Dose-response relationships for edrophonium and neostigmine as antagonists of moderate and profound atracurium blockade

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.     

Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium- induced neuromuscular block

PURPOSE: To study the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by atracurium and cisatracurium. METHODS: One hundred and twenty eight, ASA group 1 or 2 adults were given either 0.5 mg x kg(-1) atracurium or 0.1 mg x kg(-1) cisatracurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. The neuromuscular block was measured by an acceleration-responsive transducer. Responses were defined in terms of percent depression in the first twitch (T1) and train-of-four (TOF) response. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg x kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg x kg(-1)) was administered by random allocation. Neuromuscular function in another sixteen subjects was allowed to recover spontaneously. RESULTS: At five minutes, unlike edrophonium, neostigmine was equally effective against atracurium and cisatracurium with respect to T1 recovery. The neostigmine T1-ED50 was 10.3 +/- 1.06 (SEM) microg x kg(-1) after atracurium and 11.2 +/- 1.06) microg x kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 microg x kg(-1) with atracurium and 47.4 +/- 1.07 microg x kg(-1) with cisatracurium, giving a neostigmine:edrophonium potency ratios of 15.2 +/- 1.7 and 4.2 +/- 0.41 (P < 0.001) for atracurium and cisatracurium, respectively. At 10 min neostigmine was 13 +/- 1.4 times as potent as edrophonium for achieving 50% TOF recovery after atracurium paralysis. After cisatracurium the potency ratio was 11.8 +/- 1.3 (NS). CONCLUSIONS: Although there were differences at five minutes, neostigmine:edrophonium potency ratios at 10 min, were similar in both relaxants studied.     

Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.     

Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions

The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tactile evaluation of train-of-four count as an indicator of reliability of antagonism of vecuronium- or atracurium-induced neuromuscular blockade.

Recent evidence suggests that edrophonium is not the agent of choice to reverse profound neuromuscular blockade but remains an efficacious drug when the level of neuromuscular blockade to be antagonized is modest. We studied 90 healthy adults in an attempt to address the questions: 1) How much variability in such neuromuscular parameters as single twitch height and the train-of-four (TOF) fade ratio (T4/T1) exist when the TOF count first returns to four palpable responses? 2) Is edrophonium a reliable antagonist at this measured point of recovery? 3) What is the optimal dose of edrophonium needed to produce prompt (less than 10 min) and satisfactory (T4/T1 greater than 0.7) reversal when the fourth response of the thumb to indirect TOF stimulation just becomes palpable? Patients were given a bolus atracurium or vecuronium (n = 45 in each group) followed by an iv infusion sufficient to maintain single twitch as measured by electromyography at 10-15% of control values. At the end of surgery, the infusion was terminated and spontaneous recovery was allowed to begin. Once the tactile TOF count was four, edrophonium 0.3, 0.5, or 0.75 mg/kg was administered. At a count-of-four the first twitch averaged 37% of control (+/- 8.5% standard deviation; pooled data from all groups) and the mean T4/T1 ratio was 0.14 +/- 0.049. After atracurium neuromuscular blockade, edrophonium 0.3 mg/kg produced adequate antagonism in 10 min. At this time the mean T4/T1 ratio was 0.79 +/- 0.07 and the lowest observed value was 0.67. Increasing the edrophonium dose to 0.75 mg/kg accelerated recovery by 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Twitch depression and train-of-four ratio after antagonism of pancuronium with edrophonium, neostigmine, or pyridostigmine

During N2O-O2-halothane anesthesia pancuronium (3 mg/70 kg) was antagonized with neostigmine (2.5 or 5 mg/70 kg), pyridostigmine (10 or 20 mg/70 kg), or edrophonium (50 or 100 mg/70 kg) in 36 human subjects (6 in each group). Reversal was attempted at 10% spontaneous recovery of muscle twitch, which was measured using train-of-four stimulation. When first twitch tension was less than 70% of the control it was found that for the same tension, the train-of-four ratio was greater with edrophonium than with neostigmine, and greater with neostigmine than with pyridostigmine. It was concluded that the three antagonists have different mechanisms of action. In comparison with neostigmine, edrophonium is more and pyridostigmine is less effective at presynaptic (or fade) receptors.     

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.     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

Edrophonium 0.5 mg/kg or neostigmine 0.04 mg/kg were administered to two groups of 30 patients each for antagonism of atracurium- or pancuronium-induced neuromuscular block at 25% single twitch recovery. Neuromuscular block was studied using both single twitch and train-of-four (TOF) nerve stimulation. The times to 100% single twitch recovery were significantly more rapid for patients receiving edrophonium (P less than 0.01) in both groups (atracurium and pancuronium); the TOF ratios were similar for atracurium, but for pancuronium they were greater after neostigmine than after edrophonium, and only at 25 min were these ratios similar. It is concluded that edrophonium in a dose of 0.5 mg/kg antagonizes neuromuscular blockade induced by atracurium, as does neostigmine in a dose of 0.04 mg/kg, but the former does not consistently antagonize neuromuscular blockade induced by pancuronium even at 25% of single twitch recovery.     

Antagonism of an intubation dose of vecuronium

To study the problem of rapid antagonization of an intubation dose of vecuronium (0.08 mg/kg), 36 surgical patients undergoing barbiturate/halothane anesthesia were given edrophonium 0.5, 0.75, and 1.0 mg/kg or neostigmine 0.04, 0.06, and 0.08 mg/kg precisely 5 min following injection of the muscle relaxant. T1 twitch (T1/Tc) and train-of-four (TOF) ratios (T4/T1) of the hypothenar muscle were monitored every 20 s with the aid of a commercially available EMG monitor (Datex-Relaxograph). As documented by T1 and T4/T1 follow-up curves (Figs. 1 and 2) and derived parameters of relaxation as well (Dur25, Dur50, Dur75, recovery index, and reversal time; Table 4), both edrophonium and neostigmine resulted in a significantly shorter duration of vecuronium blockade (P less than 0.001). The mean time for recovery of TOF ratio to above 0.7 was between 10.8 +/- 6.0 (neostigmine 0.08 mg/kg) and 21.2 +/- 7.8 (neostigmine 0.06 mg/kg) min (mean +/- SD) following injection of the antagonist as compared to 58 +/- 18.4 min in the control group (P less than 0.001). Recurarization did not occur. Differences between drugs and dose-dependent effects were minimal; edrophonium did not prove superior to neostigmine with the exception of less pronounced muscarinic side effects, hence less bradycardia and a minimum heart rate of 57 +/- 8.2 bpm 20 min after the injection of neostigmine as opposed to 72 +/- 8.2 bpm following edrophonium (P less than 0.05; Fig. 4). As to the restitution of a ventilatory force sufficient to allow spontaneous breathing, no definite conclusions can be made.(ABSTRACT TRUNCATED AT 250 WORDS)     

ANTAGONISM OF VECURONIUM AND ATRACURIUM: COMPARISON OF NEOSTIGMINE AND EDROPHONIUM ADMINISTERED AT 5% TWITCH HEIGHT RECOVERY

In 39 healthy patients antagonism, by neostig-mine 0.07 mg kg^–1or edrophonium 0.8 mg kg^–1, of neuromuscular blockadeinduced by vecuronium or atracurium, was compared. Reversalwas attempted when the height of the single twitch (TH) hadrecovered spontaneously to 5% of the control value. The evokedresponses, initially single twitch, then train-of-four (TOF)were observed until the TOF ratio was 70%. Induced recoveryfrom TH 5% to 25% was shorter following edrophonium than followingneostigmine with both vecuronium (P < 0.05) and atracurium(P < 0.05). The recovery indices and times until TH was 75%of control and until the TOF ratio was 70% were not different.The time from a TH of 75% to a TOF ratio of 70% was shorterfollowing neostigmine than following edrophonium with both vecuronium(P < 0.01) and atracurium (P < 0.01). Edrophonium hada much more variable effect on vecuronium than on atracurium.These results show that although the onset of action of edrophoniumwas faster than that of neostigmine, this did not lead to afaster clinical recovery, and antagonism by edrophonium maybe delayed in a number of patients if vecuronium is the neuromuscularblocker.     

Dose-response curves for edrophonium, neostigmine, and pyridostigmine after pancuronium and d-tubocurarine

To determine the potencies of neostigmine, pyridostigmine, and edrophonium in reversing pancuronium and d-tubocurarine blockade, dose-response curves were established for first twitch height recovery and train-of-four ratio. One hundred and twenty ASA physical status I or II patients scheduled for elective surgery received either 0.06 mg/kg pancuronium or 0.36 mg/kg d-tubocurarine during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height had recovered spontaneously to 10% of its initial value, neostigmine (0.005, 0.01, 0.02 or 0.05 mg/kg), pyridostigmine (0.02, 0.04, 0.1, or 0.2 mg/kg), or edrophonium (0.1, 0.2, 0.4 or 1 mg/kg) was injected by random allocation. Recovery was measured 10 min after the injection of the antagonist. First twitch ED50's were 0.013, 0.085, and 0.17 mg/kg after pancuronium, and 0.017, 0.11, and 0.27 mg/kg after d-tubocurarine, for neostigmine, pyridostigmine, and edrophonium, respectively. The ED50 for pyridostigmine and edrophonium obtained after d-tubocurarine was significantly larger (P less than 0.05) than that after pancuronium. The train-of-four dose-response curves were significantly flatter for edrophonium than for the other two agents, indicating a greater ability of edrophonium to antagonize fade at low doses. It is concluded that the potency of reversal agents may be different for different relaxants, and that potency ratios might depend upon the end-point chosen as full neuromuscular recovery.     

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.     

ANTAGONISM OF PROFOUND NEUROMUSCULAR BLOCKADE INDUCED BY VECURONIUM OR ATRACURIUM: Comparison of Neostigmine with Edrophonium

The effectiveness of neostigmine 0.07mg kg^–1 and edrophonium0.8 mg kg^–1 as antagonists of profound neuromuscular blockadeinduced by vecuronium 0.1 mg kg^–1 or atracurium 0.5 mgkg^–1 was studied in 59 healthy patients. The antagonistswere administered 5 min after total ablation of the twitch responseand the end-point of recovery was a train-of-four ratio of 70%.In 30 patients given vecuronium the mean time to reach thispoint (duration TOF₇₀) was 66.7min in the control group (noantagonist), 43.5 min in the group given neostigmine and 59.8min in the group given edrophonium. The duration TOF₇₀ was shorterin the neostigmine group than in the control {P < 0.01) andedrophonium (P<0.01) groups. The duration TOF₇₀ did not differfrom control in the edrophonium group. In 29 patients givenatracurium, the durations TOF₇₀ were 66.4, 44.1 and 54.9 minin the control, neostigmine and edrophonium groups, respectively.The durations TOF₇₀ in the neostigmine (P < 0.01) and edrophonium(P < 0.01), groups were shorter than control. The durationTOF₇₀ of the neostigmine group was shorter than in the edrophoniumgroup (P < 0.01). These results show that pro-found neuromuscularblockade cannot be rapidly antagonized by either of these twoagents, but if reversal is required under these circumstances,neostigmine would be the more effective drug. ^*The initial results from the vecuronium group were presentedat the 4th Ludwig Boltzmann Symposium, Vienna, 1984.     

Intubating conditions after pipecuronium bromide: the influence of dose and time.

STUDY OBJECTIVE: To determine the intubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED95 (average dose that gives 95% block of the first twitch). DESIGN: To compare intubating conditions at 11/2 and 21/2 minutes in 41 patients receiving balanced anesthesia. SETTING: Surgical patients at Thomas Jefferson University Hospital. PATIENTS: Forty-one patients undergoing surgical procedure who received general anesthesia. INTERVENTIONS: After obtaining a stable baseline of train-of-four (TOF), 41 patients randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 11/2 or 21/2 minutes. MEASUREMENTS AND MAIN RESULTS: Intubating conditions at 21/2 minutes appeared significantly better than those at 11/2 minutes, regardless of the pipecuronium dose. The mean time for T1 (first twitch of TOF) to reach 50% and 90% suppression was 1.36 +/- 0.51 minutes and 2.29 +/- 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 +/- 0.27 minutes and 1.72 +/- 0.45 minutes, respectively, for the 0.1 mg/kg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of T1 was 68.2 +/- 22 minutes for the 0.07 mg/kg dose and 121.5 +/- 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. CONCLUSION: Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 11/2 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 21/2 minutes.     

Neostigmine,pyridostigmine and edrophonium as antagonists of deep pancuronium blockade

To compare the ability of equipotent doses of neostigmine, pyridostigmine and edrophonium to antagonize intense pancuronium neuromuscular blockade, one hundred and twenty ASA physical status I or II patients scheduled for elective surgery received 0.06 mg.kg-1 pancuronium during a thiopentone nitrous oxide-enflurane anaesthetic. Train-of-four stimulation was applied every 12 s and the force of contraction of the adductor pollicis muscle was recorded. In the first 60 patients, spontaneous recovery was allowed until ten per cent of initial first twitch height. Then neostigmine (0.005, 0.01, 0.02 or 0.05 mg.kg-1), pyridostigmine (0.02, 0.04, 0.1 or 0.2 mg.kg-1), or edrophonium (0.1, 0.2, 0.4 or 1 mg.kg-1) was injected by random allocation. Dose-response relationships were established from the measurement of first twitch height (T1) ten minutes later. From these, neostigmine, 0.04 and 0.08 mg.kg-1 was found to be equipotent to pyridostigmine, 0.2 and 0.38 mg.kg-1, and edrophonium, 0.54 and 1.15 mg.kg-1, respectively. These doses were given by random allocation to the next 60 patients, but at one per cent spontaneous recovery. Neostigmine, 0.04 mg.kg-1, produced a T1 of 73 +/- 4 per cent (mean +/- SEM), and a train-of-four ratio (TOF) of 39 +/- 3 per cent. This was significantly greater than with pyridostigmine, 0.2 mg.kg-1 (T1 = 50 +/- 6 per cent; TOF = 25 +/- 3 per cent), and edrophonium, 0.54 mg.kg-1 (T1 = 54 +/- 3 per cent; TOF = 17 +/- 2 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)     

ANTAGONISM OF BLOCKADE PRODUCED BY ATRACURIUM OR VECURONIUM WITH LOW DOSES OF NEOSTIGMINE

Neostigmine 1.25 mg or 0.625 mg was used to antagonize neuromuscularblockade produced by either atracurium 0.5 mg kg^–1 orvecuronium 0.1 mg kg^–1 in four groups of patients (n =45) when the first EMG response of the train-of-four (A') hadrecovered to 10% of control (A). The time for A'/A and the train-of-fourratio (D'/A') to reach 70% was recorded. It was found that,after both atracurium and vecuronium, neostigmine 1.25 mg considerablyaccelerated recovery and, when compared with previous results,differed little from neostigmine 5.0 mg or 2.5 mg. Neostigmine0.625 mg also significantly accelerated recovery after atracuriumand was comparable to neostigmine 1.25 mg. However, with neostigmine0.625 mg after vecuronium, recovery of D'/A' (but not A'/A)was little faster than spontaneous. Neostigmine 1.25 mg appearsto be almost as effective as neostigmine 5.0 mg or 2.5 mg inantagonizing considerable block (90% depression of twitch height)produced by either atracurium or vecuronium, but neostigmine0.625 mg is not sufficient, especially after vecuronium. ^*Present address: Southport General Hospital, Scarisbrick NewRoad, Southport, Merseyside PR8 6LF.     

Postoperative neuromuscular function in pediatric day-care patients.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.     

Pharmacodynamics of vecuronium and atracurium in the obese surgical patient

The effect of obesity on the duration of action of the nondepolarizing muscle relaxants atracurium and vecuronium was studied in 28 neurosurgical patients. In obese patients given vecuronium (0.1 mg/kg), the time to go from 5 to 25% of recovery of twitch response was statistically significantly longer (14.6 +/- 7 minutes, mean +/- SD) than it was in nonobese control patients (6.9 +/- 2 minutes). Similarly, with vecuronium times for recovery from 25 to 75% were longer (33 +/- 15 minutes) in obese patients than in control patients (13.2 +/- 2 minutes), as was time to 75% recovery, 82 +/- 30 minutes in obese patients, 50 +/- 9 minutes in controls. In contrast, obese patients given atracurium (0.5 mg/kg) exhibited no difference in recovery indexes or recovery times when compared to control patients of normal weight. The prolonged duration of action of vecuronium in obese patients is most likely related to impaired hepatic clearance and/or an overdose effect with recovery occurring during the distribution phase. That the duration of action of atracurium is not prolonged in the obese is believed due to this relaxant's not depending on organ function for elimination.     

Recovery from vecuronium neuromuscular blockade following neostigmine administration in infants, children, and adults during halothane anesthesia

To determine whether neostigmine had different effects in pediatric patients during vecuronium neuromuscular blockade, the rate of recovery following neostigmine administration was compared in infants (n = 8), children (n = 10), and adults (n = 10) during nitrous oxide-halothane anesthesia. After induction of anesthesia, patients received 100 micrograms/kg of vecuronium. The EMG response of the adductor pollicis was monitored after train-of-four (TOF) stimulation of the ulnar nerve every 20 s. When the first twitch of TOF spontaneously recovered to 10% of control value, neostigmine was injected (40 micrograms/kg in adults, 30 micrograms/kg in infants and children). During the first few minutes following neostigmine administration, no differences were observed between the three groups. After the 8 min, recovery was more rapid in children than in infants and adults up to and including the 15th min. Ten minutes after neostigmine administration, the first twitch (mean +/- SD) reached 97 +/- 3%, 99 +/- 2%, and 97 +/- 5% of control value in infants, children, and adults, respectively; TOF ratio was greater in children (0.96 +/- 0.03) than in either adults (0.82 +/- 0.17) or in infants (0.83 +/- 0.14) (P less than 0.05). During the first minutes after neostigmine administration, the lack of difference in TOF recovery in the three groups suggests that neostigmine is the main factor of recovery. In contrast, the more complete recovery after the eighth minute in children could be due to the faster rate of spontaneous recovery from vecuronium induced neuromuscular blockade in children.