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Muscle relaxants suitable for day case surgery

Geldner, G.; Wulf, H.

European Journal of Anaesthesiology: November 2001 - Volume 18 - Issue - p 43-46
Original Papers
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Summary 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.

Klinik für Anästhesiologie und Intensivtherapie, Philipps-Universität Marburg, Baldingerstr. 1, D-35033 Marburg, Germany

Correspondence: G. Geldner (E-mail: geldner@mailer.uni-marburg.de).

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Introduction

In 1994, 66% of all surgery in the USA was performed as day case surgery [1]. 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 [2]. 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 A still unpublished survey from Germany has shown that only ≈5% of all elective anaesthesia inductions with tracheal intubation are performed without administering muscle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 [8].

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 [8]. 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.

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Succinylcholine

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 [11].

Table 1

Table 1

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 [4].

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Mivacurium

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 [14]. It undergoes an enzymatic breakdown, and as with succinylcholine, this could lead to a prolonged neuromuscular block in patients with atypical plasma cholinesterase [16].

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.

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Rocuronium

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 [13]. 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) [18]. 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.

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Rapacuronium

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 [23]. The clinical duration is 15 ± 6 min and the recovery time (TOF ratio >0.7) without administering antagonists, 38 ± 21 min (Table 1) [17]. 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 [10]. 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 [10].

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Conclusion

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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References

1 Korttila K. Recovery from outpatient anaesthesia. Anaesthesia 1995; 50 (Suppl.): 22–28.
2 Andel H, Klune G, Andel D et al. Propofol without muscle relaxants for conventional or fiberoptic nasotracheal intubation: a dose-finding study. Anesth Analg 2000; 90: 458–461.
3 Brennan LJ. Modern day-case anaesthesia for children. Br J Anaesth 1999; 83: 91–103.
4 Collons L, Prentice J, Vaghadia H. Tracheal intubation of outpatients with and without muscle relaxants. Can J Anesth 2000; 47: 427–432.
5 Klemola U-M, Mennander S, Saarnivaara L. Tracheal intubation without the use of muscle relaxants: remifentanil or alfentanil in combination with propofol. Acta Anaesthesiol Scand 2000; 44: 465–469.
6 Meretoja OA, Taivainen T, Jalkanen L. A fast-onset short-acting neuromuscular blocker, ORG 9487, in infants and children. Br J Anaesth 1996; 76: A305.
7 Schlaich N, Mertzlufft F, Soltesz S, Fuchs-Buder T. Remifentanil and propofol without muscle relaxants or with different doses of rocuronium for tracheal intubation in outpatient anaesthesia. Acta Anaesthesiol Scand 2000; 44: 720–726.
8 Zhou TJ, Coloma M, White PF et al. Spontaneous recovery profile of profile of rapacuronium during desflurane, sevoflurane, or propofol anesthesia for outpatient laparoscopy. Anesth Analg 2000; 91: 596–600.
9 Sparr HJ, Mellinghoff H, Blobner M, Noldge-Schomburg G. Comparison of intubating conditions after rapacuronium (Org 9487) and succinylcholine following rapid sequence induction in adult patients. Br J Anaesth 1999; 82: 537–541.
10 Blobner M, Mirakhur RK, Wierda JMKH et al. Rapacuronium 2.0 or 2.5 mg kg−1 for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg−1. Br J Anaesth 2000; 85: 724–731.
11 Osmer C, Vogele C, Zickmann B, Hempelmann G. Comparative use of muscle relaxants and their reversal in three European Countries: a survey in France, Germany and Great Britain. Eur J Anaesthesiol 1996; 13: 389–399.
12 Rosenberg H, Gronert GA. Intractable cardiac arrest in children given succinylcholine. Anesthesiology 1992; 77: 1054.
13 Cook DR. Can succinylcholine be abandoned? Anesth Analg 2000; 90: 24–28.
14 Savarese JJ, Ali HH, Basta SJ, Embree PB. The clinical neuromuscular pharmacology of mivacurium chloride (BW B 1090U): a short-acting nondepolarizing ester neuromuscular blocking drug. Anesthesiology 1988; 68: 723–732.
15 Woelfel SK, Brandom BW, McGawan FX, Cook DR. Clinical pharmacology of mivacurium in pediatric patients less than two years old during nitrous oxide halothane anesthesia. Anesth Analg 1993; 77: 713–720.
16 Cook DR, Freeman A, Lai AA et al. Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure. Br J Anaesth 1992; 69: 580–585.
17 Miguel R, Witkowski T, Nagashima H et al. Evaluation of neuromuscular and cardiovascular effects of two doses of rapacuronium (ORG 9487) versus mivacurium and succinylcholine. Anesthesiology 1999; 91: 1648–1654.
18 Bevan JC, Fowler C, Kahwaji R et al. Early and late of rocuronium 0.45 mg/kg with neostigmine 0.07 mg/kg in adults and children. Anesth Analg 1999; 83: 333–339.
19 Wierda JM, van den Broek L, Proost JH, Verbaan BW, Hennis PJ. Time course of action and endotracheal intubating conditions of Org 9487, a new short-acting steroidal muscle relaxant; a comparison with succinylcholine. Anesth Analg 1993; 77: 579–584.
20 Wierda JMKH, Beaufort AM, Kleef UW, Smeulers KJ, Agoston S. Preliminary investigations of the pharmacology of three short-acting nondepolarizing neuromuscular blocking agents. Org 9453, Org 9489 and Org 9487. Can J Anaesth 1994; 41: 213–220.
21 Donati F. Neuromuscular blocking drugs for the new millennium: current practice, future trends-comparative pharmacology of neuromuscular blocking drugs. Anesth Analg 2000; 90: 2–6.
22 Brandom BW, Margolis JO, Bikhazi GB et al. Neuromuscular effects of rapacuronium in pediatric patients during nitrous oxide-halothane anesthesia: comparison with mivacurium. Can J Anesth 2000; 47: 143–149.
23 Debaene B, Lieutaud T, Billard V, Meistelman C. ORG 9487 neuromuscular block at the adductor muscles of the larynx and adductor pollicis. Anesthesiology 1997; 86: 1300–1305.
24 Purdy R, Bevan DR, Donati F, Lichtor JL. Early reversal of rapacuronium with neostigmine. Anesthesiology 1999; 91: 51–57.
Keywords:

NEUROMUSCULAR BLOCKING AGENTS; rapacuronium; succinylcholine; mivacurium; rocuronium; AMBULATORY SURGICAL PROCEDURES

© 2001 European Society of Anaesthesiology