The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of succinylcholine on vecuronium and pancuronium

In 105 adult patients under halothane anesthesia, the neuromuscular blocking effects of vecuronium and pancuronium were determined with prior succinylcholine 1 mg.kg-1 administration and without. Force of the evoked twitch increased 123.7% of control after recovery from succinylcholine-induced block. Prior administration of succinylcholine was associated with a leftward shift of dose-response curve of vecuronium or pancuronium. Onset of the force reduction from initial dose (0.08 mg.kg-1) was faster and recovery from initial and maintenance doses (0.02 mg.kg-1) were slower. This potentiating effect persisted at least 2 hours.     

Effects of succinylcholine on the pharmacodynamics of pipecuronium and pancuronium.

To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular blockade for rapid tracheal intubation in children: comparison of succinylcholine and pancuronium

To compare the effectiveness of succinylcholine and pancuronium for rapid intubation in children, 49 healthy children ages two to eight years were studied. After induction of anaesthesia with thiopentone and atropine, and administration of droperidol, fentanyl, nitrous oxide, and oxygen, each child received one of the following muscle relaxants: succinylcholine 1.5 mg X kg-1 (n = 12), succinylcholine 1.0 mg X kg-1 (n = 13), pancuronium 0.15 mg X kg-1 (n = 11), or pancuronium 0.10 mg X kg-1 (n = 13). The force of thumb adduction was measured by stimulating the ulnar nerve with repetitive supramaximal single twitches (0.15 Hz). The time to 95 per cent twitch depression (mean +/- S.D.) was most rapid with succinylcholine 1.5 mg X kg-1 (40.8 +/- 3.0 seconds) and succinylcholine 1.0 mg X kg-1 (51.8 +/- 14.0 seconds), slowest with pancuronium 0.10 mg X kg-1 (150.9 +/- 38.0 seconds), and intermediate with pancuronium 0.15 mg X kg-1 (80.3 +/- 21.8 seconds) (p less than 0.005). The intubating conditions were excellent in 100% of the children who received succinylcholine 1.5 and 1.0 mg X kg-1, and pancuronium 0.15 mg X kg-1, but were excellent in only 69 per cent of those who received pancuronium 0.10 mg X kg-1. We conclude that succinylcholine 1.5 mg X kg-1 produces the most rapid onset of excellent intubating conditions in children. In children in whom succinylcholine is contra-indicated, pancuronium 0.15 mg X kg-1 provides excellent intubating conditions within 80 seconds.     

Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs

The authors sought to determine whether prior administration of a small, subparalyzing dose of nondepolarizing muscle relaxant would shorten the onset time of an intubating dose of muscle relaxant. Initially, in 60 anesthetized patients, twitch response of adductor pollicis to ulnar nerve stimulation was studied after a small dose of pancuronium 0.015 mg . kg-1, metocurine 0.03 mg . kg-1, or d-tubocurarine 0.04 mg . kg-1, followed 3 min later by pancuronium 0.08 mg . kg-1 or atracurium 0.4 mg . kg-1 administered iv. After 60 s, the minimum neuromuscular block, in all patients was 79.0 +/- 5.0%. A 95% depression or twitch tension occurred between 59.1 +/- 5.3 and 86.1 +/- 5.9 s. In another 60 patients, intubating conditions under similar regimen were studied, except the small dose of muscle relaxant was given immediately prior to induction of anesthesia. At the end of 60 s, good to excellent intubating conditions were present in 100% of the patients following the second dose of pancuronium and in 83% of the patients following atracurium. In 17% of the patients, after atracurium intubating conditions were fair. When nondepolarizing neuromuscular blocking drugs are administered in divided doses, neuromuscular blockade adequate for endotracheal intubation is achieved in less than 90 s. This facilitates rapid endotracheal intubation in a time comparable to using succinylcholine, without undesirable effects of the depolarizing neuromuscular blocking drugs.     

Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans

Steady-state infusion rate requirements of vecuronium were determined in 29 patients during either halothane-nitrous oxide or fentanyl-nitrous oxide anesthesia at different levels of neuromuscular block. During N2O-halothane anesthesia (end-tidal concentration, 0.5%), the infusion rate necessary for a steady-state (defined as unchanging twitch height and infusion rate for at least 20 min) 50% depression of twitch force was 28.8 +/- 5.4 (mean +/- SD) (n = 8) and 47.6 +/- 9.7 micrograms . kg-1 . hr-1 (n = 6) at 90% reduction of twitch force. During N2O-fentanyl anesthesia, the steady-state infusion rate required for 50 and 90% decrease of twitch force was 56.3 +/- 20.0 (n = 9) and 74.8 +/- 16.0 micrograms . kg-1 . hr-1 (n = 6), respectively. The variances of vecuronium steady-state infusion dose requirements were smaller in the halothane groups than in the fentanyl anesthesia groups. The steady-state vecuronium infusion dose requirements during fentanyl anesthesia were greater than the mean infusion dose requirements during halothane anesthesia at equivalent levels of twitch depression.     

Potentiation of atracurium by pancuronium and d-tubocurarine

In 60 adult patients undergoing general surgical procedures, the effect of pancuronium or d-tubocurarine "pretreatment" on the injection of a 0.1 mg X kg-1 bolus of atracurium was measured in two separate studies. In study 1, the patients received either 0.5 mg (approximately 0.007 mg X kg-1) or 1.0 mg (approximately 0.015 mg X kg-1) pancuronium, or placebo (saline) three minutes before the injection of atracurium 0.1 mg X kg-1. In study 2, the patients received 0.05 mg X kg-1 or 0.1 mg X kg-1 d-tubocurarine, or a placebo. The degree of neuromuscular blockade was assessed by evoked mechanogram (adductor pollicis muscle) using supramaximal train-of-four stimulation. Patients receiving pancuronium or d-tubocurarine pretreatment (equal to an ED5-ED15 dose) showed significantly greater inhibition of twitch (ED70-ED80) and train-of-four ratio compared with the placebo groups (ED35-ED40). Pretreatment with the larger dose of d-tubocurarine (0.1 mg X kg-1) was associated with significant neuromuscular blockade. It is concluded that pancuronium and d-tubocurarine pretreatments potentiate the clinical action of 0.1 mg X kg-1 atracurium in man by 35-100 per cent.     

Dose-related effects of succinylcholine on the adductor pollicis and masséter muscles in children

This study was performed to determine the effects of various doses of succinylcholine on resting tension and evoked twitch height at the masseter and adductor pollicis muscles in children. Twenty patients, aged 3-10 yr, ASA physical status I or II, were randomly assigned to receive succinylcholine 0.15, 0.25, 0.50 or 1.00 mg.kg-1, during halothane-nitrous oxide anaesthesia. Supramaximal train-of-four stimulation was applied simultaneously to the ulnar nerve and the nerve to the masseter. Transducers recorded force at the jaw and the thumb. Maximum blockade of the first twitch (T1) and maximum resting tension change were measured. Potency of succinylcholine at the two muscles was estimated by linear regression of the logit transformation of T1 versus log dose. The relationship between resting tension change and log dose was established by linear regression. The masseter muscle was more sensitive to succinylcholine than the adductor pollicis with an ED95 of 0.28 +/- 0.02 (mean +/- SEM) vs 0.44 +/- 0.05 mg.kg-1 (P less than 0.05). Onset of neuromuscular blockade was faster at the masseter, and recovery occurred simultaneously in both muscles. A dose-related increase in resting tension was observed in both muscles, but its magnitude was five times greater at the masseter. With succinylcholine, 1 mg.kg-1, this increase was 51.6 +/- 16.8 g at the masseter and 9.1 +/- 2.3 g at the adductor pollicis. Tension returned to baseline within 1-2 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Comparison of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients

Thirty ASA physical status I or II outpatients scheduled to undergo short procedures (less than 1 hr in duration) requiring tracheal intubation received either 1.0 mg/kg succinylcholine or 0.20 mg/kg (2.5 x ED95) or 0.25 mg/kg (3 x ED95) mivacurium. A N2O/O2/narcotic anesthetic technique was utilized and the ulnar nerve was stimulated with subcutaneous electrodes placed at the wrist. Tracheal intubation was attempted in all patients either 2 min after mivacurium or 1 min after succinylcholine. Intubation conditions were not different between the succinylcholine and mivacurium groups or between the two mivacurium groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with mivacurium. Suppression of the T1 response to 90% of baseline occurred in 0.9 min with 1.0 mg/kg succinylcholine and at 2.2 and 1.5 min respectively, with 0.20 mg/kg and 0.25 mg/kg mivacurium. Initial recovery of the T1 response occurred at 6.4 min after 1.0 mg/kg succinylcholine and 12.7 and 13.6 min respectively after 0.20 mg/kg and 0.25 mg/kg mivacurium. Subsequent to initial recovery from the intubating dose of relaxant, infusions of mivacurium or succinylcholine were administered to maintain approximately 95% block. The mean infusion rates were 6.6 micrograms.kg-1.min-1 mivacurium and 41.2 micrograms.kg-1.min-1 for succinylcholine. Spontaneous recovery from neuromuscular blockade occurred more quickly after succinylcholine than after mivacurium: the time from cessation of infusion to recovery of T1 to 95% of baseline was 6.5 min in patients given succinylcholine and 16.7 min in patients given mivacurium. When reversal was in order, residual mivacurium-induced blockade was readily antagonized by 0.045 mg/kg neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients

Plasma concentrations and the degree of neuromuscular blockade after a 2-min infusion of 0.1 mg/kg of vecuronium bromide or pancuronium bromide (equipotent doses) were studied in 12 gynecologic patients. The plasma concentrations of both drugs declined in a triphasic manner. The difference between the intercepts and rate constants of the two drugs was not significant. Vecuronium was removed faster from the plasma than pancuronium; this was reflected in a significantly larger plasma clearance rate for vecuronium (4 ml X min-1 X kg-1 vs 1.1 ml X min-1 X kg-1 for pancuronium). The effective plasma concentrations at 50% recovery of the twitch height were 0.11 +/- 0.02 (vecuronium) and 0.2 +/- 0.03 microgram/ml (pancuronium). The disposition kinetics were adequately described by a three-compartment model. An effect compartment was added to the model to correlate the neuromuscular effects and plasma concentrations of both drugs. The ratio between concentrations of vecuronium and pancuronium in the effect compartment at 50% twitch height was 0.83. In spite of its greater potency, vecuronium has a shorter duration of action than pancuronium.     

Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant

Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.     

Effect of d-tubocurarine pretreatment on succinylcholine twitch augmentation and neuromuscular blockade

Subparalyzing doses of d-tubocurarine (dTC) given before succinylcholine decrease the duration of neuromuscular blockade. In animal preparations, they also abolish succinylcholine-induced twitch augmentation, defined as a greater-than-maximal contraction in response to a single stimulus. To determine quantitatively the effect of dTC on succinylcholine potency and on twitch augmentation in humans, 60 adult patients, ASA physical status I or II, were assigned randomly to receive either 0.05 mg/kg of dTC or saline 2 min before induction of anesthesia with fentanyl and thiopental. Train-of-four stimulation was applied every 12 s to the ulnar nerve and the force of contraction of the adductor pollicis muscle was measured. One minute after induction of anesthesia, 0.15, 0.20, 0.25, 0.35, or 0.50 mg/kg of succinylcholine was given. The height of the first twitch (T1) reached 121% +/- 6% (mean +/- SEM) of control without dTC, and was virtually abolished by dTC pretreatment (105% +/- 1%, P less than 0.01). Twitch augmentation was more noticeable with lower doses of succinylcholine, and was not observed in the response to the fourth stimulus of the train of four (T4). The potency of succinylcholine was decreased by approximately one-half in the dTC-pretreated groups. The ED50 was 0.27 +/- 0.04 mg/kg without dTC and 0.50 +/- 0.06 mg/kg with dTC (P less than 0.002). The corresponding values for ED90 were 0.51 +/- 0.07 and 1.02 +/- 0.12 mg/kg, respectively (P less than 0.02). The ED95 values were 0.63 +/- 0.09 and 1.28 +/- 0.15 mg/kg, respectively (P less than 0.02). The slopes of the regression lines did not deviate significantly from parallelism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine

The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg-1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/- 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB.     

Ketamine enhances Phase I and Phase II neuromuscular block of succinylcholine

The effect of intravenous injection of ketamine 2, 5 and 10 mg.kg-1 on the neuromuscular blocking action of succinylcholine was studied on the indirectly stimulated adductor pollicis muscle twitch of monkeys anaesthetized with 0.5-1.0 per cent halothane in oxygen. Neuromuscular block was quantified by single twitches evoked at 0.1 Hz. The changing nature of neuromuscular block from Phase I to Phase II was monitored periodically by train-of-four fade. In the absence of succinylcholine, ketamine had no consistent neuromuscular effect of its own. In the presence of succinylcholine, ketamine in a dose-dependent manner potentiated both the Phase I and the Phase II neuromuscular blocking effect of succinylcholine. In Phase I, 2 mg.kg-1 of ketamine reduced the ED50 of succinylcholine from 0.46 +/- 0.07 mg.kg-1 to 0.33 +/- 0.06 mg.kg-1 (P less than 0.01), and increased its 25-75 per cent recovery index from 4.0 +/- 0.4 min to 5.3 +/- 0.1 min (P less than 0.01). In Phase II, ketamine in the same dose deepened a steady neuromuscular block maintained by succinylcholine infusion from 48 +/- 3 per cent block to 71 +/- 2 per cent block (P less than 0.01). We concluded that ketamine potentiates the Phase I and the Phase II neuromuscular blocks of succinylcholine.     

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)     

Administration of vecuronium, atracurium and pancuronium in divided doses: effect on onset and duration of action

The time to onset of neuromuscular block (as assessed by single twitch stimulation at 0.1 Hz) and the duration to 25% recovery of twitch height were measured after administration of vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or pancuronium 0.1 mg kg-1, administered either as a single bolus or in divided doses, 10% being administered 4 min prior to the remaining 90%. The patients were anaesthetized with thiopentone, nitrous oxide in oxygen and i.v. fentanyl. There was no significant difference between the single- and divided-dose groups, either in the onset times (2.8 and 2.9 min for vecuronium, 2.7 and 2.4 min for atracurium and 3.3 min each for pancuronium for single- and divided-dose groups, respectively) or the duration to 25% recovery of twitch height (35 and 29 min for vecuronium, 45 and 39 min for atracurium and 87 and 93 min for pancuronium for single- and divided-dose groups, respectively).     

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.     

A comparison of d-tubocurarine pretreatment and no pretreatment in obstetric patients

The effect of pretreatment with d-tubocurarine on the incidences of succinylcholine-induced fasciculations and post-operative muscle pain, and the time to onset of and 50% recovery from neuromuscular blockade were studied in 75 obstetric patients. Thirty women with term pregnancies undergoing general anesthesia for elective cesarean section or cesarean section indicated by cephalopelvic disproportion were randomly assigned to two groups. Group C-1 patients received 0.05 mg/kg of d-tubocurarine followed by 1.5 mg/kg of succinylcholine, and group C-2 patients received 1.5 mg/kg of succinylcholine, and group C-2 patients received 1 ml of normal saline followed by 1 mg/kg of succinylcholine. An investigator, unaware of the relaxant regimen used, judged severity of fasciculations and postoperative muscle pain and measured times to onset of and 50% recovery from neuromuscular blockade. This same study design was followed in a group of 30 women undergoing tubal ligation 1 day after vaginal delivery (groups T-1 and T-2). The incidence of both fasciculations and postoperative muscle pain was low and was not significantly different between pretreated and nonpretreated groups. Time to 100% twitch depression was also not significantly different between pretreated and nonpretreated groups. Time to 50% recovery from neuromuscular blockade was significantly longer in both nonpretreated groups (C-2 and T-2). An additional group of 15 patients undergoing general anesthesia for cesarean section using 0.7 mg/kg of succinylcholine without d-tubocurarine pretreatment was studied (group C-3). This smaller dose of succinylcholine produced onset and 50% recovery times similar to the group pretreated with d-tubocurarine (group C-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.