Comparative potency of steroidal neuromuscular blocking drugs and isobolographic analysis of the interaction between rocuronium and other aminosteroids

We have determined the relative potency of rocuronium, pancuronium, pipecuronium and vecuronium, and examined the nature of the interaction of rocuronium with the other three steroidal neuromuscular blocking drugs. We studied the dose-response relationships of each drug and their combination with rocuronium in 200 ASA I or II patients during propofol-fentanyl-nitrous oxide-oxygen anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to single twitch stimulation of the ulnar nerve at 10-s intervals. The dose- response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess the combined effect of equipotent doses of rocuronium and vecuronium, pipecuronium or pancuronium and to define the type of interaction between these drugs. The isobolograms were constructed by plotting single-drug ED50 points on the dose co-ordinates, and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the twitch height for rocuronium, pancuronium, pipecuronium and vecuronium were 144.8 (95% confidence intervals 140.4-149.3), 32.4 (31.7-32.9), 27.1 (26.5-27.6) and 23.7 (22.7-24.8) micrograms kg-1, respectively. Corresponding doses producing 95% depression (ED95) of twitch height were, respectively, 322.1 (307.5-337.3), 58.1 (56.2-60.1), 48.7 (46.9- 50.5) and 39.9 (38.4-41.4) micrograms kg-1. Based on the estimate of ED50, the relative potency was 1:4.5:5.4:6, respectively. The interaction between rocuronium and vecuronium, pipecuronium or pancuronium was found to be additive.      

Neuromuscular and cardiovascular effects of pipecuronium

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under "balanced" and enflurance anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipecuronium was greater under enflurane (ED95 = 23.6 +/- 1.1 micrograms.kg-1 (mean +/- SEM)] than under balanced (ED95 = 35.1 +/- 17 micrograms.kg-1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 micrograms.kg-1) and enflurane anaesthesia (ED95 = 27.4 micrograms.kg-1). Following the administration of 2 x ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 x ED95 dose of pipecuronium (110.5 +/- 0.3 min) or pancuronium (115.8 +/- 8.1 min) were similar and about three times longer than that of vecuronium (36.3 +/- 2.1 min). The recovery indices of pipecuronium (44.5 +/- 8.2 min) and pancuronium (41.3 +/- 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 +/- 1.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine

We have examined the effects of different benzyl-isoquinolinium and steroidal neuromuscular blocking compounds on plasma concentrations of histamine, heart rate and arterial pressure in surgical patients. A single, rapid (5-s) bolus of mivacurium 0.2 mg kg-1, atracurium 0.6 mg kg-1, tubocurarine 0.5 mg kg-1, vecuronium 0.1 mg kg-1 or rocuronium 0.6 mg kg-1 was administered to 75 patients (n = 15 in each group). Anaesthesia was induced with thiopentone 6 mg kg-1 i.v. and maintained with isoflurane and 70% nitrous oxide in oxygen. Venous blood samples were obtained before induction, 1 min after thiopentone and 1, 3 and 5 min after administration of the neuromuscular blocking drug. Mivacurium, atracurium and tubocurarine caused 370%, 234% and 252% increases in plasma histamine concentrations at 1 min, respectively. Corresponding values at 3 min were 223%, 148% and 157%, respectively. These changes were significant (P < 0.01) at 1 and 3 min. In contrast, the rocuronium and vecuronium groups had no significant changes in either plasma histamine concentrations or haemodynamic variables.      

Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

We have determined the pharmacokinetics and pharmacokinetic- pharmacodynamic relationship of rocuronium in infants and children. We studied infants (n = 5, 0.1-0.8 yr) and children (n = 5, 2.3-8 yr), ASA II, in the ICU while undergoing artificial ventilation under i.v. anaesthesia with an arterial cannula in situ and the EMG of the adductor pollicis muscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) mg kg-1 min-1 was given i.v. over +/- 5 min until 85% neuromuscular block was obtained. Arterial blood samples were obtained over 240 min. Plasma concentrations were measured by HPLC. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. Statistical analysis was performed using the Mann-Whitney U test (P < 0.05). The mean administered dose was 0.32 (SD 0.08) mg kg-1 and 0.4 (0.1) mg kg-1 for infants and children, respectively. Infants differed from children in plasma clearance (4.2 (0.4) vs 6.7 (1.1) ml min-1 kg-1), distribution volume at steady state (231 (32) vs 165 (44) ml kg-1), mean residence time (56 (10) vs 26 (9) min), concentration in the effect compartment at 50% block (1.2 (0.4) vs 1.7 (0.4) mg litre-1) and the slope of the concentration-effect relationship (5.7 (1.3) vs 3.9 (0.5)). Calculated mean ED90 values were 0.26 and 0.34 mg kg-1 for infants and children, respectively. The time course of neuromuscular block after equipotent doses did not differ.      

The effect of adenosine triphosphate on vecuronium-induced neuromuscular block

Continuous IV adenosine triphosphate administration has been used during surgery in the expectation of analgesic and vasodilative effects. Because adenosine triphosphate inhibits neuromuscular transmission, we investigated whether the neuromuscular effect of vecuronium was enhanced by IV adenosine triphosphate in 29 patients randomly given either continuous IV adenosine triphosphate 0.1 mg.kg(-1).min(-1) or 0.9% NaCl when undergoing elective minor surgery. Anesthesia was induced and maintained with propofol. Neuromuscular monitoring was recorded from the adductor pollicis muscle using electromyography with train-of-four stimulation of the ulnar nerve. Vecuronium 25, 30, or 40 microg/kg was given and lag time, onset time, and maximum block were recorded. ED50 and ED95 values for each group were derived from least squares linear regression analysis. ED50 and ED95 values were 29 microg/kg and 44 microg/kg, respectively, for the adenosine triphosphate group and 26 microg/kg and 46 microg/kg, respectively, for the controls. Differences in lag time, onset time, and neuromuscular responses between the two groups were not statistically significant. A significantly larger number of patients in the adenosine triphosphate group showed hypotension (systolic blood pressure <80 mm Hg). Our results demonstrated that adenosine triphosphate 0.1 mg.kg(-1).min(-1) did not enhance the neuromuscular block induced by vecuronium.     

Comparison of suxamethonium and different combinations of rocuronium and mivacurium for rapid tracheal intubation in children

The use of suxamethonium in children is associated with undesirable side effects. The synergistic effect of a rocuronium-mivacurium combination can be considered as an acceptable alternative to suxamethonium in clinical practice. The calculated ED50 of the rocuronium-mivacurium mixture was only 62% of the predicted value assuming a purely additive interaction. The use of this combination has not been evaluated in children. In this two-part study, we assessed the intubating conditions and pharmacodynamics of suxamethonium, rocuronium, mivacurium or a rocuronium-mivacurium combinations in children. We studied 120 ASA I children of both sexes, aged 3-10 yr. Children were premedicated with trimeprazine 2 mg kg-1 orally, and received fentanyl 2 micrograms kg-1 and propofol 2 mg kg-1 for induction of anaesthesia. They were allocated randomly to receive one of the following drugs or drug combinations: suxamethonium 1.0 mg kg-1, mivacurium 0.2 mg kg-1, rocuronium 0.6 or 0.9 mg kg-1, mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 or mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1. In part 1, 60 s after administration of the neuromuscular blocking drug or drug combination, tracheal intubation was performed in 60 children by mimicking rapid sequence induction, and intubating conditions were evaluated by a blinded investigator according to a standard score. In part 2, neuromuscular monitoring was established before administration of neuromuscular blocking agent(s) and the time from injection of drug or drug combination until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded in another 60 children. The frequency of distribution of excellent or good intubating conditions in the higher dose of rocuronium and the combination groups were similar to those in the suxamethonium group, but significantly different (P < 0.05) from those in the mivacurium group. Mean onset time was faster in the suxamethonium (55.1 (SD 11.4) s), rocuronium 0.9 mg kg-1 (70.5 (37.7) s), mivacurium 0.1 mg kg-1 with rocuronium 0.3 mg kg-1 (67 (35.9) s) and mivacurium 0.15 mg kg-1 with rocuronium 0.45 mg kg-1 (55 (26.7) s) groups compared with the mivacurium 0.2 mg kg-1 (116 (26.8) s) and rocuronium 0.6 mg kg-1 (97.9 (29) s) groups. This study demonstrated that the combination of rocuronium 0.45 mg kg-1 and mivacurium 0.15 mg kg-1 could possibly be considered as an acceptable alternative to suxamethonium when rapid sequence induction of anaesthesia is indicated in children because it provides uniform excellent intubating conditions and complete neuromuscular block in < 60 s.      

Effects of rocuronium and vecuronium on intracranial pressure, mean arterial pressure and heart rate in neurosurgical patients

We have evaluated the effects of a single bolus dose of rocuronium 0.6 mg kg-1 (group 1, n = 10) or vecuronium 0.1 mg kg-1 (group 2, n = 10) on intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and heart rate (HR) in 20 neurosurgical patients undergoing mechanical ventilation of the lungs during continuous sedation with sufentanil and midazolam. Before and after neuromuscular block using twice the ED90 of the blockers, ICP, MAP, CPP and HR were recorded continuously for 15 min. Treatment caused no significant changes in ICP, CPP or MAP and there was no evidence of histamine release. Mean maximum block in the rocuronium group was slightly less than that in the vecuronium group (95.9 (3.1)% vs 100%; ns) The difference between the two groups in onset time (rocuronium 142 (62) s, vecuronium 192 (64) s; P = 0.04) was significant. Patients in the rocuronium group showed a slight (7(4)%) but significant (P = 0.003) increase in heart rate.      

Interactions between ORG9426 and other non-depolarizing neuromuscular blocking agents in ratsin vivo

In this study, combined neuromuscular blocking effects of ORG9426 with other non-depolarizing neuromuscular blocking agents were investigated. About 20% steady state neuromuscular block was established by a continuous infusion of one of 6 neuromuscular blocking agents (ORG9426, vecuronium, pancuronium, pipecuronium, d-tubocurarine and metocurine). Then 1/7 of the ED50 of ORG9426 or one of other neuromuscular blocking agents was administered in a single injection, and the increase in the neuromuscular block was observed. The combined neuromuscular blocking effect of ORG9426 and d-tubocurarine or ORG9426 and metocurine was significantly (P 0.05) greater than that of each corresponding control (the combination of same neuromuscular blocking agent). The effect of d-tubocurarine was also potentiated by vecuronium, pancuronium and pipecuronium. These potentiations were not observed between ORG9426 and pancuronium, pipecuronium or vecuronium. Possible mechanisms of these synergistic interactions were discussed.(Watanabe K: Interactions between ORG9426 and other non-depolarizing neuromuscular blocking agents in rats in vivo. J Anesth 6: 277–283, 1992)     

Effect of smoking on dose requirements for vecuronium

We have compared the potency of vecuronium given to 12 smokers and 12 non-smokers during propofol-alfentanil-nitrous oxide anaesthesia. After obtaining individual dose-response curves, bolus doses of vecuronium were given to maintain neuromuscular block at 90-98% for 60 min. Adductor pollicis EMG was used to monitor neuromuscular block. Mean ED95 values were 61.38 micrograms kg-1 and 47.49 micrograms kg-1 for smokers and non-smokers, respectively (P < 0.01). The dose of vecuronium to maintain 90-98% neuromuscular block was 25% higher in smokers than in non-smokers (96.80 vs 72.11 micrograms kg-1 h-1; P < 0.01). These data reflect the effects of smoking on neuromuscular block induced by vecuronium. The effect may be at the receptor level, although possible increased metabolism of vecuronium in smokers cannot be excluded.      

Neuromuscular blocking effects and train-of-four fade with cisatracurium: comparison with other nondepolarising relaxants

Neuromuscular blocking drugs exhibit different degrees of fade in response to train-of-four stimulation believed to represent their relative prejunctional effects. The present study was designed to compare the train-of-four fade after cisatracurium and compare this with other commonly used muscle relaxants. Train-of-four fade during onset and recovery of block were recorded after administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1, vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion. Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The onset and recovery of block were also measured. Train-of-four fade during onset of block was greater with the lower dose of cisatracurium compared with the higher dose of cisatracurium and all other relaxants. Train-of-four fade during recovery was similar. The median times (and ranges) for the onset of maximum block were 3.4 (2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium, respectively. The median times (and ranges) for the recovery of T1 to 25% of control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43 (37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117); and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1, atracurium, mivacurium, vecuronium and recuronium, respectively.     

Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium- induced neuromuscular block but did not increase speed of onset.      

A comparison of the pharmacodynamics of rocuronium and vecuronium during halothane anaesthesia

Thirty healthy patients were randomised to receive either a single bolus dose of rocuronium 0.6 mg.kg-1 or vecuronium 0.1 mg.kg-1 during halothane anaesthesia. Onset time, duration 25, duration 75 and train-of-four 70 were measured. The onset of neuromuscular blockade following rocuronium was more rapid than vecuronium (p = 0.0001). All other pharmacodynamic parameters were similar. During the first minute following injection of the neuromuscular blocking agent, the heart rate increased by 36% in the rocuronium group but remained stable in those patients who received vecuronium (p = 0.0008). No adverse effects were noted in either group.     

Post-tetanic count and train-of-four responses during neuromuscular block produced by vecuronium and infusion of nicardipine

We have examined onset and recovery of neuromuscular block produced by vecuronium using either post-tetanic count (PTC), or the first twitch of the train-of-four (TOF) (T1/T0) and TOF ratio (T4/T1) during continuous infusion of nicardipine. Sixty adult patients were allocated to one of four groups of 15 patients each: nicardipine-PTC, nicardipine- TOF, control-PTC and control-TOF. In the nicardipine-PTC and nicardipine-TOF groups, nicardipine 0.03 mg kg-1 was given before vecuronium 0.1 mg kg-1 and a continuous infusion of nicardipine was started immediately at a rate of 2 micrograms kg-1 min-1. Mean time from administration of vecuronium to onset of neuromuscular block in the nicardipine-PTC and nicardipine-TOF groups was significantly shorter than in the control-PTC and control-TOF groups (166 (SD 39) vs 220 (28) s; P < 0.05). There was no significant difference in recovery of PTC between the nicardipine-PTC and control-PTC groups or in recovery of TOF ratio in the nicardipine-TOF and control-TOF groups. However, during recovery, T1/T0 in the nicardipine-TOF group was significantly less than that in the control-TOF group, 60-100 min after administration of vecuronium.      

Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ketamine enhances Phase I and Phase II neuromuscular block of succinylcholine

The effect of intravenous injection of ketamine 2, 5 and 10 mg.kg-1 on the neuromuscular blocking action of succinylcholine was studied on the indirectly stimulated adductor pollicis muscle twitch of monkeys anaesthetized with 0.5-1.0 per cent halothane in oxygen. Neuromuscular block was quantified by single twitches evoked at 0.1 Hz. The changing nature of neuromuscular block from Phase I to Phase II was monitored periodically by train-of-four fade. In the absence of succinylcholine, ketamine had no consistent neuromuscular effect of its own. In the presence of succinylcholine, ketamine in a dose-dependent manner potentiated both the Phase I and the Phase II neuromuscular blocking effect of succinylcholine. In Phase I, 2 mg.kg-1 of ketamine reduced the ED50 of succinylcholine from 0.46 +/- 0.07 mg.kg-1 to 0.33 +/- 0.06 mg.kg-1 (P less than 0.01), and increased its 25-75 per cent recovery index from 4.0 +/- 0.4 min to 5.3 +/- 0.1 min (P less than 0.01). In Phase II, ketamine in the same dose deepened a steady neuromuscular block maintained by succinylcholine infusion from 48 +/- 3 per cent block to 71 +/- 2 per cent block (P less than 0.01). We concluded that ketamine potentiates the Phase I and the Phase II neuromuscular blocks of succinylcholine.     

Pipecuronium versus high dose vecuronium

The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were studied during nitrous oxide anaesthesia supplemented with isoflurane. Pipecuronium 0.06 mg.kg-1 had a similar duration of action to vecuronium 0.015 mg.kg-1 (42 vs 49 min). Patients who received vecuronium had a shorter onset time of neuromuscular blockade (p less than 0.01). The use of pipecuronium was associated with marked cumulation.     

Effects of vecuronium and rocuronium in antagonistic laryngeal muscles and the anterior tibial muscle in the cat

BACKGROUND: Adequate vocal cord paralysis and full recovery of laryngeal muscle function are important when muscle relaxants are used perioperatively. This study was designed to compare the effects of vecuronium and rocuronium at the vocal cord abductor and adductor muscles and the anterior tibial muscle in cats. METHODS: Twelve adult cats were studied under pentobarbitone-N2O/O2-anesthesia. After supramaximal electrical stimulation of the peroneal nerve and the recurrent laryngeal nerve (0.1 Hz and intermittent train-of-four) evoked electromyographic responses were obtained from the anterior tibial muscle, the posterior cricoarytenoid muscle (vocal cord abductor) and two vocal cord adductor muscles, the lateral cricoarytenoid and the vocal muscle. Six cats received bolus doses of increasing size of vecuronium (ED90 22.5 microg x kg(-1)) and six cats rocuronium (ED90 90 microg x kg(-1)). RESULTS: Equipotent doses of vecuronium and rocuronium caused a similar degree of paralysis in all muscles (vecuronium ED90: 70% blockade at the posterior cricoarytenoid, 83% at the lateral cricoarytenoid, 84% at the vocal muscle and 90% at the anterior tibial muscle; rocuronium ED90: 71% at the posterior cricoarytenoid, 67% at the lateral cricoarytenoid, 78% at the vocal muscle and 90% at the anterior tibial muscle; vecuronium 2 x ED90: 93% blockade at the posterior cricoarytenoid, 95% at the lateral cricoarytenoid, 97% at the vocal muscle and 99% at the anterior tibial muscle; rocuronium 2 x ED90: 89% blockade at the posterior and lateral cricoarytenoid, 93% at the vocal muscle and 100% at the anterior tibial muscle). Onset time was significantly shorter at the posterior cricoarytenoid muscle (290 s) compared to the lateral cricoarytenoid muscle (400 s) after vecuronium ED90 and to the vocal muscle (150 s versus 210 s) after rocuronium ED90. Compared to the anterior tibial muscle (interval 25-75%: 6.5 min after vecuronium 2 x ED90 and 3.3 min after rocuronium 2 x ED90 and to the posterior cricoarytenoid muscle (interval 25-75%: 7 min after vecuronium 2 x ED90 and 4.3 min after rocuronium 2 x ED90), recovery of laryngeal adductor muscle function was markedly delayed with both neuromuscular blocking drugs (interval 25-75% at the lateral cricoarytenoid and vocal muscle: 14 min and 15.8 min after vecuronium 2 x ED90 and 10.3 min and 11.6 min after rocuronium 2 x ED90 respectively). CONCLUSION: In cats, the time course of neuromuscular blockade after vecuronium and rocuronium differs in antagonistic laryngeal muscles. The protective laryngeal function of glottis closure recovers later than vocal cord abduction after both vecuronium and rocuronium.     

Postoperative residual block after intermediate-acting neuromuscular blocking drugs

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.     

Pharmacokinetics and disposition of pipecuronium bromide in the cat

The pharmacokinetics and hepatic disposition of pipecuronium have been investigated in cats with normal and absent renal function. A combined fluorimetric and chromatographic technique was used to determine the concentrations of pipecuronium and its metabolites in the samples. Following intravenous injection of 150 micrograms kg-1, pipecuronium disappeared from the plasma bi-exponentially with half-lives of 9.8 +/- 5.4, 77.7 +/- 9.7 min and 7.2 +/- 5.0, 100, 6 +/- 23.7 min; the Vd was 362.3 +/- 74.9 ml kg-1 and 123.7 +/- 14.6 ml kg-1 and the clearance was 5.0 +/- 0.9 ml min-1 kg-1 and 1.0 +/- 0.1 ml min-1 in the animals with and without renal function, respectively. In the animals with normal kidney function 53%, 12% and 8% of the administered dose of pipecuronium were recovered within 8 h in the urine, bile and liver, respectively. In 'nephrectomized' cats the lack of renal elimination was to a great extent compensated for by increased hepato-biliary elimination. Absence of renal function significantly altered the pharmacokinetic parameters and prolonged the time-course of the neuromuscular blocking effects of pipecuronium. Neither temporary hepatic exclusion nor intraportal administration of pipecuronium indicated any significant role of the liver in handling pipecuronium. Renal excretion seems to be the predominant route of elimination. No metabolites were found in this study.     

Rocuronium zur elektiven Narkoseeinleitung Verlauf der neuromuskulären Blockade und Intubationsbedingungen nach 2facher ED95 (0,6 mg/kg) und nach Dosisreduktion (0,4 mg/kg)

BACKGROUND: Rocuronium is a non-depolarising neuromuscular blocking agent structurally related to vecuronium. The compound has a rapid onset and an intermediate duration of action. The rapid onset is of importance in patients at risk for pulmonary aspiration, for elective induction of anaesthesia slower onset properties generally are accepted. In this context, we asked whether the induction dose of rocuronium may be reduced to doses smaller than 2 x ED95 in situations in which slower onset properties may be acceptable. METHODS: The time course of neuromuscular block and intubating conditions of two different doses rocuronium, 2 x ED95 (0.6 mg/kg) and 1.3 x ED95 (0.4 mg/kg), were investigated in 90 patients. We first determined the time course of neuromuscular block using electromyography (EMG), n = 15 for each group. In the second part the intubating conditions 3 min after injection of either rocuronium 0.6 mg/kg or rocuronium 0.4 mg/kg were evaluated, n = 30 for each group. RESULTS: In the present study reduction of the dose of rocuronium led to a slower onset (148 +/- 32 s vs. 220 +/- 30 s; P < 0.05) and a shorter clinical duration (21 min +/- 4 vs. 36 +/- 7 min; P < 0.05). The recovery index was modified by the dose reduction: 11 +/- 3 min after 0.6 mg/kg rocuronium and 9 +/- 2 min after 0.4 mg/kg. After both doses of rocuronium the intubating conditions were good to excellent, no difference between both rocuronium groups were found. CONCLUSION: In the present study dose reduction from 0.6 mg/kg rocuronium to 0.4 mg/kg rocuronium led to a slower onset and reduced clinical duration. However, the intubating conditions, evaluated 3 min after injection of the muscle relaxant were comparable. This offers new possibilities for muscle relaxation for surgical or diagnostic procedures of short duration and may reduce costs.