Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade.

BACKGROUND: Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs). OBJECTIVES: To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information. SELECTION CRITERIA: All randomized controlled trials (RCTs) on adult patients (>/= 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers. DATA COLLECTION AND ANALYSIS: We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta-analytic techniques. MAIN RESULTS: We included18 RCTs (n = 1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T(2) reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P = 0.59, I(2) = 0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P = 0.95, I(2) = 43%, 3 RCTs). AUTHORS' CONCLUSIONS: Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.

An update on sugammadex sodium.

Sugammadex sodium is the generic drug name for the novel modified gamma cyclodextrin that terminates neuromuscular blockade induced by aminosteroidal neuromuscular blocking agents. Published phase II and phase III clinical data support preclinical and clinical phase I study findings of fast, safe, and efficacious reversal of all levels of neuromuscular blockade induced by rocuronium and vecuronium. Low levels of neuromuscular blockade induced by pancuronium have also been successfully reversed by sugammadex. This agent does not reverse the bis-isoquinoline neuromuscular blocking agents. Special patient populations, including pediatric, elderly, cardiac, and renal-compromised subjects, have been studied in phase III. This update focuses on the most recent findings of phase II and III clinical studies.

[Reversal of neuromuscular blockade and complications of remaining blocking effect].

We Japanese anesthesiologists can now use rocuronium as well as vecuronium. Although the onset of rocuronium is more rapid, the non-depolarizing neuromuscular blocking (NMB) agent has similar characteristics of duration and recovery compared to vecuronium. Reversal of NMB is therefore essential to recover patients safely. Conventional standard of reversal of NMB [train of four (TOF) >0.7] is not enough to have sufficient vital capacity and inspiratory force, resulting in pulmonary regurgitation or atelectasis. Even though the reversal of NMB cannot sufficiently be completed by anti-cholinesterase (ChE) agents such as neostigmine, it is needed to reverse the NMB because of their late spontaneous recovery. We also have to take care of patients with neuromusclar diseases such as Duchenne-type muscle dystrophy, when we use anti-ChE agents. Sugammadex is a novel and unique compound designed as an antagonist of rocuronium and possibly other steroid NMB agents. Sugammadex exerts its effect by forming very tight water-soluble complexes at a 1 : 1 ratio with steroid NMB agents (rocuronium>vecuronium>>pancuronium). PhaseIII trials in Japan as well as Europe and the US have just been finished, and it is expected to be used clinically in the near future.

Is recovery of neuromuscular transmission complete after the use of neostigmine to antagonize block produced by rocuronium, vecuronium, atracurium and pancuronium?

To test if recovery of neuromuscular transmission is complete after the use of neostigmine under standardized conditions, we have measured adductor pollicis mechanical activity in response to 0.1 Hz (twitch height), train-of-four (TOF) and 100 Hz (RF 100 Hz) ulnar nerve stimulations. We studied 56 adult anaesthetized (thiopentone, fentanyl, nitrous oxide in oxygen) patients, allocated randomly to one of four groups (n = 14) to receive rocuronium (group Roc), vecuronium (group Vec), atracurium (group Atr) or pancuronium (group Pan). Recovery of neuromuscular transmission was studied for 15 min after neostigmine 40 micrograms kg-1 was given at 25% recovery of twitch height. Fifteen minutes after antagonism, the TOF ratio was 0.91 (SEM 0.01), 0.88 (0.02) and 0.92 (0.01) (ns), and RF 100 Hz was 0.78 (0.01), 0.79 (0.02) and 0.78 (0.01) (ns) respectively, in patients in groups Roc, Vec and Atr, respectively. In patients in group Pan, TOF ratio and RF 100 Hz were only 0.76 (0.01) and 0.33 (0.04) respectively (P < 0.01, one-way analysis of variance, Duncan's multiple classification range tests). In contrast with pancuronium, antagonism of rocuronium-, vecuronium- and atracurium-induced neuromuscular blocks produced a similar high degree of recovery of neuromuscular transmission.

Perioperative train-of-four monitoring and residual curarization.

It has been suggested that perioperative train-of-four (TOF) monitoring does not reduce the incidence of postoperative residual curarization (PORC). The purpose of this study was to examine whether the use of tactile assessment of the response of the adductor pollicis to supramaximal TOF stimulation of the ulnar nerve at the wrist during anaesthesia affected the incidence of PORC. Thirty-nine ASA I or II surgical patients were studied during thiopentone/fentanyl N2O/enflurane anaesthesia. Pancuronium (70-100 micrograms.kg-1) was used to facilitate tracheal intubation and additional pancuronium increments used to maintain surgical relaxation. The requirement for incremental doses of pancuronium and adequacy of recovery following reversal were assessed according to random allocation, either with (Group A; n = 20) or without (Group B; n = 19) access to TOF monitoring. Patients in the two groups received neostigmine in similar doses (Group A: 53 micrograms.kg-1 (5.9); Group B: 55 micrograms.kg-1 (5.4)). On arrival of the patient to the recovery area, neuromuscular function was assessed electromyographically (using the Datex NMT 221 to measure TOF ratio) and clinically. The incidence of PORC (TOF ratio < 70%) was greater in Group B (47%) than in Group A (15%) (P = 0.029). We conclude that the use of perioperative TOF monitoring decreases the incidence of pancuronium-induced PORC.

Train-of-four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans.

Previous studies have suggested that the increased duration of action of long-acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N2O/fentanyl anaesthesia. Study subjects were paralyzed with either pancuronium (N = 8), pipecuronium (N = 8), or the longer-acting relaxant, doxacurium (N = 8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED95 dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% of baseline response to the first supramaximal twitch (T1) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded. Spontaneous recovery to 25% of the baseline T1 response occurred at 52 +/- 14 min (mean +/- SD) following administration of either pancuronium and pipecuronium, and 85 +/- 33 min following doxacurium (P < 0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-treated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 +/- 14% and 61 +/- 16%, respectively) than with either pancuronium (75 +/- 6% and 75 +/- 10%) or pipecuronium (76 +/- 9% for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block.

We have compared the antagonism of neuromuscular block produced by pipecuronium with pancuronium in 80 anaesthetized surgical patients using mechanomyography and electromyography. Pancuronium 0.1 mg kg-1 or pipecuronium 0.07 mg kg-1 was given after induction of anaesthesia and neuromuscular block was adjusted to 75% twitch depression at the time of antagonism. The following regimens were used: edrophonium 0.5 and 1.0 mg kg-1, neostigmine 0.04 mg kg-1, pyridostigmine 0.3 mg kg-1 and edrophonium 0.25 mg kg-1 with pyridostigmine 0.15 mg kg-1. Antagonism was evaluated also by the head lift test. There was no difference between the reversibility of neuromuscular block produced by pancuronium or pipecuronium. Edrophonium produced a significantly faster antagonism than neostigmine or pyridostigmine but onset of action was not significantly faster than that of edrophonium with pyridostigmine. All regimens produced 100% (or near 100%) antagonism of twitch response within 15 min. However, TOF fade antagonism was more complete with pyridostigmine, neostigmine and edrophonium 1.0 mg kg-1 than with edrophonium 0.5 mg kg-1. The head lift test indicated somewhat less antagonism with edrophonium 0.5 and 1.0 mg kg-1. Using five monitoring methods, the rank order of reversal potency was: pyridostigmine approximately neostigmine > edrophonium 1.0 mg kg-1 > edrophonium+pyridostigmine > edrophonium 0.5 mg kg-1.

Reversal of doxacurium and pancuronium neuromuscular blockade with neostigmine in children.

Recovery after doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2-10 yr (ASA 1-2) were studied. They were randomized to receive doxacurium 30 micrograms.kg-1 or pancuronium 70 micrograms.kg-1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 micrograms.kg-1) with atropine by random allocation when first twitch height (T1) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following doxacurium (mean +/- SEM values of 45.0 +/- 3.9 vs 49.5 +/- 10.0% for T1 and 25.2 +/- 3.8 vs 14.8 +/- 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of T1 or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED70 and ED90 doses for T1 of 14.3 +/- 1.8 and 25.7 +/- 2.7 micrograms.kg-1 for doxacurium and 12.5 +/- 1.7 and 25.3 +/- 2.3 micrograms.kg-1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 micrograms.kg-1 was 2.3 +/- 1.0 and 4.2 +/- 1.7 min (P = NS) following pancuronium and doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antagonism to neuromuscular effect of subcutaneous administration of pancuronium by neostigmine].

It has been reported that subcutaneous administration of pancuronium produces prolonged neuromuscular blockade. The purpose of this study was to evaluate the antagonistic effect of neostigmine on neuromuscular blockade following subcutaneous injection of pancuronium in anesthetized patients. Fourteen male patients aged 32-67 yr, weighing 50-58 kg, and scheduled for surgical operation lasting more than 6 hr were included in the study. None of the patients had paresis. Anesthesia was induced with thiamylal and SCC. Patients under N2O-oxygen-enflurane (1.0-1.5%) anesthesia, were divided into two groups (n = 7 in each group). Group A was given an intravenous bolus of pancuronium 6 mg. Group B received pancuronium 6 mg subcutaneously in the ankle. Train-of-four responses were evaluated every 12s by measuring the force of thumb adduction produced in response to supramaximal stimulation of the ulnar nerve at the wrist. When the train-of-four ratios recovered to approximately 0.2 in groups A and B, a mixture of neostigmine 1.0 mg and atropine 0.5 mg was administered. The onset of fade in train-of-four responses was significantly more rapid in group A (intravenous administration) than in group B (subcutaneous administration). Time intervals to maximum train-of-four depression from pancuronium administration in groups A and B averaged 2.6 and 125.4 min, respectively. No significant differences in the recovery times of the train-of-four ratios from 0.2 to 0.7 following neostigmine administration in groups A and B were demonstrated. None of the patients who received pancuronium subcutaneously showed recurarization following neostigmine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block.

The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration of neostigmine than if the blockade was maintained with pancuronium alone. Anaesthesia consisted of thiopentone, N2O/O2/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg.kg-1 was monitored by the force of contraction of adductor pollicis during major abdominal surgery lasting 2-5 hr. In 24 patients--Group 1--atracurium 0.07 mg.kg-1 was repeated when the first twitch of the train-of-four (TOF) returned to 25% of control (T1/TC 25). In 28 patients--Group 2--pancuronium 0.015 mg.kg-1 was given at similar recovery of T1/TC. At the end of surgery, neostigmine 0.07 mg.kg-1 and glycopyrolate 0.015 mg.kg-1 were given to reverse the residual neuromuscular blockade which was indicated by a T1/TC of less than 25% in all patients. The time from injection of the reversal drugs to a TOF ratio of 70% was similar in both groups (Group 1, 11.6 +/- 7.6 min; Group 2, 10.1 +/- 6 min; P = NS), but the recovery index was smaller in Group 2 (Group 1, 4 +/- 2.6 min; Group 2, 2.61 +/- 1.2 min; P < 0.05). Furthermore, there was no difference between groups in the duration of action of each redose. The study showed that when compared with pancuronium, equipotent doses of atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or (b) a shorter duration of action.

Prolonged paralysis after long-term, high-dose infusion of pancuronium in anaesthetized cats.

We have studied the neuromuscular effects of a 48-h infusion of high-dose pancuronium (400 micrograms kg-1 h-1) in four cats anaesthetized with pentobarbitone, using contraction of tibialis anterior muscles after direct and indirect stimulation. After cessation of the pancuronium infusion, prolonged paralysis existed. The first twitch in the train-of-four stimuli (TOF) reappeared 8-12 h after termination of the pancuronium infusion. Twenty-four hours after termination of the infusion, TOF ratios were less than 0.08 and twitch contraction averaged 39 (SE 8)% of initial values. Twitch contraction after direct stimulation did not differ from initial values. Antagonism of paralysis was accomplished with neostigmine 60 micrograms kg-1 in two animals and neostigmine 90 micrograms kg-1 and 4-aminopyridine 500 micrograms kg-1 in the others. Steady-state plasma concentration of pancuronium (2000 ng ml-1) decreased rapidly after termination of the infusion, but then stabilized at about 130 ng ml-1. These results indicate that prolonged paralysis after long-term administration of high-dose pancuronium is caused primarily by failure of neuromuscular transmission, most likely caused by the persistent plasma concentrations of the drug in the pharmacologically active range.

Atracurium after an anticholinesterase. Does prior reversal with edrophonium or neostigmine influence the response to atracurium?

This study documents the response to atracurium (75 micrograms.kg-1) administered 30 min after a pancuronium- or tubocurarine-induced neuromuscular block has been reversed with either neostigmine (50 micrograms.kg-1) or edrophonium (0.5 mg.kg-1). Twenty-one ASA 1 or 2 patients were studied, of whom 11 received neostigmine and 10 edrophonium. The degree of neuromuscular block was measured electromyographically from the first dorsal interosseous muscle of the hand using train-of-four stimulation of the ulnar nerve. When atracrium was administered, the single twitch response compared with control was 100% in all patients and the mean train-of-four ratios were 91% and 65% in the neostigmine and edrophonium groups respectively. After atracurium (75 micrograms.kg-1), minimum values for the single twitch response compared with control were 52% and 66% in the neostigmine and edrophonium groups respectively. Prior administration of atracurium appears to potentiate the neuromuscular blocking effects of atracurium administered 30 min later.

Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat.

1. Rats were anaesthetized with sodium pentobarbitone and maximal twitches of a tibialis anterior muscle were evoked by stimulation of the motor nerve. 2. Suramin, injected intravenously in a series of cumulative bolus doses, each 15 mg kg-1, completely reversed a 90% depression of twitches maintained by a continuous intravenous infusion of pancuronium. The cumulated dose necessary to restore twitches to 50% of their control amplitude was 35 mg kg-1. Suramin did not modify a similar degree of block produced by suxamethonium, nor did it affect the amplitude of control maximal twitches, even in cumulative doses up to 150 mg kg-1. 3. The effects of bolus doses of suramin (85 mg kg-1), neostigmine (0.03 mg kg-1) and 4-aminopyridine (1.2 mg kg-1), calculated to restore pancuronium-blocked twitches to 95% of control amplitude, were compared. Suramin produced the most rapid reversal (1.1 +/- 0.5 min), but its duration of action was the shortest (9.4 +/- 1.6 min). Suramin was without effect on heart rate or blood pressure in the doses used. 4. The results showed that suramin reversed neuromuscular block produced by nondepolarizing blocking drug, pancuronium, but was without effect on a block produced by the depolarizing blocking drug, suxamethonium. Its short duration of action suggests that suramin would probably not be of value clinically as a reversal agent. However, it is possible that it might serve as a starter compound for the synthesis and development of a new class of reversal agents for use in anaesthetic practice.

Neostigmine and edrophonium antagonism of moderate neuromuscular block induced by pancuronium or tubocurarine.

Edrophonium and neostigmine are anticholinesterase drugs used commonly to antagonize competitive neuromuscular block. Although it has a faster onset of action than neostigmine, edrophonium is unreliable when used to antagonize deep neuromuscular block. We have compared the antagonist characteristics of these two drugs when used to antagonize a moderate degree of pancuronium- or tubocurarine-induced neuromuscular block. Forty ASA I or II patients undergoing surgical procedures were allocated randomly to receive either pancuronium 70 micrograms kg-1 or tubocurarine 0.5 mg kg-1, and to receive either edrophonium 0.5 mg kg-1 or neostigmine 0.05 mg kg-1. Antagonism was attempted when the first response to train-of-four (TOF) stimulation recovered spontaneously to 25% of the control height. Neuromuscular function was monitored using the evoked integrated electromyogram of the first dorsal interosseous muscle of the hand. Adequate recovery was defined as the achievement of a TOF ratio of 0.70 or greater. Only seven of 20 patients who received edrophonium demonstrated adequate recovery 30 min after antagonism. Under the conditions described in this study, edrophonium 0.5 mg kg-1 was less effective as an antagonist than neostigmine 0.05 mg kg-1.

Continuous infusions of atracurium and vecuronium, compared with intermittent boluses of pancuronium: dose requirements and reversal.

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Method of intraoperative monitoring of neuromuscular function and residual blockade in the recovery room.

We evaluated the method used intraoperatively to assess the degree of neuromuscular blockade prior to pharmacologic reversal to determine its role in preventing residual blockade in the postanesthesia care unit (PACU). We studied 38 patients who received a nondepolarizing muscle relaxant during general anesthesia for carotid endarterectomy or thoracotomy. The anesthesiologist assessed the degree of neuromuscular blockade intraoperatively prior to pharmacologic reversal either by the standard method of visually counting the number of evoked thumb twitches elicited by supramaximal train-of-four stimulation of the ulnar nerve (i.e., thumb train-of-four count), or by an alternative method such as 1) visually counting the number of evoked orbicularis oculi muscle twitches elicited by supramaximal train-of-four stimulation of the facial nerve, or 2) observing the patient for clinical evidence of partial recovery (e.g., swallowing or attempts to breathe). Residual blockade in the PACU was defined as 1) a train-of-four ratio less than 0.70 (measured by a mechanomyograph), or 2) the inability of the patient to perform clinical tests of neuromuscular function (e.g., a sustained head lift for 5 seconds) and evidence of neuromuscular weakness that was resolved following administration of edrophonium. Five of the 22 patients (23%) in whom one of the alternative methods was used had residual blockade in the PACU; none of the 16 patients with a thumb train-of-four count of 3 or 4 before pharmacologic reversal of NMB had residual blockade in the PACU (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of neostigmine and edrophonium on human erythrocyte acetylcholinesterase activity.

Erythrocyte acetylcholinesterase (AChE) activities in vivo were measured over 60 min using a spectrophotometric method after administration of neostigmine or edrophonium for antagonism of pancuronium-induced neuromuscular block in 31 patients. Erythrocyte AChE activities decreased to 11.3 (SD 1.2)% and 11.4 (0.8)% of baseline values (P less than 0.001) within 2 min, then recovered slowly and were 43.2 (6.2)% and 27.9 (2.9)% (P less than 0.001) 60 min after administration of neostigmine 0.036 mg kg-1 and 0.071 mg kg-1, respectively. However, the enzyme activity after edrophonium 1.43 mg kg-1 did not change significantly over 60 min. The results suggest that mechanisms other than AChE inhibition may be responsible for the anti-curare effect of edrophonium.

Is the diagnosis of significant residual neuromuscular blockade improved by using double-burst nerve stimulation?

This study evaluated the use of double-burst stimulation (DBS) in the diagnosis of significant post-operative residual neuromuscular blockade. Ninety patients were allocated to three equal groups. In Group A the degree of residual neuromuscular blockade was assessed by clinical criteria (CC) only; in Group B by CC and manual evaluation of the response to train-of-four (TOF) nerve stimulation; and in Group C by CC, manual evaluation of the response to TOF, and DBS stimulation. Immediately after arrival in the recovery room mechanical twitch was recorded using TOF stimulation. The mean (+/- SD) TOF ratios were 0.53 +/- 0.19 in Group A, 0.67 +/- 0.11 in Group B and 0.81 +/- 0.08 in Group C. The incidence of a TOF ratio of less than 0.7 was 83.3% in Group A, 56.7% in Group B and 6.7% in Group C. It is concluded that the use of DBS enabled the anaesthetist to recognize significant residual block and thus reduced the incidence of post-operative residual neuromuscular blockade.