Recovery Of Twitch Height Research Articles

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.

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.

COMPARISON OF NEUROMUSCULAR BLOCKADE IN THE DIAPHRAGM AND THE HAND

Neuromuscular blockade was recorded in the diaphragm and in the adductor pollicis muscle using unilateral supramaximal stimulation of phrenic and ulnar nerves and measurement of the mechanical effect of each. After administration of atracurium 0.4-0.5 mg kg-1 to 10 patients, both onset and recovery of neuromuscular blockade in the diaphragm occurred before that in adductor pollicis and there was a linear relationship between recovery in diaphragm and adductor pollicis. After administration of vecuronium 0.08-0.1 mg kg-1 to a further 10 patients, paralysis occurred in the diaphragm before adductor pollicis in all except one patient, in whom it occurred simultaneously. Reappearance of adductor pollicis twitch occurred in six patients after all four twitches had returned in the diaphragm, but the rate of recovery of twitch height in the diaphragm was more rapid than in adductor pollicis in every patient.

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 e

New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use.

The newer neuromuscular blocking drugs include vecuronium and atracurium. Vecuronium is a competitive neuromuscular blocking drug with a steroid nucleus. A dose of 0.1 mg/kg has an onset time of 2 minutes and provides surgical paralysis for 20 minutes. Recovery to 90% twitch height occurs in 40 to 50 minutes. Vecuronium has few adverse effects and its use is associated with cardiovascular stability. Atracurium is a competitive neuromuscular blocking drug which undergoes Hofmann degradation and ester hydrolysis in plasma. A dose of 0.6 mg/kg has an onset time of around 2 minutes and provides surgical paralysis for 20 to 30 minutes. Recovery to 90% twitch height occurs in 60 to 80 minutes. Histamine release, usually only localised, has been reported in association with the use of atracurium. The organ-independent metabolism of atracurium allows its use in standard dosage in patients with renal or hepatic disease. Edrophonium, although not a new drug, has recently been re-evaluated for reversal of neuromuscular blockade. In a dose of 0.5 mg/kg it has been shown to be as effective as neostigmine at reversing neuromuscular blockade after recovery has started (greater than 25% twitch height recovery). However, if blockade is profound (less than 10% recovery), edrophonium is less effective. Among the newer intravenous anaesthetics are propofol (disoprofol) and midazolam. In a dose of 1.5 to 2.5 mg/kg, propofol produces sleep rapidly with a prompt recovery in 4 to 6 minutes. Induction of anaesthesia may be associated with a transient apnoea and a fall in systolic pressure. The rapid recovery has led to its use for maintenance of anaesthesia. Midazolam is a water-soluble benzodiazepine which has been used as an anaesthetic agent. The dose needed to induce sleep varies widely (0.15 to 0.5 mg/kg); onset is slow (1.5 to 5 minutes), and recovery may be prolonged. Midazolam is also used in lower doses as a sedative. Ketamine, an intravenous induction agent, has recently been used intrathecally and extradurally to provide analgesia.

Accelerated reversal of atracurium blockade with divided doses of neostigmine.

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

Succinylcholine Pharmacodynamics in Peripartum Patients

Leighton, B. L.; Cheek, T. G.; Gross, J. B.; Apfelbaum, J. L.; Shantz, B. B.; Gutsche, B. B.; Rosenberg, H. Author Information

Succinylcholine pharmacodynamics in peripartum patients.

Serum cholinesterase activity decreases 30% during pregnancy and remains depressed during the postpartum period. However, succinylcholine recovery is not prolonged in term-pregnant patients. This contrasts with results obtained in other patients with decreased serum cholinesterase activity. To better understand this paradox, the authors compared serum cholinesterase activity and recovery from succinylcholine, 1 mg/kg, in nonpregnant (with and without oral contraceptive use), in term-pregnant, and in postpartum patients. Serum cholinesterase activity was lower in both term-pregnant (3.66 +/- 0.39 U/ml, means +/- SE) and postpartum (2.84 +/- 0.35 U/ml) patients than in nonpregnant patients not taking oral contraceptives (5.01 +/- 0.33 U/ml, P less than 0.05). Cholinesterase activity in postpartum patients also was significantly lower than in nonpregnant patients taking oral contraceptives (4.81 +/- 0.63, P less than 0.05). In contrast, the time to 25% twitch-height recovery did not differ between term-pregnant (470 +/- 56 s) and nonpregnant patients taking (499 +/- 29 s) or not taking (501 +/- 21 s) oral contraceptives, but was significantly increased in postpartum patients (685 +/- 22 s, P less than 0.001). The similar duration of action of succinylcholine in term-pregnant patients (with decreased serum cholinesterase activities) and nonpregnant patients may be related to the increased volume of distribution of succinylcholine at term.

MONITORING TECHNIQUE AFFECTS MEASUREMENT OF RECOVERY FROM SUCCINYLCHOLINE

To compare recovery time from neuromuscular blockade after the administration of a single intravenous bolus of succinylcholine (1 mg/kg), we measured, both mechanically and electromyographically, the evoked twitch responses in the hand muscles of 10 patients. Electromyographic data were obtained, electronically integrated, and recorded by a newly available clinical monitoring device. Using both the mechanical and the electromyographic devices, we recorded the times for first return of twitch, as well as for 25% and 75% recovery of twitch height compared with prerelaxant twitch baseline values and compared the values by calculating least-squares regression lines. Times given by the electromyographic device for these measures of returning neuromuscular function were notably longer than those given by the mechanical evoked force monitor. No such findings have been reported in previous studies that compared these two techniques for monitoring of muscle recovery from nondepolarizing relaxants. The specific reasons for the differences found in this study are unknown.

Antagonism of d-tubocurarine-induced neuromuscular blockade with a mixture of 4-aminopyridine and neostigmine in man.

The antagonistic properties of a mixture of 4-aminopyridine (4-AP) 3 mg X ml-1 and neostigmine 0.2 mg X ml-1 (in three patient groups) administered at 90 per cent d-tubocurarine block were compared with those of plain neostigmine (in three patient groups) in thirty-six patients during thiopentone-fentanyl-nitrous oxide-oxygen anaesthesia. The recovery variables included thumb twitch height, thenar e.m.g. peak-to-peak amplitude, and train-of-four ratio in response to supramaximal ulnar nerve stimulation. In addition, mean arterial pressure, heart rate, apnoea time and time to responsiveness to verbal command after nitrous oxide was turned off at 20 minutes of recovery were examined as circulatory and central nervous system responses to antagonism. The addition of 4-AP 30 mg to neostigmine 2 mg enhanced the recovery of train-of-four ratio from 54.2 +/- 5.2 to 80.2 +/- 5.2 per cent at 20 mins of antagonism (mean +/- SEM; p less than 0.01) while adding 4-AP 45 mg to neostigmine 3 mg increased the train-of-four ratio from 67.7 +/- 2.3 to 92.3 +/- 2.4 per cent (p less than 0.01) when compared with plain neostigmine. No statistically significant difference could be found between the groups in the recovery of twitch height or e.m.g. amplitude. The antagonism of d-tubocurarine block with 4-AP 30 mg plus neostigmine 2 mg was at least as effective as with neostigmine 3-4 mg. Mean arterial pressure increased in the group receiving 45 mg 4-AP plus 3 mg neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

DOSE-RESPONSE RELATIONSHIPS AND NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING KETAMINE ANAESTHESIA

The dose-response curves of vecuronium and pancuronium were compared during ketamine anaesthesia in 60 patients (ASA I). The relationship between the probit transformed depression of twitch height and the logarithm of the dose was analysed by linear regression. Vecuronium was found to be 1.2 times more potent than pancuronium. ED50 of vecuronium and pancuronium were 30.5 microgram kg-1 and 37.0 microgram kg-1, and the ED95 45.6 microgram kg-1 and 59.5 microgram kg-1, respectively. Using equipotent doses of vecuronium and pancuronium (1.6 ED95) indices of neuromuscular blockade were compared in a further 20 patients (ASA I). No statistically significant difference was found in onset time. The duration of action following vecuronium was significantly shorter than after pancuronium. The time to 25% recovery of twitch height following vecuronium 73 microgram kg-1 was 22.2 min compared with 66.6 min following pancuronium 99 microgram kg-1. Following supplementary doses of vecuronium, a statistically significant increase in duration of action was seen following the fourth and fifth doses. Reversal time of vecuronium to a train-of-four ratio of 0.7 was significantly shorter than that of pancuronium (8.3 min and 13.6 min, respectively).

Clinical Experience with ORG NC45 (Norcuron) as the Sole Muscle Relaxant

The neuromuscular effects of ORG NC45, used as the sole muscle relaxant, were compared with a succinylcholine-pancuronium sequence in patients during nitrous oxide-fentanyl anaesthesia. The subjects were divided into four groups with ten in each group. After induction of anaesthesia they received either succinylcholine, 1 mg-kg-1 or ORG NC45 in doses of 50, 70 or 90 μxg-kg-1 and tracheal intubation was done 90 seconds later. Neuromuscular transmission was monitored using train-of-four stimulation. Succinylcholine produced 100 per cent block with uniformly excellent intubating conditions whereas the three doses of ORG NC45 were associated with blocks of 7.5, 18.7 and 30.7 percent and acceptable conditions in only 30 per cent of subjects. Muscle relaxation was maintained in the NC45 groups with increments of 10 |xg-kg~’ and in the succinylcholine group with pancuronium, initially as a bolus of 40 μg-kg-1, followed by increments of 5 μg-kg-1 . All increments were given at 10 per cent recovery of twitch height. The overall requirement to maintain 90 per cent block with pancuronium was 1.1 μg-kg-1-min-1; compared with 1.28 μxg-kg1-min-1 with ORG NC45. No cumulative effects were seen with either drug during the first hour of neuromuscular blockade. At the end of the operation the neuromuscular block was antagonized with atropine 18 μxg-kg-1, and neostigmine 36 μxg-kg-1 and recovery was significantly more rapid with NC45 than pancuronium. We conclude that the lack of cumulation, easy reversibility and lack of cardiovascular effects suggest that NC45 has advantages over currently available non-depolarizing muscle relaxants but that its onset of action is too slow for rapid intubation.

NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING HALOTHANE ANAESTHESIA

The neuromuscular blocking properties of vecuronium (Org NC 45) and pancuronium were compared in 40 patients during halothane anaesthesia. Onset time was found to be dose-dependent, but no significant difference was found between the two drugs. The duration of action of vecuronium was significantly shorter than pancuronium. Times to 90% recovery of twitch height following vecuronium 0.03 mg kg-1 and 0.057 mg kg-1 were 32.0 min and 44.9 min, respectively, compared with 72.9 min and 124.7 min following equipotent doses of pancuronium (0.042 mg kg-1 and 0.08 mg kg-1). Recovery indices following both doses of vecuronium (10.0 min and 11.8 min) were significantly shorter than after pancuronium (31.0 min and 46.9 min). The reversal times of vecuronium (times from 10% to 90% twitch height recovery) were significantly shorter than those of pancuronium (7.9 min and 7.3 min, respectively, compared with 17.1 min and 17.7 min).

Clinical experience with ORG NC45 (norcuron) as the sole muscle relaxant.

The neuromuscular effects of ORG NC45, used as the sole muscle relaxant, were compared with a succinylcholine-pancuronium sequence in patients during nitrous oxide-fentanyl anaesthesia. The subjects were divided into four groups with ten in each group. After induction of anaesthesia they received either succinylcholine, 1 mg . kg-1 or ORG NC45 in doses of 50, 70 or 90 micrograms . kg-1 and tracheal intubation was done 90 seconds later. Neuromuscular transmission was monitored using train-of-four stimulation. Succinylcholine produced 100 per cent block with uniformly excellent intubating conditions whereas the three doses of ORG NC45 were associated with blocks of 7.5, 18.7 and 30.7 per cent and acceptable conditions in only 30 per cent of subjects. Muscle relaxation was maintained in the NC45 groups with increments of 10 micrograms . kg-1 and in the succinylcholine group with pancuronium, initially as a bolus of 40 micrograms . kg-1, followed by increments of 5 mg . kg-1. All increments were given at 10 per cent recovery of twitch height. The overall requirement to maintain 90 per cent block with pancuronium was 1.1 microgram/kg-1 . min-1 compared with 1.28 microgram . kg-1 . min-1 with ORG NC45. No cumulative effects were seen with either drug during the first hour of neuromuscular blockade. At the end of the operation the neuromuscular block was antagonized with atropine 18 micrograms . kg-1, and neostigmine 36 micrograms . kg-1 and recovery was significantly more rapid with NC45 than pancuronium. We conclude that the lack of cumulation, easy reversibility and lack of cardiovascular effects suggest that NC45 has advantages over currently available non-depolarizing muscle relaxants but that its onset of action is too slow for rapid intubation.

Succinylcholine neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase.

The relationship between plasma cholinesterase genotype and duration and type of succinylcholine neuromuscular blockade was studied in 43 anesthetized patients heterozygous for abnormal plasma cholinesterase using train-of-four nerve stimulation. Twenty-eight patients were heterozygous for the usual and the atypical gene (E1uE1a), eight were heterozygous for the usual and the silent gene (E1uE1s), three were heterozygous for the usual and the fluoride-resistant gene (E1uE1f), three were heterozygous for the fluoride-resistant and the atypical gene (E1fE1a), and one was heterozygous for the fluoride-resistant and the silent gene (E1fE1s). Mean time to 90 per cent recovery of twitch height in patients with genotypes E1uE1a, E1uE1s, and E1uE1f (14.6, 12.4, and 12.0 min, respectively) was significantly prolonged compared to patients with normal cholinesterase genotype (9.3 min). No significant difference was found between the three groups of patients with one abnormal gene (E1uE1a, E1uE1s, and E1uE1f). In 13 (46 per cent) of the 28 patients with genotype E1uE1a the twitch height did not return to control for more than 15 min after the administration of succinylcholine and in three patients (10.7 per cent) for more than 20 min after succinylcholine. The four patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s) all showed significantly prolonged paralysis following the administration of succinylcholine (mean time to 90 per cent twitch recovery was 30 min). Patients heterozygous for the usual and one of the abnormal genes (E1uE1a, E1uE1s, and E1uE1f) had typically depolarizing blocks following the administration of succinylcholine, 1 mg/kg. Patients with abnormal genes on both chromosomes (E1fE1a and E1fE1s), however, all showed desensitization type of neuromuscular blockade (phase II block).

Combination of Pancuronium and Metocurine

Combination of pancuronium and metocurine or pancuronium and d-tubocurarine produces potentiation of neuromuscular blocking effects such that administration of relatively small doses of these drugs can yield clinically effective neuromuscular blockade. The clinical characteristics of the block produced in A.S.A. class I-II patients during N2O-narcotic-thiopental anesthesia by the pancuronium-metocurine combination at the calculated ED95 (N = 8) and at twice the ED95 (N = 9) were compared with the block produced by pancuronium alone at its ED95 (N = 20) and at twice the ED95 (N = 6). Onset time (from drug injection to 95% twitch suppression) and the maximum twitch depression achieved were comparable between corresponding groups, but the 25% recovery time (from drug injection to 25% recovery of twitch height) was significantly shorter in the groups that received the pancuronium-metocurine combination. Furthermore, at twice the ED95, heart rate increased significantly more in the pancuronium group than in the pancuronium-metocurine combination group. Mean systemic blood pressure did not change significantly in either group. We conclude that patients given a combination of pancuronium and metocurine in large doses experience less hemodynamic change and more rapid recovery of neuromuscular function than do patients given equivalent doses of pancuronium alone.

The interaction between succinylcholine and subparalyzing doses of d-tubocurarine and gallamine in man.

The interaction of gallamine, 20 mg, and the interaction of d-tubocurarine, 3 mg, with succinylcholine, 1 mg/kg, were studied in 25 patients during nitrous oxide-oxygen-meperidine anesthesia. In five patients given three successive doses of succinylcholine separated by intervals of 10 and 20 minutes, no differences in times to onset, magnitudes of twitch-height depression or times of 80 per cent recovery of neuromuscular transmission were found. Prior administration of d-tubocurarine to ten patients and gallamine to another ten patients did not alter the times to onset or magnitude of twitch-height depression produced by the third dose of succinylcholine. Although mean time to 80 per cent recovery of twitch height after administration of succinylcholine was not significantly altered by gallamine, it was shortened by rf-tubocurarine from 10.9 ± 0.5 (SE) minutes to 8.9 ±0.4 minutes. In all patients, ability to sustain tetanus and absence of posttetanic facilitation indicated the absence of desensitizing neuromuscular block. It is concluded that prior administration of either gallamine or d-tubocurarine in the dose studied has little effect on the magnitude or type of neuromuscular blockade produced by suecinylcholine.