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Background: The linearity of cisatracurium elimination and its concentration-effect relation were determined as part of a traditional rich data study with three dose levels in patients receiving balanced anesthesia., Methods: Forty-eight adults with American Society of Anesthesiologists status I-II were randomized to receive an intravenous bolus dose of 0.075, 0.15, or 0.30 mg/kg cisatracurium. Anesthesia was induced and maintained with nitrous oxide-oxygen, propofol, and fentanyl. The mechanical response of the adductor pollicis muscle was recorded. Arterial blood samples were collected over 8 h. Cisatracurium, laudanosine, and the monoquaternary alcohol concentrations were measured by high-performance liquid chromatography. To assess the relative contribution of the input function, a parametric (assuming elimination from both the central and peripheral compartments) and a nonparametric pharmacokinetic-pharmacodynamic model were both applied to data., Results: Dose proportionality of the body disposition of cisatracurium and its two major metabolites at doses up to 0.30 mg/kg was confirmed. With the parametric approach, the effect compartment concentration at 50% block (EC50) significantly increased with the dose (136 vs. 157 vs. 209 ng/ml), whereas the effect compartment equilibration rate constant decreased (0.0675 vs. 0.0568 vs. 0.0478 min(-1)). A similar dose-dependent effect of the pharmacokinetic-pharmacodynamic relation was observed with the nonparametric approach, but the trend was 50% less pronounced., Conclusion: A dose-related change in pharmacokinetic-pharmacodynamic parameters was identified with both modeling approaches. A pharmacokinetic origin was ruled out, although no definite explanation of the underlying mechanism could be provided. These findings suggest that doses relevant to the anesthetic practice be used for estimation of EC50.

An 18-yr-old male asthmatic was paralyzed with atracurium for a period of seven days to facilitate mechanical pulmonary ventilation. After withdrawal of the muscle relaxant, train-of-four neuromuscular monitoring demonstrated rapid recovery of normal function. Three days later he developed acute quadriparesis without respiratory compromise. Electrophysiological studies showed normal conduction velocities, low compound muscle action potential amplitudes and evidence of denervation. Most cases of post-ventilatory weakness in the ICU involve the use of vecuronium and pancuronium. It has been suggested that the steroid nucleus in these muscle relaxants may be responsible. Our patient developed generalised weakness after treatment with atracurium, a benzylisoquinolinium muscle relaxant. Thus, it appears that the steroid nucleus of vecuronium and pancuronium is not essential in causing post-ventilatory weakness.

To determine the influence of sampling site on atracurium pharmacokinetic-pharmacodynamic relationships, blood was drawn simultaneously from the radial artery and peripheral vein during a 20-minute period after injection of atracurium, 0.2 mg/kg, in eight patients. Atracurium and laudanosine concentrations were measured by HPLC. Neuromuscular blockade was measured at the adductor pollicis, after stimulation of the ulnar nerve. Venous levels were lower than corresponding arterial values for up to 20 minutes, and this difference was marked for the early samples. Neuromuscular blockade was maximum after 5 to 7 minutes, much later than the peak venous concentration (1 to 3 minutes). Nonparametric analysis yielded (mean +/- SEM) a rate constant, concentration for 50% blockade, and slope of the effect-concentration relationship of 0.092 +/- 0.01 min-1, 379 +/- 27 ng/ml, and 7.3 +/- 1.67, respectively, when based on arterial samples. The values were statistically different (0.135 +/- 0.011 min-1, 235 +/- 42 ng/ml, and 3.41 +/- 0.37, respectively) when venous levels were used (p less than 0.05). It is concluded that forearm venous levels do not correspond to adductor pollicis neuromuscular blockade and the kinetics and kinetic-dynamic relationship for atracurium are heavily dependent on sampling site.

Suxamethonium increases neuromuscular block produced by non-depolarizing agents administered subsequently. To determine if this effect has a pharmacokinetic or pharmacodynamic origin, 18 ASA physical status I or II adults received atracurium 0.2 mg kg-1, with (n = 10) or without (n = 8) previous injection of suxamethonium 1 mg kg-1, during a thiopentone-nitrous oxide-isoflurane (0.5% end-tidal) anaesthetic. Arterial blood samples were obtained and plasma atracurium concentration measured by HPLC. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis muscle was recorded. Mean (SEM) volume of distribution was slightly greater with previous suxamethonium (143 (13) ml kg-1) than without (109 (5) ml kg-1) (P less than 0.04). Mean elimination half-life was unaffected (20.3 (0.8) min and 20.4 (1.6) min, respectively). Neuromuscular block was more intense and recovery was slower with previous administration of suxamethonium. Atracurium concentration at 50% block (Cpss50) was 305 (30) ng ml-1 with and 454 (25) ng ml-1 without previous suxamethonium (P less than 0.01). It is concluded that suxamethonium may be associated with a slight increase in the volume of distribution of atracurium, but this effect is more than compensated by a decrease in atracurium concentration required for a given effect.

This study was designed to determine the time required for potentiation of atracurium neuromuscular blockade after the introduction of enflurane. Ten ASA physical status I and II adults anesthetized with thiopental, nitrous oxide, and alfentanil were given 0.4 mg/kg atracurium besylate. The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation of the ulnar nerve was recorded. When the first twitch (T1) of the train-of-four recovered to 10% of control, an atracurium infusion was started and adjusted to keep the level of blockade constant. After 15 min of stable blockade, 1.6%-1.7% end-tidal enflurane was started and maintained for up to 2 h. Venous blood samples were drawn and plasma atracurium concentrations were measured 15 min before and 0, 5, 10, 15, 30, 45, 60, 90, and 120 min after the introduction of enflurane. Atracurium plasma concentrations were 730 +/- 127 (SEM) ng/mL at time 0. During the first 30 min, no significant decrease in plasma levels occurred; but at 45 min, concentrations were only 67% +/- 8% of their initial value (P less than 0.01) and 48% +/- 2% at 120 min (P less than 0.01). This suggests that the interaction between enflurane and atracurium is time-dependent. Clinically, the interaction between atracurium and enflurane is negligible during procedures of less than 45 min.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.

Double-burst stimulation was compared with train-of-four stimulation in 23 adult patients receiving atracurium. Train-of-four was interrupted in 11 subjects every 2 minutes by one double-burst stimulation, and re-applied 6-30 seconds later; the height of the first double-burst response, compared with its control, was depressed slightly more than T1. The relationship between double-burst stimulation ratio and train-of-four ratio was indistinguishable from the line of identity. The train-of-four response, if repeated more than 12 seconds after double-burst stimulation, was not depressed compared with pre double-burst stimulation values. Fifteen anaesthetists were asked to detect fade manually in the second part of the study, while train-of-four was recorded on the opposite arm. One hundred and fourteen determinations were made in 12 patients. Fade was detected manually more often with double-burst stimulation than with TOF.

The pharmacokinetics and pharmacodynamics of atracurium, a nondepolarizing neuromuscular blocking agent, were compared between morbidly obese patients and nonobese patients. Atracurium besylate (0.2 mg/kg) was administered intravenously as a bolus to patients who had received anesthesia. The force of contraction of the adductor pollicis was measured and plasma samples were collected for a 2-hour period. The concentrations of atracurium and its major end product, laudanosine, were determined by use of a chromatographic method. The pharmacokinetic-pharmacodynamic relationship was characterized by use of several models. No difference was observed between obese patients and nonobese patients in atracurium elimination half-life (19.8 +/- 0.7 versus 19.7 +/- 0.7 minutes), volume of distribution at steady state (8.6 +/- 0.7 versus 8.5 +/- 0.7 L), and total clearance (444 +/- 29 versus 404 +/- 25 ml/min). However, if values were expressed on a total body weight basis, there was a difference between obese and nonobese patients in the volume of distribution at steady state (0.067 versus 0.141 L/kg) and total clearance (3.5 +/- 0.2 versus 6.6 +/- 0.5 ml/min/kg). Although atracurium concentrations were consistently higher in obese patients than in nonobese patients, there was no difference in the time of recovery from neuromuscular blockade between the two groups. Consequently, the median effective concentration was higher in obese than in nonobese patients (470 +/- 46 versus 312 +/- 33 ng/ml).

We have studied the effect of prior administration of non-depolarizing neuromuscular blocking drugs on suxamethonium-induced increases in masseter muscle tension in 21 children aged 3-10 yr, anaesthetized with nitrous oxide and halothane using supramaximal stimulation of the ulnar nerve and the nerve to masseter. Resting tension and isometric force of contraction were measured in the adductor pollicis and masseter muscles. A sub-paralysing dose of tubocurarine 0.05 mg kg-1, a paralysing dose of atracurium 0.5 mg kg-1 or saline was given, followed 3 min later by suxamethonium 1 mg kg-1. Onset times of suxamethonium and atracurium block were shorter in the masseter than in the adductor pollicis muscle. When preceded by a sub-paralysing dose of tubocurarine, suxamethonium produced an increase in masseter tension (47 (SEM 15) g) similar to that produced by suxamethonium alone (59 (13) g). Prior administration of a paralysing dose of atracurium almost abolished this increase in tension (2.5 (2.5) g) (P less than 0.05 vs saline). The tension increase in adductor pollicis was 0, 3.2 (2.2) and 5.9 (1.1) g in the atracurium, tubocurarine and saline groups, respectively. Tubocurarine and atracurium prevented muscle fasciculations in all patients. It was concluded that increased muscle tone is a normal response to suxamethonium and is greater in the masseter than adductor pollicis. Sub-paralysing doses of non-depolarizing neuromuscular blockers have little effect, in contrast with paralysing doses. This suggests that the effect is mediated via postsynaptic receptors.

To determine the influence of enflurane on the ability of edrophonium to antagonize atracurium block, dose-response curves were constructed for edrophonium in the presence of 0%, 1% and 2% enflurane, and for 2% enflurane discontinued at the time of administration of edrophonium. One hundred ASA Physical Status I or II patients (four groups of 25), selected randomly and undergoing elective surgery, received atracurium 0.5 mg kg-1, with thiopentone, nitrous oxide and enflurane. Supplementary doses of fentanyl were given if needed. Train-of-four (TOF) stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height (T1) had recovered spontaneously to 10% of initial value, edrophonium 0.1, 0.2, 0.4 or 1 mg kg-1 was administered by random allocation. Enflurane concentrations remained constant, except that enflurane was discontinued in 50% of the patients who had received 2% enflurane. Monitoring was continued for at least 10 min, at which time T1 and TOF ratio (T4/T1) were measured. The ED80 for T1 recovery depended on the dose of enflurane: 0.08 (SEM 0.03), 0.21 (0.06) and 0.42 (0.18) mg kg-1 for 0%, 1% and 2% enflurane, respectively (P less than 0.005). With enflurane 2% discontinued, the ED80 was 0.095 (0.050) mg kg-1 (P less than 0.02 compared with 2% enflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

Edrophonium administered in divided doses has been reported to accelerate antagonism of neuromuscular blockade, i.e., a "priming" effect. Since measured onset times can be affected by the type of stimulation used, this effect was studied using both train-of-four (TOF) and single twitch (ST) stimulation. During thiopentone-nitrous oxide-enflurane anaesthesia 20 adults were given atracurium 0.5 mg.kg-1. Both ulnar nerves were stimulated with TOF every 12 sec until one per cent recovery of first twitch (T1). At this time, ST stimulation was applied to one arm, selected at random. When the mean value of T1 and ST reached ten per cent of control, edrophonium, 1 mg.kg-1, preceded by atropine was given either as a single dose, or in two doses consisting of 0.2 mg.kg-1 followed by 0.8 mg.kg-1 three minutes later. No statistically significant differences were observed between T1 and ST for the next ten minutes, whether edrophonium had been given in single or divided doses. Giving edrophonium in divided doses did not improve recovery significantly, measured with either T1, ST or train-of-four ratio (T4/T1). Five minutes after the first administration of edrophonium, T1 was (mean +/- SEM) 86 +/- 3 and 86 +/- 2 per cent control in the single and divided dose groups respectively. Corresponding values for ST were 89 +/- 1 and 89 +/- 2 per cent (NS), and for TOF, 49 +/- 3 and 57 +/- 3 per cent (NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The sensitivity of the masseter to atracurium was measured in ten children aged 3-10 yr undergoing elective surgery, and compared with that of the adductor pollicis. During nitrous oxide-halothane anaesthesia and mechanical ventilation, supramaximal nerve stimulation was applied to the ulnar nerve at the elbow and to the nerve to the masseter, at a point inferior to the zygomatic arch, anterior to the mandibular condyle. Jaw closure was measured by a force displacement transducer system attached to an oral airway and connected to a metal frame fixed to the operating table 10 cm caudad to the chin. Cumulative dose-response curves for atracurium were obtained by the injection of doses followed by an infusion to compensate for elimination. The mean ED50s and ED95s were similar at the masseter and the adductor pollicis. At the masseter, these were 0.150 +/- 0.013, mean +/- SEM, mg.kg-1 and 0.254 +/- 0.021 mg.kg-1, respectively. At the adductor pollicis, corresponding values were 0.145 +/- 0.009 mg.kg-1, and 0.259 +/- 0.016 mg.kg-1. However, this relationship was not constant in every patient, and in some patients the masseter was much more sensitive than the adductor pollicis. The time from injection of the first dose of atracurium to maximum blockade was 2.5 +/- 0.2 min at the masseter and 3.2 +/- 0.2 min at the adductor pollicis (P less than 0.05). It is concluded that when atracurium is administered to paediatric patients, neuromuscular blockade is usually of the same intensity at each muscle but occurs sooner at the masseter than at the adductor pollicis.(ABSTRACT TRUNCATED AT 250 WORDS)

The potency of atracurium was determined in five patients with moderate to severe generalized myasthenia gravis undergoing thymectomy. Train-of-four stimulation was applied to the ulnar nerve and the force of contraction of the adductor pollicis was measured. Cumulative dose-response curves were obtained during thiopentone-nitrous oxide-fentanyl anaesthesia. The average time to complete the dose-response studies was 12.7 +/- 1.5 minutes. The ED50, ED90 and ED95 of atracurium were (mean +/- SEM) 0.07 +/- 0.01, 0.12 +/- 0.22, and 0.14 +/- 0.04 mg.kg-1, respectively. The time to 25 per cent first twitch recovery was 35 +/- 4 min following maximum blockade. Ten normal patients were studied in the same manner. Their ED50, ED90 and ED95 were 0.13 +/- 0.01, 0.21 +/- 0.02 and 0.24 +/- 0.03 mg.kg-1, respectively. These results demonstrated that, in patients with moderate to severe generalized myasthenia gravis, atracurium was 1.7-1.9 times as potent as in normal individuals.

The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Train-of-four stimulation can shorten the apparent onset time of neuromuscular blocking drugs. This study was designed to verify whether the same occurred with neostigmine-assisted recovery, and whether this apparent acceleration could explain the previously reported effectiveness of the priming technique for reversal agents. Fourteen adults received atracurium, 0.5 mg.kg-1, during a thiopentone-nitrous oxide-enflurane anaesthetic. The ulnar nerves of both arms were stimulated with train-of-four stimulation every 12 seconds until 1 per cent recovery of first twitch, at which time stimulation in one arm was switched to single twitch. When mean first twitch height reached 10 per cent of control, neostigmine, 0.04 mg.kg-1, was administered either as a single bolus, or as a "priming" dose of 0.01 mg.kg-1, followed 3 min later by 0.03 mg.kg-1. No statistically significant differences were observed between single twitch in one arm and first twitch height of the train-of-four in the other arm for the next 10 min. With priming, first twitch height was 45 +/- (SEM) 5 per cent at 5 min and 85 +/- 6 per cent at 10 min, compared with 72 +/- 5 per cent (p less than 0.05) and 91 +/- 2 per cent (NS) respectively without priming. Train-of-four ratio was 28 +/- 3 per cent at 5 min and 65 +/- 5 per cent at 10 min with priming, versus 53 +/- 4 per cent (P less than 0.05) and 73 +/- 3 per cent (NS) respectively without priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Train-of-four stimulation was applied to the ulnar and phrenic nerves in 18 adult patients anaesthetized with nitrous oxide and halothane in oxygen. The response of the adductor pollicis and the diaphragm were measured. Incremental doses of atracurium and vecuronium were given, with an infusion to replace drug lost by elimination or distribution. The mean (SEM) doses of atracurium associated with 50% and 90% depression of response to the first stimulation in the train-of-four (ED50 and ED90) were 90 (9) and 133 (10) micrograms kg-1 at the adductor pollicis, and 130 (9) and 245 (17) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 and ED90 of vecuronium were 25 (2) and 38 (4) micrograms kg-1 at the adductor pollicis and 34 (3) and 58 (5) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 ratios were 1.56 (0.16) for atracurium and 1.47 (0.16) for vecuronium. ED90 ratios were 1.93 (0.29) and 1.55 (0.17) for atracurium and vecuronium, respectively. It is concluded that both atracurium and vecuronium exhibit a similar degree of sparing of the diaphragm.

Single twitch and train-of-four stimulation were applied at 0.08 Hz to each ulnar nerve and the force of contraction of the adductor pollicis was recorded during onset of and recovery from neuromuscular blockade by suxamethonium 1 mg kg-1 or atracurium 0.4 mg kg-1. Times to 90% first twitch blockade of train-of-four were (mean +/- SEM) 0.82 +/- 0.08 and 1.98 +/- 0.18 min for suxamethonium and atracurium, respectively, compared with times to 90% single twitch blockade of 1.00 +/- 0.07 and 3.35 +/- 0.37 min, respectively (P less than 0.05 in both cases). Apparent onset time also depended on how long train-of-four stimulation had been applied before injection of atracurium. The mode of stimulation had little effect on time to 10% recovery. The results are consistent with stimulation-induced augmentation in muscle blood flow, which increased delivery of the drug to the neuromuscular junction.

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.

To measure the ability of neostigmine and edrophonium to reverse moderate and profound atracurium blockade, dose-response relationships were established for these reversal agents given at 1% and 10% twitch height recovery. Eighty-five ASA I and II adult patients received atracurium, 0.4 mg/kg, during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 seconds, and the force of contraction of the adductor pollicis muscle was recorded. Edrophonium, 0.1, 0.2, 0.4, or 1 mg/kg; neostigmine, 0.005, 0.01, 0.02 or 0.05 mg/kg; or no reversal agent was given when there was either 1% or 10% recovery of the first twitch response. With profound blockade, the slope of the edrophonium dose-response relationship was significantly flatter (P less than 0.05) than that of neostigmine. The dose of neostigmine required to achieve 80% first twitch recovery (ED80) after 10 minutes was 0.013 +/- 0.003 mg/kg (mean +/- SEM) if given at 10% recovery, and 0.032 +/- 0.004 mg/kg if given at 1% recovery. The ED80 for edrophonium was 0.22 +/- 0.04 mg/kg and 1.14 +/- 0.33 mg/kg, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 16.6 +/- 3.5 and 35.3 +/- 8.9 at 90% and 99% blockade respectively (P less than 0.006). We conclude that the relative potency of neostigmine is greater than that of edrophonium for antagonism of profound atracurium blockade.

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)