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Time-course of action of rocuronium 0.3 mg.kg-1 in children with and without endstage renal failure.

BACKGROUND: The time-course of the neuromuscular effects of rocuronium 0.3 mg.kg-1 during nitrous oxide-halothane anaesthesia in children with and without renal failure is unknown. This study compared the neuromuscular blocking effects in these groups. METHODS: The study was approved by the Hospital Ethical Committee. In the control group, 14 healthy children without renal disease were scheduled for various elective surgical procedures. Sixteen children with endstage renal failure, 14 of whom were already on renal dialysis, were scheduled for (re)placement of dialysis catheters (n=14) or for renal transplantation (n=2). Anaesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Acceleromyographic thumb adduction after supramaximal ulnar nerve stimulation was recorded using train-of-four stimulation every 15 s. The onset time, the time to recovery of the first twitch to 25% or 75% and to recovery of a train-of-four ratio of 0.7 after rocuronium 0.3 mg.kg-1 were measured. Statistical analysis was performed with Student's t-test. P < 0.05 was considered statistically significant. RESULTS: The onset time was longer in children with renal failure (139 s, SD=71) than in control children (87 s, SD=43) (P=0.02). There were no significant differences in the duration of action of rocuronium between children without renal failure and in 15 out of 16 children with renal failure. CONCLUSIONS: In children with renal failure, aged over 1 year, a single bolus dose of rocuronium 0.3 mg.kg-1 does not cause a prolonged block, but has a slower onset than in healthy children.

Androstanols↗

Time course of neuromuscular blockade with rocuronium in children with intracardiac shunts.

OBJECTIVE: To evaluate the time course of neuromuscular blockade after rocuronium in children with intracardiac shunts. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Consecutive children (n = 52) with intracardiac shunts scheduled for elective cardiac surgery. Participants were allocated to 2 groups according to the direction of the shunt. INTERVENTIONS: Rocuronium, 0.6 mg/kg, was administered for muscle relaxation. The ulnar nerve was stimulated at 20-second intervals with a supramaximal 2-Hz train-of-4 stimulation (TOF-Guard nerve stimulator; Biomet International, Odense, Denmark). The onset time to maximal twitch depression and the time to clinical recovery were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: The time to maximal block was significantly faster in children with a right-to-left shunt: 56.8 +/- 5.3 seconds versus 77.1 +/- 6.6 seconds (p = 0.01). There was a tendency to shorter recovery in children with a right-to-left shunt: 42.3 +/- 6.1 minutes versus 55.4 +/- 4.9 minutes (p = NS). CONCLUSION: This study shows a more rapid onset of rocuronium in children with cyanotic congenital heart disease. In these patients, rocuronium is indicated, particularly for rapid airway control.

Androstanols↗

[Effect of rocuronium on the diaphragm, musculus adductor pollicis and orbicularis oculi in two groups of different age].

OBJECTIVE: Onset time and recovery from non depolarising neuromuscular blockade depends on the tested muscle and is influenced by the age of the patient. This study compares the neuromuscular blocking effect of rocuronium on the diaphragm, adductor pollicis and orbicularis oculi muscle in young and elderly patients. METHODS: After institutional ethics committee approval and written informed consent, 20 adult patients (ASA I - II), age 18 - 59 and > 65, have been included. Neuromuscular response was measured by accelerography for the adductor pollicis and orbicularis oculi muscle. Monitoring of the diaphragm consisted of measurement of the airway pressure against an occluded tracheal tube during magnetic phrenic nerve stimulation. Onset time and recovery were measured after injection of 0.6 mg/kg Rocuronium. RESULTS: The adductor pollicis had the fastest onset time ( young 2.3 min, old 2.2 min), followed by diaphragm ( young 3.6 min, old 3.4 min) and orbicularis oculi muscle ( young 3.7 min, old 4.8 min). There was a complete blockade of the diaphragm in 50 % of all patients (Adductor pollicis 100 %, orbicularis oculi 40 %). Neuromuscular recovery, recovery index and TOF 0.8 differed significantly between young and elderly patients. Onset of recovery was earlier at the diaphragm ( young 15.9 min, old 22.0 min) compared to the peripheral muscles (adductor pollicis young 25.6 min, old 37.9 min, orbicularis oculi young 23.8 min, old 27.5 min). CONCLUSION: 2 fould ED95 of rocuronium often results in an incomplete neuromuscular blockade of the diaphragm. Therefore monitoring of the peripheral muscles in patients given a single dose of rocuronium often overestimates the degree of diaphragmatic relaxation, but is a save predictor of recovery. Especially in elderly patients were prolonged neuromuscular blockade should be expected, a neuromuscular monitoring is recommended.

Adolescent↗

Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure.

We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg-1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1(25)) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg-1 min-1 and 3.7 (1.4) ml kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug.

Adult↗

Rocuronium pretreatment reduces suxamethonium-induced myalgia: comparison with vecuronium.

We have studied, in 150 patients undergoing elective oral surgery, the effectiveness and sequelae of pretreatment with rocuronium for reducing myalgia after suxamethonium. Patients were allocated randomly to one of three groups: anaesthesia was induced with propofol and fentanyl, and group V received vecuronium 1 mg, group R rocuronium 6 mg and group P placebo pretreatment. Suxamethonium 1.5 mg kg-1 was given 60 s after the pretreatment agent. All patients received ketorolac 10 mg i.v. and morphine 10 mg i.m. for analgesia. The incidence of postoperative myalgia on day 1 after rocuronium (20%) was significantly less than after vecuronium (42%) (P < 0.05) or placebo (70%) (P < 0.01). By day 4 the incidence of myalgia was 28.6% in the rocuronium group, 46.3% in the vecuronium group and 95% in the placebo group. Intubating conditions were not affected adversely by any pretreatment regimen.

Adolescent↗

Intubating conditions and time course of rocuronium-induced neuromuscular block in children.

We have investigated the potential of rocuronium 0.6 mg kg-1 (2xED95) and 0.9 mg kg-1 (3xED95) for rapid sequence induction in 100 children, aged 3-7 yr. Intubating conditions with the two different doses of rocuronium were assessed in 70 children (n = 35 in each group) undergoing elective surgery. Intubation was carried out by mimicking rapid sequence induction, and intubation conditions were evaluated according to a standard score. Intubating conditions were good to excellent in all 70 patients investigated (2xED95: excellent 29, good 6; 3xED95: excellent 33, good 2). In another 30 children (n = 15 in each group), we examined the times of rocuronium-induced neuromuscular block using electromyography. Lag time and recovery index did not differ significantly between the two groups (lag time: 37 (SD 12) vs 33 (14) s; recovery index: 9 (3) vs 10 (4) min). Three times the ED95 induced deeper neuromuscular block, 1 min after injection compared with 2xED95 (twitch height: 42 (24) vs 25 (19)%, respectively; P < 0.05). The same was true for onset time (193 (47) vs 118 (23) s; P < 0.01), clinical duration (21 (4) vs 34 (11) min; P < 0.01) and duration to 75% recovery (30 (6) vs 44 (4) min; P < 0.01). By mimicking rapid sequence induction, both doses of rocuronium offered clinically acceptable (good or excellent) intubating conditions.

Androstanols↗

Influence of induction technique on intubating conditions after rocuronium in adults: comparison with rapid-sequence induction using thiopentone and suxamethonium.

We have assessed the effect of anaesthetic technique on intubating conditions after rocuronium 0.6 mg kg-1 in four groups (n = 25 each) of unpremedicated patients in whom anaesthesia was induced with either thiopentone 5 mg kg-1 or propofol 2.5 mg kg-1 alone, or supplemented with alfentanil 20 micrograms kg-1. Fifty control patients were anaesthetized with thiopentone followed by suxamethonium. Laryngoscopy was commenced at 45 s. Overall intubating conditions after rocuronium were similar to those after suxamethonium (good and excellent > or = 96%) only when alfentanil was part of the induction regimen. However, intubation time was similar in all five groups and averaged 55 (SD 3.2) s, and the tube could be passed through open vocal cords within 70 s. After rocuronium the response of the diaphragm to intubation was more pronounced in the two groups of patients not receiving alfentanil (P < 0.0001) and in patients anaesthetized using propofol with alfentanil (P < 0.01) than in the control group. Opioids (in doses equivalent to alfentanil 20 micrograms kg-1) constitute an integral part of an induction regimen containing rocuronium 0.6 mg kg-1, regardless of whether or not thiopentone or propofol is used, in order to achieve overall intubating conditions similar to those after suxamethonium.

Adolescent↗

Potency and time course of action of rocuronium during desflurane and isoflurane anaesthesia.

We have studied the potency and onset and duration of action of rocuronium in patients anaesthetized with 1 MAC of desflurane or isoflurane (in 66% nitrous oxide). Potency was estimated using the single bolus dose technique. Neuromuscular block was measured by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The ED50 and ED95 of rocuronium were estimated as 138 (95% confidence limits 117-162) micrograms kg-1 and 281 (241-328) micrograms kg-1, and 126 (105-151) micrograms kg-1 and 283 (236-339) micrograms kg-1 during desflurane and isoflurane anaesthesia, respectively. The mean times to onset of maximum block after rocuronium 0.6 mg kg-1 were 1.0 (SD 0.10) min and 1.1 (0.15) min, respectively, during anaesthesia with desflurane and isoflurane. The respective times to recovery of T1 (the first response in the train-of-four (TOF) stimulation) to 25% and 90% were 36 (8.3) min and 54 (15.4) min during desflurane anaesthesia and 31 (8.2) min and 45 (12.7) min during isoflurane anaesthesia. The times to recovery of the TOF ratio to 0.7 were 66 (13.4) min and 52 (16.3) min and the 25-75% recovery indices 14 (5.3) min and 10 (3.2) min, respectively, in the desflurane and isoflurane groups. There were no differences in the estimated potency or onset of action of rocuronium during desflurane and isoflurane anaesthesia. However, duration of action tended to be longer curing desflurane anaesthesia although only the differences in times to TOF ratio of 0.7 and the recovery indices were close to being significantly different (P = 0.0503 and 0.0560).

Adolescent↗

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.

Adult↗

Dose-response relationships for neostigmine antagonism of rocuronium-induced neuromuscular block in children and adults.

Dose-response relationships for the antagonism of intermediate-acting neuromuscular blocking agents have not been evaluated previously in children. We have examined the dose-response relationships for neostigmine antagonism of 90% rocuronium-induced neuromuscular block in children and adults, during nitrous oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and 50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg kg-1 and accelerometry was used to monitor neuromuscular transmission. When the first twitch of the train-of-four (TOF) response (T1) recovered to 10% of its control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 micrograms kg-1 was given by random allocation to each of the study groups (n = 8 children and n = 10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after initial administration of neostigmine. Onset time of rocuronium-induced block was faster in children than in adults (mean 64.6 (95% confidence intervals 57.7-71.5) s vs 83.7 (70.7-96.6) s; P < 0.05). The time to 10% recovery of T1/T0 was shorter in children than in adults (25.4 (22.9-27.9) min vs 38.8 (36.1-41.4) min; P < 0.001). Spontaneous and antagonist-assisted recovery were more rapid in children than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and 8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate recovery was not produced in adults by any dose of neostigmine within 10 min. The effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P < 0.001). There was no advantage in administering doses of neostigmine greater than 20 micrograms kg-1 to antagonize 90% rocuronium-induced neuromuscular block in children. In contrast, it appeared prudent to use neostigmine 50 micrograms kg-1 or more for adequate antagonism of a similar degree of block in adults.

Adolescent↗

Effect of rocuronium compared with succinylcholine on intraocular pressure during rapid sequence induction of anaesthesia.

We have compared the effect of rocuronium and succinylcholine on intraocular pressure (IOP) during rapid sequence induction of anaesthesia using propofol and fentanyl, in a randomized double-blind study. We studied 30 adult patients, allocated to one of two groups. Anaesthesia was induced with fentanyl 2 micrograms kg-1 and propofol until loss of verbal response. This was followed by succinylcholine 1.5 mg kg-1 (group S; n = 15) or rocuronium 0.9 mg kg-1 (group R; n = 15). Laryngoscopy was performed 60 s later. IOP, mean arterial pressure (MAP) and heart rate (HR) were measured before induction, immediately before intubation and every minute after intubation for 5 min. A Keeler Pulsair air impulse tonometer was used to measure IOP and the mean of two readings obtained in the right eye at each measurement time was recorded. Intubating conditions were evaluated according to a simple scoring system. IOP in the succinylcholine group was significantly greater than that in the rocuronium group (mean 21.6 (SEM 1.4) mm Hg vs 13.3 (1.4) mm Hg; P < 0.001). Intubating conditions were equally good in both groups. We conclude that with rapid sequence induction of anaesthesia using propofol and fentanyl, rocuronium did not cause as great an increase in IOP as succinylcholine and may be an alternative in open eye injury cases.

Adolescent↗

Rocuronium: high risk for anaphylaxis?

Patients suspected of anaphylaxis during anaesthesia have been referred to the senior author's clinic since 1974 for investigation. Since release of rocuronium on to the worldwide market, concern has been expressed about its propensity to cause anaphylaxis. We identified 24 patients who met clinical and laboratory (intradermal, mast cell tryptase and morphine radioimmunoassay) criteria for anaphylaxis to rocuronium. The incidence of rocuronium allergy in New South Wales, Australia has risen in parallel with sales, while there has been an associated fall in reactions to other neuromuscular blocking drugs. Data from intradermal testing suggested that rocuronium is intermediate in its propensity to cause allergy in known relaxant reactors compared with low-risk agents (e.g. pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium, succinylcholine).

Anaphylaxis↗

Interstitial muscle concentrations of rocuronium under steady-state conditions in anaesthetized dogs: actual versus predicted values.

INTRODUCTION: The objective of this study was to compare rocuronium effect (C(e)) and peripheral (C(2)) compartment concentrations predicted by pharmacokinetic-pharmacodynamic (PK-PD) modelling with those measured in plasma (C(p)) and in the interstitial fluid of muscle tissue (C(ISF,u)) by microdialysis in anaesthetized dogs. METHODS: After approval by the Animal Care Committee, eight adult male dogs with a body weight ranging from 7 to 18 kg were anaesthetized with pentobarbital. Each dog received a 2-min rocuronium infusion of 0.15 mg kg(-1) min(-1) followed by a 118-min infusion of 60 microg kg(-1) min(-1) via the right jugular vein. Arteriovenous gradient across the hindlimb was measured at 40, 60, 100 and 120 min. Three microdialysis samples were collected at 40-min intervals. Once the infusion stopped, arterial samples were collected every 2 min for the first 10 min and every 20 min for the next 120 min. Neuromuscular function was monitored using train-of-four stimulation until full recovery. Dogs were then killed and a biopsy of muscle tissue was performed (C(m)). RESULTS: At steady state, the mean C(ISF,u) value was 1353 ng ml(-1). After correction for the unbound fraction in plasma, the mean C(e,corr) and C(2,corr) were 1681 and 1481 ng ml(-1), respectively. At the terminal sampling point, C(m) was 10-fold higher than C(p). CONCLUSION: Unbound concentration of rocuronium measured in the muscle interstitial fluid under steady-state conditions confirms that parametric PK-PD modelling gives reliable estimates of effect site concentrations. Rocuronium accumulates in muscle tissue, probably by non-specific protein binding in the interstitial space.

Androstanols↗

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block.

BACKGROUND: Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block. METHODS: Thirty anaesthetized adult patients received rocuronium 0.6 mg kg(-1) as an initial dose followed by increments to maintain a deep block at a level of <10 PTCs (post-tetanic counts) recorded every 6 min. Neuromuscular monitoring was carried out using accelerometry, in a train-of-four (TOF) mode using TOF-WatchSX. At recovery of T2, following at least 2 h of neuromuscular block, patients received their randomly assigned dose of 0.5, 1.0, 2.0, 4.0 or 6.0 mg kg(-1) of Org 25969. Anaesthesia and neuromuscular monitoring were continued for a minimum period of 30 min after Org 25969 administration. The main end-point of the study was the time to achieve a sustained recovery of TOF ratio to 0.9. Patients were followed up for 7 days after anaesthesia. RESULTS: The results showed a dose-related decrease in the average time taken to attain a TOF ratio of 0.9 from 6:49 (min:s) with the 0.5 mg kg(-1) dose to 1:22 with the 4.0 mg kg(-1) dose. Weighted non-linear regression analysis showed the fastest achievable time to TOF ratio of 0.9 to be 1:35. Org 25969 produced no major adverse effects. CONCLUSION: Org 25969 effectively reversed a deep and prolonged neuromuscular block induced by rocuronium. The effective reversal dose appears to be 2-4 mg kg(-1).

Adult↗

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children.

BACKGROUND: Pain from rocuronium injection is a common side-effect reported to occur in 50-80% of the patients. This randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy of pretreatment with i.v. remifentanil on prevention of withdrawal response during rocuronium injection in paediatric patients. METHODS: After obtaining parental consents, 70 paediatric patients were randomly allocated into two groups to receive either i.v. remifentanil 1 mug kg(-1) (remifentanil group, n=35) or i.v. saline 5 ml (saline group, n=35). Anaesthesia was induced with thiopental sodium 2.5% (5 mg kg(-1)) and the test drug was injected over 30 s. One minute after the test drug injection, rocuronium 1% (0.6 mg kg(-1)) was injected over 5 s and the response was recorded. Mean arterial pressure (MAP) and heart rate were recorded on arrival in the operating theatre, before and 1 min after the tracheal intubation. RESULTS: The overall incidence of withdrawal movements was significantly higher in the saline group (33 patients; 94%) than that in the remifentanil group (8 patients; 23%) (P<0.001). No patient in the remifentanil group showed generalized movement, whereas 51% of patients in the saline group did. Remifentanil prevented significant increase in MAP after intubation. CONCLUSION: This study demonstrated that pretreatment with remifentanil 1 microg kg(-1) provided a safe and simple method for reducing the incidence of rocuronium-associated withdrawal movement with haemodynamic stability in children.

Analgesics, Opioid↗

Pain on injection of rocuronium: influence of two doses of lidocaine pretreatment.

We have assessed the incidence of pain on injection of rocuronium and evaluated if pretreatment with lidocaine i.v. reduced it, in a randomized, controlled study in 90 patients. We found that 37% of patients who received lidocaine 10 mg pretreatment had pain on injection of rocuronium compared with 77% of patients who received saline pretreatment and 7% of patients who were pretreated with lidocaine 30 mg (P < 0.05 in each instance compared with control). In addition, patients pretreated with lidocaine were less likely to suffer moderate or severe pain. Both lidocaine 10 mg and 30 mg i.v. given before administration of rocuronium significantly reduced the incidence and severity of pain on injection of rocuronium, and the higher dose was more effective.

Adolescent↗

Rocuronium potency and recovery characteristics during steady-state desflurane, sevoflurane, isoflurane or propofol anaesthesia.

We have studied the potency and recovery characteristics of rocuronium during 1.25 MAC of isoflurane, desflurane, sevoflurane or propofol anaesthesia in 84 patients using electromyography. Potency was determined by a cumulative bolus technique. The mean ED50 of rocuronium was 169 (SD 41), 126 (32), 121 (28) and 136 (25) micrograms kg-1 during propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (ns), and ED90 values were 358 (62), 288 (29), 289 (28) and 250 (28) micrograms kg-1, respectively. The reduction in ED90 was statistically significant for all three inhalation anaesthetics (P < 0.05) compared with propofol. After 120 min, the cumulative infusion rate of rocuronium to obtain twitch depression of 90-95% was 9.0 (1.9), 6.3 (1.6), 6.1 (2.0) and 6.1 (1.1) micrograms kg-1 min-1 during propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (P < 0.01). Recovery index was 22 (13), 27 (10), 28 (13) and 26 (14) min under propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (ns). There were no significant differences between the three potent inhalation anaesthetics in relation to potency, infusion requirements or recovery characteristics of rocuronium.

Adult↗

The onset of rocuronium, but not of vecuronium or mivacurium, is modified by tourniquet inflation.

A previous investigation showed that inflation of a tourniquet did not interrupt onset of vecuronium neuromuscular block. To test the hypothesis that this effect depended on potency, twitch tension was measured in an arm with a tourniquet inflated during onset and compared with a control arm in 30 patients under fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Patients were randomly allocated to receive either vecuronium 0.1 mg/kg (n = 10), rocuronium 0.6 mg/kg (n = 10), or mivacurium 0.2 mg/kg (n = 10). The electromyographic response of the first dorsal interosseus to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e., twitch tension was 80% of control), the tourniquet was inflated to a pressure of 300 mm Hg. It was deflated 5 min later. In the vecuronium and mivacurium groups, the tourniquet did not influence onset of block. In the rocuronium group, maximum neuromuscular block was (mean +/- SD) 79% +/- 10% in the tourniquet arm, compared with 96% +/- 4% in the perfused arm (P < 0.05). The maximum rate of onset was half that of the perfused arm. The difference in maximum neuromuscular block between arms was 17% +/- 7%, 5% +/- 5%, and 0% +/- 2% in the rocuronium, vecuronium, and mivacurium groups (P < 0.05). To explain that onset of block continues in spite of interruption of blood flow, drug molecules must gain access to the neuromuscular junction via routes other than the circulation. The results of this investigation are consistent with the hypothesis that there is redistribution of drug from extrajunctional to junctional areas during onset of action of muscle relaxants and this process is more important for the more potent drugs (vecuronium and mivacurium) than for rocuronium.

Adult↗