Summary

Background and objective: The ease of endotracheal intubation has been recently shown to affect the incidence of laryngeal injury. There remains controversy as to whether or not a muscle relaxant is routinely required for tracheal intubation. This study examined conditions of intubation in our routine practice, which employs a relaxant-sparing approach. Methods: All adult patients scheduled for surgery with general anaesthesia were prospectively included. A muscle relaxant was used to facilitate intubation when it was required for the surgical procedure and/or otherwise regarded as necessary by the anaesthesiologist. In the remaining patients, a relaxant-free intubation was performed. Intubating conditions were evaluated in all the patients as well as the post-intubation laryngeal symptoms. Results: Between March and July 2003, 612 patients were consecutively included. A muscle relaxant was used in 32% of patients and no relaxant in the remaining patients (68%). Clinically acceptable intubating scores were observed in 98.4% overall with no significant difference between the two groups. Excellent conditions occurred more frequently in the relaxant group as compared to the relaxant-free group, 87% vs. 72%, P = 0.005. Laryngeal symptoms occurred in 184 (33%) patients with no difference between the two groups. Conclusions: Our relaxant-sparing approach did not increase the incidence of poor conditions of intubation nor laryngeal symptoms. However, excellent conditions occurred more frequently in the relaxant group. A more flexible approach to the issue of the need for neuromuscular blockade prior to intubation is proposed.

Summary

The use of muscle relaxants, considered until recently as common practice in current neurosurgical anaesthesia protocols, becomes increasingly more questionable today. The reasons rely on the evolution of neurosurgery including the advent of new surgical techniques, the evolution of anaesthesia having the benefit of new drugs and devices, and the rationale for using muscle relaxants balanced against their potential side-effects and possible pharmacodynamic alterations in neurosurgical patients.

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 need for a rapid-acting non-depolarizing neuromuscular blocking agent with a short duration of action resulted in the synthesis of rapacuronium. The onset of maximum block with rapacuronium occurs in 60–90 s with doses of 1.5–2.5 mg kg−1 with a duration of clinical relaxation of 15–30 min. Rapacuronium provides clinically acceptable intubating conditions in 60 s in a majority of patients with these doses, although the conditions are somewhat inferior to those obtained with succinylcholine in lightly anaesthetized patients, such as those undergoing a rapid-sequence induction. The main drawbacks of rapacuronium are the occurrence of dose-related pulmonary side-effects (increased airway pressure and/or overt bronchospasm) and hypotension and tachycardia. The cause of pulmonary side-effects is not certain but these have been serious enough to make its worldwide introduction doubtful.

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.

There is some confusion about the contribution of reversal of residual paralysis to the occurrence of postoperative nausea and vomiting. The aim of this review is to discuss whether antagonism of residual paralysis is a cause of postoperative nausea and vomiting, and to assess the risk of residual paralysis if the reversal is omitted. Data from a meta-analysis published before 1998 were considered, along with trials published after that date to assess the influence of reversal of residual paralysis on postoperative nausea and vomiting, and the likelihood of harm when antagonism was omitted. Moreover, an overview of pathophysiological consequences, incidence and clinical consequences of residual paralysis is given and the actual criteria of the adequacy of neuromuscular recovery presented.

When emetic outcomes are combined across all trials and all different neostigmine doses, there is no beneficial effect from omitting neostigmine on postoperative nausea and vomiting, but there is some evidence of a dose-responsiveness with neostigmine; higher doses may have emetic properties. However, omitting reversal introduces a non-negligent risk of residual paralysis. An improved understanding of the pathological consequences of residual paralysis (i.e. impaired laryngeal and pharyngeal muscle function, alterations in hypoxic ventilatory control, reduced margin of safety) led to establishment of more rigorous criteria for defining adequacy of neuromuscular recovery. A train-of-four ratio of ≥0.9 is now accepted as the index of adequate recovery of neuromuscular function. Applying this new definition, residual paralysis becomes a frequent adverse side-effect. Neuromuscular recovery should therefore be routinely monitored in ambulatory patients and residual paralysis prevented by reversing neuromuscular block.

Rapacuronium is a new non-depolarizing relaxant with a fast onset and rapid recovery. It was approved for the market in the United States in August 1999. The reasons for its acceptance in practice and the niche it fills are the subject of this review. Rapacuronium has been accepted wherever rapid onset and short duration of action are advantageous. It has received the greatest acceptance in brief outpatient procedures that require tracheal intubation. The average time of recovery to a train-of-four ratio of 80% is about 25 min after a usual intubating dose of 1.5 mg kg−1, when block is reversed. Its rapid onset has led some to use it in rapid-sequence induction, but the exact place in this scenario is still being defined. Its spontaneous recovery is rapid enough that many practitioners do not reverse the block if the procedure is long enough. Data suggest that this is reasonable after 60 min and may even be earlier, even 30 min, if verified by monitoring. The main adverse effects of rapacuronium are bronchospasm, hypotension and tachycardia. Of these, only bronchospasm has had significant clinical impact. These effects are dose related and the recommended dose of 1.5 mg kg−1 may keep problems to a minimum. Because rapacuronium is a new drug with unique properties its use gradually increased in its first year. Because of the problems associated with succinylcholine, rapacuronium may have advantages for brief outpatient procedures and in cases where rapid termination of block is desired, provided its adverse effects can be minimized.

The aim of this paper is to provide an outline of the current developments in drug discovery. However, in doing so, it is important to put these developments into an historical perspective and to acknowledge the impact that the previous research effort has had on research in progress.

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.

Mitochondrial myopathies are rare complex multisystem disorders, which can present several potential anaesthetic problems. A 49-year-old man with mitochondrial myopathy was anaesthetized successfully for cataract extraction using propofol and alfentanil infusions. Vecuronium sensitivity was apparent, with a prolonged duration of action, despite dosage reduction

Adequate relaxation of the masseter muscle is important during endotracheal intubation and for the patency of a patient’s airway during recovery from anaesthesia. We evaluated onset and recovery from cisatracurium-induced neuromuscular block at the masseter and adductor pollicis muscles. Thirty patients were randomly allocated to receive either 0.1 or 0.15 mg kg−1 cisatracurium. The evoked response was measured at both muscles using acceleromyography. Onset time was significantly shorter at the masseter muscle than at the adductor pollicis (0.1 mg kg−1 cisatracurium: 155±52 vs. 229±44 s; 0.15 mg kg−1 cisatracurium: 105±24 vs. 174±35 s). Following 0.1 mg kg−1 cisatracurium, recovery to a TOF-ratio of 0.7 was faster at the masseter compared to the adductor pollicis (P < 0.05). In the 0.15 mg kg−1 cisatracurium group recovery of T1 to 75% of control and to a TOF-ratio of 0.7 occurred sooner at the masseter (P < 0.05). We conclude that onset and recovery from cisatracurium neuromuscular block occurs more rapidly at the masseter than at the adductor pollicis. It appears unlikely that residual paralysis is present at the masseter once neuromuscular function at the adductor pollicis has completely recovered.

This study was undertaken to investigate the neuromuscular blocking profile and cardiovascular effects of Org 9487, a new aminosteroidal, non-depolarizing, neuromuscular blocking agent structurally related to vecuronium, in anaesthetized animals and in isolated muscle preparations. In in vitro functional assays of neuromuscular blocking activity, Org 9487 was between eight and 15 times less potent than vecuronium. In cats and monkeys the potency of Org 9487 was approximately one-seventh and one-twentieth, respectively, that of vecuronium. In both species, Org 9487 induced rapidly developing (onset times between 1.5 min and 1.9 min) neuromuscular paralysis, which was shorter-lasting than that of vecuronium and similar in time course to suxamethonium. The vagal: neuromuscular blocking dose ratio for Org 9487 was 3 and ganglion block was seen only at approximately 20 times the neuromuscular blocking dose. There was no evidence in the rat that Org 9487, administered at doses up to 3mg kg−1, inhibited noradrenaline re uptake. In anaesthetized dogs, Org 9487 (3 × 90% blocking dose) induced only relatively small and transient haemodynamic effects. The administration of clinically relevant doses of neostigmine or pyridostigmine shortened the time–course profile of Org 9487, even when administered during profound neuromuscular block. In animals, Org 9487 is a low potency, nondepolarizing neuromuscular blocking agent with a time course profile similar to that of suxamethonium. Although Org 9487 is less selective than vecuronium for the neuromuscular junction, it is unlikely to produce prohibitive cardiovascular side effects in man.

Anaesthetic agents for day-case surgery ideally should have a short duration of action. This study was designed to compare the efficacy and safety of mivacurium and vecuronium for healthy adults undergoing dental day-case surgery. Thirty fit healthy adult patients (ASA I or II) randomly received either mivacurium 0.15 mg kg−1 (n = 15) or vecuronium 0.1 mg kg−1 (n = 15). Anaesthesia included propofol, fentanyl, nitrous oxide and isoflurane. Maximum depression of T1 was greater in the vecuronium group (99.8%) than in the mivacurium group (98.3%). There was no difference between grade of intubation at 2 min between the two groups, although patients receiving vecuronium had a more profound block at the time of intubation than those who received mivacurium (89.2% vs. 78.9%). Recovery to 10% T1 was faster in the mivacurium group (11.2 min vs. 33.1 min). All patients in the vecuronium group received neostigmine at the termination of surgery. The neostigmine evoked recovery index in the vecuronium group (4.39 min) was less than the spontaneous recovery index in the mivacurium group (6.78 min). One patient in the mivacurium group had a low plasma cholinesterase concentration (0.43 ku L−1); recovery times however, fell within the 95% confidence intervals (CI) for the group. There was no correlation between cholinesterase levels and recovery time. Mivacurium may be the more appropriate agent for dental day-case surgery because it has a shorter duration of action and does not generally require antagonism with an anticholinesterase.