In 1994, 66% of all surgery in the USA was performed as day case surgery . In contrast, in Germany in 1999, only 22% of all surgery was performed as ambulatory surgery, although the number is rising. Induction of anaesthesia is commonly facilitated by administration of a combination of short-acting hypnotic drugs, opioids and depolarizing or non-depolarizing muscle relaxants . There is a need for an ideal muscle relaxant for day case surgery [1,3]. Although several authors have shown that tracheal intubation is possible with propofol and opioids without using muscle relaxants [2,4–6], the technique may be associated with adverse side-effects such as hoarseness; also, intubating conditions have often proved unsatisfactory [2,7]. A still unpublished survey from Germany has shown that only ≈5% of all elective anaesthesia inductions with tracheal intubation are performed without administering muscle relaxants.
Whether to use neuromuscular blocking agents or not depends on the patient factors, the type of anaesthetic that is planned, and the surgical procedure. However, specific surgical procedures, such as laparoscopic surgery, some ear, nose and throat procedures and microsurgery, require muscle relaxation .
Once the decision to use a neuromuscular blocking agent is made, there is a choice of several agents. As day case procedures are generally short, the onset time of the agent used should be short (1–2 min) and as most day case procedures last about 30 min, duration of action should also be short, with or without antagonism. Haemodynamic stability and a low incidence of histamine release are further requirements. From an economic point of view, a competitive price is another factor in the choice of relaxants in day case anaesthesia . The agents fulfilling some of these requirements include succinylcholine, mivacurium, low-dose intermediate-acting agents, such as rocuronium, atracurium and vecuronium, and the recently introduced rapacuronium.
Succinylcholine, a rapid onset, short-acting depolarizing neuromuscular blocking agent was introduced into clinical practice some 50 years ago. It produces a profound neuromuscular block rapidly in all muscles, including those of the vocal cords, and usually provides excellent intubating conditions [9,10]. The recovery is most rapid compared with all other available neuromuscular blocking agents (Table 1). It is also quite inexpensive and is therefore still the most often used neuromuscular blocking agent for day case surgery in Germany .
Succinylcholine, however, has many side-effects and should be avoided for elective procedures, particularly in infants and children. These include profound cardiovascular effects, increases in intraocular, intragastric and intracranial pressures, hyperkalaemia, myoglobinaemia and malignant hyperthermia. Life-threatening side-effects occur occasionally, especially in children and infants. Several reports led the American manufacturers to revise the label in November 1993 and to restrict the use of succinylcholine in children in March 1995 [12,13]. In addition, due to its depolarizing mode of action, it causes patient discomfort, which is especially disturbing in day case surgery. The use of succinylcholine in one report produced muscle pains in over 70% of subjects, regardless of the prophylaxis used .
Mivacurium was the first non-depolarizing relaxant with a short duration introduced into clinical use. Its clinical duration is approximately half as long compared with other intermediate-acting agents such as atracurium and vecuronium [14,15], but still more than twice that of succinylcholine (Table 1). However, mivacurium has undesirable effects, rapid administration inducing significant histamine release [14,15] and, therefore, possibly cardiovascular side-effects in higher dose. Higher doses also result in prolonged duration of action and administration of anticholinesterases produces only a marginal reduction in its duration of action . It undergoes an enzymatic breakdown, and as with succinylcholine, this could lead to a prolonged neuromuscular block in patients with atypical plasma cholinesterase .
Mivacurium, however, does have duration of action suitable for day case surgery, the major disadvantage being a long onset time, which is about 2–3 min, even after administering 0.25 mg kg−1 (3 × ED95 dose) [13,17]. This slow onset may discourage anaesthesiologists from using it in the setting of day case surgery of short duration and a high turnover rate.
Rocuronium is perhaps the most widely used intermediate-acting neuromuscular blocking agent today in the developed world. When used at twice the recommended ED95 dose of 0.6 mg kg−1, it produces a profound neuromuscular blockade within 60–90 s and offers intubating conditions comparable with those of succinylcholine . It causes only a transient small increase in heart rate without any other significant cardiovascular side-effects.
The main disadvantage of rocuronium when used in this dose is its clinical duration of ≈40 min, which is perhaps too long for the majority of day case procedures. Therefore, Bevan and colleagues advocated its use in procedures of more than 1 h duration using a reduced dose to 0.45 mg kg−1 and reversing with neostigmine 0.07 mg kg−1 (Table 1) . However, the onset of action of this dose is relatively slow at about 2–3 min for acceptable intubating conditions to be present. The clinical duration of this dose is ≈25 min. As day case surgery is usually of short duration (median of 24 min), an onset time of 3 min is about 13% of the whole operation time. Also, the time to a full spontaneous recovery (train-of-four [TOF] ratio >0.7) is rather long (>30 min). The use of reversal agents is not without problems in a day case setting. Therefore, rocuronium may not be the ideal, but at a low dose, rocuronium has a place in day case surgery.
Rapacuronium is the first non-depolarizing relaxant combining both, rapid onset and short duration of action [6,19–22]. Maximum block was achieved in 86 ± 7 s at the vocal cords and in 97 ± 4 s at the adductor pollicis, respectively, after administering a dose of 1.5 mg kg−1 . The clinical duration is 15 ± 6 min and the recovery time (TOF ratio >0.7) without administering antagonists, 38 ± 21 min (Table 1) . However, its effects can be reversed as early as 2 min after injection [19,24], which makes it very suitable for short procedures. While it provides acceptable intubations similar to those after succinylcholine in the majority of well-anaesthetized patients, these are perhaps not as good during a rapid-sequence induction [9,10].
Termination of its effect is mainly by redistribution. Along with vecuronium and rocuronium, rapacuronium has an elimination half-life of 1–2 h, similar to long-acting drugs. However, an extensive redistribution process starts immediately after injection, resulting in plasma concentrations of the drug decreasing to levels consistent with recovery before the elimination phase begins. This termination of effect by redistribution and the presence of an active metabolite may give rise to a prolonged duration of action following repeated administration or after an infusion.
Histamine release-linked side-effects, such as bronchospasm, have, however, been reported after its use [9,10]. The bronchospasm may be overt or reflected as an elevated airway pressure, especially in smokers and those undergoing rapid-sequence induction . It also produces a mild, dose-related tachycardia and hypotension, but these changes are short lived [10,17]. All these effects are more pronounced when using a higher dose (2.0 or 2.5 mg kg−1), as in a rapid-sequence induction setting .
The goal of having an ideal neuromuscular blocking agent with a rapid onset and short duration of action is getting closer. For the time being, succinylcholine remains the drug of choice for rapid sequence induction. Although it is cheap, it has a wide range of contraindications and side-effects. Rapacuronium offers certain benefits, such as a rapid onset and a short duration of action, but its side-effects, particularly respiratory, may restrict its use in day surgery and elsewhere. Mivacurium or low-dose rocuronium are perhaps the current choices, with the latter providing a more rapid onset of action.
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