Clinical pharmacology of pipecuronium bromide

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2-3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were non-invasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium. The mean +/- SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the train-of-four was 2.6 +/- 0.8, 2.0 +/- 0.6, and 2.1 +/- 0.6 min following the 70 micrograms/kg, 85 micrograms/kg, and 100 micrograms/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 +/- 18.2 min in the group given 70 micrograms/kg. This was significantly longer in patients given 85 micrograms/kg (71.9 +/- 15.7 min) or 100 micrograms/kg (71.8 +/- 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Pancuronium, gallamine, and d-tubocurarine compared: is speed of onset inversely related to drug potency?

The relative potency and speed of onset of action of pancuronium, gallamine, and d-tubocurarine was studied in 55 adult female patients receiving nitrous oxide/oxygen-narcotic anesthesia. The integrated electromyogram of the adductor pollicis muscle was monitored using a cumulative dose-response technique; train-of-four stimuli were administered at 0.05 Hz. The measured ED95 values for pancuronium and gallamine were 0.069 and 2.38 mg/kg, respectively. In three separate groups, pancuronium 0.07 mg/kg, gallamine 2.4 mg/kg, or d-tubocurarine 0.45 mg/kg were given as a single bolus and the speed of onset and time to maximum effect determined. Peak twitch depression was essentially identical in all groups (92.7 +/- 1.4 [SE] vs. 93.3 +/- 1.1 vs. 93.7 +/- 1.1%, respectively). The rate of onset of neuromuscular blockade in these three groups was, however, quite different. After administration of pancuronium (n = 10) the times to 5%, 20%, 50%, and 80% twitch depression were 68 +/- 5, 97 +/- 6, 141 +/- 8, and 222 +/- 18 s. The comparable times following gallamine (n = 10) were 29 +/- 2, 42 +/- 3, 66 +/- 5, and 136 +/- 14 s; d-tubocurarine (n = 10) was intermediate in speed with onset times of 40 +/- 4, 63 +/- 6, 99 +/- 11, and 178 +/- 25 s. It appears that the onset times of different nondepolarizing blocking agents (even when given in equipotent doses) may vary by clinically appreciable amounts. The results of this study support the hypothesis that nondepolarizing neuromuscular blocking agents of low potency may have a more rapid onset of action than that seen with agents of high potency.     

Neuromuscular and cardiovascular effects of pipecuronium

Pipecuronium bromide (Arduan) is a bisquaternary, steroid-type neuromuscular blocking agent in clinical use in Eastern Europe. Before its introduction into clinical practice in the USA, in the first phase of this study the neuromuscular potency of pipecuronium was determined under "balanced" and enflurance anaesthesia by the cumulative log dose-response method in 30 patients each. In the second phase the intubation and onset times, clinical duration of the first and repeated doses, spontaneous recovery index, reversibility of its residual neuromuscular effect by an anticholinesterase and its effect on heart rate and blood pressure was compared with the same variables observed in patients, anaesthetized with identical techniques but who had received vecuronium or pancuronium. The neuromuscular potency of pipecuronium was greater under enflurane (ED95 = 23.6 +/- 1.1 micrograms.kg-1 (mean +/- SEM)] than under balanced (ED95 = 35.1 +/- 17 micrograms.kg-1) anaesthesia. Pipecuronium was more potent than vecuronium under both balanced (ED95 = 45.8 micrograms.kg-1) and enflurane anaesthesia (ED95 = 27.4 micrograms.kg-1). Following the administration of 2 x ED95 doses there were no clinically significant differences in the intubation or onset times of pipecuronium, vecuronium and pancuronium. Under balanced anaesthesia the clinical duration of 2 x ED95 dose of pipecuronium (110.5 +/- 0.3 min) or pancuronium (115.8 +/- 8.1 min) were similar and about three times longer than that of vecuronium (36.3 +/- 2.1 min). The recovery indices of pipecuronium (44.5 +/- 8.2 min) and pancuronium (41.3 +/- 4.2 min) were also similar and about three times longer than that of vecuronium (14.3 +/- 1.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular effect of pipecuronium bromide in infants and children during nitrous oxide-alfentanil anesthesia

To determine in infants and children the neuromuscular effect of pipecuronium during alfentanil-N2O/O2 anesthesia, the authors studied 32 ASA Physical Status 1 and 2 pediatric patients undergoing minor elective surgery, divided into three groups according to their age: group 1 included 12 infants, 1.9 +/- 0.2 months old (mean +/- SE; range, 20 days to 3 months), weighing 5.2 +/- 0.3 kg; group 2, 10 infants, 6.1 +/- 0.9 months old (range, 3-11 months), 6.9 +/- 0.4 kg; and group 3, 10 children 5.6 +/- 0.9 yr old (range, 2-9 yr), 19.6 +/- 2.2 kg. Neuromuscular blockade at the ulnar nerve-adductor pollicis muscle was measured by electromyography. Incremental iv doses of pipecuronium were given (one 20 micrograms/kg first dose, followed by 10 micrograms/kg increments) to reach a 95 +/- 2% twitch depression (ED95). In children ED50 and ED95 of pipecuronium were 45.0 +/- 5.8 micrograms/kg (mean +/- SE) and 70.5 +/- 9.3 micrograms/kg, respectively. In 3- to 12-month-old infants ED50 and ED95 were 25.8 +/- 1.5 micrograms/kg and 48.7 +/- 3.5 micrograms/kg, respectively, and both significantly (P less than 0.05) less than those in children. In 0- to 3-month-old infants ED50 and ED95 were 23.7 +/- 1.7 micrograms/kg and 46.5 +/- 2.9 micrograms/kg, respectively, and also significantly (P less than 0.05) less than those measured in children. Time from maximal initial neuromuscular blockade to 75% recovery was 64.5 +/- 8.8 min in children and significantly shorter (P less than 0.05) in the two infant groups (0- to 3-month-old: 38.7 +/- 5.7 min, 3- to 12-month-old: 43.8 +/- 5.3 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

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-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

Nitrous oxide potentiates succinylcholine neuromuscular blockade in humans.

Sixty ASA physical status I and II adults received 0.3 mg/kg succinylcholine to determine the effect of prolonged administration of thiopental and that of nitrous oxide on succinylcholine neuromuscular blockade. Succinylcholine was administered either 1 min (group 1) or 6 min (groups 2 and 3) after induction of anesthesia with thiopental. In group 2, anesthesia was maintained with thiopental and the patients' lungs were ventilated with oxygen. In group 3, anesthesia was maintained with only 70% nitrous oxide in oxygen. Train-of-four stimulation of the ulnar nerve was started 30 s before the administration of succinylcholine and repeated every 12 s. The force of contraction of the adductor pollicis muscle was measured. Maximum blockade (mean +/- SEM) did not vary significantly between group 1, where thiopental had been administered for 1 min, and group 2, where it had been administered for 6 min (group 1: 61% +/- 6%; group 2: 54% +/- 8%). However, the addition of nitrous oxide increased neuromuscular blockade (group 3: 80% +/- 6%; P less than 0.05 compared with group 2). The degree of twitch augmentation, i.e., greater than maximal response, and times to twitch augmentation and to maximum blockade did not vary significantly among the groups. It is concluded that nitrous oxide increases succinylcholine neuromuscular blockade and that this is manifest within 6 min. This effect is not due to the duration of the anesthetic because thiopental, administered over a similar time period, did not potentiate succinylcholine.     

Pretreatment with d-tubocurarine, vecuronium, and pancuronium attenuates succinylcholine-induced increases in plasma norepinephrine concentrations in humans.

We studied in patients the effect of d-tubocurarine, which has sympathetic ganglion blocking action, on succinylcholine-induced increases in plasma levels of catecholamines, and compared it with the effects of vecuronium and pancuronium, which have little sympathetic ganglion blocking action. Thirty-two patients were divided into five groups: seven were given 3 mL saline; seven received 1 mg/kg succinylcholine; and six, seven, and five patients were given 0.08 mg/kg d-tubocurarine, 0.01 mg/kg vecuronium, and 0.01 mg/kg pancuronium, respectively, all of which were injected 5 min before 1 mg/kg succinylcholine. Succinylcholine alone significantly increased plasma norepinephrine concentrations, systolic blood pressure, and heart rate from 187 +/- 39 pg/mL (mean +/- SEM), 93 +/- 2 mm Hg, and 77 +/- 4 beats/min to 429 +/- 61 pg/mL, 120 +/- 7 mm Hg, and 102 +/- 6 beats/min, respectively, with onset of fasciculations. Pretreatment with d-tubocurarine, vecuronium, and pancuronium significantly and equally attenuated both the fasciculations and the cardiovascular responses to succinylcholine. These results suggest that the sympathetic ganglion blocking action of neuromuscular relaxants when given before succinylcholine is not an important factor in attenuation of succinylcholine-induced increases in plasma levels of catecholamines.     

The Intubating Dose of Succinylcholine: The Effect of Decreasing Doses on Recovery Time

Background: The usually cited "intubation dose" of succinylcholine is 1.0 mg/kg. In the majority of patients, this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted. This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine.

Methods: During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization, neuromuscular function was recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and twitch height was monitored for at least 20 min thereafter.

Results: The onset times to maximal effect were 105 +/- 23 s, 81 +/- 19 s, and 71 +/- 22 s, respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch depression. The times to 90% twitch recovery at the adductor pollicis in the three groups were 6.6 +/- 1.5 min, 7.6 +/- 1.6 min, and 9.3 +/- 1.2 min, respectively.     

Neuromuscular effects of pipecuronium bromide.

The neuromuscular effects of pipecuronium bromide have been evaluated in 90 adult patients anaesthetized with thiopentone, nitrous oxide in oxygen and intravenous fentanyl with or without halothane. Eighty patients received pipecuronium 45 micrograms kg-1 and the remaining ten 70 micrograms kg-1. A separate group of 10 patients received pancuronium in a dose of 60 micrograms kg-1 (equipotent to pipecuronium 45 micrograms kg-1). Neuromuscular block was measured using a single-twitch or train-of-four mode of stimulation. The time to onset of maximum block with pipecuronium 45 micrograms kg-1 varied between 3.5 and 5.7 min depending on the mode of stimulation and the anaesthetic technique used. The time to 25% recovery of this dose varied between 41 and 54 min. The recovery index (time from 25 to 75% recovery) averaged 29 min. These values were generally similar in the group receiving pancuronium 60 micrograms kg-1. The time to onset of complete block with 70 micrograms kg-1 of pipecuronium averaged 2.5 min and the duration to 25% recovery 95 min. There were no significant changes in heart rate and arterial pressure with the use of pipecuronium. The results show pipecuronium to be a drug resembling pancuronium in its neuromuscular effects when used in equipotent doses.     

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)     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium

High-dose narcotic anesthetic inductions usually avoid circulatory depression better than do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred-one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 micrograms/kg, pancuronium 100 micrograms/kg); group FV (fentanyl 50 micrograms/kg, vecuronium 80 micrograms/kg); group SP (sufentanil 10 micrograms/kg, pancuronium 100 micrograms/kg); and group SV (sufentanil 10 micrograms/kg, vecuronium 80 micrograms/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.

The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.     

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.     

The "intubating dose" of succinylcholine: the effect of decreasing doses on recovery time

BACKGROUND: The usually cited "intubation dose" of succinylcholine is 1.0 mg/kg. In the majority of patients, this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted. This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine. METHODS: During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization, neuromuscular function was recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and twitch height was monitored for at least 20 min thereafter. RESULTS: The onset times to maximal effect were 105 +/- 23 s, 81 +/- 19 s, and 71 +/- 22 s, respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch depression. The times to 90% twitch recovery at the adductor pollicis in the three groups were 6.6 +/- 1.5 min, 7.6 +/- 1.6 min, and 9.3 +/- 1.2 min, respectively. CONCLUSIONS: Reducing the dose of succinylcholine from 1.0 mg/kg to 0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than 90 s. The authors believe that even this modest decrease in the duration of drug-induced paralysis is often worth pursuing.     

Clinical evaluation of different doses of pipecuronium bromide during nitrous-oxide-fentanyl anaesthesia in adult surgical patients.

The neuromuscular and cardiovascular effects of three different doses of pipecuronium were studied in 60 adult patients. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 0.1 Hz and 2 Hz. Three subgroups (A, B, C) of 20 patients received pipecuronium doses of 60, 80 and 100 micrograms kg-1, respectively, as an intubating dose and, when necessary, maintenance doses were administered at 25% single twitch recovery in a dose of one-quarter of the initial one. The onset time was 5.4 +/- 2.0 min for 60 micrograms kg-1 and similar for 80 and 100 micrograms kg-1 (3.9 +/- 1.1 and 3.6 +/- 1.1 min). The duration of action was 45 +/- 10 min for 60 micrograms kg-1, 74 +/- 25 and 94 +/- 21 for 80 and 100 micrograms kg-1, respectively. The recovery indices were measured in all patients after neostigmine administration (Groups B and C) and after neostigmine and edrophonium (Subgroup A, 10 patients each). TOF ratio was significant only 2 min after edrophonium administration in Group A patients. Variations of heart rate and blood pressure were not significant.     

The potency of pancuronium at the adductor pollicis and diaphragm in infants and children

To measure the potency of pancuronium at the diaphragm and adductor pollicis in infants and children, train-of-four stimulation was applied to the ulnar and phrenic nerves under N2O-halothane anesthesia. The force of contraction of the adductor pollicis was measured and compared with the diaphragmatic electromyogram (EMG). Cumulative dose response curves were determined for pancuronium in 18 patients divided equally into three age groups: 0-1 yr, 1-3 yr, and 3-10 yr. The potency of pancuronium at both muscles decreased with increasing age (P less than 0.05), while the adductor pollicis:diaphragm potency ratio remained constant. The mean doses (+/- SEM) required to depress adductor pollicis first twitch responses by 90% (ED90) were 42 +/- 3.3 micrograms/kg in the 0-1-yr group, 47 +/- 4.2 micrograms/kg in the 1-3-yr group, and 62 +/- 4.1 micrograms/kg in the 3-10-yr group. Corresponding figures for the diaphragm were 70 +/- 4.3 micrograms/kg, 81 +/- 5.1 micrograms/kg, and 101 +/- 4.4 micrograms/kg, respectively. The ED90 ratios (diaphragm ED90/adductor pollicis ED90) in the three age groups were 1.69 +/- .07, 1.75 +/- .14, and 1.64 +/- .09, respectively. These results are consistent with similar rates of maturation of the diaphragm and the adductor pollicis muscles in infancy and childhood. Thus, train-of-four monitoring of the adductor pollicis is likely to overestimate the degree of neuromuscular blockade of the diaphragm in pediatric patients.     

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)