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.     

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.     

Closed-loop infusion of atracurium with four different anesthetic techniques

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.     

Effects of propofol and isoflurane on the neuromuscular block induced by atracurium]

Speed of onset, duration of action and recovery time for a bolus injection of atracurium were measured in two groups of patients. In group I anaesthesia considered of propofol, fentanyl, nitrous oxide and oxygen mixture. The induction dose of propofol was 2 mg/kg-1 followed by an infusion of 9.0 mg/kg-1/h-1 for first half hour and 4.5 mg/Kg-1/h-1 subsequently. In group II anaesthesia consisted of isoflurane, fentanyl, nitrous oxide and oxygen mixture. Isoflurane was given upon clinical needs. Speed of onset, duration of action, and recovery time for atracurium were measured in the two groups. No statistically significant differences between speed of onset and duration of action between the two groups were found. The recovery period from T1 = 10% to T1 = 70% twitch response was considerably longer with isoflurane (25 min +/- 6) than with propofol (18 min +/- 3) (p less than 0.01). Results obtained suggest that for adequate relaxation during tracheal intubation smaller doses of atracurium are not needed during isoflurane than propofol administration. Because of the longer recovery period of residual neuromuscular blockade during isoflurane anaesthesia decreasing doses of atracurium and careful monitoring of twitch depression tension are also suggested.     

Continuous infusion of atracurium in children

Atracurium infusion requirements were determined in 28 children anesthetized with N2O:O2 narcotic, N2O:O2 halothane (1% inspired), and N2O:O2 enflurane (2% inspired). When the patient was recovering from a bolus dose of 0.4 mg/kg atracurium, a continuous infusion of atracurium was started and the rate was adjusted to maintain 90-99% muscle twitch depression. Patients receiving enflurane anesthesia required atracurium at an infusion rate of 4.9 +/- 0.3 micrograms X kg-1 X min-1 which was a significantly lower rate (P = 0.0001) than those anesthetized with halothane (8.3 +/- 0.4 micrograms X kg-1 X min-1) or with N2O:O2 and narcotic (9.3 +/- 0.5 micrograms X kg-1 X min-1). At the onset of neuromuscular blockade, the twitch response disappeared faster after train-of-four stimulation repeated every 10 s than after single twitch rates of stimulation at 0.1 Hz. In children, during halothane anesthesia after 0.4 mg/kg atracurium, the response of the adductor of the thumb was ablated in 2.0 +/- 0.3 min with train-of-four stimulation, and in 3.7 +/- 0.4 min with single twitch stimulation. The authors recommend the use of a nerve stimulator during continuous infusion of atracurium because of the marked interpatient differences in infusion-rate requirements.     

Assessment of the interaction between atracurium and suxamethonium at 50% neuromuscular block using closed-loop feedback control of infusion of atracurium

We have studied the effect of prior administration of suxamethoniumon the infusion requirements of atracurium at 50% neuromuscularblock in patients undergoing elective general surgery. Anaesthesiawas maintained with nitrous oxide in oxygen, propofol and fentanyl.Of 20 patients given atracurium, only 10 were given prior administrationof suxamethonium 1 mg kg^–1. At the beginning of the infusion,atracurium 0.3 mg kg^–1 was given by bolus administration.Interaction between the two drugs was assessed by determiningthe steady state rate of infusion necessary to produce a constant50% neuromuscular block. This was accomplished by applying non-linearcurve fitting to data on the cumulative dose requirements duringanaesthesia. The neuromuscular blocking effect was found tobe similar with or without prior administration of suxamethonium.The mean steady-state rate of infusion for atracurium was 0.19(SD 0.03) mg kg^–1 h^–1 for patients given suxamethoniumand 0.18 (0.09) mg kg^–1 h^–1 for those who were notgiven suxamethonium. Thus prior administration of suxamethoniumdid not affect the infusion requirements of atracurium at 50%neuromuscular block, unlike the situation at constant 90% neuromuscularblock.     

Onset of the effect and intubation conditions following atracurium, verocuronium and suxamethonium

1. The onset of neuromuscular blockade following i.v. injection of atracurium 0.3, 0.4, or 0.5 mg/kg; vecuronium 0.08 or 0.1 mg/kg; and succinylcholine 1.0 mg/kg was studied in 205 adult patients during induction of anesthesia by means of the compound action potential (EMG) of the hypothenar muscle, which was indirectly stimulated via the ulnar nerve above the wrist, using the Datex Relaxograph. At the same time, the intubation conditions at 0.5, 1, 2, or 3 min after injection were assessed using a scoring system (Crul 1983) related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of the extremities. 2. Neuromuscular blockade and intubation conditions 2 min after administration of atracurium 0.3 mg/kg were 60 +/- 10% and 8.7 +/- 0.3; after 0.4 mg/kg 74 +/- 4% and 10.3 +/- 0.3; and after 0.5 mg/kg 86 +/- 5% and 11.8 +/- 0.2. After 0.08 mg/kg vecuronium 76 +/- 3% and 7.4 +/- 0.5 were recorded and after 0.1 mg/kg 85 +/- 6% and 10.5 +/- 0.4. Motor blockade 1 min after succinylcholine was 98 +/- 2% and intubation conditions scored 11.3 +/- 0.3. Relating intubation conditions to neuromuscular blockade yielded a close correlation and surprisingly good or very good intubation conditions (score more than 10) at a motor blockade of 80% (resp. 20% transmission). 3. Although succinylcholine is still the muscle relaxant with the most rapid onset of action, the new drug atracurium seems to satisfactorily facilitate tracheal intubation within an acceptably short time interval of 2 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cumulation and reversal with prolonged infusions of atracurium and vecuronium

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atracurium for short surgical procedures: a comparison with succinylcholine

A comparison was made between atracurium and succinylcholine in 40 patients undergoing short gynaecological procedures of 30 minutes or less. Good intubating conditions were produced in 76.7 +/- 39.3 seconds (mean +/- S.D.) with succinylcholine 1 mg . kg-1 and 198 +/- 84 seconds with atracurium 400 micrograms . kg-1. Muscle relaxation was maintained with the initial dose of atracurium or with repeated boluses of succinylcholine. The mean time of surgery was 17.65 +/- 5.3 minutes in the atracurium group and 15.2 +/- 4.6 minutes in the succinylcholine group. Residual neuromuscular block with atracurium was reversed with neostigmine 0.036 mg . kg-1 and atropine 0.018 mg . kg-1. Recovery of neuromuscular function following reversal, assessed by return of all responses to train-of-four stimulation occurred in 5.05 +/- 4.6 minutes in the atracurium group but half the above doses of neostigmine and atropine were repeated in three patients. We conclude that a single dose of atracurium 400 micrograms . kg-1 is suitable for intubation and maintainance of muscle relaxation for short surgical procedures. However, the onset of action is slow, compared to succinylcholine. Residual neuromuscular block can be antagonised with standard doses of neostigmine, less than 20 minutes after the initial dose of relaxant. Atracurium appears to be a suitable alternative for short procedures where succinylcholine is unsuitable or contraindicated.     

Comparison of the effects of succinylcholine and atracurium on intracranial pressure in monkeys with intracranial hypertension

The effects of succinylcholine (1.5 mg X kg-1 IV) administered five minutes after a defasciculating dose of curare (0.05 mg X kg-1 IV), were compared with the effects of atracurium (0.5 mg X kg-1 IV) on intracranial pressure (ICP) in 13 cynomolgus monkeys with intracranial hypertension (ICP approximately 25 mmHg). Neither succinylcholine nor atracurium increased ICP during general anaesthesia with 60 per cent N2O/O2, 0.5-1 per cent halothane. During a rapid sequence induction and intubation with thiopentone 5 mg X kg-1 IV, ICP increased equally with intubation following both atracurium (25 +/- 1 to 32 +/- 2 mmHg) and succinylcholine (25 +/- 1 to 31 +/- 2 mmHg) (p less than 0.05). Intubation was also associated with significant increases in PaCO2, CVP and MAP. We conclude that in this primate model of intracranial hypertension, neither atracurium nor succinylcholine (when given following a defasciculating dose of curare) elevates ICP. In terms of the elevation of ICP associated with intubation, atracurium was found to offer no advantage over succinylcholine.     

Model-based adaptive closed-loop feedback control of atracurium-induced neuromuscular blockade

Closed-loop control of atracurium-induced neuromuscular blockade by a model-based adaptive feedback algorithm is described. Mean offsets (+/- s.d.) from setpoints at 50, 70 and 90% neuromuscular blocks using the Relaxograph were 1.1 +/- 1.3, 0.2 +/- 0.7 and 0.1 +/- 0.4%, respectively. Correspondingly, the mean steady-state rates of infusion of atracurium were 0.20 +/- 0.06, 0.25 +/- 0.03 and 0.39 +/- 0.10 mg.kg-1.h-1. The described controller provides reasonable control of atracurium dosing at different degrees of neuromuscular blockade. It gives a solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.     

Atracurium infusion in total intravenous anesthesia

The neuromuscular blocking effect of atracurium given as a bolus dose (0.5 mg X kg-1) followed by a maintenance infusion was studied during two different anesthetic techniques. It has been reported that benzodiazepines interact with non-depolarising neuromuscular blockers. In this study no difference was found in the effect of atracurium given with conventional fentanyl/nitrous oxide anesthesia when compared to total intravenous anesthesia using midazolam/alfentanil. More than 90% twitch depression was achieved after 123 and 137 s, respectively. Recovery time to 10% twitch height following the bolus dose was around 32 min. The dosage range for atracurium given by infusion (0.29-0.44 mg X kg-1 X h-1) was confirmed.     

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.     

The optimal priming dose for atracurium

To determine the optimal priming dose for administration in divided doses, atracurium was given to 77 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.04, 0.05, 0.06, 0.07, 0.08 or 0.09 mg X kg-1, followed three minutes later by the remainder of the 0.5 mg X kg-1 dose. Patients were anaesthetized throughout the study. When atracurium was given as a single bolus of 0.5 mg X kg-1, the mean time to complete neuromuscular block was 141.5 seconds. Administration in divided doses accelerated the onset time (p less than 0.01), that is the time from the intubating dose to the complete suppression of train-of-four (TOF) response. The TOF ratio decreased slightly but statistically significantly following the priming doses. When the priming dose was 0.05 mg X kg-1, the mean onset time was 70.9 seconds and priming with larger doses did not add any further advantage. It is concluded that 0.05 mg X kg-1 appears to be the optimal priming dose for the administration of atracurium in divided doses. When 0.05 mg X kg-1 is given three minutes before the intubating dose, tracheal intubation can be accomplished in less than 90 seconds.     

Atracurium infusions in major ophthalmic surgery

Fifteen patients who were undergoing major ophthalmic surgery were anaesthetized using controlled ventilation with nitrous oxide, oxygen, midazolam and fentanyl after induction with thiopentone. Each was then given a bolus dose of 0.6 mg kg-1 atracurium followed immediately by an infusion of the drug at the rate of 0.6 mg kg-1 h-1, neuromuscular function being monitored throughout. Even slight movement can jeopardize the success of this type of surgery but good control of neuromuscular blockade was achieved without inhalational supplementation. The mean duration of the atracurium infusion was 118 min (range 30-247 min). The mean time from stopping the infusion to recovery of the first twitch of the train of four (TOF) to 20% was 25 min (range 11-44 min). Atropine (1.2 mg) and 5.0 mg neostigmine were then given in divided doses and a rapid and complete recovery was achieved. This technique can be used safely even in bad-risk patients but the infusion should be discontinued about 25 min before the end of surgery.     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs

Pancuronium decreases the minimal alveolar anesthetic concentration (MAC) of halothane in humans, while atracurium has a metabolite, laudanosine, which is a known cerebral stimulant. To determine if these muscle relaxants significantly alter cerebral function, their effects on cerebral metabolic rate (CMRo2), cerebral blood flow (CBF), intracranial pressure (ICP), EEG, and the cerebral energy state were studied in halothane-anesthetized dogs. Group A dogs (n = 6) were maintained at 0.86% end-expired (1.0 MAC) halothane. Thereafter, a sequence of 1) pancuronium 0.1 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; and 3) pancuronium 0.2 mg . kg-1 produced no changes in CMRo2, CBF, ICP, or EEG. Group B dogs (n = 6) also were maintained at 0.86% end-expired halothane and received the following in sequence: 1) atracurium 0.5 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; 3) atracurium 1.0 mg . kg-1; and 4) atracurium 2.5 mg . kg-1. There were no changes in CMRo2, CBF, or ICP; EEG evidence of cerebral arousal occurred in only one dog with the final dose of atracurium. Group C dogs (n = 6) received tetracaine spinal anesthesia and the minimal halothane concentration (mean +/- SE = 0.69 +/- 0.03% end-expired) that would maintain an "anesthetic" EEG pattern. Each Group C dog received the following in sequence: 1) atracurium 1.0 mg . kg-1, and 2) atracurium 2.5 mg . kg-1. EEG evidence of cerebral arousal occurred in all six Group C dogs. Arousal was not accompanied by significant increases in CBF, CMRo2, or ICP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade

Whether succinylcholine causes an increase in intracranial pressure (ICP) in patients with brain lesions is uncertain and, if increased ICP does occur, its pathophysiology remains unknown. The authors investigated both the effect of succinylcholine on ICP and its modification with prior neuromuscular blockade by measuring ICP (subarachnoid bolt) in 13 consecutive patients with brain tumors who received succinylcholine both before and after complete neuromuscular blockade with vecuronium. Anesthesia was induced with thiopental, 6 mg X kg-1 iv, and nitrous oxide, 70% in oxygen, while ventilation was controlled (PaCO2 = 37.2 mmHg +/- 1.7 SE). Succinylcholine, 1 mg X kg-1 iv, was administered and ICP, heart rate (HR), and blood pressure (BP) were recorded until normal twitch tension was restored. Complete neuromuscular blockade was then established with vecuronium, 0.14 mg X kg-1 iv; 3 min later, succinylcholine, 1 mg X kg-1 iv, was repeated. The resulting changes in ICP, HR, and BP were recorded for 3 min. Following the first dose of succinylcholine, mean ICP increased from 15.2 mmHg +/- 1.3 SE to 20.1 mmHg +/- 2.0 SE (P less than 0.05), with five of the patients sustaining increases in ICP of 9 mmHg or greater. In contrast, when succinylcholine was given after vecuronium-induced paralysis, no patient developed an increase in ICP greater than 3 mmHg (P less than 0.05 compared with the incidence of ICP greater than or equal to 9 mmHg observed after the first dose of succinylcholine). A second group of six patients received two doses of succinylcholine according to the same protocol but without an intervening dose of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental pharmacology of atracurium dibesylate

Atracurium dibesylate is a new non depolarizing muscle relaxant, metabolized by a non enzymic pathway, the Hofmann elimination. The potency of atracurium in animals was similar to d-tubocurarine and six times less than that of pancuronium. In the cat, the ED50 was 130 micrograms . kg-1; an intravenous dose of 250 micrograms . kg-1 atracurium was sufficient to cause complete neuromuscular block; its duration was 29 min. Single twitch block was readily antagonized by neostigmine 50-100 micrograms . kg-1 or edrophonium 200 micrograms . kg-1. Halothane potentiated the block given by atracurium. Dose ratio for 50% vagal block (ED50) and 50% neuromuscular block was 24; atracurium had weak ganglioplegic effects. 2,000 micrograms . kg-1 atracurium (eight times the neuromuscular blocking dose) reduced mean aortic pressure, heart rate, cardiac output and peripheral resistance. Such effects could be prevented by giving histamine receptor blockers prior to injecting atracurium.