Background and objective: The aim was to compare the effects of two different priming doses and priming intervals with the standard intubating dose of rocuronium on the onset time and intubation conditions.

Methods: After induction of anaesthesia, 75 patients were randomly assigned to one of five groups. Patients in Group 1 received a priming dose of rocuronium 0.06 mg kg−1 followed 2 min later by rocuronium 0.54 mg kg−1, Group 2 received a priming dose of 0.10 mg kg−1 followed 2 min later by a rocuronium injection of 0.50 mg kg−1. Group 3 was given a priming dose of 0.06 mg kg−1 followed 3 min later by administration 0.54 mg kg−1, where Group 4 received a priming dose of 0.10 mg kg−1 followed 3 min later by injection of 0.50 mg kg−1. Group 5 received a placebo injection followed 3 min later by rocuronium 0.60 mg kg−1.

Results: Priming with a 3 min priming interval shortened the onset time of rocuronium irrespective of the dosage of (P < 0.001). Clinical duration of action was significantly longer after priming in Group 4 than in Group 5. Clinically acceptable intubation conditions were obtained in all patients.

Conclusions: Priming with a 3 min priming interval was effective when rapid tracheal intubation with rocuronium was necessary. However, priming with rocuronium should be used carefully with special attention given to the possibility of hypoxia and aspiration of gastric contents in awake patients.

Background and objective: Monitoring of neuromuscular blockade still often relies on clinical judgement. Moreover, there are substantial national differences in the use of agents to 'reverse' their effects. We investigated the recovery characteristics and incidence of postoperative residual curarization after cisatracurium and rocuronium infusions for long duration interventions without systematic antagonism.

Methods: In 30 patients undergoing major surgery, we measured infusion dose requirements for rocuronium and cisatracurium during propofol anaesthesia. Infusions were discontinued at the beginning of surgical closure; spontaneous recovery of neuromuscular function was awaited in both groups. Neostigmine (50 μg kg−1) was administered only when a patient started to wake without a train-of-four ratio (TOF) of 0.9.

Results: In the cisatracurium and rocuronium groups, four (27%) and one (7%) patients, respectively, had a TOF ratio ≥0.9 at the end of surgery. The TOF ratio in each group at that time was 51 ± 32% for cisatracurium and 47 ± 31% for rocuronium (P = 0.78). Six patients (40%) in the cisatracurium group and seven (47%) in the rocuronium group required neostigmine. The TOF ratio at the time of reversal was 63 ± 7% for cisatracurium and 40 ± 19% for rocuronium (P = 0.01). The time interval between the end of surgery and a TOF ratio of 0.9 was 10 ± 9 min for cisatracurium and 18 ± 13 min for rocuronium (P = n.s.).

Conclusions: Patients receiving a cisatracurium or rocuronium infusion have a high incidence of postoperative residual curarization when the block is not antagonized. When ‘reversal’ is not attempted, cisatracurium seems to be safer than rocuronium.

Muscle relaxants are given as part of a rapid-sequence induction to facilitate tracheal intubation. Among all the muscle relaxants available, succinylcholine is the only one with a fast (≅1 min) onset and a fast recovery. Therefore it is still the most frequently used muscle relaxant for rapid-sequence induction despite its well-known side-effects. The short duration of action of succinylcholine is, however, no substitute for aggressive airway management in the case of an unexpectedly difficult intubation in order to prevent life-threatening hypoxia. A preoperative assessment of the airway is mandatory in any patient and may indicate the need for using intubation techniques without a muscle relaxant. Rocuronium in large doses (i.e. ≥1 mg kg−1) is an alternative to succinylcholine in a classical rapid-sequence setting under relatively light anaesthesia. With respect to rapid tracheal intubation, the timing and priming principles offer little advantage over the use of rocuronium in doses of 0.6 mg kg−1 in combination with an appropriate induction technique (i.e. including an opioid) or over the use of larger doses of rocuronium (≥1.0 mg kg−1) under relatively light anaesthesia, and may even be potentially harmful.

In contrast to rocuronium, the use of rapacuronium in a rapid-sequence setting has been associated with dose-dependent respiratory side-effects that limit its usefulness in doses higher than 1.5 mg kg−1 for this indication.

The choice of hypnotics and opioids for rapid-sequence induction, and the use of premedication, is influenced by the choice of the muscle relaxant. Anaesthetic agents have a major influence on the quality of intubation when rapid-sequence induction is achieved without a muscle relaxant. Premedication is important, along with a high dose of propofol (2.5 mg kg−1 or more) and a short-acting opioid such as alfentanil (30–40 μg kg−1) or remifentanil (up to 4 μg kg−1). It has also been demonstrated that i.v. lidocaine can improve intubating conditions. When a muscle relaxant is used, the choice of the anaesthetic agents depends on the onset of action of the relaxant. With a rapid-acting compound such as rocuronium at a dose of 0.6 mg kg−1, the hypnotic agents need to be supplemented with only a small dose of opioids, e.g. alfentanil 10–20 μg kg−1. When succinylcholine, rocuronium 1.0 mg kg−1 or rapacuronium 1.5 mg kg−1 are used, excellent intubating conditions may be obtained by relatively smaller doses of hypnotic agents even without opioids; however, haemodynamic and intraocular pressure changes are better controlled when small doses of opioids are administered.

Neuromuscular blocking agents are used as adjuvants in day case anaesthesia to facilitate tracheal intubation and/or surgery. Although the majority of day case procedures are performed without the use of neuromuscular blocking agents, there are procedures, such as laparoscopic surgery, microsurgery, open eye surgery, some ear, nose and throat procedures and some paediatric procedures, which may require neuromuscular blockade. The characteristics of an ideal neuromuscular blocking agent for day case surgery are a short onset, a short clinical duration and a short recovery time, with or without reversal. It should also lack histamine release, provide haemodynamic stability, and be competitively priced. This paper reviews the neuromuscular blocking agents currently available and used, such as succinylcholine and mivacurium, low doses of an intermediate-acting neuromuscular block, such as rocuronium and the recently introduced rapacuronium. Their advantages and disadvantages are described and discussed, with special reference to the needs of day case surgery. Rapacuronium offers certain benefits compared with the currently available neuromuscular blocking agents for day care anaesthesia.

It has been estimated that more than 60% of all paediatric surgery is performed on a day case basis. The benefits of this type of surgery in children include reduced costs, avoidance of the stress of hospitalization and less disruption to family life. The growth of day surgery in children has been facilitated by the development of non-depolarizing neuromuscular blocking agents characterized by short and intermediate duration of action and fewer side-effects. The more rapid onset and shorter duration of action of non-depolarizing neuromuscular blocking agents in children should facilitate the use of these agents in place of succinylcholine for day case procedures.

Background and objective In the present study, we investigated the combination of etomidate and s-ketamine with regard to its suitability for modified rapid-sequence induction using rocuronium for muscle relaxation.

Methods In a prospective, randomized and double-blinded study, 90 patients were assigned to one of three groups for induction of anaesthesia in combination with etomidate (0.3 mg kg−1) and muscle relaxation with rocuronium (0.6 mg kg−1). The groups were as follows: (a) control, i.e. placebo; (b) fentanyl, fentanyl (1.5 μg kg−1); (c) ketamine, s-ketamine (0.5 mg kg−1). Tracheal-intubating conditions after 1 min were classified as excellent, good or poor. During the induction of anaesthesia, arterial pressure and heart rate were measured every 60 s.

Results Intubating conditions were best using etomidate and s-ketamine (23 excellent, 7 good, 0 poor) compared with the control (8, 16, 6 respectively) and fentanyl groups (7, 21, 2 respectively) (P < 0.01). While heart rate and arterial pressure remained stable in the control and fentanyl groups during induction, both significantly increased in the ketamine group (P < 0.01).

Conclusions The combination of etomidate and s-ketamine for anaesthesia induction produces mostly excellent intubating conditions after 60 s using only 0.6 mg kg−1 of rocuronium. This combination of drugs may be a useful alternative, if succinylcholine needs to be avoided, for modified rapid-sequence induction.

The aim of this study was to elucidate the influence of four neuromuscular blocking substances on coronary vascular tone using the model of isolated porcine coronary artery segments. We studied the effects of four muscle relaxants, atracurium, pancuronium, rocuronium, and vecuronium (0.1, 1, and 10 μg mL−1 each), on the contractile response to three vasoconstrictors: acetylcholine, histamine, and serotonin. None of the neuromuscular blocking agents under investigation exerted a significant influence on the vasoconstricting effects of these mediators except for pancuronium, which dose-dependently attenuated acetylcholine-mediated contractions (−10.8% attenuation for 10 μg mL−1 pancuronium, P < 0.05). There was no difference between vessels with intact endothelium and denuded preparations. It is concluded that high-dose pancuronium exerts an antimuscarinic effect in vascular smooth muscle. The other neuromuscular agents studied do not alter vascular reactivity of isolated porcine coronary arteries.

Following administration of 0.6 mg kg−1 rocuronium, the pharmacokinetics and the pharmacodynamics were studied in six obese and six control (normal weight) patients receiving balanced anaesthesia. Twelve gynaecological patients were allocated into two groups, according to body mass index (normal weight: body mass index: 20–24, obese weight: body mass index > 28). Venous plasma concentrations were determined by high-pressure liquid chromatography before administration of rocuronium, at 1, 2, 4, 6, 8,10, 15, 20, 25, 30, 35, 40, 48, 60, 75, 120, 180, 240, 300, 360 and 420 min after administration of rocuronium and at recovery of single twitch to 25% and 75% of control twitch height. Onset time was shorter (NS) in the obese compared with normal weight (obese weight: 65 ± 16, normal weight: 100 ± 39 s, mean±SD). Duration 25% (obese weight: 29.5 ± 5.3, normal weight: 28.4±5.3 min) and spontaneous recovery time (obese weight: 12.6 ± 2.7, normal weight: 12.5 ± 2.3 min) did not show any differences between the two groups. The pharmacokinetics of rocuronium were comparable in the two groups. The volume of distribution at steady state Vss (mL kg−1) was 208 ± 56 in normal weight and 169 ± 37 in obese weight. Distribution (T1/2α) and elimination half-life (T1/2β) as well as mean residence time were 15.6 ± 3.7, 70.3 ± 23.9 and 53.2 ± 9.8 min in normal weight and 16.9 ± 3.8, 75.5 ± 25.5 and 51.1 ± 18.9 min in obese weight,respectively. Also, no differences were observed in plasma clearance (3.89 ± 0.58 in normal weight and 3.62 ± 1.42 mL kg−1 min−1 obese weight). This study indicates that the pharmoacodynamics and pharmacokinetics of rocuronium are in female patients not altered by obesity.

After an intubating dose of rocuronium satisfactory intubating conditions are achieved before the onset time at the adductor pollicis. We examined the possibility that measurement of the relaxation of the masseter muscle is a more appropriate guide when determining the intubating time. Simultaneous accelerometry with a 0.1-Hz single twitch stimulation of the chin and thumb was performed in 20 patients after 0.6 mg kg=1 rocuronium. We observed a significantly more brief mean lag time and onset time at the masseter muscle (22.5 and 61 vs. 32.5 and 160 s). The corresponding mean relaxation at the onset time was also significantly more pronounced at the masseter muscle (99.6 vs. 97.6%). A mean onset time at the masseter muscle of 61 s as produced by rocuronium corresponds clinically with excellent or good intubating conditions. From these results, we suggest that measurement of the onset time of muscle relaxation at the masseter muscle appears to be a better predictor of good intubating conditions than measurements made using the adductor pollicis muscle after administration of rocuronium.

In order to compare the neuromuscular effects following rocuronium 0.6 mg kg−1 and atracurium 0.5 mg kg−1 30 children aged from 18 to 67 months were studied under the same anaesthetic conditions. After induction of anaesthesia with etomidate and fentanyl, neuromuscular blockade was monitored by recording the electromyographic response of the adductor pollicis muscle to a supramaximal train-of-four (TOF) stimulation of the ulnar nerve at 2 Hz for 2 s at 20-s intervals. Intubation was performed when more than 90% muscle relaxation was achieved, thereafter anaesthesia was maintained with 70% nitrous oxide in oxygen and isoflurane 0.5% end-tidal. Mean onset of action was significantly faster following rocuronium (86±44.9 s) (mean±SD) compared with atracurium (126.3±61.0 s). Clinical duration with rocuronium was 22.8±5.31 min and thus significantly shorter than that of atracurium, which was 31.5±6.01 min. A statistically significant difference between rocuronium and atracurium also had been found for recovery of T1 to 50%, 75% and 90% as well as for the time taken to a TOF ratio of 70%. The recovery index for rocuronium and atracurium was not significantly different with 9.2±3.43 min and 10.9±2.65 min, respectively. Thus, rocuronium may be more advantageous than atracurium for short-lasting surgical procedures in young children.

Rocuronium administration may cause tachycardia and an increase in cardiac index. Pancuronium, another steroidal non-depolarizing muscle relaxant, augments release of, and blocks re-uptake of catecholamines at adrenergic nerve endings. This study compared the haemodynamic effects of, and changes in catecholamine concentrations following administration of vecuronium (0.12 mg kg−1) or rocuronium (0.9 mg kg−1) to elderly patients. Thirty patients, 65 years or older, not receiving β-blockers, were studied. During thiopentone, fentanyl, nitrous oxide anaesthesia, either rocuronium (0.9 mg kg−1) or vecuronium (0.12 mg kg−1) was administered, according to random allocation. In all 30 patients, blood pressure and heart rate were measured before induction of anaesthesia, immediately and 1 min after induction, 1 and 2 min after muscle relaxant administration, and immediately, 1 and 2 min after tracheal intubation. In the latter 20 patients, samples for plasma catecholamine estimation were obtained prior to, and 1 min after muscle relaxant administration and 1 min after tracheal intubation. Blood pressure and heart rate were similar in the two groups throughout the study. Plasma noradrenaline concentrations were similar in the vecuronium and rocuronium groups prior to muscle relaxant administration (589(SD240) and 444(SD213) pg mL−1, respectively), 1 min after muscle relaxant administration (602(SD220) and 520(SD392) pg mL−1, respectively) and 1 min after tracheal intubation (597(SD351) and 440(SD181) pg mL, respectively). There was no significant change in either plasma noradrenaline or adrenaline concentrations in either group following muscle relaxant administration or tracheal intubation. The use of rocuronium (0.9 mg kg−1) in elderly patients does not result in a clinically significant change in heart rate, blood pressure or plasma catecholamine concentration.

The influence of acute moderate haemodilution on the relation between dose and response for rocuronium was evaluated in 60 adult patients, ASA grade I, undergoing elective plastic surgery. The patients were randomly allocated to either the control or the haemodilution group. Following the induction of general anaesthesia, the status of acute moderate haemodilution in the haemodilution group was achieved by draining venous blood, and intravenous infusion of lactated Ringer's solution, 6% dextran or gelofusine, during which the levels of haemoatocrit and haemoglobin dropped from 44% to 27.5% and from 148.3 to 91.3 g L−1, respectively. Neuromuscular function was assessed mechanomyographically with train-of-four stimulation at the wrist every 12 s and the percentage depression of T1 response was used as the study parameter. The relation between dose and response for rocuronium in the two groups was determined by the cumulative dose–response technique. The results showed that the dose–response curve for rocuronium during acute moderate haemodilution was shifted in a parallel fashion to the left and the potency of rocuronium was increased. There were significant differences in ED50, ED90 and ED95 between the two groups. The ED50, ED90 and ED95 of rocuronium in the haemodilution group was decreased by 28.2%, 35.4% and 38.8%, respectively, compared with the control group.

The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during propofol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback controller. At 90% block the steady-state infusion of rocuronium was 0.55 ± 0.16 mg kg−1 h−1 and the corresponding concentration 1714 ± 281 ng mL−1 in patients receiving propofol. At 50% block the corresponding infusion rate was 0.27 ± 0.11 mg kg−1 h−1 and the concentration 1077 ± 244 ng mL−1, respectively. At 50% block isoflurane reduced the rate of infusion by 52% (P < 0.005) and the concentration by 59% (P < 0.001); at 90% block both the mean infusion rate and the concentration of rocuronium were reduced by 35% (P <0.005). The mean rocuronium clearance at 50% block was unaffected by the type of anaesthesia; it was 4.1 ± 1.6 and 4.9 ± 2.7 mL kg−1 min−1 in the groups receiving propofol and isoflurane anaesthesia, respectively. We conclude that isoflurane reduces the infusion requirements of rocuronium by changing the pharmacodynamic behaviour.

The effect of the duration of stabilization of control responses on the onset and duration of clinical relaxation of suxamethonium 1 mg kg−1 and rocuronium 0.6 mg kg−1 were investigated in 90 patients. The control responses were allowed to stabilize for 1, 5, 10, 15 or 20 min prior to administration of rocuronium and for 1, 5, 10 or 15 min prior to suxamethonium. The mean onset time for rocuronium decreased from 150 to 46 s as the duration of stabilization increased from 1 to 20 min (P < 0.001) although the maximal effect was observed within the first 5 min. The average duration of clinical relaxation also increased from 25 to 40 min (P < 0.001). No effect was observed for either variable in the case of suxamethonium.

A general relation between the rate of onset and rate of recovery from non-depolarizing blockade has been demonstrated, with recovery consistently about ten times slower than onset. This observation has led to the suggestion that non-depolarizing agents share a common mechanism of action. Rocuronium, a recently introduced steroidal non-depolarizing agent, is claimed to have a very rapid onset but an intermediate duration and appears to test this hypothesis. To investigate this paradox we have calculated the rates of onset and recovery of rocuronium using the isolated human forearm and compared them with those of pipecuronium. The mean ratio of recovery time/onset time for rocuronium was 31.3, which is significantly greater than that for pipecuronium, 11.6 (P < 0.01). Whilst pipecuronium conforms to the same general relation between onset and offset described previously for other non-depolarizing agents, rocuronium appears to have a disproportionately rapid rate of onset for its rate of recovery. This suggests that onset, recovery, or both onset and recovery, from rocuronium blockade occur in a different manner to that of other non-depolarizing agents.