Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade

Neostigmine 0.06 mg.kg-1 or edrophonium 1 mg.kg-1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (+/-SEM) of edrophonium (18.1 +/- 2.4 sec) was significantly more rapid (P less than 0.01) than that of neostigmine (47.6 +/- 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P less than 0.01) in the neostigmine than in the edrophonium group (499.3 +/- 62 vs 767 +/- 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P less than 0.01), 0.78 +/- 0.02 vs 0.68 +/- 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg.kg-1 and edrophonium 1 mg.kg-1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 +/- 0.002 and 1.3 +/- 0.05 mg.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T₄/T₁ > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-offour (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg · kg^?1, during thiopentone-N₂O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg · kg^?1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg · kg^?1, was given. Two minutes later, edrophonium, 0.1 mg · kg^?1, was given if T₄/T₁ did not reach 0.7. After another two minutes, edrophonium, 0.2 mg · kg^?1, was given if T₄/T₁ did not reach 0.7 or more. Finally, if T₄/ T₁ was still < 0.7, a dose of 0.4 mg · kg^?1 was given. Seventeen patients (42.5%) required 0.1 mg · kg^?1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg · kg^?1 and six patients (15%) required 0.4 mg · kg^?1. Only one patient received 0.8 mg · kg^?1. There was a good correlation between T₄/ T₁ two minutes after the first dose of edrophonium and pre-reversal T₄/T₁ (r = 0.6; P = 0.00014). All patients with pre-reversal T₄/ T₁ > 0.23 required at most 0.2 mg · kg^?1 of edrophonium for successful reversal. We conclude that when all four twitches are clearly visible following train-of-four stimulation, small doses of edrophonium (0.1-0.2 mg · kg^?1) might be sufficient to antagonize vecuronium neuromuscular blockade.     

Clindamycin-induced neuromuscular blockade

The purpose of this article is to report the case of a patient who developed prolonged neuromuscular block after a large dose of clindamycin (2400 mg). A 58-yr-old, 65 kg woman with severe rheumatoid arthritis was admitted for wrist arthrodesis. After d-tubocurarine (3 mg) and fentanyl (1.5 μg · kg^?1), anaesthesia was indúced with thiopentone (4 mg · kg^?1) followed by succinycholine (1.5 mg · kg^?1) and was maintained with N₂O in O₂ and isoflurane (0.75-1.0% end tidal) and ventilation was controlled. No further neuromuscular relaxants were given although full return of neuromuscular activity in response to train-of-four and 100 Hz tetanic stimulation was observed after succinylcholine. An overdose of clindamycin (2400 mg, instead of the intended 600 mg) was given iv soon after the start of surgery. At the end of surgery, 75 min later, the patient made no attempt at spontaneous ventilation, was unresponsive to painful stimuli and naloxone (0.2 mg iv) was ineffective. Controlled ventilation was continued in the Recovery Room where neuromuscular testing showed a train-of-four ratio of 0.27 which improved to only 0.47 five minutes after calcium chloride (1.5 mg · kg^?1 iv), and to 0.62 after edrophonium (20 mg) and neostigmine (2 mg). Nine hours later the patient began to cough, the TOF had returned to 1.0 and two hours later the trachea was extubated and spontaneous ventilation was resumed. Large doses of clindamycin can induce profound, long-lasting neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from succinylcholine has been demonstrated.     

Rapid tracheal intubation with atracurium: the timing principle

The “Timing Principle” utilises a single bolus of nondepolarising neuromuscular blocking drug followed by thiopentone given at the onset of clinical weakness. The purpose of this study was to compare the intubating conditions after succinylcholine and after atracurium used according to the “timing principle.” Eighty patients were randomly assigned to four groups of 20. Three study groups were given atracurium 0.5, 0.75 or 1 mg · kg^?1 (Groups I, II and III respectively) and the control group (Group IV) received succinylcholine 1.5 mg · kg^?1. The study groups received fentanyl 1 μg · kg^?1, atracurium three minutes later, followed by thiopentone 4–6 mg · kg^?1 at the onset of ptosis. The control group had a defasciculating dose of atracurium (0.025 mg · kg^?1) and fentanyl (1 μg · kg^?1) followed by thiopentone (4–6 mg · kg^?1) and succinylcholine three minutes later. The trachea was intubated one minute after thiopentone was given. The intubating conditions were then graded by a laryngoscopist who was unaware of the induction sequence. All patients were interviewed on the day after surgery. Intubation scores of patients in Group I were worse than in Groups II, III and IV (P < 0.005) but there were no differences between Groups II, III and IV. The technique was not associated with severe haemodynamic changes. All patients, except one were able to cough well after administration of atracurium, before induction of anaesthesia with thiopentone. Patients were generally satisfied with this method of induction. It is concluded that atracurium, when used according to the timing principle, can be an alternative to succinylcholine during rapid-sequence induction.     

Onset of vecuronium neuromuscular block is more rapid in patients undergoing Caesarean section

This investigation was carried out in ten patients undergoing elective Caesarean section and the results were compared with those of a control group of ten nonpregnant females of the same age group. The study investigated the onset of vecuronium neuromuscular block and the conditions of tracheal intubation when ketamine (1.5 mg.kg-1)-vecuronium 100 micrograms.kg-1) sequence was used for rapid-sequence induction of anaesthesia. The ulnar nerve was stimulated supra-maximally at the wrist with train-of-four stimuli every 20 sec, and the electromyographic response of the adductor pollicis muscle was displayed. The onset of 50% neuromuscular block as monitored by electromyography was shorter in the Caesarean group (80 +/- 30 sec) than in the control group (144 +/- 43 sec). The conditions of intubation at 50% block were adequate in both groups. Also, the onset of 90% block was shorter in the Caesarean group. The time of recovery to T1/control ratio of 25% was longer in the Caesarean group (46 +/- 10 min) than in the control patients (28 +/- 10 min). The results show that administration of vecuronium according to body weight results in a more rapid onset and delayed recovery of neuromuscular block in pregnant women undergoing Caesarean section than in the nonpregnant control patients.     

Pharmacokinetics and cardiovascular dynamics of pipecuronium bromide during coronary artery surgery

The haemodynamic effects of 200 micrograms.kg-1 pipecuronium and pancuronium were compared under etomidate/piritramide anaesthesia in 20 patients scheduled for elective coronary artery surgery. Following the completion of the haemodynamic measurements (ten minutes), anaesthesia was maintained by etomidate/sufentanil infusion. The mean changes in cardiac output were approximately -19 and -2 per cent and in heart rate -1 and +26 per cent for pipecuronium and pancuronium respectively. Plasma and urine concentrations of pipecuronium were also measured and the pharmacokinetic variables obtained indicated rapid initial decrease in plasma concentration (t1/2 = 7.6 minutes) followed by a longer terminal phase (t1/2 = 161 minutes). The central compartment volume was 102 +/- 24 ml.kg-1 and plasma clearance was 1.8 +/- 0.4 ml.kg-1 min-1. Approximately 56 per cent of the dose was recovered from the urine within 24 hours of administration and about 25 per cent of this was the metabolite, 3-desacetyl pipecuronium. High-dose pipecuronium administration under the anaesthetic regimen employed did not produce deleterious haemodynamic effects. The pharmacokinetic variables after bolus injection of pipecuronium did not deviate from those reported under normothermic conditions.     

Interaction between succinylcholine and cimetidine in rats

The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (+/- 1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg.kg-1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (+/- 2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (+/- 0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (+/- 4.6) micrograms.ml-1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.     

Left ventricular regional wall motion and haemodynamic changes following bolus administration of pipecuronium or pancuronium to adult patients undergoing coronary artery bypass grafting

The objective of this study was to compare the haemodynamic and myocardial effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting (CABG) during benzodiazepine/sufentanil anaesthesia. Twenty-seven ASA III–IV patients received lorazepam (1–3 mg) po and midazolam (<0.1 mg · kg^?1) iv before induction of anaesthesia with sufentanil (3–8 μg · kg^?1). Vecuronium (0.1 mg · kg^?1) was administered to facilitate tracheal intubation. According to random allocation, each patient received either pipecuronium (150 μg · kg^?1) or pancuronium (120 μg · kg^?1) after stemotomy but before heparinization. Mean arterial pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), ST segment position and ECG (leads HI, V₅, AVF) were monitored continuously throughout the procedure. Thermodilution determinations of CO in triplicate were made immediately before, and at two and five minutes after muscle relaxant administration. Multiplane transoesophageal echocardiography (TEE, midpapillary short axis views of the left ventricle) images were continuously recorded from ten minutes before until ten minutes after muscle relaxant administration and graded by two experienced echocardiographic readers. Heart rate, MAP and CO increased after administration of pancuronium (by 13.6 beats · min^?1, 10.8 mmHg and 1.0 L · min^?1 respectively) but not after pipecuronium (P < 0.05). Evidence of myocardial ischaemia was not detected in any patients using ECG ST segment analysis or TEE assessment of left ventricular wall motion. We conclude that pancuronium caused increases in HR, MAP and CO but that neither pancuronium nor pipecuronium caused myocardial ischaemia.     

Different priming techniques,including mivacurium,accelerate the onset of rocuronium

Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg · kg^?1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg · kg^?1 followed three minutes later by mivacurium 0.135 mg · kg^?1. Group III received rocuronium 0.6 mg · kg^?1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group V received a priming dose of mivacurium 0.015 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group VI received an initial dose of rocuronium 0.06 mg · kg^?1 followed by mivacurium 0.135 mg · kg^?1. Group VII received succinykholine 1.0 mg · kg^?1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg · kg^?1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57–90) sec) or mivacurium (58 (47–69) sec) were similar to those after succinykholine (54 (40–68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinykholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinykholine in both the onset of action and intubating conditions.     

Postoperative neuromuscular block following atracurium or alcuronium in children

Postoperative neuromuscular block (NMB) was evaluated in 60 children who received randomly either atracurium or alcuronium to induce and maintain an 85-95 per cent NMB during balanced anaesthesia. The EMG-monitor was turned away from the anaesthetist 10-15 min before the end of surgery. The average NMB was comparable between the groups at the time of reversal with neostigmine 50 micrograms.kg-1 (84 +/- 9 per cent, mean +/- SD) as were the NMB and the train-of-four ratio when the tracheas were extubated on a clinical basis (32 +/- 20 per cent and 50 +/- 18 per cent, respectively). Patients who had been paralyzed with atracurium arrived at the recovery room earlier and on arrival had greater train-of-four ratios than the patients paralyzed with alcuronium (P less than 0.01). Time to a train-of-four ratio of greater than 90 per cent was significantly shorter in the atracurium group (10 +/- 5 min vs 26 +/- 15 min, P less than 0.001). Thus, an intermediate-acting muscle relaxant offers a safer recovery profile of the NMB than a long-acting muscle relaxant in paediatric patients.     

Localized hypothermia influences assessment of recovery from vecuronium neuromuscular blockade

The purpose of this study was to determine the extent to which localized hypothermia of a monitored extremity alters the assessment of recovery from vecuronium- induced neuromuscular blockade. Bilateral integrated evoked electromyographic (IEMG) responses were measured in the ulnar distribution of 14 anaesthetized patients who had differing upper extremity temperatures as measured at the adductor pollicis to determine whether localized hypothermia alters the clinical assessment of spontaneous recovery from vecuronium- induced neuromuscular blockade. All patients received general anaesthesia with thiopentone, N₂O/ O₂ and opioid; 11/14 patients received isoflurane for blood pressure control. Bilateral adductor pollicis, oesophageal and ambient temperatures, and IEMG evoked response (t₁) expressed as percent unparalyzed control were recorded during the anaesthetic. The difference in evoked response between the warmer and the colder upper extremity was calculated at 25%, 50% and 75% spontaneous recovery from neuromuscular blockade in the warm extremity. Differences in temperature between extremities ranged from 0.2–11° C. The difference in IEMG- evoked response between extremities was proportional to the difference in temperature, and there was a direct correlation (r = 0.78) between IEMG response and extremity temperature; IEMG response was absent when extremity temperature was less than 25° C. We concluded that localized hypothermia in the monitored extremity decreases the IEMG- evoked response to vecuronium neuromuscular blockade; the greater the temperature decrease, the less the evoked response. Thus, the administration of nondepolarizing relaxants may be inappropriately influenced by monitoring neuromuscular blockade in a cold extremity, especially if its temperature is <25° C.     

Vecuronium is more potent in montreal than in Paris

This study was undertaken to compare the potency of vecuronium in patients anaesthetized in Montreal or Paris. Anaesthesia was induced with thiopentone and maintained with N2O, and intermittent boluses of thiopentone and fentanyl in 18 patients in Paris and 19 in Montreal. Neuromuscular blockade was measured using train-of-four stimulation of the ulnar nerve. The force of contraction of the adductor pollicis muscle was measured. Single doses of vecuronium, 20, 30, or 40 micrograms.kg-1 were given by random allocation. Dose response curves were constructed by obtaining the linear regression of the logit of the first response (T1) neuromuscular blockade versus log dose. The patients in Paris required 27% more vecuronium (95% confidence limits 5-53%; P = 0.01) for the same intensity of blockade. In Montreal, the ED50 and ED90 (+/- SEE for the mean) values were 26.0 +/- 1.4 and 44.2 +/- 2.5 micrograms.kg-1 compared with 33.0 +/- 3.3 and 71.9 +/- 7.2 micrograms.kg-1 in Paris respectively. The patients were comparable with respect to age, sex, height and weight. These results confirm, for vecuronium, the transatlantic difference in potency of neuromuscular blocking drugs which was previously observed with d-tubocurarine between London and New York.     

Estimation of the potency of ORG 9426 using two different modes of nerve stimulation

The potency of ORG 9426, a new nondepolarising muscle relaxant, has been estimated using two different modes of nerve stimulation in patients anaesthetised with thiopentone, nitrous oxide-oxygen and intravenous fentanyl. The force of contraction of adductor pollicis was measured following a single twitch (ST) at 0.1 Hz or a train-of-four (TOF) mode of stimulation at 2 Hz every ten seconds. Dose-response curves were constructed using a single-dose method. The ED50, ED90 and ED95 were 147,272 and 305 micrograms.kg-1 respectively using the ST mode and 125,230 and 257 micrograms.kg-1 using the TOF mode of stimulation. The ED50S were not significantly different but the differences between ED90S and ED95S were significant (P less than 0.05) indicating greater sensitivity of the neuromuscular junction using TOF stimulation. The results of this study suggest that the information obtained by single-twitch stimulation is not the same as that obtained from the first response of the TOF stimulation, suggesting apparently increased sensitivity (and apparently greater potency) with the TOF mode of stimulation. Org 9426 appears to be a drug with relatively low potency.     

Haemodynamic interactions of muscle relaxants and sufentanil in coronary artery surgery

The haemodynamic interactions between sufentanil (S) and muscle relaxants (MR) were studied in 40 ASA physical status III or IV patients (four groups of ten) scheduled for coronary artery bypass grafting (ABG). Group I received pancuronium (P) 0.08 mg.kg-1, Group II received vecuronium (V) 0.1 mg.kg-1, Group III received atracurium (A) 0.5 mg.kg-1 and Group IV metocurine 0.1 mg.kg-1 plus pancuronium 0.02 mg.kg-1 (M-P). Sufentanil, 20 micrograms.kg-1 was administered before sternotomy, 10 micrograms.kg-1 being injected before tracheal intubation and 10 micrograms.kg-1 afterwards. Heart rate (HR), ECG leadII and V5, systolic, diastolic and mean arterial and pulmonary blood pressures, central venous pressure (CVP) and pulmonary capillary wedge pressure (W) were measured and recorded at the time of seven strategic events between the pre-induction of anaesthesia period and sternotomy. Cardiac output (CO) and systemic vascular resistances (SVR) were also measured before induction of anaesthesia and after the administration of S 10 micrograms.kg-1 plus the MR. The HR decreased from baseline values in the post-tracheal intubation period in all groups except in P group. The mean arterial pressure also decreased significantly in all groups except in the P group. The CO did not change from baseline values but SVR decreased in all groups. There was no evidence of new myocardial ischaemia according to the ECG monitoring and there was no significant difference in the HR changes between patients who had or who had not received beta-blockers in any group. We conclude that within the present study conditions and design, HR and blood pressure changed least with pancuronium.     

Propranolol pretreatment reduces cardiorespiratory toxicity due to plain,but not epinephrine-containing,intravenous bupivacaine in rats

The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 μg · ml^{? 1}) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 μg · kg^{? 1}, and Groups II and IV recei ved iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg · kg^{? 1}, and Groups III and IV received 4 mg· kg^{? 1} of 0.5% bupivacaine with epinephrine, 5 μg · ml^{? 1} iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P < 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 μg · ml^{? 1} to bupivacaine eliminated the protective effect of propranolol.     

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.     

Comparative evaluation of propofol and thiopentone for total intravenous anaesthesia

Sixty unpremedicated ASA physical status I or II patients scheduled for surgical procedures of intermediate duration (15 to 60 min) were studied to evaluate the safety and efficacy of propofol, to measure recovery times and to compare the return of psychomotor and cognitive function with thiopentone. Patients were randomly allocated into two groups. Anaesthesia was induced and maintained by either propofol (2.0-2.5 mg.kg-1 followed by a continuous infusion 0.1-0.2 mg.kg-1.min-1) or thiopentone (4.0-5.0 mg.kg-1, and infusion rate 0.16-0.32 mg.kg-1.min-1), titrated to patient response. Succinylcholine was administered to facilitate tracheal intubation and maintain neuromuscular blockade. Induction of anaesthesia was slightly longer with propofol than thiopentone (42.2 vs 29.8 sec) and was smooth with both drugs. Post-intubation increases in heart rate, and systolic and diastolic blood pressures were attenuated by propofol when compared with thiopentone. After the administration of propofol, times to eye opening (6.4 +/- 4.3 vs 13.9 +/- 15.9 min), response to verbal command (7.6 +/- 6.3 vs 15.4 +/- 16.6 min) and orientation (22.7 +/- 12.8 vs 36.2 +/- 23.1 min), were significantly shorter. Psychomotor and cognitive function returned earlier with propofol and fewer side effects were noted. At 24 hr there was no distinguishable difference between groups. Propofol is a safe anaesthetic agent with the potential for early patient discharge and street fitness after outpatient procedures.     

Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized patients

Since clonidine, an α₂-agonist, inhibits the release of norepinephrine or acetylcholine which can decrease nondepolarizing muscle relaxant-induced neuromuscular blockade, the authors examined whether clonidine given as an oral preanaesthetic medication would alter the onset, duration or recovery of a vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight patients (aged 20–73 yr) randomly received oral clonidine either approximately 5 μg · kg^?1 (n = 21) or none (n = 17), 90 min before arrival in the operating room. We measured acceleration of thumb contraction with ulnar nerve stimulation at the wrist to assess neuromuscular blockade. The onset time (the time from injection to decrease to 5% of baseline twitch height), duration (the time interval between injection and return of the first twitch to 25% of the baseline value), and recovery index (the time interval of the first twitch from 25% to 75% of the baseline value) of neuromuscular blockade from a single bolus of vecuronium 0.1 mg · kg^?1 iv were determined and compared between the clonidine-treated and control patients during lower abdominal or extremity surgery under epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No differences were noted between the control and clonidine groups in onset time (100 ± 6 sec (mean ± SE) vs 101 ± 6 sec), duration (44.5 ±2.7 min vs 42.9 ±2.7 min), or recovery index (21.6 ± 2.8 min vs 19.1 ± 1.9 min) of neuromuscular blockade from vecuronium, respectively. These results show that oral preanaesthetic medication of clonidine 5 μg · kg^?1 does not alter neuromuscular blockade induced with vecuronium 0.1 mg · kg^?1 in patients during combined epidural and fentanyl/nitrous oxide general anaesthesia.     

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)     

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg⁻¹ po and an inhalational induction with up to 3 MAC of either agent in 70% N₂O and O₂. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg⁻¹) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T₁ > 95%, T₄/T₁ > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. L’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg⁻¹ et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N₂O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg⁻¹). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T₁ > 95%, T₄/T₁ > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

---

Supported in part by a grant from Abbott Laboratories, Chicago, Illinois.