Effects of Succinylcholine Chloride on the Response of Fast and Slow Muscle in the Cat

Fast and slow muscle fibres differ histochemically, electrophysiologically and pharmacologically. In vivo, the effect of 0.05, 0.075 and 0.1 mg X kg-1 succinylcholine on the response of the indirectly stimulated gastrocnemius (fast) and soleus muscle (slow) to single, train-of-four and tetanic stimuli was studied. There was a significant difference between the response of the two muscles. Maximum twitch suppression occurred 2 min after injection and was more significant in the gastrocnemius than the soleus. The duration of the neuromuscular blockade was 9 min or more in both groups. The train-of-four ratio dropped below 0.7 in the gastrocnemius preparation at all doses and in the soleus when 0.1 mg X kg-1 succinylcholine was used. Sustained tetanus was achieved in both muscles at 5 and 10 min, respectively. There was evidence of fatigue in the soleus muscle at the 5-min observation suggestive of the presence of a phase II block, a phenomenon not observed in the gastrocnemius.     

Characterization of the train-of-four response in fast and slow muscles: effect of d-tubocurarine, pancuronium, and vecuronium

The in vivo cat soleus and gastrocnemius muscles were used to compare isometric contraction strength and the train-of-four (T4) response (2 Hz for 2 s) of two muscle types (fast and slow) during onset of competitive neuromuscular blockade in order to determine the extent of the correlation between twitch depression and T4 fade. Prior to drug administration the muscles that were studied differed significantly in that the T4 ratio was 1.0 in the gastrocnemius and only 0.87 in the soleus. Three competitive neuromuscular-blocking agents were compared: d-tubocurarine, pancuronium, and vecuronium. d-Tubocurarine was found to produce a close correlation between the degrees of twitch strength depression and T4 for both muscles. However, these muscles demonstrated significantly different ED50 values (105 micrograms/kg for gastrocnemius, 150 micrograms/kg for soleus). Pancuronium also produced a similar relationship between twitch strength depression and T4 decrement for each muscle. In this case, however, there was little difference in their ED50 values for twitch depression (11.5 micrograms/kg for gastrocnemius, 13 micrograms/kg for soleus). The effects of vecuronium were quite different from the other two muscle relaxants. Although vecuronium produced a comparable correlation between twitch tension and T4 fade in fast muscle, no such relationship was found to exist in slow muscle. Even when the twitch strength was blocked to 18% of control, the soleus T4 response was depressed to only 75% of control. These results highlight major differences among competitive neuromuscular-blocking agents and suggest multiple sites of action.     

Posttetanic potentiation and fade in the response to tetanic and train-of-four stimulation during succinylcholine-induced block

We designed this study to confirm anecdotal observations that neuromuscular block after a single administration of succinylcholine is characterized by fade to train-of-four (TOF) or tetanic stimulation, as well as posttetanic potentiation. This prospective, randomized, 2-center observational study involved 100 patients. Patients were allocated to 1 of 5 groups and received 0.1, 0.3, 0.5, 0.75, or 1.0 mg/kg succinylcholine during propofol/fentanyl/nitrous oxide anesthesia. Neuromuscular function was monitored by TOF using mechanomyography. At 10%-20% spontaneous recovery of the first twitch of TOF, the mode of stimulation was changed from TOF to 1-Hz single-twitch stimulation followed by a tetanic stimulus (50 Hz) for 5 s. Three seconds later, the single twitch (1 Hz) was applied again for approximately 30 s followed by TOF stimulation until full recovery of the TOF response. Succinylcholine-induced neuromuscular block had the following characteristics: 1) twitch augmentation before twitch depression, which was seen more frequently in patients given smaller doses (0.1 and 0.3 mg/kg) than in those given larger doses (0.5-1.0 mg/kg); 2) TOF fade during onset and recovery of the block; 3) tetanic fade; and 4) and posttetanic potentiation. Posttetanic potentiation was related to the pretetanic twitch height but was not related to the dose of succinylcholine administered. Some characteristics of Phase II block were detectable during onset and recovery from doses of succinylcholine as small as 0.30 mg/kg. Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. IMPLICATIONS: Posttetanic potentiation and fade in response to train-of-four and tetanic stimuli are characteristics of neuromuscular block after bolus administration of different doses of succinylcholine. We also conclude that some characteristics of a Phase II block are evident from an initial dose (i.e., as small as 0.3 mg/kg) of succinylcholine.     

Neuromuscular sensitivity to atracurium in humans

The relation between plasma concentration and the effects of atracurium was studied in seven patients anaesthetised with thiopentone, fentanyl and nitrous oxide-oxygen. The response to train-of-four stimulation at ten-second intervals with tetanic stimuli applied every five minutes were recorded. The first sign of transmission returning after complete blockade was usually the post-tetanic facilitated twitch, which was noted when the mean atracurium concentration was 1.15 mg 1(-1) (SD 0.77). The most sensitive parameter was the train-of-four ratio, which recovered to 0.5 when the concentration was 0.217 mg 1(-1) (SD 0.56), compared with a concentration of 0.271 (SD 0.85) at 50% recovery for twitch height, 0.221 (SD 0.029) for tetanic peak and 0.231 (SD 0.079) for tetanic fade. The value for the train-of-four ratio differed significantly (P less than 0.05) from that for the twitch height, but other differences were not significant. Once recovery commenced, these four parameters recovered at similar rates, with recovery indices (25 to 75% responses) of 14.8 (SD 1.7), 14.0 (SD 1.0), 14.3 (SD 1.8) and 13.7 (SD 2.1) minutes respectively. Post-tetanic facilitation was most marked during severe but incomplete blockade and tetanic stimulation temporarily reversed the atracurium-induced decrease in train-of-four ratio. Clinically, the use of tetanic stimulation did not improve the sensitivity of neuromuscular monitoring, but post-tetanic count may be useful where monitoring of profound relaxation is required.     

Evolution of single twitch and train-of-four responses and of tetanic fade in relation to plasma concentrations of fazadinium in man

The evolution of single twitch and train-of-four (2 Hz) responses and tetanic fade (100 Hz) in relation to plasma concentration of fazadinium was determined during stable anesthesia (fentanyl-N2O) in six healthy adult patients after a bolus injection of 0.75 mg/kg of fazadinium. The interval between injection and 50% recovery and the corresponding fazadinium plasma concentrations were (mean +/- SEM): 47 +/- 4 minutes and 1.44 +/- 0.18 microgram/ml for the single twitch; 66 +/- 7 minutes and 1.01 +/- 0.10 microgram/ml for the train-of-four; and 83 +/- 11 minutes and 0.82 +/- 0.08 microgram/ml for tetanic fade. The results indicate that train-of-four and tetanic fade are more sensitive tests for evaluation of residual neuromuscular block than is measurement of single twitch responses.     

Train-of-four fade of non depolarizing muscle relaxants: an insight into the mechanism of precurarization

This study was carried out to assess the prejunctional effect of non depolarizing muscle relaxants during the onset of neuromuscular blockade using the train-of-four ratio (TR). The prejunctional effect was compared with previous results concerning the ability of the relaxants to prevent suxamethonium-induced fasciculations. Fifty-three adult patients were relaxed with small incremental doses of either alcuronium (0.03 mg.kg-1), atracurium (0.04 mg.kg-1), pancuronium (0.01 mg.kg-1), d-tubocurarine (0.05 mg.kg-1) or vecuronium (0.01 mg.kg-1) during anaesthesia with thiopentone, fentanyl and nitrous oxide in oxygen. The muscle relaxant was given after recovery from an initial suxamethonium blockade needed for tracheal intubation. The evoked integrated EMG response to supramaximal train-of-four (2 Hz) stimulation was recorded every 20 s. TR % was calculated at different first twitch (T1) levels during the onset of neuromuscular blockade. Significant changes occurred at the 100% and 90% T1 levels, alcuronium having the lowest mean TR values. Atracurium, pancuronium and vecuronium gave similar TR values. Results with d-tubocurarine placed it between alcuronium and the others. These train-of-four ratio results were compared with the ability of non depolarizing muscle relaxants to prevent fasciculations. In conclusion, the stronger the train-of-four fade, the greater was the ability of the relaxant to prevent suxamethonium-induced fasciculations. This supports the theory that the blockade of prejunctional cholinergic receptors is the mechanism of action of precurarization.     

Electromyographic and mechanomyographic characteristics of neuromuscular block by magnesium sulphate in the pig

In spite of its well known propensity to cause accidental paralysis by a specific mechanism of action, Mg(2+)-induced neuromuscular block has not been examined systematically for its characteristics of muscle response to nerve stimulation. We examined in seven anaesthetized domestic pigs the mechanomyographic (MMG) and neurally evoked compound electromyographic (ncEMG, EMG) responses of the tibialis anterior muscle to stimulation of its motor nerve, at baseline and during three levels of neuromuscular block induced by infusion of MgSO4 (at approximately 25%, 50% and 75% depression of the 0.1-Hz EMG). We observed that: at 0.1 Hz, the MMG tended to be more depressed than the EMG; the train-of-four (2 Hz) was essentially non-fading; the tetanic force (50 Hz) showed tetanic ascent instead of tetanic fade and reached its baseline control value at 5 s in spite of depression of the twitch; the EMG counterpart of the tetanus showed escalation of the train of ncEMG, so that the fourth ncEMG was much greater than the first; and the post-tetanic twitch was also relatively spared from Mg(2+)-induced neuromuscular block. Sparing of the tetanus and post-tetanic twitch resulted in large gains in the tetanus:twitch ratio and the post-:pre- tetanic twitch ratio, which increased at the 75% level of depression from 2.8 (SD 0.7) to 11.5 (4.0), and from 1.5 (0.3) to 4.6 (1.4) (P < 0.01), respectively. These characteristics of neuromuscular block by Mg2+ reflect its prejunctional mechanism of action by depression of transmitter release.      

Twitch, tetanus and train-of-four as indices of recovery from nondepolarizing neuromuscular blockade

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P less than 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P less than 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.     

Criteria of adequate clinical recovery from neuromuscular block

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P < 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P < 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.     

Studies on fazadinium bromide (ah 8165): a new non-depolarizing neuromuscular blocking agent.

Intravenous dose-response relationships were used to correlate neuromuscular paralysis with the effects of fazadinium (AH 8165) on autonomic mechanisms in anaesthetized cats and rhesus monkeys and with cardiovascular effects in man. In cats and monkeys neuromuscular paralysis of the twitch responses of the gastrocnemius muscle by fazadinium was accompanied by impairment of the vagally induced bradycardia, but cardiovascular disturbances were small. Blockade of sympathetic mechanisms and hypotension were only evident with supra-maximal doses. In man tachycardia was a common occurrence and in some patients hypertension occurred with doses of the drug needed for complete neuromuscular paralysis. Fazadinium was three to four times more potent in rhesus monkeys than in cats and its course of action was considerably longer. The potency of the drug in man corresponded more closely to that in cats than in rhesus monkeys but its course of action in patients was similar to that in monkeys. In man, dose-response curves were constructed for the contractions of the adductor pollicis muscles elicited by tetanic and single twitch stimuli applied to the corresponding ulnar nerves. The onset of paralysis of the tetanic contractions after the intravenous injection of fazadinium (0.4 mg/kg) occurred within two minutes, but recovery was slow and about 50 minutes were needed for its completion. Depression of the simultaneously recorded twitch responses was less marked, slower in onset and recovery was slightly more rapid. These effects were similar to those obtained with tubocurarine (0.2 mg/kg) but the action of fazadinium was slightly shorter. Tetanic-tension ratios were computed after 30 and 50 per cent recovery from neruomuscular blockade in man. These ratios were lower with fazadinium than with tubocurarine and indicated taht tetanic fade was greater and more persistent after fazadinium than after tubocurarine.     

Electromyographic assessment of neuromuscular block at the gastrocnemius muscle

We have assessed neuromuscular block electromyographically at the gastrocnemius muscle and compared it with that at the abductor digiti minimi muscle in 60 adult patients undergoing cervical spine surgery under general anaesthesia. All patients were in the prone position. After vecuronium 0.2 mg kg-1, times to onset of neuromuscular block at the gastrocnemius and abductor digiti minimi muscles were mean 147 (SD 24) and 145 (14) s, respectively (ns). Times to return of the first response of the post-tetanic count (PTC1) at the gastrocnemius and abductor digiti minimi muscles were 27.7 (5.6) and 37.0 (5.9) min, respectively (P = 0.0001). Times to return of the first response of the train-of-four (TOF) at the gastrocnemius and abductor digiti minimi muscles were 41.0 (9.1) and 49.9 (8.7) min, respectively (P = 0.01). Recovery of PTC, T1/T0 and TOF ratio at the gastrocnemius muscle were significantly faster than at the abductor digiti minimi muscle.      

Twitch augmentation and train-of-four fade during onset of neuromuscular block after subclinical doses of suxamethonium

We have studied the train-of-four (TOF) response mechanomyographically during onset of neuromuscular block produced by subclinical doses of suxamethonium in order to follow the augmentation of the first twitch of the TOF (T1) and TOF fade compared with control TOF responses before the drug was given. In the groups given suxamethonium 0.05, 0.1, 0.2 and 0.3 mg kg-1, the increments in T1 after administration of the drug were observed before twitch depression occurred; these were mean 22.3 (SEM 8.1)%, 19.2 (3.3)%, 10.8 (2.0)% and 4.2 (2.2)%, respectively. This effect was more marked with the lower doses (P < 0.05). The degree of TOF fade was moderate during onset of neuromuscular block and depended on the dose of drug. The results of this study suggest that low doses of suxamethonium produced transient increase in muscle tension and twitch depression with significant TOF fade. We conclude that suxamethonium was associated with presynaptic effects as a consequence of brief stimulation of acetylcholine release followed by progressive diminution at the neuromuscular junction.      

Train-of-four ratio after antagonism of atracurium with edrophonium: influence of different priming doses of edrophonium

This study was designed to investigate the effect of different priming doses of edrophonium on the relationship between the the recovery of the first twitch of the train-of-four (T1) and train-of-four (TOF) ratio. This relationship was studied after the administration of the full dose of the antagonist in all groups. Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I, controls) or in an initial dose of 0.05, 0.1, 0.15 or 0.2 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to V. Reversal was attempted at the ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Of all the groups studied, Group V had a significantly greater recovery in the TOF ratio at any given T1 value. When first twitch tension (T1) had recovered to 100 per cent of the control, it was found for the same tension that the TOF ratio was greater in Group V, being 0.75 compared to 0.63, 0.65, 0.65 and 0.64 in Groups I to IV respectively. The implication is that this differential ability to reverse fade (or prejunctional activity) may be involved in the acceleration of recovery.     

Blood flow and mivacurium-induced neuromuscular block at the orbicularis oculi and adductor pollicis muscles

We have studied the pattern of blood flow and pharmacodynamic profile of mivacurium-induced block at the adductor pollicis and orbicularis oculi muscles. We studied 30 adult patients anaesthetized with fentanyl, thiopentone, nitrous oxide-isoflurane, and mivacurium 0.2 mg kg-1. Neuromuscular transmission was monitored with accelerometry (TOF Guard, Biometer, Denmark). Blood flow was measured at the two muscles with the use of a laser Doppler flowmeter (Laserflo BPM2, Vasamedics, USA). All patients developed 100% neuromuscular block at the adductor pollicis muscle. Mean maximum neuromuscular block at the orbicularis oculi was 96.4 (SD 3.5)% (ns). Onset time, time required for 25% and 75% recovery of the first twitch in the train-of-four (T1), and a train- of-four ratio (T4/T1) of 90% at the orbicularis oculi were respectively, mean 130.4 (SD 28.5) s, 9.1 (3.2) min, 16.2 (3.9) min and 20.2 (4.3) min and were significantly shorter than the corresponding values at the adductor pollicis: 202.7 (37.2) s, 12.9 (3.9) min, 21.1 (5.1) min and 30.8 (7.4) min. For a given T1, there was significantly less train-of-four fade (T4/T1) at the orbicularis oculi than at the adductor pollicis muscle during recovery. Blood flow was comparable at the two muscles before induction of anaesthesia. Thiopentone significantly increased thenar muscle blood flow from 2.9 (1.5) to 12.3 (6.8) ml 100 g-1 min-1, with a further increase to 22.7 (8.0) ml 100 g- 1 min-1 after isoflurane (P < 0.001). Blood flow at the orbicularis oculi was not altered by thiopentone or isoflurane and was consistently lower than that at the adductor pollicis muscle. We conclude that the different pharmacodynamic profiles of mivacurium-induced block at the orbicularis oculi and adductor pollicis muscles were not related primarily to a difference in blood flows.      

Neuromuscular blocking effects and train-of-four fade with cisatracurium: comparison with other nondepolarising relaxants

Neuromuscular blocking drugs exhibit different degrees of fade in response to train-of-four stimulation believed to represent their relative prejunctional effects. The present study was designed to compare the train-of-four fade after cisatracurium and compare this with other commonly used muscle relaxants. Train-of-four fade during onset and recovery of block were recorded after administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1, vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion. Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The onset and recovery of block were also measured. Train-of-four fade during onset of block was greater with the lower dose of cisatracurium compared with the higher dose of cisatracurium and all other relaxants. Train-of-four fade during recovery was similar. The median times (and ranges) for the onset of maximum block were 3.4 (2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium, respectively. The median times (and ranges) for the recovery of T1 to 25% of control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43 (37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117); and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1, atracurium, mivacurium, vecuronium and recuronium, respectively.     

Tumor necrosis factor‐alpha antagonist administration recovers skeletal muscle dysfunction in ovariectomized rats

Skeletal muscles deteriorate after ovariectomy. Molecular pathway of this deterioration has not been defined. Tumor necrosis factor (TNF)‐alpha activation is assumed to trigger muscle atrophy and administration of its antagonist is hypothesized to recover this atrophy in rats. Slow‐twitch soleus and fast‐twitch extensor digitorum longus muscle functions were investigated in intact, ovariectomized (OVX), and OVX plus 10 µg/g/week TNF‐alpha antagonist administered female rats. Maximum isometric twitch and tetanic contraction responses were lower in the OVX groups. Maximum isometric twitch amplitudes recovered in the extensor digitorum longus but not in the soleus muscles after TNF‐alpha antagonist administration. The decrease in responses to tetanic stimulations recovered in the OVX–TNF group at frequencies higher than 20 Hz in both muscle types. OVX animals body weight was 21% higher than intact animals. Muscle weight to body weight ratios of the OVX groups were higher than the control group which recovered after TNF‐alpha antagonist administration. Findings suggest that the functional loss in OVX rat muscles is TNF‐alpha pathway dependent. Skeletal muscle atrophy and function after OVX recovered by TNF‐alpha antagonist administration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:275–280, 2011     

Effect of Tubocurarine on Human Soleus and Gastrocnemius Muscles

The effect of a bolus injection of tubocurarine (0.1-0.13 mg × kg^-1 i. v.) was followed in six young male subjects by registration of the rectified smoothed electromyogram (rsEMG) from them. soleus (71±5.1 (s.e.mean) % slow twitch muscle fibers) and from the m. gastrocnemius (54±3.1% slow twitch muscle fibers). Volitional muscle strength was recorded in isometric plantar flexions with the knee fully (0°) extended where m. soleus and m. gastrocnemius both are active, and with the knee bent 90° where m. soleus is dominating force development. During maximal action of the drug, the rsEMG from the soleus muscle was reduced to 30±4.0% of the control value, while the rsEMG from the gastrocnemius muscle was reduced to 53±5.2% (P<0.01). Muscle strength with the knee extended showed 53±7.5% force left, while 44±6.4% of the muscle strength remained when the knee was bent (P<0.01). The results suggest that tubocurarine aflects human muscles in proportion to their slow twitch muscle fiber content.     

The effects of acute and chronic hydrocortisone treatment on neuromuscular blockade in the anesthetized cat

It is fairly widespread clinical practice to administer large doses of corticosteroids to patients in cases of shock; doses of hydrocortisone as high as 50 mg X kg-1 given intravenously have been proposed and used. Hydrocortisone, when administered in this way during surgery, has been implicated in interactions with neuromuscular blocking agents. In order to determine the type and mechanism of this interaction, the authors undertook further investigation. The effects of hydrocortisone were studied in two ways. Firstly, a constant 50% depression of the indirectly elicited twitch tension of the tibialis-anterior muscle was established in cats, using a constant intravenous infusion of either pancuronium (1.0 +/- 0.2 micrograms X kg-1 X min-1) or succinylcholine (3.6 +/- 0.8 micrograms X kg-1 X min-1). The effects of intravenous hydrocortisone then were studied on this block. Secondly, cats chronically were treated with 2 mg X kg-1 of intramuscular hydrocortisone three times a week for 1 month, and then dose-response curves were constructed for pancuronium or succinylcholine. Acute administration of intravenous hydrocortisone (1-15 mg X kg-1) alone had no affect on the twitch tension of either the tibialis-anterior or soleus muscles, however, the corticosteroid (7 and 15 mg X kg-1) did significantly (P less than 0.05) enhance the 50% depression of the indirectly elicited twitch tension of the tibialis-anterior muscle produced by the constant intravenous infusion of pancuronium. The soleus muscle was affected similarly (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Neostigmine after spontaneous recovery from neuromuscular blockade

The effect of neostigmine on neuromuscular function was examined after spontaneous recovery from an atracurium-induced neuromuscular blockade, which reached a train-of-four ratio of either 0.5 or 0.9. Two doses of neostigmine 2.5 mg were given 5 minutes apart. Neuromuscular recovery was assessed with train-of-four and tetanic stimuli. The first dose of neostigmine antagonised the neuromuscular blockade. The second dose diminished tetanic height and increased tetanic fade. The train-of-four measured mechanically was adversely affected to a small degree, but when measured with the electromyograph no significant change occurred. Neostigmine may adversely affect neuromuscular function after spontaneous recovery from a non-depolarising block. This is unlikely with a single modest dose and any effects are probably short-lived.