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.     

Cigarette smoking does not affect thiopentone pharmacodynamic or pharmacokinetic behaviour

Purpose

Smoking affects the pharmacodynamic and pharmacokinetic behaviour of several drugs. In smokers, induction of anaesthesia is often stormy. In this study we have determined whether cigarette smoking affected thiopentone pharmacodynamic or pharmacokinetic behaviour during induction of anaesthesia.

Methods

Fifteen smokers and 15 non-smokers, scheduled for elective surgery, were studied. Heart rate, invasive arterial pressures and middle latency auditory evoked potentials were recorded awake and during thiopentone induction (9 mg·kg^?1 lean body mass), before and after tracheal intubation. Blood was sampled up to 24 hr after induction to measure thiopentone plasma concentrations and to calculate pharmacokinetic parameters.

Results

Anaesthesia was adequate in all patients, although haemodynamic intubation response was not blunted. Latencies or amplitudes of middle latency auditory evoked potentials (MLAEP) did not differ between the groups. The postintubation latencies of Nb waves were 48.9 ± 8.1 msec (mean ± SD) in smokers and 48.1 ± 8.5 msec in nonsmokers. Pharmacokinetic data showed no differences between smokers and non-smokers. Clearance of thiopentone was 2.9 ± 1.1 ml·min^?1 ·kg^?1 in smokers and 3.3 ± 1.0 ml·min^?1 ·kg^?1 in non-smokers and elimination half life of thiopentone was 12.5 ± 6.3 hr in smokers and 10.7 ± 3.1 hr in non-smokers, respectively. The haemodynamic response after the induction dose of thiopentone and after tracheal intubation were similar in smokers and non-smokers. Mean postintubation systolic arterial pressures were 192 ± 35 vs 189 ± 20 mmHg and mean postintubation heart rates were 103 ± 12 vs 102 ± 17 beat per minute (bpm) in smokers and non-smokers, respectively.

Conclusion

We conclude, that cigarette smoking does not affect the pharmacodynamic or pharmacokinetic behaviour of thiopentone.     

Prolonged mivacurium infusion in young and elderly adults

Purpose

This study was designed to evaluate phanmacodynamically and phamnacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients.

Methods

The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18–59 yr. and 19 elderly (> 60 yr.) patients dunng N₂O:O₂:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 ± 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response.

Results

The mean mivacurium infusion requirement to maintain 97 ± 1 (mean ± SD)% depression of the twitch response was 6.0 ± 0.4 μg· kg^?1· min^?1 in young adults, and 4.3 ± 0.3 μg· kg^?1· min^?1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 ± 1.2 μg· kg^?1· min^?1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with tow cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients.

Conclusion

When the mivacurium infusion was titrated to maintain 95 ± 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.     

Intubating conditions and neuromuscular block after divided dose mivacurium or single dose rocuronium

Purpose

To evaluate the tracheal intubating conditions and neuromuscular blocking charactenstics of divided dose mivacurium or single dose rocuronium.

Methods

Thirty-two patients undergoing elective surgery were studied. Anaesthesia was with propofol 2 mg · kg^?1, followed by an infusion of l50 μg · kg^?1 · min^?1. Patients were randomized to receive either mivacurium-0.15 mg · kg^?1 followed 30 sec later by 0.1 mg · kg^?1, or rocuronium-0.9 mg · kg^?1, followed 30 sec later by placebo. Tracheal intubating conditions were assessed 90 sec after the initial dose of relaxant by an anaesthetist who was unaware of patient group. The electromyographic (EMG) response of the first dorsal interosseus muscle to ulnar nerve train-of-four was measured.

Results

Successful tracheal intubation was performed in all patients after both mivacurium and rocuronium. Intubating conditions (jaw relaxation, open visible vocal cords) were judged to be good-excellent in all but one patient before insertion of the tracheal tube. However, patients receiving mivacunum were more likely to experience coughing and bucking after tracheal tube insertion (10/16 patients) than those receiving rocuronium (3/16 patients, P < 0.05). No patient in the rocuronium group experienced moderately vigorous coughing and bucking after insertion of the tracheal tube vs six patients in the mivacurium group (P < 0.05). Time to 10 and 25% recovery of neuromuscular function was faster (P < 0.05) after divided dose mivacunum (20 ± 1 and 23 ± 1 min, respectively) than after rocuronium (45 ± 5 and 57 ± 8 min, respectively).

Conclusion

The results suggest that, during conditions of the study, divided dose mivacurium is not recommended for a 90-sec tracheal intubation in patients where moderate coughing and bucking is deemed unacceptable.     

Excellent intubating conditions with remifentanil–propofol and either low-dose rocuronium or succinylcholine

Purpose

The shortest time to tracheal intubation, the best intubating conditions, and the shortest duration of muscle paralysis are achieved with succinylcholine. During a lidocaine–remifentanil–propofol induction of anesthesia, we compared intubating conditions 90 s after administering low-dose rocuronium (0.3 mg · kg^?1) with intubating conditions 60 s after administering succinylcholine 1.5 mg · kg^?1.

Methods

The randomized double-blind study included 184 healthy adult patients scheduled for elective surgery. Anesthesia was induced in all patients with lidocaine 1.5 mg · kg^?1, remifentanil 2 μg · kg^?1, and propofol 2 mg · kg^?1 administered over 30 s. In one group, rocuronium 0.3 mg · kg^?1 was administered before the induction sequence, and in the other group, succinylcholine 1.5 mg · kg^?1 was administered after the induction sequence. Laryngoscopy was attempted 90 s after rocuronium administration and 60 s after succinylcholine administration. Intubating conditions were assessed as excellent, good, or poor on the basis of ease of laryngoscopy, position of the vocal cords, and reaction to insertion of the tracheal tube and cuff inflation.

Results

There were 92 patients per group. In the rocuronium group, intubating conditions were excellent in 83 patients (90%), good in 8 (9%), and poor in 1 (1%), not significantly different from the intubating conditions in the succinylcholine group, which were excellent in 88 patients (96%), good in 3 (3%), and poor in 1 (1%) (P = 0.3).

Conclusion

During a lidocaine–remifentanil–propofol induction of anesthesia, rocuronium 0.3 mg · kg^?1 administered before the induction sequence provides intubating conditions comparable to those achieved with succinylcholine 1.5 mg · kg^?1 administered after the induction sequence.     

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.     

Rocuronium prevents succinylcholine-induced fasciculations

Purpose

The aim of this study was to assess the effect of rocuronium pretreatment at 3 and 1.5 min before succinylcholine administration on fasciculations, neuromuscular blockade and intubating conditions.

Methods

Sixty ASA I or II adults scheduled for elective surgery were anaesthetised with midazolam, fentanyl, propofol, N₂O and isoflurane. They were randomised in a double blind manner into three groups: group ROC-3 min (n = 22) received 0.05 mg·kg^?1 rocuronium, 3 min before 2 mg·kg^?1 succinylcholine; group ROC-1.5 min (n = 20) received 0.05 mg·kg^?1 rocuronium 1.5 min before 2 mg·kg^?1 succinylcholine; and group NO ROC (n = 18) had no rocuronium before injection of 2 mg·kg^?1 succinylcholine. Fasciculations and intubating conditions were evaluated by the same physician who was unaware of the randomisation. Neuromuscular block was measured at the adductor pollicis with an accelerometer.

Results

The incidence of fasciculations was lower in the ROC-3 min (9%) and ROC-1.5 mm (30%) groups than in the NO ROC group (83%;P < 0.001 ). The intensity of fasciculations was also less in both pretreatment groups. No statistical difference was noted between pretreatment at 3 and 1.5 min. Intubating conditions, onset time and duration of succinylcholine blockade were comparable in all three groups.

Conclusion

The incidence and severity of succinylcholine fasciculations can be reduced by giving 0.05 mg·kg^?1 rocuronium either 1.5 min or 3 min before succinylcholine. The effects of 2 mg·kg^?1 succinylcholine with rocuronium pretreatment, and 1 mg·kg^?1 succinylcholine, without pretreatment, are similar with respect to intubating conditions, onset of paralysis and duration of blockade.     

Residual neuromuscular blockade after cardiac surgery: pancuroniumvs rocuronium

Purpose

To determine the incidence of residual neuromuscular blockade after cardiac surgery in patients receiving either rocuronium or pancuronium for muscle relaxation.

Methods

In a prospective, controlled, double-blind study, 20 patients undergoing coronary artery bypass were randomized to receive either rocuronium (n= 10) or pancuronium (n = 10) dunng surgery. Anaesthesia was induced with sufentanil, benzodiazepine and propofol or ketamine, and maintained with air/O₂/sufentanil/isoflurane. Neuromuscular blockade was induced with 0.1 ml·kg^?1 from blinded synnges containing rocuronium (6 mg·ml^?1) (Group R) or pancuronium (I mg·ml^?1) (Group P). Relaxants were administered according to clinical criteria and reversal agents were not given. After surgery, neuromuscular transmission was assessed by train-of-four stimulation of the ulnar nerve/adductor pollicis EMG (Datex Relaxograph). Mean values from three trains of stimuli were recorded and repeated 30 min later if TOF ratio was < 0.7. Time to extubation was recorded.

Results

On arrival in the ICU, nine of 10 patients in group R but only three of 10 patients in group P demonstrated four visible responses (P < 0.05). Mean TOF ratio in group P, 0.03 ± 0.05, was less than in group R, 0.68 ± 0.34 (P < 0.001). All patients in group P and 4 of 10 patients in group R had TOF ratio < 0.7 (P = 0.01). Time to extubation in group P (median 18, range 6–48 hr) was not statistically different from that in group R (14, 5–44 hr).

Conclusion

Residual neuromuscular block, TOF ratio < 0.7, is common after cardiac surgery but the incidence is less when pancuronium is replaced by rocuronium.     

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.     

Ketamine, but not priming, improves intubating conditions during a propofol–rocuronium induction

Purpose

Both ketamine and priming may shorten the onset time of rocuronium. This study investigates the effects of ketamine and priming as components of a propofol induction on intubating conditions and onset of neuromuscular block.

Methods

This prospective randomized double-blind study was performed in 120 American Society of Anesthesiologists (ASA) I–II patients who were assigned to one of four groups of 30 patients each: control, priming, ketamine, and ketamine-priming. Ketamine 0.5 mg ? kg^?1 or saline was given before priming and induction. Rocuronium 0.06 mg ? kg^?1 or saline was injected 2 min before propofol 2.5 mg ? kg^?1. This was followed by rocuronium 0.6 mg ? kg^?1 or by rocuronium 0.54 mg ? kg^?1 if priming was given. Intubation was performed one minute later. Intubating conditions were graded as excellent, good, or poor. Heart rate, noninvasive blood pressure, and train-of-four (TOF) response were monitored.

Results

Intubating conditions were graded excellent in 20% of the control group, 30% of the priming group, 47% of the ketamine group, and 57% of the ketamine-priming group. Analysis using forward stepwise regression indicated that ketamine improved intubating conditions (P = 0.001) but priming did not (P = 0.35). Time to reach a TOF count of zero was shortened by ketamine (P = 0.001) but not by priming (P = 0.94): 216 ± 20 s in the control group, 212 ± 27 s in the priming group, 162 ± 18 s in the ketamine group, and 168 ± 22 s in the ketamine-priming group.

Conclusion

A low-dose ketamine used with a propofol–rocuronium induction improved intubating conditions and shortened onset time. Priming did not influence intubating conditions or onset time.     

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.     

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.     

Bradycardia produced by pyridostigmine and physostigmine

Purpose

The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists.

Methods

Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M₁ receptors were blocked with hexamethonium and pirenzepine, respectively. M₂ receptors were blocked with gallamine, pancuronium and AFDX-116.

Results

With pyridostigmine and physostigmine, the dose-response relationship for the decrease in heart rate (ED₅₀ 1.05 ± 0.25 and 0.198 ± 0.03 mg·kg^?1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED₅₀ 0.094 ± 0.03 and 0.032 ± 0.01 mg·kg^?1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 ± 0.08 and 0.32 ± 0.08 mg·kg^?1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyndostigmine and physostigmine was blocked by hexamethonium (ED₅₀ 10 ± 1.3 and 15.3 ± 2.4 mg·kg^?1, respectively), pirenzepine (ED₅₀ 68 ± 16 and 138 ± 32 μg·kg^?1. respectively), gallamine (56 ± 11 and 67 ± 17 μg·kg^?1, respectively ), pancuronium (32 ± 10 and 30 ± 4 μg·kg^?1, respectively), and AFDX-116 (31 ± 4 and 28 ± 4 μg·kg^?1, respectively).

Conclusion

The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscannic M₁ and a high sensitivity to muscarinic M₂ receptor antagonists.     

Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery

Purpose

To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery.

Methods

Twenty patients in two equal groups were studied. Anaesthesia was induced with sufentanil and midazolam after a standard premedication. Doxacurium was administered at 3 × ED₉₅ (80μ·kg^?1), and anaesthesia was maintained with 0.5 μg·kg^?1 hr^?1 sufentanil, 0.05 mg·kg^?1 midazolam and isoflurane 0.5–1%. Systemic temperature for patients in the normothermic and hypothermic groups was maintained at 33–36C and 26–30C respectively. Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach.

Results

For the normothermic and hypothermie groups, terminal elimination half-life (t_1/2B) was 100.1 ± 28 and 183.8 ± 60 min (P < 0.05) respectively, elimination half-life during the CPB phase (T_1/2 CPB) 114.5 ± 10 and 183.8 ± 60 min (P < 0.05), mean residence time 108.8 ± 25 and 164.8 ± 34 min (P < 0.05) and apparent volume of distribution at steady state 0.20 ± 0.03 and 0.26 ± 0.04 L·kg^?1 (P < 0.05). Compared with the hypothermie group, the normothermic group had a higher rate of renal clearance (1.40 ± 0.4 vs 0.93 ± 0.3 ml·min^?1·kg^?1;P < 0.05) and a higher value for renal clearance as a percentage of the total clearance (76.2 ± 10 vs 58.3 ± 20%).

Conclusion

The elimination rate of doxacurium during normothermic CPB is faster than that in hypothermic CPB.     

Haemodynamic and electroencephalograph responses to intubation during induction with propofol or propofol/fentanyl

Purpose

To observe the changes in EEG bispectral index (BIS), 95% spectral edge frequency (95% SEF) and median frequency (MF) with haemodynamic changes to intubation during induction with propofol or propofol and 2 μg· kg^?1 fentanyliv.

Methods

Twenty four ASA 1–11 patients were randomized to receive either propofol infusion preceded by normal saline (group P, n= 12) or propofol preceded by 2 μg· kg^?1 fentanyl (group PF, n= 12). Intubation was performed five minutes after maintenance of BIS within 45 ± 5. EEG and haemodynamic variables were recorded at before induction, and before and after intubation.

Results

Haemodynamic responses to intubation were greater in group P than in group PF (P < 0.05). Postintubation SBP, DBP and HR increased, compared with preinduction values, more in group P than in group PF Postintubation BIS values increased from 45.5 ± 3.5 and 44.2 ± 4.1 to 51.1 ± 4.1 and 50.9 ± 5.3 in groups P and PF, respectively, compared with preintubation values. The BIS values were not different between treatment groups before and after intubation, and 95% SEF and MF values did not increase after intubation.

Conclusion

Fentanyl, 2 μg· kg^?1 iv, blunted the haemodynamic responses to intubation, but failed to attenuate the arousal of cerebral cortical activity. The different haemodynamic responses postintubation but similar BIS and 95% SEF changes in the two groups suggest that BIS or 95% SEF cannot predict the haemodynamic responses to intubation during anaesthesia induction with propofol and fentanyl.     

Neostigmine requirements for reversal of neuromuscular blockade following an infusion of mivacurium

Purpose

To study the efficacy of neostigmine compared with placebo for the antagonism of neuromuscular blockade at the end of a mivacunum infusion, and to determine its optimal dose.

Methods

One hundred adult patients undergoing an elective surgical procedure received a standardized anaesthetic with 20–30 mg·kg^?1 alfentanil, a propofol infusion and nitrous oxide. Muscle relaxation was maintained at 90–95% T1 depression with 0.2 mg·kg^?1 mivacunum followed by an infusion. Neuromuscular blockade was measured with an integrated evoked electromyogram in response to train-of-four (TOF) stimuli at the ulnar nerve every 20 sec. Patients were randomized into four groups. At the end of surgery, the mivacunum infusion was stopped and patients received. immediately, in a double-blind manner, neostigmine (10, 20. or 40 mg·kg^?1) or placebo according to a random number table. The Tl and TOF ratio were recorded until adequate recovery of neuromuscular function (TOF ratio > 0.70). During the reversal penod, non-invasive blood pressure and heart rate were recorded every minute. The incidence of postoperative nausea and vomiting (PONV) was recorded in the recovery room.

Results

Data from 94 patients who completed the protocol were analysed. Compared with placebo, neostigmine 10 gmg·kg did not reduce the time to TOF > 0.70 (17.0 ± 5.1 vs 14.6 ± 4.2 mm respectively). However the time was decreased with neostigmine 20μg·kg and 40 μ·?^?1 (P < 0.001), but with no difference between these last two groups (11.4 ± 3.0 and 11.4 ± 3.5 min respectively). Changes in systolic blood pressure and heart rate were not different between the four groups. Very few PONV events were observed in all groups (global incidence 7.4%).

Conclusion

Recovery of neuromuscular blockade following a mivacunum infusion is accelerated by neostigmine. A dose of neostigmine 20μ·kg^?1 appears optimal with no further reduction in recovery time obtained from a larger dose.     

The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized,multicentre trial

Background

Succinylcholine provides rapid onset of neuromuscular blockade and short duration of action, but its administration may be associated with hyperkalemia. Rocuronium is not known to increase potassium concentration, has fast onset of activity, and can be rapidly reversed by sugammadex. This study evaluated changes in plasma potassium concentrations in patients randomized either to rocuronium followed by sugammadex reversal or to succinylcholine in ambulatory surgery.

Methods

In this multicentre randomized active-controlled study, adult patients undergoing short surgical procedures in an outpatient setting received either rocuronium 0.6 mg·kg^?1 for intubation with sugammadex 4.0 mg·kg^?1 for reversal (n = 70) or succinylcholine 1.0 mg·kg^?1 with spontaneous recovery (n = 80). Blood potassium concentrations were assessed at baseline (before study drug administration) and at intervals up to 15 min after rocuronium, sugammadex, and succinylcholine.

Results

At the primary endpoint, five minutes post-administration, the changes in potassium concentrations from baseline were significantly smaller in patients treated with rocuronium than in those given succinylcholine [mean (SD): ?0.06 (0.32) vs 0.30 (0.34) mmol·L^?1, respectively; P < 0.0001]. At baseline, potassium concentrations were similar in both groups, but they were greater at two, five, ten, and 15 min after succinylcholine than after rocuronium (P < 0.0001) for all time points. After sugammadex administration, there were no significant changes in mean potassium concentration from the pre-rocuronium baseline. No adverse effects related to hyperkalemia were observed.

Conclusion

Succinylcholine was associated with a modest increase in potassium concentration; these changes were not seen after rocuronium or sugammadex (Clinical trial registration number: NCT00751179).     

Low incidence of the oculocardiac reflex and postoperative nausea and vomiting in adults undergoing strabismus surgery

Purpose

To investigate the incidence of the oculocardiac reflex (OCR), and of postoperative nausea and vomiting (PONV) in adults undergoing strabismus surgery.

Methods

Adults (18 86 yr) undergoing inpatient strabismus surgery received 10 μg·kg atropine and 10 μg·kg alfentaniliv and were randomly allocated to: (A) 5 mg·kg^?1 thiopentoneiv, isoflurane/N₂O maintenance; (B) 3 mg·kg^?1 propofoliv. propofol/N₂O maintenance (10–14 mg·kg^?1hr·t-1); © 3 mg·kg^?1 propofoliv, propofol/air/O₂ maintenance (10–14 mg·kg^?1·hr^?1). Analyses were with the number-needed-to-treat/harm.

Results

In 97 adults the absolute nsk of OCR (13–20%) and PONV (21–31% after 24 hr) was low. with no differences between groups. Number-needed-to-treat to prevent PONV with propofol with or without N₂O compared with thiopentone-isoflurane was 7 to 11. Number-needed-to-harm for one OCR with propofol compared with thiopentone-isoflurane was 17.

Conclusion

Adults undergoing strabismus surgery with prophylactic atropine had a low risk of OCR and PONV independent of the anaesthetic technique used.     

Potency and hourly maintenance requirement of combinations of mivacurium and pancuronium in adults

Purpose

To evaluate the dose-response and maintenance requirements of a combination of mivacurium and pancuronium (cMP) in clinical practice.

Methods

In a randomised, open clinical study, 70 patients, 17–50 yr of age, were anaesthetised with propofol, alfentanil and nitrous oxide in oxygen. Thirty patients received mivacurium and 20 patients received pancuronium to establish dose-response curves for these agents. Hourly maintenance requirements of mivacurium and pancuronium to maintain 90–95% neuromuscular blockade (NMB) were determined. Thereafter, 20 additional patients received cMP in incremental doses to establish a cumulative dose-response curve for cMP followed by maintenance doses of cMP NMB was recorded by adductor pollicis electromyography.

Results

The ED₉₅ values for mivacurium and pancuronium were 100 and 66μg·kg^?1, respectively; and for the cMP 2:1 (in mg:mg basis), 32 μg·kg^?1 mivacurium together with 16 μg·kg^?1 pancuronium. This cMP was 1.8 times more potent than one parent agent (P < 0.0001 ). When cMP 2:1 was used, 60% of normal maintenance requirement of pancuronium reduced the requirement of mivacurium by > 90%. If cMP 20:1 was used, then 20% of normal maintenance requirement of pancuronium reduced the requirement of mivacurium by > 70%. Neostigmine 35 μg·kKg^?1 given at T₁ 10% recovery following cMP reversed the NMB to a TOF ratio of 0.70 in 9.5 ±3.9 min.

Conclusion

These results reflect considerable synergism between mivacurium and pancuronium. The cMP is near intermediate-acting and the NMB is easily reversed with neostigmine. By using cMR it may be possible to save some pharmacological costs during maintenance of anaesthesia.     

High-dose dexmedetomidine increases the opioid-free interval and decreases opioid requirement after tonsillectomy in children

Purpose

Dexmedetomidine, a selective α₂ adrenoreceptor agonist, has analgesic and sedative properties, minimal impact on respiratory parameters, and reportedly decreases analgesic requirements after surgery. Given its pharmacodynamic profile, dexmedetomidine might have a role for postoperative pain control in children undergoing tonsillectomy. In this study, we hypothesized that dexmedetomidine would delay and decrease opioid requirements after tonsillectomy.

Methods

In a double-blind controlled trial, participants undergoing tonsillectomy were randomized to receive one intravenous dose of fentanyl (1 μg·kg^?1 or 2 μg·kg^?1) or dexmedetomidine (2 μg·kg^?1 or 4 μg·kg^?1) immediately after endotracheal intubation. Primary outcomes included requirement for rescue morphine in the initial postoperative period.

Results

One hundred and one children were enrolled. During the postoperative period, dexmedetomidine (2 and 4 μg·kg^?1 groups combined) significantly prolonged the opioid-free interval of children who underwent tonsillectomy compared with fentanyl (1 and 2 μg·kg^?1 groups combined) (P < 0.001). Children treated with dexmedetomidine 2 μg·kg^?1 vs dexmedetomidine 4 μg·kg^?1 had similar cumulative incidence curves for time to morphine rescue, whereas there was a small difference in time to first morphine rescue administration when comparing fentanyl 1 μg·kg^?1 vs fentanyl 2 μg·kg^?1. Furthermore, length of stay in the postanesthesia care unit was significantly longer for children treated with dexmedetomidine vs children treated with fentanyl (P = 0.0016).

Conclusions

High-dose dexmedetomidine decreases opioid requirements, prolongs the opioid-free interval after tonsillectomy, and prolongs length of stay in the postanesthesia care unit. It is conceivable that these early opioid-sparing effects could benefit patients at risk for respiratory complications early in the postoperative course after tonsillectomy (e.g., patients with obstructive sleep apnea). (ClinicalTrials.gov number, NCT00654511).