Vecuronium pharmacokinetics in patients with major burns.

BACKGROUND: Burn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. METHODS: Twenty adults, aged 23-58 yr, with 27-81% total body surface area (TBSA) burn, were studied at 4-57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg(-1) was given i.v. as a single bolus within 10 s. Blood samples (n=20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration-time profiles for burns and non-burns. RESULTS: A three-compartment model best described vecuronium concentration-time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min(-1), P<0.0001), which yielded shorter elimination half-life for vecuronium (5.5 vs 6.6 h, P<0.001). BURN was the single most significant covariate that explained the altered vecuronium disposition in burns. CONCLUSIONS: The altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.

Effect of bolus injection of 20 ml saline with arm elevation on the onset time of vecuronium administered via a peripheral vein: a randomised controlled trial.

We investigated whether a bolus injection of 20 ml saline with arm elevation might shorten the onset time of vecuronium administered via a dorsal hand vein. Thirty patients were randomly allocated to the bolus saline group or control group. General anaesthesia was induced and maintained with remifentanil and propofol. Vecuronium 0.1 mg.kg(-1) was administered to all patients, followed in the treatment group by bolus injection of 20 ml saline and arm elevation. Response to train-of-four stimulation was measured by acceleromyography at the adductor pollicis muscle. The mean (SD) lag time was 47.2 (14.5) s in the bolus saline group and 67.9 (12.2) s in the control group (p = 0.0002). The time to 95% block of T1 was 104.6 (29.9) s in the bolus saline group and 128.3 (15.8) s in the control group (p = 0.011). Bolus saline injection results in shortened lag time and onset time of neuromuscular block with vecuronium.

The pharmacodynamics of vecuronium in chronic renal failure patients: the impact of different priming doses.

PURPOSE: The concept of priming was introduced to facilitate a faster onset of nondepolarizing neuromuscular blocker for endotracheal intubation. Vecuronium is still very much in use for most chronic renal failure patients posted for renal transplantation. The aim of this study was to examine the pharmacodynamics of vecuronium without and with preceding different small doses. METHODS: One hundred chronic renal failure patients were assigned into four groups according to the used vecuronium priming regimen. The first control group (V(0)-group), where no priming dose was given. The other three priming groups (V(10)- , V(15)- , and V(20)-groups), where 10%, 15%, and 20% of ED(95) of vecuronium were administrated 5 min prior to the remaining intubating dose (2 × ED(95)) of vecuronium. Neuromuscular blockade was measured via acceleromyographic response of the ulnar nerve. Train-of-four (TOF) ratio was measured every minute during priming interval. Any unpleasant symptoms during precurarization were recorded. Lag time and onset time (from injection of intubating dose) were recorded. Endotracheal intubation condition was scored blindly. The duration and recovery times were also recorded. RESULTS: The significant higher incidence of symptoms of paresis was encountered in V(20)-group in comparison with other two priming groups. TOF ratio started to decrease significantly at the first minute in V(20)-group, at the second minute in V(15)-group, and at the third minute in V(10)-group, till the fourth minute in the priming interval. Although TOF ratio was still above 0.90 in V(10)-group, it was below 0.80 in V(20)-group. Priming groups did not show significant intergroup difference in onset time. However, duration and recovery times were significantly longer in priming groups in comparison with V(0)-group without priming. CONCLUSION: Priming the chronic renal failure patients with 10% of ED(95) vecuronium dose acquit the best pharmacodynamics with the fewest signs of muscle weakness. Larger vecuronium priming doses are unfavorable and convey no more clinical utility.

Development and potential clinical impairment of ultra-short-acting neuromuscular blocking agents.

Developing a non-depolarizing neuromuscular blocking agent that, like succinylcholine, has a rapid onset and a short duration of effect remains a goal of ongoing research. While rocuronium fills a portion of this need, the large doses required for rapid intubation render it a much longer-acting neuromuscular blocking agent. Postoperative residual neuromuscular block (NMB) is an increasingly recognized complication of non-depolarizing neuromuscular blocking agents. This occurs because of dosing choices for neuromuscular blocking agents and anticholinesterases as well as insensitivity of typically used monitors of depth of NMB. While antagonism of NMB is necessary with partial recovery, it is unnecessary with more complete recovery. Even when monitoring with an accelerograph, reversal of NMB is complicated. In addition to the pharmacodynamics of the individual neuromuscular blocking agents, factors such as timing of anticholinesterase administration, dose of anticholinesterase, concomitant medications, electrolyte abnormalities, and hepatic or renal disease can influence the degree of reversal. Sugammadex works differently than anticholinesterases and, when administered in appropriate doses, can reverse even profound block induced with vecuronium or rocuronium. Two new fumarate neuromuscular blocking agents have a rapid onset of effect and can be reversed at any time by administration of cysteine, which could significantly reduce the risk of postoperative residual NMB.

[Comparison of atracurium, cisatracurium and vecuronium during anaesthesia for laparoscopic surgery]. / Ocena porównawcza atrakurium, cisatrakurium i wekuronium podczas znieczulenia ogólnego do operacji laparoskopowych.

BACKGROUND: The aim of the study was to compare the intubating conditions, onset time, and duration of action of atracurium, cisatracurium, and vecuronium, when used for muscle relaxation in laparoscopic surgery with carbon dioxide inflation. In trying to find an "ideal" relaxant we compared the relative potency of these drugs, and also measured pH, PaCO2 and skin temperature. METHODS: Ninety-five ASA I and II patients were randomly allocated to three groups, to receive atracurium (I), cisatracurium (II), or vecuronium (III), during propofol/fentanyl anaesthesia. Neuromuscular transmission was monitored using accelerography (TOF GUARD). Patients were intubated after the injection of 0.5 mg kg-1 atracurium (I), 0.1 mg kg(-1) cisatracurium (II), or 0.1 mg kg(-1) vecuronium (III). Muscle relaxation was maintained with incremental doses of 0.1 0.2 mg kg(-1) and 0.03 mg kg(-1) of the relaxants respectively, given after a second response to TOF stimulation was noted. Recovery time was defined as the time from a maximal block (TOF=0) to spontaneous recovery of TOF 75%. RESULTS: Conditions for performing tracheal intubation were noted to be excellent in groups I and III, and good in group II. The mean recovery time was significantly shorter in groups II and III, than in group I. No significant correlations were found between the duration of neuromuscular blockade and pH, PaCO2 or palm skin temperature. CONCLUSIONS: Vecuronium, besides providing excellent conditions for tracheal intubation, had the fastest onset time and optimal duration of action. We found the drug to be the most suitable for laparoscopic surgery.

Sedation after intubation using etomidate and a long-acting neuromuscular blocker.

BACKGROUND: Etomidate is an imidazole hypnotic which is commonly used by emergency medicine physicians during rapid sequence intubation. Etomidate's duration of action is significantly shorter than that of commonly used long-acting paralytic medications (3-12 minutes vs 25-73 minutes). If additional sedative medications are not administered in the paralyzed patient before the conclusion of etomidate's duration of action, patients are at risk for experiencing paralysis without adequate sedation. OBJECTIVE: To evaluate the frequency of the administration of additional sedation in pediatric emergency department patients undergoing endotracheal intubation with etomidate and a long-acting paralytic agent. METHODS: This study was a retrospective review of pediatric patients undergoing endotracheal intubation in a tertiary pediatric emergency department between July 2001 and December 2005. All patients intubated with etomidate and rocuronium or vecuronium were eligible for inclusion; patients with seizures were excluded. Data elements included the following: demographic variables, presenting complaint, intubation indication, medications used, time from etomidate administration to the administration of an additional sedative, Glasgow Coma Scale (GCS) score, and patient disposition. RESULTS: During the study period, 276 pediatric intubations were reviewed with 104 patients receiving etomidate and rocuronium or vecuronium. Twenty cases were excluded, 15 cases with documented seizures and 5 incomplete/missing charts. Eighty-four records were included in the final analysis. The mean age is 84 +/- 65 months; 62 (73.8%) patients were male; the mean GCS was 8.44 +/- 3.9, with a median GCS of 8 (interquartile range 6,11), and 41 (48.8%) of patients presented with blunt trauma. The mean time from etomidate to the administration of additional sedation was 46 +/- 49 minutes. Eleven (13.1%) patients received no additional sedative after etomidate administration, whereas only 20 (23.8%) patients were given a sedative within 15 minutes of the administration of etomidate. Fifty-three (63.1%) patients received an additional sedative more than 15 minutes after the administration of etomidate. CONCLUSIONS: A significant proportion of pediatric patients receiving etomidate and rocuronium or vecuronium during endotracheal intubation are likely experiencing ongoing paralysis without adequate sedation. Emergency medicine physicians should be cognizant of this when using these medications for facilitating intubation.

Morphine metabolite pharmacokinetics during venoarterial extra corporeal membrane oxygenation in neonates.

OBJECTIVE: To examine morphine metabolite serum concentrations in neonates undergoing venoarterial extra corporeal membrane oxygenation (ECMO) and to quantify clearance differences between these neonates and those subjected to noncardiac major surgery. PATIENTS AND METHODS: This was an observational study in level III referral centre. Fourteen neonates (< 7 days old) undergoing ECMO were included. Morphine and concomitant medications were given by protocol, adapted to the clinical conditions of the neonates. Pharmacokinetic findings were compared with those from a previous study in infants after noncardiac major surgery. Nonlinear mixed-effect modelling was used. Parameter estimates were standardised to a 70 kg person using allometric modeling RESULTS: Morphine-3-glucuronide (M3G) was the predominant metabolite. Formation clearance to M3G at the start of ECMO on day 1 was lower than those in postoperative children, but matured more rapidly. After 10 days formation clearances of M3G in neonates on ECMO equalled those of postoperative children. Higher ECMO flows were associated with reduced formation clearances. Elimination clearances of M3G, but not morphine-6-glucuronide (M6G), were lower in the ECMO neonates; this was attributable to reduced renal clearance. These elimination clearances were correlated positively with ECMO flow and negatively with dopamine dose. Haemofiltration cleared M3G and M6G, but not morphine. CONCLUSION: Formation clearance to M3G, the predominant metabolite, is reduced during the first 10 days of ECMO. Elimination clearance of M3G and M6G is related to creatinine clearance. ECMO flow had a small effect on metabolite clearance. Higher flows were associated with decreased formation clearances, possibly reflecting illness severity. Dopamine dose reflected decreased renal clearance.

The efficacy of intratracheal administration of vecuronium in rats, compared with intravenous and intramuscular administration.

To investigate the suitability of the intratracheal (IT) route as an alternative route for the administration of vecuronium, we compared the pharmacodynamic parameters for neuromuscular block in three groups of rats given vecuronium via the IT, IM, and IV routes. We also examined the pharmacokinetics of vecuronium in the three groups. The doses for the IT, IV, and IM groups were set at 1.50, 0.300, and 2.25 mg/kg, respectively. The onset of action in the IT group (127 +/- 17 s) was significantly earlier than that in the IM group (267 +/- 62 s), and significantly later than that in the IV group (18 +/- 7 s) (P < 0.05 by analysis of variance and the Tukey-Kramer analysis). The duration of action in the IT group (794 +/- 162 s) was significantly longer than that in the IV group (93 +/- 30 s) but not significantly different from that in the IM group (743 +/- 131 s). The recovery index in the IT group (134 +/- 30 s) was significantly shorter than that in the IM group (222 +/- 47 s) and significantly longer than that in the IV group (32 +/- 12 s). Although IT administration of vecuronium is still slower than IV administration, it appears to be more advantageous as compared with IM administration, given the more rapid absorption and faster onset of action.

Randomised controlled trial comparing cisatracurium and vecuronium infusions in a paediatric intensive care unit.

OBJECTIVE: To evaluate and compare the efficacy, infusion rate and recovery profile of vecuronium and cisatracurium continuous infusion in critically ill children requiring mechanical ventilation. DESIGN AND SETTING: Prospective, randomised, double-blind, single-centre study in critically ill children in a paediatric intensive care unit in a tertiary children's hospital. METHODS: Thirty-seven children from 3 months to 16 years old (median 4.1 year) were randomised to receive either drug; those already receiving more than 6 h of neuromuscular blocking drugs were excluded. The Train-of-Four (TOF) Watch maintained neuromuscular blockade to at least one twitch in the TOF response. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 70%. RESULTS: The cisatracurium infusion rate in nineteen children averaged 3.9+/-1.3 microg kg(-1) min(-1) with a median duration of 63 h (IQR 23-88). The vecuronium infusion rate in 18 children averaged mean 2.6+/-1.3 microg kg(-1) min(-1) with a median duration of 40 h (IQR 27-72). Median time to recovery was significantly shorter with cisatracurium (52 min, 35-73) than with vecuronium (123 min, 80-480). Prolonged recovery of neuromuscular function (>24 h) occurred in one child (6%) on vecuronium. CONCLUSIONS: Recovery of neuromuscular function after discontinuation of neuromuscular blocking drug infusion in children is significantly faster with cisatracurium than vecuronium. Neuromuscular monitoring was not sufficient to eliminate prolonged recovery in children on vecuronium infusions.