Reversal of atracurium-induced neuromuscular block in paediatric patients

We studied the efficacy of neostigmine and edrophonium to reverse an atracurium-induced 90% neuromuscular block in 80 paediatric patients anaesthetized with thiopentone, fentanyl and nitrous oxide. The patients were divided into five age groups: 0–2 months, 3–11 months, 2–5 years, 6–10 years, and 11–15 years. At the end of surgery, the neuromuscular block was randomly antagonized with either neostigmine 50 μg kg^-1 with atropine 20 μg kg^-1 or with edrophonium 1 mg kg^-1 with atropine 10 μg kg^-1. In general, the first EMG response and train-of-four (TOF) ratio recovered fastest in the youngest age groups following either reversal agent ( P <0.05). However, in each age group edrophonium had a faster onset of effect than neostigmine ( P <0.05) even though a greater TOF-ratio was finally reached with neostigmine. The effects of neostigmine were less variable and more predictable than those of edrophonium. Therefore, we recommend the use of neostigmine for routine paediatric practice.     

Succinylcholine apnoea: attempted reversal with anticholinesterases

Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.     

Edrophonium and plasma cholinesterase activity

Plasma cholinesterase activity was estimated following administration of edrophonium 0.5 or 1.0 mg X kg-1 given for antagonism of atracurium-induced neuromuscular block. There was no inhibition of enzyme activity for up to three hours following edrophonium administration. This is in contrast to profound and prolonged inhibition of enzyme activity seen following neostigmine and pyridostigmine.     

Neostigmine but not edrophonium prolongs the action of mivacurium

Purpose  

To examine the influence of anticholinesterase drugs neostigmine and edrophonium (which have different effects on plasma cholinesterase activity) administered for antagonism of neuromuscular block on the duration of action of mivacurium (a neuromuscular blocking drug metabolised by plasma cholinesterase).     

Neostigmin und Edrophonium Antagonisierung einer tiefen und oberflächlichen Mivacuriumblockade

Mivacurium has a short duration of action because it is rapidly hydrolysed by plasma cholinesterase. There is ongoing controversy concerning the antagonism of mivacurium-induced neuromuscular block, firstly because of its short spontaneous recovery time, and secondly because the metabolism of mivacurium may be inhibited by anticholinesterases. We therefore compared neostigmine and edrophonium reversal of deep and moderate mivacurium-induced blocks. Methods: After approval by the local ethics committee, 48 ASA class I and II adult patients were investigated during nitrous oxide-fentanyl-thiopental anaesthesia using train-of-four (TOF) stimulation and monitoring of the isometric force of adduction of a thumb. The patients received 0.2?mg/kg mivacurium i.v. Neuromuscular transmission was allowed to recover spontaneously in 10 patients (group SP). In 2 other groups the neuromuscular block was antagonised by administration of 0.04?mg/kg neostigmine (group N5; n=9) or 1.0?mg/kg edrophonium (group E5; n=10) when T1 had recovered spontaneously to 5% of control. In two other groups the neuromuscular block was antagonised with the same doses of neostigmine or edrophonium in 10 patients (group N25) and 9 patients (group E25), respectively, when T1 had recovered spontaneously to 25% of control. Results: Neostigmine or edrophonium administered when T1 had recovered spontaneously to 25% of control shortened the recovery time (time from administration of antagonist to a T4/T1-ratio of 0.7) significantly from 10.7±2.2?min (mean±SD) in the SP group to 5.1±2.0 and 5.3±1.5?min in the N25 and E25 groups, respectively (P<0.05). The corresponding recovery times in the SP, N5, and E5 groups were 15.9±2.9, 10.0±1.9, and 7.7±2.2?min, respectively. The difference between the SP and E5 groups was significant (P<0.05). The recovery indices (time from 25% to 75% recovery of T1) of 3.0±1.3 and 1.7±0.9?min for the E5 and E25 groups, respectively, were shorter than those of the SP group at 6.1±2.0?min (P<0.05). Conclusions: Two theoretical reasons, the very rapid onset time and the fact that it does not inhibit plasma cholinesterase, suggest edrophonium to be the preferred antagonist of a mivacurium-induced blockade. These two characteristics are reflected in our results: only edrophonium was able to shorten the recovery index significantly and, administered at a profound level of mivacurium-induced neuromuscular block, only edrophonium was successful in shortening recovery time significantly. Therefore, edrophonium should be the anticholinesterase of choice to antagonise a mivacurium-induced neuromuscular block.     

Advantages of Glycopyrrolate over Atropine during Reversal of Pancuronium Block

Atropine 0.015 mg kg^-1 and glycopyrrolate 0.0075 mg kg^-1 were compared as antimuscarinic agents during reversal of pancuronium block with neostigmine 0.03 mg kg^-1 in 30 patients anaesthetized with thiopental—N₂O-fentanyl and undergoing minor surgery. The decrease of heart rate was more pronounced in patients who received atropine-neostigmine. The mean of the lowest heart rate was 44.3 beats min^-1 in the atropine group compared with 54.3 beats min^-1 in the glycopyrrolate group. Five patients treated with atropine-neostigmine developed a transient nodal rhythm as compared with two of those receiving glycopyrrolate-neostigmine (non-significant difference). Recovery from anaesthesia, as assessed by the awakening after the discontinuation of N₂O administration, was more rapid in patients given glycopyrrolate. In conclusion, glycopyrrolate seems to have advantages over atropine when used during reversal of pancuronium block with neostigmine.     

Haemodynamic Responses to Antagonism of Pancuronium and Alcuronium Block

Using non-invasive methods, haemodynamic responses to antagonism of pancuronium (Pc) and alcuronium (Ac) block were compared in patients anaesthetized with thiopental-N₂O-fentanyl and undergoing minor surgery. Neuromuscular block (90%) was maintained with Pc in 10 patients and Ac in 10 patients. After surgery, atropine 0.015 mg kg^-1 and neostigmine 0.03 mg kg^-1 (AN) were given simultaneously. The rate of reversal of the block was equal in the two groups. Between 4 and 16 min after AN, the decrease of heart rate (HR) was more pronounced in patients who had received Pc. The mean of the lowest HR was 43.2 beats min^-1 in the Pc group, compared with 62.0 beats min^-1 in the Ac group. The bradycardia was associated with a moderate decrease in arterial pressure in patients treated with Pc. However, due to an increase in stroke volume, mean cardiac output (CO) was not lower in the Pc group. Some patients treated with Pc developed a temporary nodal rhythm after AN and this was associated with a considerable decrease in CO. It is concluded that, in spite of marked bradycardia during antagonism of Pc block, circulation is well maintained, provided that sinus rhythm is present.     

Effect of succinylcholine on subsequently administered mivacurium in children

The interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block was studied in 30 children 2-12 years of age anaesthetized with propofolalfentanil-N₂O-O₂. Neuromuscular response was monitored by adductor pollicis EMG. Fifteen patients received 200 μg. kg^-1 of mivacurium (Group M), and another fifteen received 1500 μg. kg^-1 of succinylcholine followed by 200 μg. kg^-1 of mivacurium when the first EMG response recovered to 5% of calibration value (Group SchM). Plasma cholinesterase (pChE) activity was normal in each patient. The recovery times following mivacurium did not differ between the two groups. Times required for recovery of the first EMG response from 25 to 75% of full EMG recovery were 3.6±1.0 (mean±SD) and 4.0±0.7 min for the Groups M and SchM, respectively. The time from administration of mivacurium to the recovery of train-of-four ratio 0.70 was 13.2±3.3 min for the Group M and 13.6±3.1 min for the Group SchM (NS). Thus, in patients with normal pChE activity preceding administration of succinylcholine did not influence the recovery of neuromuscular function from subsequent mivacurium.     

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)     

ANTAGONISM OF INTENSE ATRACURIUM-INDUCED NEUROMUSCULAR BLOCK IN CHILDREN

Antagonism of intense neuromuscular block induced by atracurium0.5 mg kg^–1 was attempted in four groups of six childrenusing one of two doses of neostigmine (0.05 mg kg^–1 and0.1 mg kg^–1) or of edrophonium (0.5 mg kg^–1 and1.0 mg kg^–1) when the first twitch of the post-tetaniccount (PTC1) was 10% of control. For comparison with normalpractice, a fifth group received neostigmine 0.05 mg kg^–1when the first twitch of the train-of-four was 10% of control.Total recovery time from PTC1 10% to a train-of-four ratio of0.8 was not reduced by early administration of the anticholinesterases,compared with conventional administration of neostigmine atT1 10%. However, recovery from intense block was faster afterneostigmine than edrophonium (P < 0.01). Doubling the dosesof the anticholinesterases did not reduce the recovery timeand had the effect of increasing variability. We conclude thatthere is no clinical advantage in attempting to antagonize intenseneuromuscular block in children using normal or increased dosesof neostigmine or edrophonium.     

Neuromuscular blocking action of suxamethonium after antagonism of vecuronium by edrophonium, pyridostigmine or neostigmine

The reported effects of edrophonium on a subsequent dose of suxamethonium are variable and the effects of pyridostigmine have not been evaluated extensively. We have studied this interaction in patients anaesthetized with propofol and sufentanil. After recovery from an initial bolus (1 mg kg-1) of suxamethonium, vecuronium was infused to produce 75% block. After 30 min, the infusion was discontinued and saline 5 ml, edrophonium 0.75 mg kg-1, pyridostigmine 0.24 mg kg-1 or neostigmine 0.05 mg kg-1 was given. Fifteen minutes later the mean durations of a second bolus of suxamethonium were: 10.5 (SD 3.9) min (saline), 10.9 (3.7) min (edrophonium), 18.7 (5.4) min (pyridostigmine) and 23.8 (7.4) min (neostigmine). Corresponding plasma cholinesterase activities (percentage of baseline) were: 91 (18), 87 (9), 21 (10) and 52 (26). When both treatment groups and individual patients were compared, the changes in duration of action did not correlate with changes in cholinesterase activity. These data suggest that other mechanisms in addition to cholinesterase inhibition may contribute to this drug interaction.      

Effect of prior administration of succinylcholine on duration of action of vecuronium during enflurane anaesthesia

The effects of succinylcholine, which was given to facilitate tracheal intubation on the duration of action of subsequently administered vecuronium bromide, were evaluated in 54 adult patients who underwent abdominal surgeries under enflurane anaesthesia. The electromyographic response to train–of–four ulnar nerve stimulation was measured. Twenty–seven patients received 1 mg–kg^-1 of succinylcholine, followed by 0.15 mg kg^-1 of vecuronium when the electromyographic response recovered to 50% of control after succinylcholine–induced neuromuscular blockade. The other 27 patients served as the control group, receiving 0.15 mg kg^-1 of vecuronium without prior administration of succinylcholine. In both groups, administration of supplemental 0.04 mg kg^-1 of vecuronium was repeated whenever the electromyographic response recovered to 25% of control during surgical procedures. The duration of blockade induced by the initial 0.15 mg kg^-1 of vecuronium was 56.5 ± 12.8 (mean ± s.d.) min for the group with succinylcholine, and 58.5 ± 21.5 min for the control group. In both groups, the average duration of four consecutive supplemental doses of vecuronium was approximately 35 min. No significant differences between groups were found in the duration of neuromuscular blockade induced by initial and supplemental doses of vecuronium.     

Comparison of intubating conditions after rocuronium and suxamethonium following "rapid-sequence induction" with thiopentone in elective cases

Background : Rocuronium (Org 9426) was shown to have the fastest onset of action of all currently available non-depolarizing neuromuscular blocking drugs and to provide intubating conditions similar to those of suxamethonium 60 to 90 s after administration. We compared the intubating conditions after rocuronium and suxamethonium following rapid-sequence induction of anaesthesia.
Methods : Fifty unpremedicated patients of ASA physical status I or II, scheduled for elective surgery were studied. Anaesthesia was induced with thiopentone 6 mg kg^-1 followed randomly by suxamethonium 1 mg kg^-1 or rocuronium 0.6 mg kg^-1 and, 45 s later, intubation was commenced. Muscle fasciculations, intubating conditions and intubation time, haemodynamic variables and oxygenation were assessed.
Results : Intubation time did not differ between suxamethonium (9.8±2.2 s) (mean±SD) and rocuronium (10.5±2.9 s), respectively. Intubating conditions were clinically acceptable (good or excellent) in all patients given suxamethonium and in 96% of the patients given rocuronium. However, the condition of the vocal cords was better (P<0.05) and diaphragmatic response to intubation was less pronounced with suxamethonium (P<0.05). Changes in heart rate and arterial blood pressure were similar in both groups.
Conclusion : The authors conclude that rocuronium is a suitable alternative to suxamethonium for rapid tracheal intubation even under unsupplemented thiopentone anaesthesia, at least in elective, otherwise healthy patients. Its use for rapid-sequence induction under emergency conditions, however, needs further investigation.     

PROLONGED PARALYSIS FOLLOWING SUXAMETHONIUM AND THE USE OF NEOSTIGMINE

A case of prolonged neuromuscular block following the administrationof suxamethonium is reported. Three hours after administrationof suxamethonium, a well defined, recovering phase II blockwas demonstrated with a T4: T1 ratio of 0.25, and neostigminewas administered. Although the T4: T1 ratio was improved to0.9, T1 remained at 25% of control, and significant paralysispersisted which responded to administration of cholinesterase.It is concluded that neuromuscular monitoring cannot reliablypredict reversibility in such cases and that, even after 3 h,antagonism of prolonged suxamethonium block should commencewith cholinesterase, followed by neostigmine if necessary.     

Effects of cholinesterase inhibitors on the neuromuscular blocking action of suxamethonium

Prolonged neuromuscular block occurs when suxamethonium is givenafter neostigmine or pyridostigmine; however, studies of edrophoniumand suxamethonium have yielded conflicting results. We havestudied, therefore, interactions between suxamethonium and allthree anticholinesterases in rats anaesthetized with pentobarbitone.After recovery from an initial bolus of suxamethonium, saline,edrophonium, pyridostigmine or neostigmine was administeredand a second dose of suxamethonium was then given. All threeanticholinesterases prolonged the duration of neuromuscularblock (90% suppression to 50% twitch recovery) to 127(SEM 9)%,127(10)% and 138 (11)% of baseline for edrophonium, pyridostigmineand neostigmine, respectively. Recovery index (25% to 75% twitchrecovery) was increased also to 125 (9)%; 149 (10%) and 185(15)% of baseline, respectively for the three drugs. Presented in part at the 1992 annual meetings of the AmericanSociety of Anesthesiologists and the California Society of Anesthesiologists.     

Comparison of the neuromuscular effects of mivacurium and suxamethonium in infants and children

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2–12 months and children 1–12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2×ED₉₅ was used in four groups of infants and children, while 3.4×ED₉₅ was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium ( P =0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min ( P ×0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4×ED₉₅ did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T₂₅) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively ( P ×0.05). In children given 3.4×ED₉₅ of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2×ED₉₅, with spontaneous recovery to T₂₅ prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.     

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.     

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.     

SUXAMETHONIUM-NEOSTIGMINE INTERACTION IN PATIENTS WITH NORMAL OR ATYPICAL CHOLINESTERASE

The effect of neostigmine 0.05 mg/kg on the neuromuscular blockproduced by suxamethonium was investigated in 10 normal patientsand in five patients with atypical plasma cholinesterase activity,by recording the twitch response to ulnar nerve stimulation.In the normal patients, neostigmine potentiated the block producedby suxamethonium whether it was of the depolarizing or descensitizingtype. On the other hand, in patients with atypical plasma cholinesteraseactivity, neostigmine potentiated the depolarizing phase ofsuxamethonium block, while antagonizing the desensitizing phase.The degree of antagonism was not related to the magnitude ofneuromuscular block, but was proportional to the degree of desensitizationat the time of antagonism.     

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.