Détermination de la courbe dose-effet du vécuronium chez l'homme anesthésié

Dose-response curves have been determined in 37 healthy subjects, after injection of a single bolus of Organon NC 45 (vecuronium or Norcuron®). The doses used were 0.0125, 0.025, 0.037 and 0.05 mg · kg^?1. The ulnar nerve was stimulated at the wrist and the force of thumb adduction measured. No premedication was used. Anesthesia was induced with thiopentone and fentanyl, and maintained by a nitrous oxide/oxygen mixture under controlled ventilation. Paco₂ was 37 ± 0.5 mmHg and temperature 36.8 ± 0.1 °C. The effective doses (ED) were : ED₅₀ at 0.024 mg · kg^?1, ED₉₀ at 0.034 mg · kg^?1 and ED₉₅ at 0.037 mg · kg^?1. At 0.05 mg · kg^?1, the degree of twitch inhibition was 99.2 ± 0.6 %, the delay of maximum effect was 7.7 ± 1.4 min, and the length of action (up to 90 % recovery) was 27.2 ± 2.3 min. Vecuronium is therefore a potent neuromuscular blocking agent with a relatively short duration of action.     

Rocuronium in infants, children and adults during balanced anaesthesia

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED₅₀ doses (mean ± SD) being 149 ± 36 μg˙kg^?1 in infants, 205 ± 52 μg˙kg^?1 in children and 169 ± 47 μg˙kg^?1 in adults (P<0.05 between infants and children) and the ED₉₅ doses being 251 ± 73 μg˙kg^?1, 409 ± 71 μg˙kg^?1 and 350 ± 77 μg˙kg^?1, respectively (P<0.05 between all groups). The emg recovery following an average 94.5 ± 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED₉₅ dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.     

Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block

The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration of neostigmine than if the blockade was maintained with pancuronium alone. Anaesthesia consisted of thiopentone, N₂O/O₂/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg · kg^?1 was monitored by the force of contraction of adductor pollicis during major abdominal surgery lasting 2–5 hr. In 24 patients — Group 1 — atracurium 0.07 mg · kg^?1 was repeated when the first twitch of the train-of-four (TOF) returned to 25% of control (T₁/ TC 25). In 28 patients — Group 2 — pancuronium 0.015 mg · kg^?1 was given at similar recovery of T₁/ TC. At the end of surgery, neostigmine 0.07 mg · kg^?1 and glycopyrrolate 0.015 mg · kg^?1 were given to reverse the residual neuromuscular blockade which was indicated by a T₁/TC of less than 25% in all patients. The time from injection of the reversal drugs to a TOF ratio of 70% was similar in both groups (Group 1, 11.6 ± 7.6 min; Group 2, 10.1 ± 6 min; P = NS), but the recovery index was smaller in Group 2 (Group 1, 4 ± 2.6 min; Group 2, 2.61 ± 1.2 min; P < 0.05). Furthermore, there was no difference between groups in the duration of action of each redose. The study showed that when compared with pancuronium, equipotent doses of atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or (b) a shorter duration of action.     

Dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block during N2O-enflurane-alfentanil anaesthesia

The purpose of this study was to determine the dose-response relationships for edrophonium antagonism of mivacuriuminduced neuromuscular block. Seventy-five ASA I or II adults were given mivacurium 0.15 mg · kg^{? 1} followed by an infusion (7 μg · kg^{? 1} · min^{? 1}) during alfentanil-propofol-N₂O-enflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 20 sec and the response of the adductor pollicis was recorded (Relaxograph NMT-100. Datex, Helsinki, Finland). Mivacurium infusion was modified at five-minute intervals in order to keep the height of the first twitch in TOF (T₁) at 5% of its control value. At the end of surgery, edrophonium (0.0. 0.125, 0.25, 0.5. or 1.0 mg · kg^{? 1}) combined with glycopyrrolate (0.0, 0.0012, 0.0025, 0.005, or 0.01 mg · kg^{? 1}) were administered by random allocation. Edrophonium doses of 0.25, 0.5 and 1.0 mg · kg^{? 1} were different from placebo with regard to time to attain a TOF ratio (fourth twitch in TOF/ T,) = 0.7 (13.8 ± 4.5, 11.1 ± 3.5, 11.4 ± 3.0 vs 19.7 ± 4.7 min P < 0.05). Doses of 0.5 and 1.0 mg · kg^{? 1} permitted faster recovery time of T₁ from 10 to 95% (T_{10– 95}) than did placebo (7.5 ± 3.8,8.9 ± 3.5 vs 14.5 ± 5.0 min P < 0.05). Edrophonium 0.5 mg · kg^{? 1} was different from placebo with regard to recovery time of T₁ from 25 to 75% (T_{25– 75}) (3.3 ± 2.0 vs 6.7 ± 2.0 min P < 0.05). Only edrophonium 0.5 mg · kg^{? 1} provided faster recovery than placebo with regard to all three indices. It is concluded that edrophonium 0.5 + glycopyrrolate 0.005 mg · kg^{? 1} allow the fastest recovery from a mivacurium-induced block during enflurane-N₂O anaesthesia.     

Surgeon-controlled mivacurium administration during elective Caesarean section

We have compared the dose requirements and recovery characteristics of a continuous mivacurium infusion given by the anaesthetist to maintain 95–100% block at the hand muscles with that of a surgeon-controlled, on-demand dosing technique based on the direct assessment of abdominal muscle tone during elective Caesarean section. Twenty-four full term pregnant patients were included. A rapid-sequence induction using thiopentone 3–5 mg· kg^?1 and succinylcholine 1 mg· kg^?1 was used. Anaesthesia was maintained with fentanyl, N₂O and iso-flurane 0.5%. The mechanomyographic response of the adductor pollicis muscle to supramaximal train-of-four (TOF) ulnar nerve stimulation was recorded. Muscle relaxation was achieved initially with mivacurium 0.1 mg· kg^?1 followed either by a continuous infusion of mivacurium to maintain 95–100% block at the adductor pollicis muscle (n = 12) or by surgeon-controlled relaxation (SCR) technique using a syringe pump for patient-controlled analgesia to administer on-demand doses of mivacurium 0.05 mg · kg^?1 (n = 12). The lockout interval was three minutes and the maximum hourly dose of mivacurium allowed was 0.6 mg · kg^?1. The total doses of mivacurium (mean ±SD) were 23.2 ± 10.4 and 12.4 ± 3.5 mg in the infusion and SCR groups, P < 0.01. On-demand, surgeon-controlled doses of mivacurium were injected at a mean of T₁ 42.3 ± 36%. At the end of surgery, T₁ and TOF ratio were respectively 16.7 ± 13%, 5 ± 10% and 48 ± 37%, 30 ± 24% in the infusion and SCR groups. Five patients in the SCR group and one patient in the infusion group did not receive antagonist at the end of surgery. The time to adequate recovery, TOF 75%, after skin closure was 8.2 ± 2.3 and 5.3 ± 4 min in the infusion and SCR groups, P = 0.05. It is concluded that, compared with a continuous mivacurium infusion, the SCR technique is associated with reduced mivacurium requirements, a substantial degree of neuromuscular recovery at the end of surgery and a reduced need for neostigmine reversal in full term pregnant patients undergoing elective Caesarean section.     

Early neuromuscular recovery characteristics following administration of mivacurium plus vecuronium

Purpose

This study was designed to describe the early recovery characteristics, as well as the speed of onset of neuromuscular block, after a combination of mivacurium and vecuronium.

Methods

In this controlled, randomized study, 30 consenting ASA I–III patients were assigned to three treatment groups. The “2M2V” group received twice the dose necessary to cause 95% depression of the evoked twitch response (2 × ED₉₅) of mivacurium (0.15 mg · kg^?1) plus 2 × ED₉₅ of vecuronium (0.1 mg · kg^?1); the “2V” group received 2 × ED₉₅ of vecuronium; and the “4V” group received 4 × ED₉₅ of vecuronium. Evoked neuromuscular responses of the adductor pollicis were assessed with an adductor pollicis force transducer. The time until maximum block and times to 10% and 25% recovery (T₁₀ and T₂₅) in each group were expressed as mean ± standard deviation and compared using ANOVA.

Results

Onset of block in the 2M2V group was 27% faster than in the 2V group (2.0 ± 0.6 vs. 2.7 ± 0.8 min respectively, P < 0.05) and was similar to the 4V group (1.95 ± 0.3 min, P = NS). The times until 10% recovery were similar in the 2M2V and 4V groups (59.9 ± 12 vs 68.2 ± 25 min, P = NS) and were slower than in the 2V group (37.2 ± 9 min, P < 0.05). Between T₁₀ and T₂₅, recovery after 2M2V resembled that after 2V (6.7 ± 3 vs 5.7 ± 1 min, P = NS) and was faster than after 4V (10.9 ± 7 min, P<0.05).

Conclusions

When 2 × ED₉₅ of mivacurium is added to 2 × ED₉₅ of an intermediate or long-acting relaxant, recovery after T₁₀ will proceed as if one had administered the longeracting agent alone.     

PRETREATMENT WITH NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS AND SUXAMETHONIUM-INDUCED INCREASES IN RESTING JAW TENSION IN CHILDREN

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

Propofol reduces succinylcholine induced increase of masseter muscle tone

Purpose

Succinylcholine is known to increase the tone of the masseter muscles. As excessive jaw tension may complicate rapid sequence induction, we investigated three induction techniques, all including the use of succinylcholine, with respect to masseter muscle tone, neuromuscular blockade, intubation conditions, and time course of intubation.

Methods

Sixty adult patients were allocated to one of three induction groups: Group THIO received 5 mg · kg^?1 thiopentone, Group THIO/ATR received 5 mg · kg^?1 thiopentone plus 0.05 mg · kg^?1 atracurium for precurarization, and Group PROP received 2.5 mg · kg^?1 propofol. All patients received 3 μg · kg^?1 fentanyl and 1.5 mg · kg^?1 succinylcholine. Time for induction of anaesthesia was recorded, and, after inserting a Grass Force Transducer between upper and lower incisors, jaw tone and the time course of jaw tension was recorded before and after the administration of succinylcholine.

Results

No differences in the onset of sleep were observed among the three groups (Group THIO 33 ± 2 sec: THIO/ATR 30 ± 2 sec: PROP 35± 2 sec, mean ± SE). Masseter preloads following induction of anaesthesia were similar in all three groups (THIO 16.4 ± 2.1 N: THIO/ATR 15.1 ± 2.0 N: PROP 12.7 ± 1.6 N). However, after administration of succinylcholine, the increase in masseter tone was less in Groups PROP (5.0 ±1.1 N) and THIO/ATR (6.4 ± 2.1 N) than in Group THIO (12.4 ± 3.0 N;P < 0.05).

Conclusion

Jaw tension after administration of succinylcholine is influenced by the choice of induction agent. The increase of masseter muscle tone is lower following propofol or thiopentone/atracurium induction than with thiopentone alone.     

Neuromuscular effects of vecuronium and neostigmine in Montreal and Paris

The potency of vecuronium was reported to be greater in Montréal than in Paris. This study was designed to determine whether there were differences in onset, duration, and reversibility with neostigmine between both centres. Twenty ASA I or II adults (ten men, ten women), aged 18–65 yr were studied in each of the two cities, during a standard thiopentone-fentanyl-nitrous oxide (60–70%) — isoflurane 0.5% end-tidal anaesthetic. Train-of-four stimulation was applied every 20 sec to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 0.1 mg · kg^?1, was given as a bolus, and neostigmine, 0.04 mg · kg^?1, was administered, with atropine 0.02 mg · kg^?1, at 25% first twitch height recovery. Onset time to maximum blockade was (mean ± SD) 3.9 ± 1.3 min in Paris vs 4.5 ± 1.3 min in Montréal (NS). Duration from injection to 25% first twitch recovery was shorter (28.5 ± 6.8 min) in Paris than in Montréal (39.1 ± 7.3 min) (P < 0.0001). Time from injection of neostigmine to a train-of-four ratio of 70% was not different in Paris (6.3 ± 2.2 min) from Montréal (5.6 ± 1.9 min). It is concluded that the duration of an “intubating” dose of vecuronium is longer in Montréal, but, when given at 25% first twitch recovery, neostigmine has the same efficacy in Montréal as in Paris.     

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.     

Different properties of the bradycardia produced by neostigmine and edrophonium in the cat

Purpose

The bradycardia produced by neostigmine and edrophonium was examined according to its relation to cholinesterase inhibition and to its sensitivity to block by muscarinic receptor antagonists. For comparison, the ability of muscdrinic antagonists to block the bradycardia produced by electrical stimulation of the vagus nerve was determined.

Methods

Cats were anaesthetized, vagotomized and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. The right vagus nerve was isolated for electrical stimulation. The muscarinic antagonists used were atropine, glycopyrrolate, pancuronium, gallamine, and AFDX-116.

Results

Neostigmine produced a dose-dependent decrease in cholinesterase activity which, reached a plateau at a cumulative dose of 0.16 mg · kg^?1 (ED₅₀ 0.009 ± 0.003 mg · kg^?1). Neostigmine produced a dose-dependent decrease in heart rate with the. dose-response relationship (ED₅₀ 0.1 ± 0.01 mg · kg^?1; P = 0.0006) shifted to the right of that for the inhibition of cholinesterase activity. In contrast to the anticholinesterase effect, the bradycardic effect did not reach a plateau and continued to increase even at doses at which the cholinesterase inhibition was maximal. The maximal decrease in heart rate when the heart was still in sinus rhythm was by 81 ± 13 bpm (49 ± 7% of baseline), which was produced by a dose of 0.32 mg · kg^?1. Edrophonium produced dose-dependent decreases in cholinesterase activity and heart rate, which were highly correlated (correlation coefficient r = 0.99, P < 0.0001).The ED₅₀ of the reduction in heart rate (0.9 ± 0.75 mg · kg^?1) and cholinesterase activity (0.89 ± 0.12 mg · kg^?1) produced by edrophonium were similar. Moreover, the reduction in heart rate and cholinesterase activity produced by edrophonium reached a plateau at the same dose (6.4 mg · kg^?1). At this dose, heart rate decreased by 22 ± 2 bpm (14.6 ± 0.9% of baseline). Compared to the bradycardia produced by stimulation of the vagus nerve, that produced by neostigmine was blocked by muscarinic antagonists at significantly lower doses while that produced by edrophonium was blocked at similar doses.

Conclusions

The neostigmine-induced bradycardia is poorly correlated with cholinesterase inhibition compared to that produced by edrophonium, and has a higher sensitivity to muscarinic receptor antagonists compared to that produced by edrophonium or vagus nerve stimulation. These results are consistent with the hypothesis that the neostigmine-induced bradycardia is, in pari, the result of neostigmine directly activating cholinergic receptors within the cardiac parasympathetic pathway. The bradycardia produced by edrophonium may be accounted for solely by an anticholinesterase action.     

Quantifying the effect of enflurane on atracurium infusion requirements

The present study was designed to evaluate the interaction between atracurium and enflurane in 40 adult surgical patients using closed-loop feedback control of infusions of atracurium. Anaesthesia was induced with thiopentone and fentanyl and intubation was facilitated with atracurium 0.5 mg· kg^?1 lean body mass. During the first 90 min, anaesthesia was maintained with nitrous oxide in oxygen (2:1) and fentanyl. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: Group I, control, fentanyl-nitrous oxide anaesthesia; Group II, enflurane 0.3%-nitrous oxide; Group III, enflurane 0.6%-nitrous oxide; Group IV, enflurane 0.9%-nitrous oxide. The possible interaction of atracurium with enflurane was quantified by determining the asymptotic steady-state rate of infusion (I_ss) of atracurium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirements. Every patient served as his/her own control and the changes in the infusion rates were determined individually. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular blockade constant at the setpoint, did not differ among groups. In Group II I_ss decreased from 0.33 ± 0.12 to 0.26 ± 0.08 mg· kg^?1· hr^?1 (P < 0.01), in Group III from 0.32 ± to 0.12 to 0.24 ± 0.08 mg· kg^?1· hr^?1 (P < 0.001) and in Group IV from 0.29 ± 0.09 to 0.21 ± 0.09 mg· kg^?1 · hr^?1 (P < 0.001). In the control group atracurium requirements remained unchanged throughout the study. Enflurane reduces atracurium requirements in a dose-dependent manner. During enflurane anaesthesia the rate of atracurium infusion should be reduced but because of interindividual differences the monitoring of the neuromuscular function is important to ensure the appropriate level of neuromuscular block.     

Monitoring orbicularis oculi predicts good intubating conditions after vecuronium in children

Purpose

The aim of the study was to compare visual estimation of onset of neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis oculi (OO) in children and to determine if monitonng the OO could predict good intubating conditions during vecuronium-induced neuromuscular blockade.

Methods

Thirty ASA I–II children (1.5–9 yr) were studied. Anaesthesia was induced with 6–8 mg · kg^?1 thiopentone. The ulnar nerve at the wrist and the temporal branch of the facial nerve were stimulated every 10 sec using train of-four (TOF) stimuli. Vecuronium. 0.15 mg · kg, was administered as a bolus. The responses at both the OO and the AP were evaluated visually. Patients were randomly divided into two groups. In the AP group (n = 15), the trachea was intubated when the AP was completely blocked. In the OO group (n = 15), intubation was performed when the OO was completely blocked. Intubating conditions were scored on a scale of 1 to 4.

Results

All the patients had complete blockade at both the orbicularis oculi and the adductor pollicis. In the two groups, time from injection of vecuronium to complete neuromuscular blockade was shorter at the orbicularis oculi than at the adductor pollicis, 1.5 ± 0.5 min vs 2.3 ± 0.7 min, respectively, (P < 0.05; mean ± SD) in the AP group, 1.7 ± 0.3 min vs 2.3 ± 0.8 min, respectively, in the OO group (P < 0.05). Intubating conditions were excellent in all patients except one. where it was rated as good. They did not differ between groups.

Conclusion

Following administration of 0.15 mg · kg^?1 vecuronium in children, monitoring of the OO can detect good intubating conditions 0.7 min earlier than with monitoring of the AP.     

Smoking increases the requirement for rocuronium

Purpose

To compare the potency of rocuronium in non-smokers and smokers during general anaesthesia.

Methods

In a randomized, open clinical study, 40 patients, 17–62 yr of age, were anaesthetized with propofol, alfentanil and nitrous oxide in oxygen. After obtaining individual dose-response curves for rocuronium, bolus doses of rocuronium were given to maintain neuromuscular block at 90–99% for 60 min. Evoked adductor pollicis electromyography (EMG) was used to monitor neuromuscular block.

Results

The ED₉₅ values (± SEM) for rocuronium were 460.5 ± 28.9 and 471.5 ± 22.1 μg·kg^?1 for nonsmokers and smokers, respectively (P:NS). However, doses of rocuronium to maintain 90–99% neuromuscular block (± SEM) were 620.1 ± 46.7 and 747.4 ± 56.0 μg·kg^?1·hr^?1 for non-smokers and smokers, respectively (P = 0.0504).

Conclusion

The results may indicate increased metabolism of rocuronium in smokers rather than increased requirement of rocuronium at the receptor site.     

Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide-halothane anaesthesia

Rocuronium bromide (Zemuron) is a new steroidal nondepolarizing neuromuscular blocking drug. We were interested in determining the effect of a bolus of rocuronium in infants during halothane anaesthesia as we did previously in older children. Eighteen infants (2-11 months) received a bolus of 600 μg·kg^?1, which is equal to twice the dose of rocuronium estimated to produce 95% depression of neuromuscular function (ED₉₅) in children (2-12 yr). Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Time (mean ± SEM, range) from administration of 600 μg·kg^?1 rocuronium to 90% (B₉₀) and 100% (B₁₀₀) neuromuscular block was 37 ± 2 (20-60) s and 64 ± 10 (20-180) s, respectively. The time to recovery of neuromuscular transmission to 10% (T₁₀) was 35.3 ± 3.0 (20.7-57.8) min and to 25% of baseline (T₂₅) was 41.9 ± 3.2 (24.3-67.7) min. The recovery index (T₂₅-T₇₅) was 26.6 ± 2.7 (11.7-44.5) min, and the time to recovery of the train-of-four ratio (T₄/T₁) ± 0.75 was 82.1 ± 6.9 (53.2-138.3) min. The plasma concentration of rocuronium when T₁ had recovered to about 30% was 654 ± 34 (417-852) ng·ml^?1 which is similar to that observed in children. Six-hundred μg·kg^?1 of rocuronium has a rapid onset of effect in infants and prolonged duration of action in infants compared to children.     

Pancuronium dose-response revisited

We were interested in determining the cumulative dose-response relationship of pancuronium in infants and children during nitrous oxide–halothane anaesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10 s intervals. Forty patients were divided into four equal groups according to age: 3–6 months, 7–12 months, 13–47 months and 48–83 months. The effective dose, ED₅₀ (mean ± SEM), of pancuronium in these age groups was 24 ± 2, 30 ± 2, 34 ± 3, 29 ± 2 μgμkg^-1, respectively; the ED₉₅ (mean ± SEM) was 45 ± 2, 52 ± 3, 62 ± 6, 62 ± 4 μgμkg^-1, respectively. The ED₉₅ of pancuronium was significantly less (P < 0.05) for infants from 3 to 6 months of age than for children from 13 to 83 months of age. Infants thus appear to be more sensitive than children to the neuromuscular blocking effects of pancuronium during halothane anaesthesia.     

Speed and ease of tracheal intubation: priming with mivacurium compared with succinylcholine

This study examined the efficacy of mivacurium priming (0.015 mg · kg^?1) with five minutes between the priming and intubating doses by comparing the effects of one, two and three times the ED₉₅ dose (0.075 mg · kg^?1) of mivacurium after priming (Groups 1, 2 and 3, respectively), with a saline prime and 2 × ED₉₅ mivacurium (Group 4) or 1 mg · kg^?1 dose of succinylcholine (Group 5). The time from the intubating dose injection to intubation was measured and intubating conditions were rated on a five-point scale with 4 being optimal and 0 being failure. Mean times (± SEM) in seconds between the administration of the intubating dose and tracheal intubation were: 106.4 ± 5.1, 89.6 ± 6.7, 81.9 ± 2.7, 169.9 ± 7.8 and 82.9 ± 3.5 for Groups 1–5 respectively. The times for Group 2 (2 × ED₉₅ with priming), Group 3 (3 × ED₉₅ with priming) and Group 5 (succinylcholine with saline) were shorter than the times of Groups 1 (1 × ED₉₅ with priming) and 4 (2 × ED₉₅ with saline) P < 0.05. Mean intubating condition scores (± SD) for the five groups respectively were 3.1 ± 0.6, 3.4 ± 0.6, 3.5 ± 0.5, 3.2 ± 0.6 and 3.8 ± 0.4. Scores for Groups 2, 3 and 5 were higher than those of Group 1 (P < 0.05). The data demonstrated that (1) priming with mivacurium shortens the intubation time and is accompanied by good intubating conditions with doses 2× and 3× ED₉₅, and (2) intubating times and conditions similar to those achieved with succinylcholine can be obtained using mivacurium 2× (total dose 0.150 mg · kg^?1) or3 × ED₉₅ (total dose 0.215 mg · kg^?1) with a five-minute priming interval. Priming provides an alternative technique in those clinical circumstances where succinylcholine is contraindicated.     

Prolonged duration of succinylcholine in patients receiving anticonvulsants: evidence for mild up-regulation of acetylcholine receptors?

Succinylcholine (SCh) normally causes a small increase in serum potassium concentration, but certain conditions may predispose to severe hyperkalaemia. This is due to “up-regulation” of skeletal muscle acetylcholine receptors (AChR), which also results in resistance to non-depolarizing muscle relaxants (NDMR). Anticonvulsant therapy causes NDMR resistance because of sub-clinical blockade, and diminished release, of acetylcholine. We studied nine patients chronically receiving anticonvulsants (phenytoin and /or carbamazepine) and nine control patients. Anaesthesia was induced typically with thiopentone or propofol; isoflurane and N₂O were used for maintenance. The ulnar nerve was supramaximally stimulated and mechanical twitch height was measured with a force transducer at the adductor pollicis, before and after SCh 1 mg · kg^{? 1}, until return to baseline height. Plasma potassium concentration was measured before and at three, five, and ten minutes following SCh. Mean maximum potassium rise was 0.2 mEq · L^{? 1} in each group. The time for return to baseline twitch height was 14.3 ± 2.3 min (mean ± SD) in the anticonvulsant group and 10.0 ± 1.6 min in the control group, P = 0.001. The recovery index (time for 25% to 75% recovery) was 2.6 ± 0.9 min in the anticonvulsant group and 1.4 ± 0.3 min in the control group, P < 0.01. The normal potassium response coupled with prolonged duration suggests a hypersensitivity to SCh that is consistent with an anticonvulsant-induced mild upregulation of AChR.     

ATRACURIUM AND VECURONIUM: EFFECT OF DOSE ON THE TIME OF ONSET

The time intervals measured from the administrations of eitheratracurium or vecuronium to maximum or 95% neuromuscular blockade(T_max) were compared in 70 patients using the evoked compoundaction potential of the adductor pollicis muscle. Equipotentdoses, calculated from the relationship between dose and responsefor both drugs obtained in an earlier study, were compared.The doses of atracurium and vecuronium ranged from 0.135 to0.5 mg kg^–1 and from 0.02 to 0.1 mg kg^–1, respectively.The dose range for both drugs included the ED₅₀, ED₉₅ and thedose required to produce 100% blockade (ED_"100"). No significantchanges in mean T_max occurred for doses of atracurium in therange 0.135–0.2 mg kg^–1 and in the range 0.24–0.5mg kg^–1. Similarly, no change in T_max occurred at dosesof vecuronium in the range 0.02–0.05 mg kg^–1 and0.06–0.1 mg kg^–1. T_max, changed significantly inthe dose ranges atracurium 0.2–0.24 mg kg^–1 andVecuronium 0.05–0.06 mg kg^–1. There was no significantdifference in T_max when equipotent doses of atracurium and vecuroniumwere compared.     

Pharmacodynamic behaviour of rocuronium in the elderly

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I– II patients (60, âgéd 65–80 yr, and 40, âgéd 20–45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N₂O/O₂ and fentanyl, rocuronium 120,160, 200, or 240 μg · kg ^?1 was administered to determine dose-response curves. When maximum block had been obtained,further rocuronium to a total of 300 μg · kg ^?1 was given. Additional doses of 100 μg · kg^?1 were administered when the first twitch height (T₁) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T₁ was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED₅₀ was 196 ±8 (SEE for the mean) in elderly,vs 215 ±17 iμg · kg ^{? 1} in young patients (NS). When individual cumulative dose-response curves were constructed, the ED₅₀ was 203 ± 7(SEM) and 201 ± 10 μg · kg ^{? 1} in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 ±1.1 (SD) vs 3.1 ± 0.9 min, P < 0.05). The time to 25% T ₁ recovery was longer in the elderly (11.8 ± 8.1 vs 8.0 ± 6.5 min,P <0.05) as was the recovery index, time from 25 to 75% T₁ recovery (15.5 ± 6.2 vs 11.2 ± 4.9 min, P< 0.05). The duration of neuromuscular block after each maintenance dose was longer in the elderly (P <0.01) and increased gradually with time. It is concluded that rocuronium is an intermediate-acting neuromuscular blocking drug with a similar potency in elderly and young patients, but the onset and recovery of neuromuscular blockade are slower in the elderly.