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.     

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.     

Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia

Purpose

To determine the magnitude of the potentiation of rocuronium by desflurane, isoflurane and sevoflurane 1.5 MAC anaesthesia.

Methods

In a prospective, randomised, study in 80 patients, the cumulative dose-effect curves for rocuronium were determined during anaesthesia with desflurane, sevoflurane and isoflurane (with N₂O 70%, 15 min steady state) or total intravenous anaesthesia (TIVA) using propofol/fentanyl. Neuromuscular block was assessed by acceleromyography (TOF-Guard®) after train-of-four (TOF) stimulation of the ulnar nerve (2Hz every 12sec, 200 μsec duration), Rocuronium was administered in increments of 100 μg·kg^?1 until first twitch (T₁) depression > 95%.

Results

Rocuronium led to more pronounced T₁ depression with desflurane or sevoflurane anaesthesia than with TIVA. The ED₅₀ and ED₉₅ were lower during desflurane (95 ± 25 and 190 ± 80 μg·kg^?1) and sevoflurane (120 ±30 and 210 ± 40 μg·kg^?1) than with TIVA (150 ± 40 and 310 ± 90 μg·kg^?1) (P < .01), while the difference was not significant for isoflurane (130 ± 40 and 250 ± 90 μg·kg^?1). Following equi-effective dosing (T₁ > 95%) the duration to 25% T₁ recovery, recovery index (25/75), and TOF_0.70 was: 13.2 ± 1.8, 12.7 ± 3.4, and 26.9 ± 5.7 min during anaesthesia with desflurane; 15.5 ± 5.0, 11.4 ± 3.8, and 31.0 ± 6.0 min with sevoflurane; 13.9 ± 4.7, 10.7 ± 3.3, and 26.3 ± 8.9 min with isoflurane; and 13.9 ± 3.9, 11.3 ± 5.7, and 27.5 ± 8,2 min with TIVA anaesthesia (P: NS).

Conclusion

Interaction of rocuronium and volatile anaesthetics resulted in augmentation of the intensity of neuromuscular block but did not result in significant effects on duration of or recovery from the block.     

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.     

Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

Purpose

To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery.

Methods

Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 × ED₉₀ rocuronium (0.6 mg·kg^?1; n = 20) or atracurium (0.5 mg·kg^?1; n = 21) during intravenous propofol/alfentanil anaesthesia with N₂O/O₂ ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers.

Results

Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 ± 22.2vs 98.6 ± 41.4 sec;P < 0.001) and clinical duration of action (33.3 ± 7.1vs 44.7 ± 7.2 min;P < 0.001), but longer spontaneous recovery index (9.6 ± 2.41vs 6.9 ± 1.89 min;P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 ± 6.31vs 59.2 ± 7.59 min;P =0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck.

Conclusion

Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

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.     

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.     

Comparison of reversal with neostigmine of low‐dose rocuronium vs. reversal with sugammadex of high‐dose rocuronium for a short procedure

Some short procedures require deep neuromuscular blockade, which needs to be reversed at the end of the procedure. Forty‐four patients undergoing elective laryngeal micro‐surgery were randomly allocated into two groups: rocuronium 0.45 mg.kg^?1 with neostigmine (50 μg.kg^?1 with glycopyrrolate 10 μg.kg^?1) reversal (moderate block group) vs. rocuronium 0.90 mg.kg^?1 with sugammadex (4 mg.kg^?1) reversal (deep block group). The primary outcome was the intubating conditions during laryngoscopy secondary outcomes included recovery of neuromuscular block; conditions for tracheal intubation; satisfaction score as determined by the surgeon; onset of neuromuscular block; and postoperative sore throat. The onset of neuromuscular block was more rapid, and intubation conditions and ease of intra‐operative laryngoscopy were more favourable, and the satisfaction score was lower in the moderate block group compared with the deep block group. No difference was found in the incidence of postoperative sore throat. In laryngeal micro‐surgery, the use of rocuronium 0.9 mg.kg^?1 with sugammadex for reversal was associated with better surgical conditions and a shorter recovery time than rocuronium 0.45 mg.kg^?1 with neostigmine.     

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.     

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.     

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.     

Sevoflurane and isoflurane impair edrophonium reversal of vecuronium-induced neuromuscular block

Purpose

A dose-response relationship study for edrophonium to examine the modification of volatile anaesthetics on reversal of vecuronium block.

Methods

One hundred and twenty ASA (I–II) patients were anaesthetized with sevoflurane, isoflurane (I minimum alveolar anaesthetic concentration [MAC] end-tidal concentration), or fentanyl-diazepam anaesthesia, in combination with 66% nitrous oxide (n = 40 for each group). The evoked electromyogram (EMG) response of the abductor digiti minimi was monitored at 20 sec intervals following train-of-four (TOF) stimulation of the ulnar nerve. The initial neuromuscular block was produced by vecuronium 100 μg · kg^?1. When the amplitude of the first response (T₁) had spontaneously recovered to 10% of the control, edrophonium (0, 125, 400, 700 or 1000 μg · kg^?1; eight patients each) was randomly administered, and the ratio of the fourth TOF to the first response (TOFR ) was monitored at one minute intervals for 10 min.

Results

Sevoflurane and isoflurane impaired the edrophonium-assisted TOFR recovery in an edrophonium dose and time dependent manner. The dose-response curves at 10 min exhibited a greater shift to the right in the sevoflurane and isoflurane groups than in the fentanyl-diazepam-nitrous oxide group (P < 0.05). Higher ED₅₀ values (the edrophonium dose required to obtain TOFR value of 50%) in the sevoflurane (> 1000 μg · kg^?1) and isoflurane groups (851 · μg · kg^?1) were observed than in the fentanyl-diazepam-nitrous oxide group (339 μg · kg^?1) (P < 0.05).

Conclusion

One MAC sevoflurane and isoflurane anaesthesia impair edrophonium reversal of vecuronium block to a similar degree.     

COMPARISON OF THE TRAIN-OF-FOUR FADE PROFILES PRODUCED BY VECURONIUM AND ATRACURIUM

In this double-blind study, we have allocated randomly 40 ASAI-III patients to one of four groups. After a standard anaestheticinduction, patients received vecuronium 0.08 mg kg^–1 or0.10 mg kg^–1, or atracurium 0.4 mg kg^–1 or 0.5 mgkg^–1. Using an electromyogram (Datex Relaxograph) thetrain-of-four (TOF) response was measured during onset of andrecovery from neuromuscular block. A greater degree of fadeof TOF was observed with atracurium during onset of neuromuscularblock than with equivalent doses of vecuronium. During recoveryof neuromuscular transmission, vecuronium was associated withmore fade than atracurium. The differences in the TOF profilesof these two drugs may be important when judging the adequacyof antagonism of neuromuscular block using the TOF response.     

A comparison between vecuronium and atracurium in myasthenia gravis

We evaluated the effect of vecuronium bromide and atracurium besylate on the train–of–four response in the management of muscle relaxation in 20 patients with myasthenia gravis (MG) who were undergoing thymectomy. We confirmed the safe use of these two non–depolarizing muscle relaxants in MG patients. Vecuronium (0.04 mg–kg^-1) demonstrated a lesser clinical duration than did atracurium (0.2 mg–kg^-1) (38± 19 vs 50 ± 21 min, mean ± s.e.mean). The recovery time for vecuronium patients was shorter than that for atracurium patients (22 ± 18 vs 38± 18 min), but the time until onset of neuromuscular blockade was longer with vecuronium (246 ±105 vs 107 ± 103 s). During spontaneous recovery from neuromuscular relaxation, at Tl/C of 25% and 100%, the train–of–four fade with vecuronium was significantly greater than that with atracurium (0.04 ± 0.02, 0.16 ± 0.03 vs 0.17 ±0.01, 0.83 ± 0.03), suggesting that vecuronium had a greater prejunctional effect than did atracurium.     

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.     

A rapid precurarization technique using rocuronium

Purpose

To evaluate a rapid and time-saving precurarization technique using rocuronium to prevent succinylcholine-induced myalgia.

Method

In a prospective, double blind randomized study, 42 ASA 1–2 patients were assigned to one of three pretreatment groups: 0.01 ml · kg^?1 normal saline, 0.1 mg · kg^?1 atracurium, and 0.1 mg · kg^?1 rocuronium. Anaesthesia commenced with 1.5 μg · kg^?1 fentanyl and 0.5 mg · kg^?1 lidocaine at time zero. Pretreatment was administered 60 sec later, followed by 2.5 mg · kg^?1 propofol. At 90 sec, 1.5 mg · kg^?1 succinylcholine was injected and 30 sec later, the trachea was intubated and the ease of intubation was graded. The patient was observed for the presence and severity of fasciculations. Myalgias were recorded on postoperative days 1, 2 and 7.

Results

The incidence of fasciculations in the rocuronium group (21.4%) was lower (P < 0.001) than atracurium (78.5%) or placebo (92.8%) groups. On postoperative day 1, the incidence of postoperative myalgia in the rocuronium group (14.2%) was less than the placebo group (78.2%;P < 0.002) and atracurium group (85.7%;P < 0.001). The incidence of myalgia in the rocuronium group (7.1%) was lower than in the placebo group (78.5%;P < 0.001) but not different from the atracurium group (42.8%;P = 0.077) on postoperative day 2. On postoperative day 7, there was no difference among the three groups. Fasciculations were related to post-operative myalgia. There was no difference in intubating conditions among the three groups.

Conclusion

Rocuronium pretreatment given just before induction of anaesthesia with propofol reduces fasciculations and succinylcholine-induced myalgia.     

Rocuronium is the best non-depolarizing relaxant to prevent succinylcholine fasciculations and myalgia

Purpose

To determine which non-depolarizing relaxant amongd-tubocurarine, vecuronium, atracurium, mivacurium and rocuronium prevented muscular fasciculations and myalgia following succinylcholine.

Methods

In this double blind randomized study, 120 female patients scheduled for laparoscopic procedures were studied. They were divided into six groups of 20 according to the non-depolarizing pretreatment used: NaCl 0.9%(control), 0.05 mg·kg^?1 d-tubocurarine, 0.01 mg·kg^?1 vecuronium, 0.05 mg·kg^?1 atracurium, 0.02 mg·kg^?1 mivacurium and 0.06 mg·kg^?1 rocuronium. Four minutes after the pretreatment, 1.5 mg·kg^?1 succinylcholine was injected. Side effects of the pretreatment, the presence and magnitude of fasciculations, the ease of tracheal intubation, myalgia 1, 24 and 48 hr after surgery were observed. A Puritan Bennett Date? 221 NMT Relaxograph monitor was used to evaluate the neuromuscular block.

Results

Muscle fasciculations were observed in 19 of the 20 patients in the control group and in 3 of the 20 patients in the rocuronium group, the best of the pretreatments in that aspect. Four patients in the mivacurium group were unable to sustain more than four seconds head-lift after pretreatment (P < 0.05). Tracheal intubation conditions were better and the onset of block was faster and longer after succinylcholine in the control group (P < 0.05). Myalgias were present in 71 % of the patients 24 hr postoperatively and the frequency was not different among the groups.

Conclusion

Among the pretreatments tested, 0.06 mg·kg^?1 rocuronium was the best to prevent muscular fasciculations following succinylcholine injection. In the population studied, pretreatment did not prevent postoperative myalgia. Succinylcholine 1.5 mg·kg^?1 was more effective without a non-depolarizing pretreatment.     

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans andtrans-trans) undergo rapid metabolism by plasma cholinesterase (t_1/2 β<2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5– 10% of control T₁ amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg · kg^{? 1} (Group EDR- 1), 0.25 mg · kg^{? 1} (Group EDR- 2), or 0.50 mg · kg^{? 1} (Group EDR- 3), in addition to a corresponding dose of atropine. 4Spontaneous recovery, from a T₁ response of<10% to a TOF ratio ≥0.7, required 13.5 ± 2.6 min (PLAC Group). In comparison, patients in the EDR- 1 group required 9.2 ± 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of ≥ 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an E^UE^A genotype, whereas the two patients with delayed recovery in the EDR- 1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg · kg^{? 1}) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg · kg^{? 1} provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.     

Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium

We examined the use of neostigmine for reversing shallow (defined as train‐of‐four ratio of 0.5), cisatracurium‐ and rocuronium‐induced neuromuscular block in 112 patients, by use of 0 μg.kg^?1, 10 μg.kg^?1, 20 μg.kg^?1 or 40 μg.kg^?1 dose of neostigmine for reversal. The times from neostigmine administration to train‐of‐four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train‐of‐four ratio of 1.0 was significantly shorter with neostigmine 40 μg.kg^?1 compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train‐of‐four ratio of 0.5–1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 μg.kg^?1 was the most effective at reducing recovery time after neuromuscular blockade.     

Optimum time for neostigmine reversal of atracurium-induced neuromuscular blockade

Purpose

The aim of the study was to determine the optimum time for administration of neostigmine during recovery from atracurium-induced neuromuscular blockade.

Methods

The study comprised 103 patients anaesthetised with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation was induced with atracurium 0.5 mg·kg^?1 and maintained with supplements of 0.15 mg·kg^?1. The ulnar nerve was stimulated with train-of-four (TOF) and double burst stimulation (DBS). Evoked MMG responses were recorded. Patients were randomized to spontaneous recovery (n = 20) or to assisted recovery by neostigmine (0.07 mg ·kg^?1) at varying intervals (6–50 min) from the last atracurium dose (n = 83).

Results

The reversal time (time from administration of neostigmine to TOF ratio 0.7) was always < 13 min, when T₁ (first twitch in TOF) was detectable or when D₁ (first twitch in DBS) was > 5%. Total assisted recovery time (time from last supplemental atracurium dose to TOF ratio 0.7) increased with increasing T₁ and D₁ twitch heights (P < 0.05). The curve fitted to the scattergram with total assisted recovery time vs time from last atracurium supplement to neostigmine administration decreased to reach a minimum after which it increased to approach the line of identity. The minimum of the curve (total assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min after last atracurium supplement. At this time the T₁ and D₁ twitch height averaged 4 and 8% respectively. If prolongation of the minimum total recovery time of 2.5% is accepted, neostigmine can be given at T₁ and D₁ twitch height values of 0 to 8% and 4 to 15%, respectively.

Conclusion

The optimum time for neostigmine administration, taking both the reversal time and total recovery time into consideration, is when 0 < T₁ < 8% or when 5 < D₁ < 15%. Giving neostigmine at more profound degrees of blockade prolongs reversal time, while giving neostigmine later in the recovery phase prolongs total recovery time.