A comparison of antagonism of rocuronium-induced neuromuscular blockade during sevoflurane and isoflurane anaesthesia

Volatile anaesthetic agents potentiate neuromuscular blocking agents and retard their rate of reversal. We hypothesised that there was a difference in the rate of reversal of rocuronium-induced neuromuscular blockade based on the selection of inhalation agent. Thirty-eight patients undergoing elective surgical procedures received either sevoflurane or isoflurane, by random allocation. Neuromuscular blockade was induced using rocuronium 0.6 mg.kg-1 followed by continuous intravenous infusion to maintain 90% suppression of the single twitch response. Upon completion of surgery, the rocuronium infusion was discontinued, neostigmine 50 microg.kg-1 and glycopyrrolate 10 microg.kg-1 were administered. Times from reversal to T1 = 25, 50 and 60% and train-of-four ratio = 0.6 were recorded. The mean (SD) times to train-of-four ratio = 0.6 in the isoflurane and sevoflurane groups were 327 (132) and 351 (127) s, respectively. The mean (SD) times to single twitch response T1 = 25, 50 and 60% in the isoflurane group were 81 (33), 161 (59) and 245 (84) s, respectively, and in the sevoflurane group were 95 (35), 203 (88) and 252 (127) s, respectively. It is concluded that reversal of rocuronium-induced neuromuscular blockade is similar during isoflurane and sevoflurane anaesthesia.     

A comparison of the neuromuscular blocking effects and reversibility of cisatracurium and atracurium

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mgkg⁻¹ were compared with those of atracurium 0.5 mgkg⁻¹ during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 μgkg⁻¹ at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹, respectively. After cisatracurium 0.1 mgkg⁻¹ had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mgkg⁻¹ and atracurium 0.5 mgkg⁻¹ were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Effect of milrinone on vecuronium-induced neuromuscular block

We examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 microg x kg-1x min-1 for 10 min, followed by an infusion at a rate of 0.5 microg x kg-1x min-1. Subjects in the control group received normal saline at a rate of 0.1 ml x kg-1 x h-1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg x kg-1 and fentanyl 2 microg x kg-1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg-1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train-of-four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train-of-four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train-of-four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train-of-four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

A multicenter evaluation of the time-course of action of two doses of rapacuronium after early and late reversal with neostigmine

Early reversal of rapacuronium may accelerate return of neuromuscular function. This study was designed to compare early (2 min after rapacuronium) or late (at 25% recovery of the first twitch [T1] of train-of-four) reversal of rapacuronium with neostigmine. We studied 119 subjects between the ages of 18 and 75 yr. Anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide, propofol, and fentanyl. Mechanomyographic neuromuscular monitoring was performed by using train-of-four stimulation of the ulnar nerve. Two groups received 1.5 mg/kg rapacuronium followed by neostigmine (50 microg/kg) and glycopyrrolate (10 microg/kg) either at 2 min after rapacuronium bolus or at 25% T1 recovery. The other two groups received 2.0 mg/kg rapacuronium, after which neostigmine was similarly given. For each rapacuronium dose, the time from the administration of rapacuronium to the start of T1 recovery or 25% T1 recovery was significantly shorter in subjects who received the reversal 2 min after rapacuronium. However, late recovery, defined by times from administration of rapacuronium to 70%, or 80% T4/T1 recovery, was not influenced by early reversal administration. We conclude that initial recovery is accelerated by early administration of neostigmine. Time to full recovery after rapacuronium administration is, however, dose-dependent and not significantly altered by early administration of neostigmine. IMPLICATIONS: "Rescue reversal," which includes the administration of neostigmine shortly after the administration of rapacuronium, may accelerate the return of spontaneous breathing (early recovery), but does not shorten the time to complete recovery of upper airway function.     

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

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.      

Priming with anticholinesterases — the effect of different combinations of anticholinesterases and different priming intervals

This study was designed to investigate the effect of different combinations of neostigmine and edrophonium when administered in divided doses and the effect of different intervals (priming intervals) between the doses. Seventy-two patients divided into 12 groups (n = 6 in each) were included in the study. An initial dose of neostigmine 0.012 mg.kg-1 or edrophonium 0.2 mg.kg-1 was administered, followed at different priming intervals (1, 2 or 3 min) by either edrophonium 0.8 mg.kg-1 or neostigmine 0.048 mg.kg-1 for antagonism of atracurium-induced neuromuscular blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. Adequate reversal of neuromuscular block (train-of-four ratio of 0.75) was achieved in all patients. Significant (p less than 0.05) acceleration of the recovery index (time taken for the twitch height to recover from 25 to 75 per cent of control) and reversal time (time taken from the end of injection of the priming dose until TOF ratio value had reached 0.75) was obtained in groups which received edrophonium-edrophonium combination. Recovery indices and reversal times were found to be significantly shorter (p less than 0.05) with a 1 min priming interval. In two additional groups of patients premedicated and anaesthetized as the others equipotent mixtures of the antagonists were administered as a single bolus dose. Reversal times were significantly longer (p less than 0.05) when compared to those given the same amounts of the combination but in divided doses with a 1 min priming interval.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance to vecuronium in burned children

We compared the time-course of action of vecuronium in 16 burned children undergoing excision and autograft surgery with that of ten unburned children. Standardized anaesthesia was induced with thiopentone 4-6 mg kg-1 and fentanyl 1 microgram.kg-1 and maintained with endtidal 1-1.5% isoflurane in N2O/O2. Neuromuscular responses were monitored by acceleromyography (TOF-Guard, Organon Teknika/Biometer) with supramaximal train-of-four (TOF) stimuli delivered every 15s. Vecuronium 0.1 mg kg-1 was administered intravenously. Onset was recorded as the time, in seconds, between the initial bolus of vecuronium and a decline in the first twitch of TOF (T1) to 5% of control. The times for the recovery of T1-25%, 50% and 75% of control, recovery index and the recovery of TOF 25% and 50% were recorded. Onset of action was found slower in burned patients (189 +/- 70 s) than in control (98 +/- 20 s) (P < 0.01). Recovery times of T1(25), T1(50), T1(75), TOF25 and TOF50 were significantly shorter in burned patients indicative of decreased sensitivity to vecuronium (P < 0.01).     

Myasthenia gravis and pipecuronium--report of two cases.

The use of pipecuronium in two patients with myasthenia gravis undergoing thymectomy is described. Neuromuscular function was monitored throughout using the train-of-four (TOF) mechanical twitch response. The cumulative dose-response to pipecuronium was determined in both patients during nitrous oxide-oxygen-narcotic anaesthesia. Both patients were sensitive to pipecuronium. The ED50 doses of pipecuronium were 11.6 and 11.1 micrograms.kg-1 and the ED95 doses were 35 and 33.3 micrograms.kg-1 in patients #1 and 2 respectively. Edrophonium 1 mg.kg-1 and neostigmine 0.06 mg.kg-1 were administered to patients #1 and 2 respectively for antagonism of residual neuromuscular blockade at 25 per cent spontaneous recovery of first twitch (T1) of the TOF stimulation. As with other non-depolarizing muscle relaxants pipecuronium in reduced dosage and with careful neuromuscular monitoring can be used to provide surgical relaxation safely in patients with controlled myasthenia gravis.     

Edrophonium and Neostigmine for Reversal of the Neuromuscular Blocking Effect of Vecuronium

The effect of edrophonium for reversal of the non-depolarizing neuromuscular blockade produced by a continuous infusion of vecuronium was compared to that of neostigmine in 20 adult patients during neurolept anaesthesia. When antagonism was attempted at 10% twitch height recovery, reversal time to a train-of-four ratio of 0.7 was significantly shorter following neostigmine 0.04 mg/kg than after edrophonium 0.75 mg/kg (9.8 min and 18.7 min, respectively) but the same after edrophonium 1.5 mg/kg (10.3 min). There was no statistically significant difference in reversal time between neostigmine 0.04 mg/kg given at 10% twitch height and edrophonium 0.75 mg/kg given at 25% twitch height recovery (6.0 min). Additional doses of atropine were necessary following edrophonium 1.5 mg/kg.     

Long-term succinylcholine infusion during isoflurane anesthesia

The characteristics of the neuromuscular blockade produced by prolonged succinylcholine infusion were compared in 40 patients anesthetized with either nitrous-oxide-isoflurane (0.75-1.50% inspired) or nitrous-oxide-fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15% of its control value. Initially, all patients exhibited a depolarizing-type block, and the infusion rates were similar in the isoflurane (61 micrograms . kg-1 . min-1) and fentanyl (57 micrograms . kg-1 . min-1) groups. Tachyphylaxis developed in both groups and correlated well with the onset of non-depolarizing (phase II) block. Both occurred sooner and at a lower cumulative dose in the isoflurane groups. After 90 min, infusion rates were similar in both groups (isoflurane: 107 micrograms . kg-1 . min-1, fentanyl;: 93 micrograms. kg-1 . min-1). After the infusion was stopped, the recovery of the train-of-four ratio was inversely related to the dose and duration of exposure to succinylcholine, and was slower with nitrous-oxide-isoflurane anesthesia. After 10 min of recovery, patients receiving isoflurane exhibited train-of-four ratios of 0.5 or less after 8.5 mg/kg succinylcholine and 103 min. Corresponding figures for fentanyl patients were 13 mg/kg and 171 min. The block in all 13 patients (eight with isoflurane, five with fentanyl) who did not recover spontaneously was antagonized successfully with atropine and neostigmine. It was concluded that with succinylcholine infusion of 90 min or less, isoflurane accelerates the onset of tachyphylaxis and phase II neuromuscular block without affecting succinylcholine requirements. These results, with isoflurane, were similar to those reported previously with enflurane or halothane.     

Influence of neostigmine on the course of neuromuscular blockade with rocuronium or cisatracurium: a randomized, double-blind trial

OBJECTIVES: To compare the time-course of neuromuscular blockade with rocuronium or cisatracurium during intravenous anesthesia, in terms of both the time to spontaneous recovery or time to reversal after administration of neostigmine. MATERIAL AND METHODS: Patients classified as ASA 1-2 were randomized to receive blinded administration of a single injection of twice the 95% effective dose of rocuronium or cisatracurium for general anesthesia, and then neostigmine plus atropine at recovery of the first train-of-4 (TOF) twitch at 5% or 25%, or normal saline solution as placebo at recovery of the first TOF twitch at 25%. The neuromuscular blockade was monitored by acceleromyography. Intergroup comparisons were carried out by Student t test and analysis of variance. RESULTS: Sixty patients were enrolled. Mean (SD) time to onset was faster with rocuronium at (1.04 [0.32] minutes) compared with cisatracurium at (2.58 [0.81] minutes) and duration was shorter: time to the first twich at 5% was 30 (6.4) minutes with rocuronium and 38.1 (9.7) minutes with cisatracurium. The total duration of blockade (time to the 80% TOF ratio) was also shorter with rocuronium when the neuromuscular blockade was reversed, but there were no differences in the time to block reversal when neostigmine was not used: 62 (18.9) minutes to recovery from the rocuronium blockade vs 66.96 (15.9) minutes to recover from a cisatracurium blockade. A high percentage of patients had less than an 80% TOF ratio at 60 and 90 minutes of administration of the neuromuscular blockerswhen reversal was not used (patients receiving rocuronium, 60% at 60 minutes, and 20% at 90 minutes; patients receiving cisatracurium, 80% at 60 minutes, and 40% at 90 minutes). CONCLUSION: Not antagonizing a rocuronium- or cisatracurium-induced neuromuscular blockade in surgical procedures lasting less than 90 minutes can lead to a high percentaje of residual blockade (TOF ratio <80%).     

Effects of residual concentrations of isoflurane on the reversal of vecuronium-induced neuromuscular blockade.

Thirty-six anesthetized patients (ASA physical status 1 or 2) undergoing elective surgery were monitored (isometric adductor pollicis mechanical activity) to detect the effects of discontinuing isoflurane anesthesia upon the reversal of vecuronium-induced neuromuscular blockade. Neuromuscular blockade was produced by vecuronium 100 micrograms/kg and additional doses of 20 micrograms/kg until completion of surgery. The patients were randomly divided into three groups: in the control group (n = 12), only fentanyl/N2O was given; in the "isostable" group (n = 12), isoflurane at an end-tidal concentration of 1.25% was maintained throughout anesthesia; in the "isostop" group (n = 12), isoflurane 1.25% was discontinued before neostigmine administration. In all groups, paralysis was antagonized with 15 micrograms/kg intravenous (iv) atropine and 40 micrograms/kg iv neostigmine when the twitch height (0.1 Hz) had regained 25% of its control value. The measured parameters were twitch height, train-of-four, and 50--100-Hz tetanic fade. No significant differences were found among the three groups with respect to the final twitch heights and tetanic fades at 50 Hz. In the isostable group, final mean train-of-four was significantly less (75%) than in the other patients (88%) (P less than 0.01). Mean tetanic fade at 100 Hz was significantly less in the isostable group (31%) than in the isostop group (57%) (P less than 0.01) and control group (84%) (P less than 0.01). We conclude that discontinuing isoflurane anesthesia for 15 min improves the reversal of a vecuronium paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of atracurium with neostigmine

In 36 patients in whom anaesthesia was maintained with nitrous oxide and 0.5% isoflurane an atracurium-induced neuromuscular block was either allowed to recover spontaneously or antagonised with one of four doses of neostigmine (15 micrograms/kg, 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg). The recovery times to a train-of-four ratio of 0.5, 0.75 and 0.9 were recorded. In patients given neostigmine, antagonism was at an average T1 of between 8.8% and 14.9%. There was no difference in the recovery times between the patients given neostigmine 35 micrograms/kg, 55 micrograms/kg or 75 micrograms/kg. Recovery after neostigmine 15 micrograms/kg was significantly slower than after the higher doses. One patient given neostigmine 75 micrograms/kg showed an unusual bimodal pattern of recovery. There appears to be no benefit in giving a larger dose than 35 micrograms/kg of neostogmine as a single bolus.     

Dose-response relations of doxacurium and its reversal with neostigmine in young adults and healthy elderly patients.

Dose-response relationships for doxacurium and neostigmine were established in 24 young (18-40 yr) and 24 elderly (70-85 yr) patients, ASA physical status I or II, anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. Mechanomyographic response of the adductor pollicis muscle to the train-of-four stimulation of the ulnar nerve was recorded. Doxacurium (5, 10, 15, or 20 micrograms/kg IV) was administered by random allocation. After maximal blockade, and additional dose, for a total of 30 micrograms/kg, was administered. When first twitch height recovered to 25%, incremental doses of 5 micrograms/kg were administered for maintenance of relaxation. Neostigmine (5, 10, 20, or 40 micrograms/kg) was injected at 25% first twitch recovery, and neuromuscular monitoring was continued for 10 min. The doses of doxacurium (+/- SEM) required to produce a 50%, 90%, and 95% depression of twitch tension in the young patients were, respectively, 13.3 +/- 1.6, 23.6 +/- 2.8, and 28.6 +/- 3.4 micrograms/kg, not statistically different from corresponding values in the elderly, 11.8 +/- 1.3, 21.2 +/- 2.3, and 25.9 +/- 2.9 micrograms/kg, respectively. Time to 25% recovery after 30 micrograms/kg was 80.2 +/- 12.2 min in the young versus 133.0 +/- 17.1 min in the elderly (P less than 0.05). Neostigmine-assisted recovery was not significantly different in both groups. The estimated doses of neostigmine to obtain 70% train-of-four recovery after 10 min were 53.6 +/- 7.5 micrograms/kg in the young and 41.6 +/- 5.8 micrograms/kg in the elderly (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of enflurane and fentanyl on the clinical characteristics of long-term succinylcholine infusion

The characteristics of the neuromuscular block produced by prolonged succinylcholine infusion were compared in 40 patients anaesthetized with either nitrous oxide with enflurane (1-2 per cent inspired) or nitrous oxide and fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15 per cent of its control value. Initially, all patients, exhibited a depolarizing-type block all twitches of the train-of-four being roughly the same size, and the infusion rates were similar in the enflurane (54 microgram X kg-1/min) and the fentanyl (58 microgram X kg-1/min) groups. Tachyphylaxis developed later in both groups and correlated well with the onset of phase II block (dual block). This occurred sooner and at a lower cumulative dose in the enflurane group. Fourth to first twitch ratios decreased to 50, 25 and 0 per cent in 31, 46 and 59 minutes in the enflurane group, at cumulative succinylcholine doses of 2.2, 3.2 and 4.2 mg X kg-1 respectively. Corresponding figures for the fentanyl group were 52, 73 and 86 minutes, with dose of 3.4, 5.0 and 5.9 mg X kg-1. Infusion rates increased markedly after establishment of dual block, but were similar with enflurane (0.99 mg X kg-1/min) and fentanyl (1.12 mg X kg-1/min). Ten minutes after stopping the infusion fourth to first twitch ratios failed to reach 50 per cent in most patients given enflurane who had received more than 6 mg X kg-1 succinylcholine over more than 90 minutes. Corresponding figures for fentanyl patients were 13 mg x kg-1 and 150 minutes. The block in all 15 patients (9 enflurane, 6 fentanyl) who did not recover spontaneously was successfully antagonized with atropine and neostigmine.     

Clinical study of interaction between rocuronium and some commonly used antimicrobial agents

The onset and duration of clinical relaxation and reversibility of rocuronium bromide (ORG 9426) 0.6 mg kg-1 were studied following administration of netilmicin 2 mg kg-1 (n = 10) or cefuroxime 20 mg kg-1 (n = 10) in patients undergoing urological surgery; and cefuroxime 20 mg kg-1 (n = 10) metronidazole 7.5 mg kg-1 (n = 10), metronidazole 7.5 mg kg-1 and cefuroxime 20 mg kg-1 (n = 10), or placebo (n = 10) in patients undergoing abdominal surgery under anaesthesia with thiopentone, nitrous oxide in oxygen, fentanyl and halothane. The antimicrobial agents were administered intravenously 5 min before rocuronium. Neuromuscular function was monitored using mechanomyography and train-of-four (TOF) mode of stimulation. Onset of neuromuscular block occurred in approximately 60 s with all patients achieving complete block. The mean clinical duration (+/- SD) was 50 +/- 10.7 and 44 +/- 6.7 min following netilmicin and cefuroxime respectively in patients undergoing urological surgery; and 49 +/- 13.7, 44 +/- 11.1, 48 +/- 11.1 and 38 +/- 7.3 min in the groups undergoing abdominal surgery receiving cefuroxime, metronidazole, cefuroxime and metronidazole combination and placebo respectively. There were no statistically significant differences between the groups in either the onset or the duration of clinical relaxation. Reversal of neuromuscular block with neostigmine carried out at spontaneous recovery of T1 (first response in the TOF) of 25% or more was easily achieved in all groups in 2-4 min. It is concluded that there is no significant interaction between rocuronium and single doses of the antimicrobial agents used in the present study.     

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurance, isoflurane or propofol

PURPOSE: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine. METHODS: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded. RESULTS: The times (mean +/- SD) to recovery of the TOF ratio to 0.8 were 12.0 +/- 5.5 and 6.8 +/- 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 +/- 8.3 and 5.5 +/- 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 +/- 2.8 and 4.7 +/- 1.5 min in the propofol continued and propofol stopped groups (P < 0.5-01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P < 0.001 for sevoflurane). CONCLUSIONS: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.     

Spontaneous or neostigmine-induced recovery after maintenance of neuromuscular block with Org 9487 (rapacuronium) or rocuronium following an initial dose of Org 9487

We have examined spontaneous and neostigmine-induced recovery after an initial dose of Org 9487 1.5 mg kg-1 followed by three repeat doses of Org 9487, a 30-min infusion of Org 9487 or two incremental doses of rocuronium. Mean clinical duration after incremental doses of Org 9487 0.5 mg kg-1 increased from 12.3 (SD 3.4) min to 14.0 (4.0) and 15.9 (5.9) min (P < 0.01), and after rocuronium from 14.4 (5.2) min to 19.2 (5.9) min (P < 0.01). Times for spontaneous recovery from a T1 of 25% to a TOF ratio of 0.8 after the last bolus dose of Org 9487 and after a 30-min infusion were 72.4 (16.5) and 66.1 (26.9) min compared with 36.7 (15.8) min in the group receiving reocuronium. These times were significantly reduced to 9.9 (4.5), 8.6 (6.1) and 5.7 (2.5) min, respectively, after neostigmine administration at a T1 of 25% (P < 0.05). We conclude that administration of Org 9487 by repeat bolus doses or infusion was associated with slow spontaneous recovery but neostigmine administration resulted in adequate recovery in less than 10 min.