kim, Raymond J; Quyyumi, Arshed A; Cole, Robert T; Anderson, Allen S; Wilcox, Jane E; Skopicki, Hal A; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai I; Gheorghiade, Mihai; Butler, Javed

2017-04-01

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

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 ).

Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.

PubMed

Tveita, Torkjel; Sieck, Gary C

2012-08-01

Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.

Arterial thrombosis after vehicular trauma and humeral fracture in a dog.

PubMed

DePaula, Kristina M; deLaorcade, Armelle M; King, Ryan G; Hughs, Holly; Boudrieau, Randy J

2013-08-01

A 3-year-old 19-kg (42-lb) spayed female mixed-breed dog was referred after being hit by a car. Injuries included pneumothorax, hemothorax, pulmonary contusions, a full-thickness axillary skin wound, and a grade I transverse fracture of the midshaft of the right humerus. Following patient stabilization, open reduction and internal fixation of the fracture were performed. The dog had weight-bearing lameness at the time of discharge. Eight days after fracture repair, the dog was reevaluated for acute onset of signs of pain and non-weight-bearing lameness in the right forelimb. Physical examination findings in the right forelimb (knuckling and coolness, with absent digital pulses) were suggestive of a thrombus. Ultrasonography confirmed a right brachial artery thrombus with minimal blood flow to the affected limb. Unfractionated heparin was administered via continuous IV infusion for the first 36 hours of hospitalization. Clopidogrel administration was also started at this time. During hospitalization, rapid clinical improvement occurred, and the dog was discharged 48 hours after admission. The transition to outpatient therapy was achieved by discontinuation of the unfractionated heparin infusion at 36 hours and beginning SC administration of dalteparin. Outpatient treatment with dalteparin and clopidogrel was continued. Repeated physical examination and ultrasonography 5 weeks later revealed resolution of the thrombus and normal blood flow to the limb. Anticoagulant administration was discontinued at that time. Thrombosis should be suspected in any dog with signs of acute pain after severe trauma or fracture repair, with or without concurrent lameness, that do not resolve with appropriate treatment. Restoration of blood flow to the affected limb after initiation of unfractionated heparin and clopidogrel administration followed by outpatient treatment with dalteparin and clopidogrel was achieved in this case.

Ceruletide decreases food intake in non-obese man.

PubMed

Stacher, G; Steinringer, H; Schmierer, G; Schneider, C; Winklehner, S

1982-01-01

Cholecystokinin decreases food intake in animals and in man. This study investigated whether the structurally related ceruletide reduces food intake in healthy non-obese man. Twelve females and 12 males participated, after an over-night fast, in each of two experiments. During the basal 40 min, saline was infused IV. Thereafter, the infusion was, in random double blind fashion, either continued with saline or switched to 60 or 120 ng/kg b. wt/hr ceruletide. Butter was melted in a pan and scrambled eggs with ham were prepared in front of the subjects, who were instructed to eat, together with bread and mallow tea, as much as they wanted. With 120 ng/kg/hr ceruletide, the subjects ate significantly less (16.8 percent) than with saline (3725 kJ +/- 489 SEM and 4340 kJ +/- 536, respectively; p less than 0.025). They also reported less hunger (p less than 0.005) and activation (p less than 0.005) and activation (p less than 0.01), and had longer reaction times (p less than 0.01) and a weaker psychomotor performance (p less than 0.025). 60 ng/kg/hr ceruletide decreased food intake only slightly (6.6%; 3089 kJ +/- 253 and 3292 kJ +/- 300 respectively) and no significant changes in the above measures occurred. In conclusion, ceruletide reduces food intake in man, thus resembling the effects of cholecystokinin.

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.

Opioid-free general anesthesia in patient with Steinert syndrome (myotonic dystrophy)

PubMed Central

Gaszynski, Tomasz

2016-01-01

Abstract Introduction: We report on the anesthetic management using opioid-free method of a patient with Steinert syndrome (myotonic dystrophy, MD), autosomal dominant dystrophy which is characterized by consistent contracture of muscle following stimulation. A myotonic crisis can be induced by numerous factors including hypothermia, shivering, and mechanical or electrical stimulation. In patients with MD, hypersensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative management. If opioids are employed (systemic or neuraxial), then ICU care and continuous pulse oximetry must be considered given the high risk for respiratory depression and aspiration. Patients with MD present high sensitivity to the usual anesthetics such as volatile and muscle relaxants (both depolarizing and nondepolarizing). Opioids may induce muscle rigidity in this type of MD. Therefore, omitting opioids is recommended. Due to hypersensitivity to opioids and increased susceptibility to intra- and postoperative complications, it is recommended to introduce opioid-free anesthesia (OFA), for example, with use of dexmedetomidine (DEX). This is a new method of conducting general anesthesia without opioids and is based on concept of multimodal approach to pain management. Methods: A 31-year-old male patient (183 cm, 69 kg) was scheduled for laparoscopic operation of cholecystectomy. The patient received intravenously (IV): propofol in a dose of 250 mg followed by continuous infusion, rocuronium in a dose of 20 mg, and DEX in a loading dose of 0.6 μg/kg over 10 minutes followed by continuous infusion of dose of 0.2 μg/kg/hour. Results: The course of anesthesia and postoperative period were uneventful. The patient exited the operating theatre in a good medical state, with vitals within normal limits and fully regained consciousness. Conclusion: DEX is effective and safe for moderately painful procedures in patients with the elevated risk of respiratory and cardiovascular failure. This substance provides adequate analgesia level during surgeries of patients suffering from MD. PMID:27631259

Opioid-free general anesthesia in patient with Steinert syndrome (myotonic dystrophy): Case report.

PubMed

Gaszynski, Tomasz

2016-09-01

We report on the anesthetic management using opioid-free method of a patient with Steinert syndrome (myotonic dystrophy, MD), autosomal dominant dystrophy which is characterized by consistent contracture of muscle following stimulation. A myotonic crisis can be induced by numerous factors including hypothermia, shivering, and mechanical or electrical stimulation. In patients with MD, hypersensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative management. If opioids are employed (systemic or neuraxial), then ICU care and continuous pulse oximetry must be considered given the high risk for respiratory depression and aspiration. Patients with MD present high sensitivity to the usual anesthetics such as volatile and muscle relaxants (both depolarizing and nondepolarizing). Opioids may induce muscle rigidity in this type of MD. Therefore, omitting opioids is recommended. Due to hypersensitivity to opioids and increased susceptibility to intra- and postoperative complications, it is recommended to introduce opioid-free anesthesia (OFA), for example, with use of dexmedetomidine (DEX). This is a new method of conducting general anesthesia without opioids and is based on concept of multimodal approach to pain management. A 31-year-old male patient (183 cm, 69 kg) was scheduled for laparoscopic operation of cholecystectomy. The patient received intravenously (IV): propofol in a dose of 250 mg followed by continuous infusion, rocuronium in a dose of 20 mg, and DEX in a loading dose of 0.6 μg/kg over 10 minutes followed by continuous infusion of dose of 0.2 μg/kg/hour. The course of anesthesia and postoperative period were uneventful. The patient exited the operating theatre in a good medical state, with vitals within normal limits and fully regained consciousness. DEX is effective and safe for moderately painful procedures in patients with the elevated risk of respiratory and cardiovascular failure. This substance provides adequate analgesia level during surgeries of patients suffering from MD.

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.

Self-Administered Outpatient Antimicrobial Infusion by Uninsured Patients Discharged from a Safety-Net Hospital: A Propensity-Score-Balanced Retrospective Cohort Study.

PubMed

Bhavan, Kavita P; Brown, L Steven; Haley, Robert W

2015-12-01

Outpatient parenteral antimicrobial therapy (OPAT) is accepted as safe and effective for medically stable patients to complete intravenous (IV) antibiotics in an outpatient setting. Since, however, uninsured patients in the United States generally cannot afford OPAT, safety-net hospitals are often burdened with long hospitalizations purely to infuse antibiotics, occupying beds that could be used for patients requiring more intensive services. OPAT is generally delivered in one of four settings: infusion centers, nursing homes, at home with skilled nursing assistance, or at home with self-administered therapy. The first three-termed healthcare-administered OPAT (H-OPAT)--are most commonly used in the United States by patients with insurance funding. The fourth--self-administered OPAT (S-OPAT)--is relatively uncommon, with the few published studies having been conducted in the United Kingdom. With multidisciplinary planning, we established an S-OPAT clinic in 2009 to shift care of selected uninsured patients safely to self-administration of their IV antibiotics at home. We undertook this study to determine whether the low-income mostly non-English-speaking patients in our S-OPAT program could administer their own IV antimicrobials at home with outcomes as good as, or better than, those receiving H-OPAT. Parkland Hospital is a safety-net hospital serving Dallas County, Texas. From 1 January 2009 to 14 October 2013, all uninsured patients meeting criteria were enrolled in S-OPAT, while insured patients were discharged to H-OPAT settings. The S-OPAT patients were trained through multilingual instruction to self-administer IV antimicrobials by gravity, tested for competency before discharge, and thereafter followed at designated intervals in the S-OPAT outpatient clinic for IV access care, laboratory monitoring, and physician follow-up. The primary outcome was 30-d all-cause readmission, and the secondary outcome was 1-y all-cause mortality. The study was adequately powered for readmission but not for mortality. Clinical, sociodemographic, and outcome data were collected from the Parkland Hospital electronic medical records and the US census, constituting a historical prospective cohort study. We used multivariable logistic regression to develop a propensity score predicting S-OPAT versus H-OPAT group membership from covariates. We then estimated the effect of S-OPAT versus H-OPAT on the two outcomes using multivariable proportional hazards regression, controlling for selection bias and confounding with the propensity score and covariates. Of the 1,168 patients discharged to receive OPAT, 944 (81%) were managed in the S-OPAT program and 224 (19%) by H-OPAT services. In multivariable proportional hazards regression models controlling for confounding and selection bias, the 30-d readmission rate was 47% lower in the S-OPAT group (adjusted hazard ratio [aHR], 0.53; 95% CI 0.35-0.81; p = 0.003), and the 1-y mortality rate did not differ significantly between the groups (aHR, 0.86; 95% CI 0.37-2.00; p = 0.73). The S-OPAT program shifted a median 26 d of inpatient infusion per patient to the outpatient setting, avoiding 27,666 inpatient days. The main limitation of this observational study-the potential bias from the difference in healthcare funding status of the groups-was addressed by propensity score modeling. S-OPAT was associated with similar or better clinical outcomes than H-OPAT. S-OPAT may be an acceptable model of treatment for uninsured, medically stable patients to complete extended courses of IV antimicrobials at home.

Double-blind, placebo-controlled study of intravenous prostacyclin on hemodynamics in severe Raynaud's phenomenon: the acute vasodilatory effect is not sustained.

PubMed

Kingma, K; Wollersheim, H; Thien, T

1995-09-01

In 12 patients with severe Raynaud's phenomenon (RP: ischemic ulcers or intractable pain despite use of narcotic analgetics), we studied the acute and long-term hemodynamic effects of epoprostenol on systemic and finger skin circulation. Epoprostenol was infused intravenously (i.v., initial infusion rate of 2 ng/kg/min, with a subsequent increase of 2 ng/kg/min every 30 min to the individually tolerated maximal dose of 8 ng/kg/min) in a triple, 5-h, double-blind, placebo-controlled cross-over study. During epoprostenol infusion, systolic blood pressure (SBP) remained stable, while diastolic BP (DBP) decreased (-8 mm Hg, p < 0.02), with a simultaneous increase in heart rate (HR + 14 beats/min, p < 0.001). Forearm blood flow (FBF) increased and forearm vascular resistance (FVR) decreased during epoprostenol as compared with placebo infusion (p < 0.01). Epoprostenol caused a significant increase in fingertip skin temperature (p < 0.01) as well as in laser Doppler flux (p < 0.02) before and after a standardized cooling test of the hand as compared with placebo. The increase in transcutaneous oxygen tension reached significant difference only during recovery (p < 0.02). No long-term improvement was noted during two additional cooling tests performed 1 and 6 weeks after the completed epoprostenol or placebo triple-infusion cycle. Repeated long-lasting epoprostenol infusion immediately improves the microcirculation, but these effects are not sustained after 1 week.

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

PubMed

Bray, M J; Vick, T M; Shah, N; Anderson, S M; Rice, L W; Iranmanesh, A; Evans, W S; Veldhuis, J D

2001-07-01

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.

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

PubMed

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

1994-01-01

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

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.

Low-dose ketamine for treatment resistant depression in an academic clinical practice setting.

PubMed

Feifel, David; Malcolm, Benjamin; Boggie, Danielle; Lee, Kelly

2017-10-15

Recent studies demonstrating a rapid, robust improvement in treatment resistant depression (TRD) following a single sub-anesthetic infusion of ketamine have generated much excitement. However, these studies are limited in their generalizability to the broader TRD population due to their subject exclusion criteria which typically limit psychiatric comorbidity, concurrent medication, and level of suicide risk. This paper describes the safety and efficacy of sub-anesthetic ketamine infusions in a naturalistic TRD patient sample participating in a real-world TRD treatment program within a major university health system. The effects of a sub-anesthetic dose (0.5mg/kg) of ketamine infused IV over forty minutes on TRD patients participating in a treatment program at the University of California, San Diego was investigated by retrospectively analyzing the medical charts of 41 adult TRD patients with a diagnosis of Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Subjects were aged 48.6, 78% white, 36.6% female, and 82.9% had MDD. Significant psychiatric comorbidity existed in 73%. Average pre-infusion BDI score was 32.6 ± 8.4 (S.D) and dropped to 16.8 ± 3.1 at 24-h post-infusion (p < 0.001). The 24-h response (≥ 50% reduction from pre-infusion) and remission (BDI <13) rates were 53.7% and 41.5%, respectively. Three quarters of responders maintained responder status at 7-days. Ketamine infusions were well tolerated with occasional nausea or anxiety and mild hemodynamic effects during the infusion. Retrospective nature of this study, lack of control group and use of self-report depression ratings scales. This is the first published study of sub-anesthetic ketamine infusions in a real-world TRD population. The results suggest that this treatment is effective and well tolerated in this population. Copyright © 2017. Published by Elsevier B.V.

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.

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

Bovine acute-phase response following different doses of corticotrophin-releasing hormone (CRH) challenge

USDA-ARS?s Scientific Manuscript database

Fourteen weaned, halter-trained Angus steers (BW = 191 ± 2.1 kg) were fitted with indwelling jugular catheter and rectal temperature monitoring device on d -1 of the study. On d 0, steers were ranked by body weight and randomly assigned to receive 1 of 3 infusion treatments (i.v.): 1) 0.1 micrograms...

NASA EEE Parts and Advanced Interconnect Program (AIP)

NASA Technical Reports Server (NTRS)

Gindorf, T.; Garrison, A.

1996-01-01

none given From Program Objectives: I. Accelerate the readiness of new technologies through development of validation, assessment and test method/tools II. Provide NASA Projects infusion paths for emerging technologies III. Provide NASA Projects technology selection, application and validation guidelines for harware and processes IV. Disseminate quality assurance, reliability, validation, tools and availability information to the NASA community.

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.

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.

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.

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.

Evaluation of gastric emptying time, gastrointestinal transit time, sedation score, and nausea score associated with intravenous constant rate infusion of lidocaine hydrochloride in clinically normal dogs.

PubMed

Johnson, Rebecca A; Kierski, Katharine R; Jones, Brian G

2017-05-01

OBJECTIVE To quantify nausea and sedation scores, gastric emptying time, and gastrointestinal transit time after IV administration of a lidocaine hydrochloride bolus followed by a constant rate infusion (CRI) in clinically normal dogs. ANIMALS 6 Beagles. PROCEDURES In a crossover study, dogs were fed thirty 1.5-mm barium-impregnated spheres (BIPS) and received a saline (0.9% NaCl) solution bolus (0.05 mL/kg) IV (time 0) followed by a CRI at 10 mL/h, a lidocaine bolus (1 mg/kg) IV followed by a CRI at 25 μg/kg/min, or a lidocaine bolus (1 mg/kg) IV followed by a CRI at 50 μg/kg/min; CRIs were for 12 hours. Nausea and sedation scores were assessed and abdominal radiographs obtained immediately after feeding of BIPS and every hour for 12 hours and again 16 hours after CRI start. Percentage of BIPSs in the small and large intestines, gastric emptying time, and gastrointestinal transit time were assessed. RESULTS Gastric emptying time did not differ significantly among treatments. Significantly more BIPS were in the large intestine 4 to 7 hours after treatment start for the 50-μg/kg/min treatment than for the other 2 treatments. Six hours after treatment start, significantly more BIPS were in the large intestine for the 25-μg/kg/min treatment than for the saline solution treatment. Higher sedation and nausea scores were associated with the 50-μg/kg/min CRI. CONCLUSIONS AND CLINICAL RELEVANCE In clinically normal dogs, lidocaine CRI did not significantly affect gastric emptying. However, gastrointestinal transit time was mildly decreased and sedation and nausea scores increased in dogs administered a lidocaine CRI at clinically used doses.

[Intravenous lysine clonixinate for the treatment of migraine: an open pilot study].

PubMed

Krymchantowski, A V; Barbosa, J

1999-09-01

Several oral nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Despite its efficacy to treat migraine and other pain, there are a few commercial NSAIDs available for intravenous (i.v.) administration. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has been proven effective in various algic syndromes such as renal colic, nerve compression, muscular pain and odontalgias. The aim of this study was to evaluate the efficacy of the i.v. LC in the treatment of severe attacks of migraine. We studied prospectively 19 patients, 17 women and 2 men, ages from 18 to 57 years, with the diagnosis of migraine according to the International Headache Society criteria. The patients were oriented to proceed to the clinic once the headache has started, and were placed under an i.v. infusion of LC and saline in a superficial vein of the forearm, once the intensity reached severe. Evaluating the headache intensity after 30, 60 and 90 minutes, as well as the presence of side effects, we observed that all of the 19 patients were headache free after 90 minutes. Some patients presented mild adverse effects and the vital signs were not significantly affected. We then concluded that the i.v. infusion of the NSAID LC (2-3-chloro-o-toluidin)piridin-3-lysine carboxilate), a derived from the nicotinic acid with a chemical structure that resembles the flufenamic acid, was efficient abolishing a severe migraine attack after 90 minutes in 19 patients. Controlled studies with a double-blind and randomized design, and treating a greater number of patients and attacks are necessary to confirm these initial observations.

Comparison of ultrarapid and rapid intravenous hydration in pediatric patients with dehydration.

PubMed

Nager, Alan L; Wang, Vincent J

2010-02-01

The purpose of this study is to test the efficacy of ultrarapidly infused vs rapidly infused intravenous (IV) hydration in pediatric patients with acute gastroenteritis and moderate dehydration. Patients 3 to 36 months, with vomiting and/or diarrhea and moderate dehydration, were eligible. Subjects were randomly assigned "ultra" (50 mL/kg normal saline for 1 hour) vs "standard" (50 mL/kg normal saline for 3 hours) after failing an oral fluid challenge. Subjects were weighed and had serum electrolyte testing, and urine was obtained before/after IV hydration. Input/output and vital signs were tabulated hourly during the study. Subjects were discharged after fulfilling specified criteria. A follow-up questionnaire was completed 24 hours after discharge. Comparison data included success and timing of rehydration, number of patients who returned and/or were admitted, output during the rehydration period, laboratory differences, and serious complications. Eighty-eight of 92 subjects completed the study: 45 ultra and 43 standard. Four patients failed treatment (1 ultra and 3 standard), were hospitalized, and excluded from the study. Groups were similar regarding sex, days of symptoms, episodes of vomiting/diarrhea before treatment, capillary refill time, tears, and vital signs and laboratory results. No subject had evidence of serious complications. Ninety-one percent of subjects completed the follow-up questionnaire. Seven ultra and 6 standard subjects returned. Six ultra subjects received oral fluid, one received IV fluid, and all were discharged. Five standard subjects received oral fluid, one received IV fluid, and all were discharged. Based on this pilot study, ultrarapid hydration for 1 hour preliminarily appears to be an efficacious alternative to standard rapid hydration for 3 hours and improves emergency department throughput time. Copyright 2010 Elsevier Inc. All rights reserved.

Improved usability of a multi-infusion setup using a centralized control interface: A task-based usability test

PubMed Central

Cnossen, Fokie; Dieperink, Willem; Bult, Wouter; de Smet, Anne Marie; Touw, Daan J.; Nijsten, Maarten W.

2017-01-01

The objective of this study was to assess the usability benefits of adding a bedside central control interface that controls all intravenous (IV) infusion pumps compared to the conventional individual control of multiple infusion pumps. Eighteen dedicated ICU nurses volunteered in a between-subjects task-based usability test. A newly developed central control interface was compared to conventional control of multiple infusion pumps in a simulated ICU setting. Task execution time, clicks, errors and questionnaire responses were evaluated. Overall the central control interface outperformed the conventional control in terms of fewer user actions (40±3 vs. 73±20 clicks, p<0.001) and fewer user errors (1±1 vs. 3±2 errors, p<0.05), with no difference in task execution times (421±108 vs. 406±119 seconds, not significant). Questionnaires indicated a significant preference for the central control interface. Despite being novice users of the central control interface, ICU nurses displayed improved performance with the central control interface compared to the conventional interface they were familiar with. We conclude that the new user interface has an overall better usability than the conventional interface. PMID:28800617

Improved usability of a multi-infusion setup using a centralized control interface: A task-based usability test.

PubMed

Doesburg, Frank; Cnossen, Fokie; Dieperink, Willem; Bult, Wouter; de Smet, Anne Marie; Touw, Daan J; Nijsten, Maarten W

2017-01-01

The objective of this study was to assess the usability benefits of adding a bedside central control interface that controls all intravenous (IV) infusion pumps compared to the conventional individual control of multiple infusion pumps. Eighteen dedicated ICU nurses volunteered in a between-subjects task-based usability test. A newly developed central control interface was compared to conventional control of multiple infusion pumps in a simulated ICU setting. Task execution time, clicks, errors and questionnaire responses were evaluated. Overall the central control interface outperformed the conventional control in terms of fewer user actions (40±3 vs. 73±20 clicks, p<0.001) and fewer user errors (1±1 vs. 3±2 errors, p<0.05), with no difference in task execution times (421±108 vs. 406±119 seconds, not significant). Questionnaires indicated a significant preference for the central control interface. Despite being novice users of the central control interface, ICU nurses displayed improved performance with the central control interface compared to the conventional interface they were familiar with. We conclude that the new user interface has an overall better usability than the conventional interface.

Absorption of subcutaneously infused insulin: influence of the basal rate pulse interval.

PubMed

Hildebrandt, P; Birch, K; Jensen, B M; Kühl, C; Brange, J

1985-01-01

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

PubMed

Vallejo, C T; Pérez, J E; Domínguez, M E; Leone, B A; Machiavelli, M R; Lacava, J A; Romero, A O; Ortiz, E H; Grasso, S; Amato, S; Rodríguez, R; Barbieri, M; Romero Acuña, J; Focaccia, G; Suttora, G; Scenna, M; Boughen, J M; Romero Acuña, L A; Langhi, M J

2000-10-01

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

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.

Effects of intraoperative dexmedetomidine with intravenous anesthesia on postoperative emergence agitation/delirium in pediatric patients undergoing tonsillectomy with or without adenoidectomy: A CONSORT-prospective, randomized, controlled clinical trial.

PubMed

Cao, Jun-Li; Pei, Yu-Ping; Wei, Jing-Qiu; Zhang, Yue-Ying

2016-12-01

Postoperative emergence agitation/delirium (POED) is a common complication in pediatric surgery patients, which increases the risk of developing postoperative airway obstruction and respiratory depression. This study aims to investigate the safety and efficacy of intraoperative infusion of dexmedetomidine (DEX) and its effects on POED in pediatric patients undergoing tonsillectomy with or without adenoidectomy.Sixty patients scheduled for tonsillectomy with or without adenoidectomy, aged 2 to 8 years, were randomly allocated into 2 groups (n = 30). Pediatric patients in the group DEX received intravenous (IV) DEX 1 μg/kg over 10 minutes, followed by 0.5 μg/kg/h continuous infusion, and the same volume of 0.9% saline was administrated in the group control. Anesthesia was maintained with target-controlled infusion (TCI) of propofol and remifentanyl. Intraoperative heart rate (HR), noninvasive blood pressure (NIBP), blood oxygen saturation (SPO2), recovery time, and extubation time were recorded. Pain level was evaluated using the objective pain score (OPS), pediatric anesthesia emergence delirium (PAED) scale and Cole 5-point scale (CPS) was used to evaluate POED when patients at 0, 5, 15 minutes, and then at intervals of 15 minutes for 60 minutes after parents arrival at postanesthesia care unit (PACU).The results showed that intraoperative HR was significantly lower in group DEX (P <0.05), mean diastolic and systolic NIBP was not statistically different between groups. Time to wake and time to extubation were lengthened in group DEX as compared with group control (P <0.05). OPS and CPS were lower in group DEX at 15, 30, and 45 minutes time points (P <0.05); however, there were no significantly differences in the PAED score at different time points in the PACU.The present data suggested that intraoperative infusion of dexmedetomidine combined with intravenous anesthetics can provide satisfactory intraoperative conditions for pediatric patients undergoing tonsillectomy with or without adenoidectomy, without adverse hemodynamic effects, though the lower incidence of POED was not observed.

Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.

PubMed

Tadros, Elizabeth M; Frank, Nicholas; Donnell, Robert L

2013-07-01

To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups. Results supported the hypothesis that EMS affects horses' inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution.

PubMed

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler's formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly "adaptable" and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time.

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution

PubMed Central

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler’s formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly “adaptable” and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time. PMID:29123436

The effects of subanesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine-dependent research volunteers.

PubMed

Dakwar, Elias; Levin, Frances; Foltin, Richard W; Nunes, Edward V; Hart, Carl L

2014-07-01

Cocaine dependence involves problematic neuroadaptations that might be responsive to modulation of glutamatergic circuits. This investigation examined the effects of subanesthetic ketamine infusions on motivation for quitting cocaine and on cue-induced craving in cocaine-dependent participants, 24 hours postinfusion. Eight volunteers with active DSM-IV cocaine dependence not seeking treatment or abstinence were entered into this crossover, double-blind trial. Three 52-min intravenous infusions were administered: ketamine (.41 mg/kg or .71 mg/kg) or lorazepam 2 mg, counterbalanced into three orderings in which ketamine .41 mg/kg always preceded the .71 mg/kg dose. Infusions were separated by 48 hours, and assessments occurred at baseline and at 24 hours postinfusion. Outcomes were change between postinfusion and preinfusion values for: 1) motivation to quit cocaine scores with the University of Rhode Island Change Assessment; and 2) sums of visual analogue scale craving ratings administered during cue exposure. Compared with the active control lorazepam, a single ketamine infusion (.41 mg/kg) led to a mean 3.9-point gain in University of Rhode Island Change Assessment (p = .012), which corresponds to an approximately 60% increase over preceding values. There was a reduction of comparable magnitude in cue-induced craving (p = .012). A subsequent ketamine infusion (.71 mg/kg) led to further reductions in cue-induced craving compared with the control. Infusions were well-tolerated. Subanesthetic ketamine demonstrated promising effects on motivation to quit cocaine and on cue-induced craving, 24 hours postinfusion. Research is needed to expand on these preliminary results and to evaluate the efficacy of this intervention in clinical settings. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Graphical user interface simplifies infusion pump programming and enhances the ability to detect pump-related faults.

PubMed

Syroid, Noah; Liu, David; Albert, Robert; Agutter, James; Egan, Talmage D; Pace, Nathan L; Johnson, Ken B; Dowdle, Michael R; Pulsipher, Daniel; Westenskow, Dwayne R

2012-11-01

Drug administration errors are frequent and are often associated with the misuse of IV infusion pumps. One source of these errors may be the infusion pump's user interface. We used failure modes-and-effects analyses to identify programming errors and to guide the design of a new syringe pump user interface. We designed the new user interface to clearly show the pump's operating state simultaneously in more than 1 monitoring location. We evaluated anesthesia residents in laboratory and simulated environments on programming accuracy and error detection between the new user interface and the user interface of a commercially available infusion pump. With the new user interface, we observed the number of programming errors reduced by 81%, the number of keystrokes per task reduced from 9.2 ± 5.0 to 7.5 ± 5.5 (mean ± SD), the time required per task reduced from 18.1 ± 14.1 seconds to 10.9 ± 9.5 seconds and significantly less perceived workload. Residents detected 38 of 70 (54%) of the events with the new user interface and 37 of 70 (53%) with the existing user interface, despite no experience with the new user interface and extensive experience with the existing interface. The number of programming errors and workload were reduced partly because it took less time and fewer keystrokes to program the pump when using the new user interface. Despite minimal training, residents quickly identified preexisting infusion pump problems with the new user interface. Intuitive and easy-to-program infusion pump interfaces may reduce drug administration errors and infusion pump-related adverse events.

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.

Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial.

PubMed

Bakes, Katherine; Haukoos, Jason S; Deakyne, Sara J; Hopkins, Emily; Easter, Josh; McFann, Kim; Brent, Alison; Rewers, Arleta

2016-04-01

The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 × maintenance rate) or high volume (20 mL/kg bolus + 1.5 × maintenance rate) (n = 25 in each). After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher-volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4-1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats.

PubMed

Dahan, A; Yassen, A; Bijl, H; Romberg, R; Sarton, E; Teppema, L; Olofsen, E; Danhof, M

2005-06-01

There is evidence from animal studies suggesting the existence of a ceiling effect for buprenorphine-induced respiratory depression. To study whether an apparent ceiling effect exists for respiratory depression induced by buprenorphine, we compared the respiratory effects of buprenorphine and fentanyl in humans and rats. In healthy volunteers, the opioids were infused i.v. over 90 s and measurements of minute ventilation at a fixed end-tidal PCO2 of 7 kPa were obtained for 7 h. Buprenorphine doses were 0.7, 1.4, 4.3 and 8.6 microg kg(-1) (n=20 subjects) and fentanyl doses 1.1, 2.1, 2.9, 4.3 and 7.1 microg kg(-1) (n=21). Seven subjects received placebo. In rats, both opioids were infused i.v. over 20 min, and arterial PCO2 was measured 5, 10, 15 and 20 min after the start of fentanyl infusion and 30, 150, 270 and 390 min after the start of buprenorphine infusion. Doses tested were buprenorphine 0, 100, 300, 1000 and 3000 microg kg(-1) and fentanyl 0, 50, 68 and 90 microg kg(-1). In humans, fentanyl produced a dose-dependent depression of minute ventilation with apnoea at doses > or = 2.9 microg kg(-1); buprenorphine caused depression of minute ventilation which levelled off at doses > or = 3.0 microg kg(-1) to about 50% of baseline. In rats, the relationship of arterial PCO2 and fentanyl dose was linear, with maximum respiratory depression at 20 min (maximum PaCO2 8.0 kPa). Irrespective of the time at which measurements were obtained, buprenorphine showed a non-linear effect on PaCO2, with a ceiling effect at doses > 1.4 microg kg(-1). The effect on PaCO2 was modest (maximum value measured, 5.5 kPa). Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

PubMed

Dalziel, Stuart R; Furyk, Jeremy; Bonisch, Megan; Oakley, Ed; Borland, Meredith; Neutze, Jocelyn; Donath, Susan; Sharpe, Cynthia; Harvey, Simon; Davidson, Andrew; Craig, Simon; Phillips, Natalie; George, Shane; Rao, Arjun; Cheng, Nicholas; Zhang, Michael; Sinn, Kam; Kochar, Amit; Brabyn, Christine; Babl, Franz E

2017-06-22

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

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.

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.

Glucose intolerance in dairy goats with pregnancy toxemia: Lack of correlation between blood pH and beta hydroxybutyric acid values

PubMed Central

Lima, Miguel S.; Cota, João B.; Vaz, Yolanda M.; Ajuda, Inês G.; Pascoal, Rita A.; Carolino, Nuno; Hjerpe, Charles A.

2016-01-01

This study assessed the response to a glucose tolerance test in dairy goats with pregnancy toxemia (PT), in healthy, pregnant, non-lactating dairy goats in the last month of gestation (HP), and in healthy, lactating, non-pregnant, dairy goats in mid-lactation (HL). A 500 mL volume of a 5% glucose solution was administered by the IV route. Blood glucose concentrations returned to pre-infusion levels by 90 min in all 8 HL goats, and by 180 min in all 8 HP goats. In contrast, concentrations of blood glucose were still significantly above pre-infusion levels at 180 min post-infusion in all 8 PT goats. Thus, marked glucose intolerance was demonstrated in the PT goats, and mild intolerance was noted in the HP goats. In 25 goats diagnosed with PT and having blood beta hydroxybutyric acid (BHBA) values ≥ 2.9 mmol/L, the correlation coefficient for BHBA with blood pH was non-significant. PMID:27247464

Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice

PubMed Central

Garofalo, Stefano; D’Alessandro, Giuseppina; Chece, Giuseppina; Brau, Frederic; Maggi, Laura; Rosa, Alessandro; Porzia, Alessandra; Mainiero, Fabrizio; Esposito, Vincenzo; Lauro, Clotilde; Benigni, Giorgia; Bernardini, Giovanni; Santoni, Angela; Limatola, Cristina

2015-01-01

Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/Mφ infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment. PMID:25818172

Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit.

PubMed Central

Lipton, J M; Ticknor, C B

1979-01-01

1. Taurine infused I.C.V. after I.V. injection of leukocytic pyrogen (LP) inhibited the initial rise in body temperature and prolonged fever when infusion was stopped. 2. Similar infusion of taurine also inhibited the hypertermic effect of I.C.V. PGE2 (0.5 microgram) but did not cause prolonged hyperthermia. 3. I.C.V. administration of the taurine analogues hypotaurine and beta-alanine, compounds which have been shown previously to compete with taurine for facilitated transport in C.N.S. tissue, also inhibited the initial increase in body temperature and prolonged LP fever. 4. These results suggest that taurine prolongs LP fever by preferentially occupying a carrier system normally required for termination of the effects of endogenous pyrogens or related central mediators of fever. There was no evidence that taurine prolongs fever by blocking inactivation of central PGE2, a substance proposed previously to be a central mediator of fever. PMID:107309

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.

Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

PubMed Central

Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H.

2009-01-01

The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [14C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]3-BrPA was 1.8 ± 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit. PMID:18591216

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

PubMed

Sigal, R J; Purdon, C; Fisher, S J; Halter, J B; Vranic, M; Marliss, E B

1994-10-01

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Analgesia before a spinal block for femoral neck fracture: fascia iliaca compartment block.

PubMed

Yun, M J; Kim, Y H; Han, M K; Kim, J H; Hwang, J W; Do, S H

2009-11-01

In this prospective randomized study, the authors compared the analgesic effect of a fascia iliaca compartment (FIC) block with that of intravenous (i.v.) alfentanil when administered to facilitate positioning for spinal anaesthesia in elderly patients undergoing surgery for a femoral neck fracture. The 40 patients were randomly assigned to one of two groups, namely, the FIC group (fascia iliaca compartment block, n=20) and the IVA group (intravenous analgesia with alfentanil, n=20). Group IVA patients received a bolus dose of i.v. alfentanil 10 microg/kg, followed by a continuous infusion of alfentanil 0.25 microg/kg/min starting 2 min before the spinal block, and group FIC patients received a FIC block with 30 ml of ropivacaine 3.75 mg/ml (112.5 mg) 20 min before the spinal block. Visual analogue pain scale (VAS) scores, time to achieve spinal anaesthesia, quality of patient positioning, and patient acceptance were compared. VAS scores during positioning (mean and range) were lower in the FIC group than in the IVA group [2.0 (1-4) vs. 3.5 (2-6), P=0.001], and the mean (+/- SD) time to achieve spinal anaesthesia was shorter in the FIC group (6.9 +/- 2.7 min vs. 10.8 +/- 5.6 min; P=0.009). Patient acceptance (yes/no) was also better in the FIC group (19/1) than in the IVA group (12/8)(P=0.008). An FIC block is more efficacious than i.v. alfentanil in terms of facilitating the lateral position for spinal anaesthesia in elderly patients undergoing surgery for femoral neck fractures.

Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

PubMed

Husson, Marie-Caroline; Schiff, Manuel; Fouilhoux, Alain; Cano, Aline; Dobbelaere, Dries; Brassier, Anais; Mention, Karine; Arnoux, Jean-Baptiste; Feillet, François; Chabrol, Brigitte; Guffon, Nathalie; Elie, Caroline; de Lonlay, Pascale

2016-09-23

The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases. Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another treatment for hyperammonemia (sodium phenylacetate + sodium benzoate, haemofiltration). Eighteen side effects were reported related to the i.v. infusion (local diffusion, oedema). This 10-year retrospective study shows that i.v. sodium benzoate associated with an emergency regimen is an effective and safe treatment for acute episodes of UCD.

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

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

Fisher, B.; Packard, B.S.; Read, E.J.

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenousmore » (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.« less

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

Intraosseous infusion of blood products and epinephrine in an adult patient in hemorrhagic shock.

PubMed

Burgert, James M

2009-10-01

A 79-year-old woman presented in the postanesthesia care unit with hematemesis following replacement of a jejunostomy tube. Her medical history included recurrent stage IIIC ovarian cancer. The patient rapidly decompensated despite blood products administered through the patient's implanted medication port. The anesthesia service was consulted for resuscitative support. Examination revealed an alert, hypotensive elderly female in hemorrhagic shock. While peripheral intravenous (IV) access was sought, her condition further deteriorated. Attempts at peripheral access were determined futile and central venous access would be required. An intraosseous (IO) catheter was placed in the proximal medial aspect of the left tibia using the EZ-IO device (Vidacare Corp, San Antonio, Texas). Crystalloid and colloid fluids, blood products, and drugs were administered via the IO route, stabilizing the patient's condition during the central access procedure. The IO route was used throughout the resuscitative effort. Hemostasis was achieved, and the patient was admitted to the intensive care unit. Intraosseous infusion is a valuable and underutilized technique in managing patients in hemorrhagic shock with poor IV access. Anesthesia providers should seek education and training from those experienced in IO placement techniques and consider use of the IO route early in the resuscitative process.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

PubMed

Milano, G; Thyss, A; Serre Debeauvais, F; Laureys, G; Benoit, Y; Deville, A; Dutour, C; Robert, A; Otten, J; Behar, C

1990-04-01

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Effects of denopamine (TA-064), a new positive inotropic agent, on myocardial oxygen consumption and left ventricular dimension in anesthetized dogs.

PubMed

Ikeo, T; Nagao, T

1985-10-01

We compared the effects of denopamine (TA-064) and isoproterenol on hemodynamics, myocardial oxygen consumption and the left ventricular (LV) dimension in halothane-N2O anesthetized dogs. Denopamine (0.25-1 micrograms/kg/min, i.v., infusion X 15 min) produced a maximum increase in LV dp/dtmax by 64% of the control, without affecting aortic pressure significantly. Doses of isoproterenol (0.01-0.04 micrograms/kg/min, i.v., infusion X 15 min) were selected to produce a positive inotropic action similar to that of denopamine. Denopamine produced significantly less increasing effects in heart rate, cardiac output and myocardial oxygen consumption and had more reducing effects in LV internal diameter than isoproterenol, while isoproterenol tended to produce a more potent increase in coronary blood flow, but a smaller decrease in LV end-diastolic pressure than denopamine. PQ interval was similarly reduced. Denopamine caused no substantial increase in myocardial oxygen consumption at a lower dose, at which LV dp/dtmax was significantly increased. A weak effect of denopamine on myocardial oxygen consumption may result partly from a weak positive chronotropic effect and partly from a reduction of preload and cardiac size.

Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial.

PubMed

Glaser, Nicole S; Ghetti, Simona; Casper, T Charles; Dean, J Michael; Kuppermann, Nathan

2013-09-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of IV fluid infusion and the development of cerebral edema (CE), the most common and the most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and CE have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently, there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (FLuid therapies Under Investigation in DKA) study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically overt CE and long-term neurocognitive outcomes following DKA. © 2013 John Wiley & Sons A/S.

Telemedicine Support Groups for Home Parenteral Nutrition Users.

PubMed

Nelson, Eve-Lynn; Yadrich, Donna Macan; Thompson, Noreen; Wright, Shawna; Stone, Kathaleen; Adams, Natasia; Werkowitch, Marilyn; Smith, Carol E

2017-12-01

Patients receiving home parenteral nutrition (HPN), a life-sustaining intravenous (IV) infusion that provides nourishment and hydration to patients with short gut or inflammatory bowel diseases, are often isolated and not in visual contact with peers or health providers. One completed clinical trial (Clinical Trials.gov NCT0190028) and 1 ongoing clinical trial (Clinical Trials.gov NCT02987569) are evaluating a mobile videoconferencing-delivered support group intervention for patients on HPN and their caregivers. This home-based telemedicine intervention uses encrypted tablet-based videoconferencing to connect multiple families in real time. The twice-daily IV regimen is challenging for patients who may experience infusion catheter-related bloodstream infections, difficulties with fatigue, loss of sleep, depressive disorders, and worry over the potential life-threatening side effects and the expenses of this therapy. Using secure telemedicine, the facilitated support group intervention aims to enhance HPN home care, daily functioning, and quality of life. The authors provide the rationale for the telemedicine approach with HPN users and caregivers. They provide "how-to" information about the content and process of the facilitated support group sessions via secure videoconferencing. They share lessons learned from the ongoing evaluation of the telemedicine approach.

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.

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

PubMed

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

2006-01-01

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

Effects of Esmolol on the Prevention of Haemodynamic Responses to Tracheal Extubation after Craniotomy Operations

PubMed Central

Alkaya, Murat Alp; Saraçoğlu, Kemal Tolga; Pehlivan, Gökhan; Eti, Zeynep; Göğüş, Fevzi Yılmaz

2014-01-01

Objective The aim of this study was to evaluate the effects of esmolol infusion on the prevention of haemodynamic responses to tracheal extubation in patients undergoing elective craniotomy. Methods With approval from the Medical School Ethics Committee at Marmara University and the patients’ written consent, 30 patients between 20–65 years of age undergoing elective craniotomy were randomly placed in either the Group Esmolol (n=15) or the Group Control (n=15). Anaesthesia was induced with 5–7 mg kg−1 thiopental sodium, 1 μg kg−1 remifentanil, and 0.1 mg kg−1 vecuronium bromide iv, and was maintained with 1 MAC sevoflurane in oxygen-air mixture (50:50) and 0.25 μg kg−1 min−1 remifentanil infusion. At the end of the operation, patients inhaled 100% oxygen after the discontinuation of the anaesthetic agents. For Group Esmolol, 5 min before extubation 2 mg kg−1 esmolol in 50 mL was infused over 10 min (0.2 μg kg−1 min−1), while for Group Control, 50 mL saline was infused over 10 min. The quality of extubation was evaluated with a 5 point scale, recording heat rate, systolic, diastolic, and mean arterial pressures before infusion, 1 min after infusion, during extubation, and at 1, 3, 5, and 10 min after extubation. Results In the esmolol group, systolic, diastolic, and mean arterial pressures, as well as heart rate, decreased significantly after esmolol infusion and were significantly lower than in the control group after extubation (p<0.05). The ratio of patients with an extubation score of one was significantly higher in the esmolol group than in the control group (p<0.05). Conclusion We concluded that 2 mg kg−1 esmolol infusion before extubation can prevent hypertension and tachycardia caused by extubation in patients undergoing elective craniotomy. PMID:27366396

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

PubMed Central

George, Sobenna; Weber, David R.; Kaplan, Paige; Hummel, Kelly; Monk, Heather M.

2015-01-01

Context: Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited. Objective: The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients. Design, Setting, and Participants: This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia. Results: Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025–0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation. Conclusion: Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population. PMID:26308295

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

Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.

PubMed

Duncan, Michael A; McNicholas, Walter; O'Keeffe, Declan; O'Reilly, Maeve

2002-01-01

Sternal fracture pain is severe and is difficult to alleviate due to the forces acting on the chest wall during respiration. We describe a continuous infusion regional analgesic technique for pain due to sternal fracture. A 47-year-old woman presented with a spontaneous sternal fracture, precluding effective coughing. Diclofenac and increasing doses of opioids did not give adequate pain relief and led to opioid toxicity. Two brief periods of analgesia were achieved with deep subcutaneous infiltration of bupivacaine. An epidural catheter was positioned periosteally, and an infusion of bupivacaine was commenced at 5 mL/h, achieving long-lasting analgesia. The bupivacaine concentration was reduced in a stepwise fashion from 0.5% to 0.25% and was changed to levobupivacaine after 3 days. Adding morphine (5 mg/60 mL levobupivicaine) permitted a reduction in infusion rate. The catheter was removed after 14 days because a local infection developed that resolved uneventfully with antibiotic therapy. Continuous infusion of local anesthetic and opioid to a sternal fracture site using a periosteally positioned catheter led to successful analgesia and hence improved respiratory function. Clinicians should consider placing a periosteal catheter when pain associated with sternal fracture cannot be adequately controlled with conventional methods.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

PubMed

Wang, Chen-Yu; Lai, Yu-Ju; Hwang, Kwei-Shuai; Chen, Chi-Huang; Yu, Mu-Hsien; Chen, Huei-Tsung; Su, Her-Young

2016-10-01

Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment. Copyright © 2016. Published by Elsevier B.V.

Effect of microbubble contrast on intracranial blood flow velocity assessed by transcranial Doppler.

PubMed

Logallo, Nicola; Fromm, Annette; Waje-Andreassen, Ulrike; Thomassen, Lars; Matre, Knut

2014-03-01

Ultrasound contrast agents (UCA) salvage a considerable number of transcranial Doppler (TCD) exams which would have failed because of poor bone window. UCA bolus injection causes an undesirable increase in measured blood flow velocity (BFV). The effect of UCA continuous infusion on measured BFV has not been investigated, and some in vitro experiments suggest that gain reduction during UCA administration may also influence measured BFV. This study aimed to investigate the effect of UCA continuous infusion on BFV measured by TCD and the influence of gain reduction on these measurements in a clinical setting. The right middle cerebral artery of ten patients with optimal bone window was insonated using a 2 MHz probe. UCA were administered using an infusion pump. BFV was measured (1) at baseline, (2) during UCA infusion, (3) during UCA infusion with gain reduction, and (4) after UCA wash-out phase. Gain reduction was based on the agreement between two neurosonographers on the degree of gain reduction necessary to restore baseline Doppler signal intensity (DSI). Actual DSI was estimated offline by analysis of raw data. BFV measured during UCA infusion with no gain adjustment was significantly higher than baseline BFV [peak systolic velocity (PSV): 85.1 ± 19.7 vs. 74.4 ± 19.7 cm/s, p < 0.0001; Mean velocity (MV): 56.5 ± 11.8 vs. 50.2 ± 12.3 cm/s, p < 0.0001]. BFV measured during UCA infusion with gain reduction was not significantly higher than baseline BFV (PSV: 74.3 ± 18.9 vs. 74.4 ± 19.4 cm/s, p = 0.8; MV: 49.4 ± 11.0 vs. 50.2 ± 12.3 cm/s, p = 0.8). Actual DSI during UCA infusion with gain reduction was not significantly higher than baseline DSI (13 ± 1 vs. 13 ± 1 dB). This study shows that UCA continuous infusion leads to an increase in measured BFV which may be counteracted by reducing Doppler gain thus restoring pre-contrast DSI.

Intravenous Sedation with Low-Dose Dexmedetomidine: Its Potential for Use in Dentistry

PubMed Central

Ogawa, Sachie; Seino, Hiroaki; Ito, Hiroshi; Yamazaki, Shinya; Ganzberg, Steven; Kawaai, Hiroyoshi

2008-01-01

This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures. PMID:18788843

Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.

PubMed

Dubuc, I; Pain, C; Suaudeau, C; Costentin, J

1994-01-01

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered. The response to a test dose of [D-Trp11]neurotensin (75 ng per rat) injected intracerebroventricularly at the 10th day of the chronic infusion revealed a complete tolerance to its hypothermic effect. Thus, it appears that the analgesic effect of [D-Trp11]neurotensin is independent of a hypothermic or an incapacitating effect of the peptide and does not give rise to tolerance after a 10-day continuous administration, in contrast to the hypothermic effect.

Physical and chemical stability of high-dose ifosfamide and mesna for prolonged 14-day continuous infusion.

PubMed

Zhang, YanPing; Kawedia, Jitesh D; Myers, Alan L; McIntyre, Chelsey M; Anderson, Peter M; Kramer, Mark A; Culotta, Kirk S

2014-02-01

Ifosfamide plus mesna have been used recently in a high-dose regimen that allows this chemotherapy to be given to outpatients with less toxicity over 14 days using a portable pump. However, there is a need for published stability information. The aim of this study was to investigate the physicochemical stability of ifosfamide with mesna in normal saline at room temperature over a prolonged period of 14 days. Infusion solutions of 1:1 ifosfamide and mesna at final concentrations of 10, 20 and 30 mg/mL were prepared with 0.9% sodium chloride in PVC bags. Solutions were stored at room temperature. Concentrations of ifosfamide and mesna were measured at 0 and 1, 3, 7 and 14 days using a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection. Ifosfamide and mesna were both physicochemically stable (>94%) for 14 days in all tested infusion solutions (10, 20 and 30 mg/mL). Our stability data indicate that ifosfamide and mesna (1:1) combination can be administered as a prolonged continuous infusion with portable pump in an outpatient setting without replacement of the infusion bag. We suggest 20 mg/mL as a reasonable concentration for infusion rates of about 2-4 cc/hr over prolonged periods of time.

Physical and Chemical Stability of Urapidil in 0.9% Sodium Chloride in Elastomeric Infusion Pump.

PubMed

Tomasello, Cristina; Leggieri, Anna; Rabbia, Franco; Veglio, Franco; Baietto, Lorena; Fulcheri, Chiara; De Nicolò, Amedeo; De Perri, Giovanni; D'Avolio, Antonio

2016-01-01

Urapidil is an antihypertensive agent, usually administered through intravenous bolus injection, slow-intravenous infusion, or continuous-drug infusion by perfusor. Since to date no evidences are available on drug stability in elastomeric pumps, patients have to be hospitalized. The purpose of this study was to validate an ultra-performance liquid chromatographic method to evaluate urapidil stability in an elastomeric infusion pump, in order to allow continuous infusion as home-care treatment. Analyses were conducted by diluting urapidil in an elastomeric pump. Two concentrations were evaluated: 1.6 mg/mL and 3.3 mg/mL. For the analyses, a reverse-phase ultra-performance liquid chromatographic- photodiode array detection instrument was used. Stressed degradation, pH changes, and visual clarity were used as stability indicators up to 10 days after urapidil solution preparation. The drug showed no more than 5% degradation during the test period at room temperature. No pH changes and no evidences of incompatibility were observed. Stress tests resulted in appreciable observation of degradation products. Considering the observed mean values, urapidil hydrochloride in sodium chloride 0.9% in elastomeric infusion pumps is stable for at least 10 days. These results indicate that this treatment could be administered at home for a prolonged duration (at least 7 days) with a satisfactory response. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body model.

PubMed

Sobol, Eyal; Bialer, Meir

2004-05-01

In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t(1/2)). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation:C=Ae(-alpha t)+Be(-beta t), where A and B are concentration unit-coefficients and alpha and beta are exponential coefficients. The relationships between t(1/2) and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t(1/2). In the current paper new equations have been developed that describe the relationships between the terminal t(1/2) (or t(1/2 beta)) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). A critical value (CV) equals to the quotient of (1-ln2) and (1-beta/alpha) (CV=(1-ln2)/(1-beta/alpha)=0.307/(1-beta/alpha)) has been derived and was compared with the fraction (f(1)) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f(1)=A/alpha/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1-ln2) and infinity. As long as f(1)t(1/2) and vice versa, and when f(1)=CV, then MRT=t(1/2). Following i.v. infusion and oral administration the denominator of the CV equation does not change but its numerator increases to (0.307+beta T/2) (T-infusion duration) and (0.307+beta/ka) (ka-absorption rate constant), respectively. Examples of various drugs are provided. For every drug that after i.v. bolus shows two-compartment disposition kinetics the following conclusions can be drawn (a) When f(1)<0.307, then f(1)t(1/2). (b) When beta/alpha>ln2, then CV>1>f(1) and thus(,) MRT>t(1/2). (c) When ln2>beta/alpha>(ln4-1), then 1>CV>0.5 and thus, in order for t(1/2)>MRT, f(1) has to be greater than its complementary fraction f(2) (f(1)>f(2)). (d) When beta/alpha<(ln4-1), it is possible that t(1/2)>MRT even when f(2)>f(1), as long as f(1)>CV. (e) As beta gets closer to alpha, CV approaches its maximal value (infinity) and therefore, the chances of MRT>t(1/2) are growing. (f) As beta becomes smaller compared with alpha, beta/alpha approaches zero, the denominator approaches unity and consequently, CV gets its minimal value and thus, the chances of t(1/2)>MRT are growing. (g) Following zero and first order input MRT increases compared with i.v. bolus and so does CV and thus, the chances of MRT>t(1/2) are growing. Copyright 2004 John Wiley & Sons, Ltd.

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.

Propionate supplementation improves nitrogen use by reducing urea flux in sheep.

PubMed

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

2015-10-01

Feeding and postruminal infusion of propionate is known to increase N retention in ruminants. Our aim was to determine the role of rumen propionate on urea N recycling and gluconeogenesis in growing sheep. In Exp. 1, wether sheep ( = 6; 32.5 ± 3.57 kg BW) fitted with a rumen cannula were fed to 1.8 × ME requirement a concentrate-type ration (172 g CP/kg DM and 10.4 MJ ME/kg DM) and continuously infused into the rumen with isoenergetic (10% of dietary ME intake) solutions of either sodium acetate (control) or sodium propionate for 9-d periods in a crossover design. In Exp. 2, a different group of wether sheep ( = 5; 33.6 ± 3.70 kg BW) fitted with a rumen cannula were fed, on an isonitrogenous basis, either a control (151 g CP/kg DM and 8.4 MJ ME/kg DM) or sodium propionate-supplemented (139 g CP/kg DM and 8.9 MJ ME/kg DM) diet at 2-h intervals. [N] urea was continuously infused intravenously for the last 5 d of each period, and total urine was collected by vacuum and feces were collected by a harness bag. Over the last 12 h, [C]glucose was continuously infused intravenously and hourly blood samples were collected during the last 5 h. Propionate treatments increased ( < 0.001) the proportion of rumen propionate in both experiments. In Exp. 1, N retention was not affected by propionate infusion as compared with isoenergetic acetate. There was no effect on urea entry (synthesis) rate (UER) in Exp. 1; however, sodium propionate infusion tended ( < 0.1) to increase urinary urea elimination (UUE). In Exp. 2, feeding propionate increased ( < 0.01) N retention by 0.8 g N/d. In addition, UER was reduced by approximately 2 g urea N/d, leading to a reduction ( < 0.05) in UUE (7.0 vs. 6.2 g urea N/d). Between the 2 experiments, the proportion of UER recycled to the gut was greater with the forage-type diet in Exp. 2 (approximately 60%) compared with the concentrate-type diet in Exp. 1 (approximately 40%), although urea N fluxes across the gut remained unchanged in both experiments. In Exp. 1, glucose entry and gluconeogenesis were greater ( < 0.05) and plasma glucose tended ( < 0.1) to be greater with sodium propionate infusion than with sodium acetate infusion, but there was no difference in Cori cycling. In Exp. 2, glucose entry, gluconeogenesis, Cori cycling, and plasma glucose increased ( < 0.05) with dietary propionate. Our studies indicate that propionate inclusion in feed, but not continuous infusion in to the rumen, improves N utilization in growing sheep. The propionate effect is likely mediated by providing additional precursors for gluconeogenesis.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats

NASA Technical Reports Server (NTRS)

Morrow, B. A.; Holt, M. R.; Starcevic, V. P.; Keil, L. C.; Severs, W. B.

1992-01-01

Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non-traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics.