Background and objective: Non-depolarizing neuromuscular blocking agents have a shorter duration of action on the diaphragm than on skeletal muscles. It was to be tested if this also held true for rapacuronium, a shortacting, amidosteroid non-depolarizing neuromuscular blocker, lately withdrawn from the market, using a novel technique for stimulating the diaphragm and assessing its function.

Methods: Anaesthesia was induced with propofol 2 mg kg−1 and remifentanil 1 μg kg−1, and the trachea was intubated after topical anaesthesia. Rapacuronium was given at a dose of 1.5 mg kg−1. The diaphragm was stimulated by cervical magnetic stimulation of the phrenic nerves (2 Tesla, single coil) and airway pressure responses were measured at the endotracheal tube connector. The neuromuscular effects at the adductor pollicis and orbicularis oculi muscles were measured by acceleromyography.

Results: Fifteen males and five females (ASA I and II; 27 ± 8 yr; 73 ± 13 kg; mean ± SD) were recruited. Median maximal relaxation was less (P < 0.01) for the diaphragm (89%) than for the adductor pollicis or orbicularis oculi muscles (each 100%). The time to 25% recovery was shorter for the diaphragm than for adductor pollicis or orbicularis oculi (7.5 ± 3.1 versus 14.1 ± 3.7 and 15.1 ± 3.5 min, respectively, P < 0.01). Recovery from 25 to 75% was identical for the diaphragm and adductor pollicis (9.4 ± 2.9 versus 9.1 ± 3.5 min), but longer for orbicularis oculi (13.4 ± 4.2 min, P < 0.01). The median recovery time to TOF0.8 was shorter for the diaphragm (23.9 min) than for the adductor pollicis or orbicularis oculi muscles (31.5 and 28.4 min, respectively; P < 0.05).

Conclusions: As with other non-depolarizing muscle relaxants, the duration of the clinical effect of rapacuronium was shorter for the diaphragm than for skeletal muscle. The recovery index was identical for the diaphragm and adductor pollicis.

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.

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 rapid onset and offset of rapacuronium can be explained from its pharmacokinetic and pharmacodynamic characteristics. A unique property of rapacuronium is its high value for ke0, indicating a rapid access to the receptor site. The reason for this high ke0 may be related to the low intrinsic potency of rapacuronium, but this is not yet fully clarified.

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.