The time between induction of anaesthesia and intubation of the trachea should be kept as short as possible in patients considered to be at risk of regurgitation or vomiting (e.g. trauma patients, patients with an ‘acute abdomen’, morbidly obese and obstetric patients) and subsequent pulmonary aspiration of gastric contents. The anaesthetic technique used for this purpose is known as ‘rapid-sequence induction’ (rapid-sequence intubation, ‘crash’ intubation). The components of the rapid-sequence induction technique used today are preoxygenation, intravenous induction and application of cricoid pressure and avoidance of positive pressure ventilation until securing the airway.
Muscle relaxants are given as part of rapid-sequence induction to facilitate tracheal intubation. According to anaesthetic textbooks succinylcholine is the preferred muscle relaxant for rapid-sequence induction . However, no data are available about the risk of aspiration if the tube is introduced into the trachea at 60–120 s instead of the usually advocated 60 s . The use of a muscle relaxant, even one with a very fast onset and a short duration of action, e.g. succinylcholine, does not rule out complications that may occur during rapid-sequence induction, including regurgitation and failed tracheal intubation . Muscle relaxants should not be administered in any case if difficulties with intubation are anticipated, and alternative methods of securing the airway, such as the use of fibreoptic intubation, awake intubation, tracheostomy, etc. are used.
The incidence of clinically apparent aspiration is relatively low, and pulmonary aspiration seems to be more common in emergency than in elective surgery. Warner and colleagues reported an incidence of 1 : 895 and 1 : 3886 in emergency and elective cases, respectively . The results of a more recent survey, however, revealed that aspiration occurs twice as often in elective as in emergency surgery . Only 56% of aspirations took place during induction of anaesthesia, and passive regurgitation occurred three times more often than during active vomiting. Of the 131 reported incidents of aspiration, 118 (90%) occurred with either facemask or laryngeal-mask anaesthesia .
Is there a standard technique for rapid-sequence induction?
Thwaites and colleagues recently published the results of a questionnaire that aimed to find how anaesthetists in the United Kingdom performed rapid-sequence induction in obstetric practice . The study confirmed that rapid-sequence induction is clearly not a standard technique, and that considerable variation exists in the timing and application of cricoid pressure, the choice and dose of drugs used and the timing of their administration. There are at least two distinct techniques of rapid-sequence induction, one ‘fast’ technique where a fixed dose of an induction agent (still commonly thiopental) is given rapidly, followed immediately by the muscle relaxant; and a ‘slow’ rapid-sequence induction technique where the i.v . anaesthetic is injected slowly or titrated against the response and where the muscle relaxant is not given before sleep has been confirmed .
Another important issue with respect to rapid-sequence induction is the application of cricoid pressure. A recent review indicated that there are no studies which prove that application of cricoid pressure is beneficial, yet there is evidence that it is often ineffective and that it may increase the risk of failed intubation and regurgitation .
Succinylcholine for rapid-sequence induction
Among all the muscle relaxants available succinylcholine is the only one with a very fast (≈1 min) onset and a very fast recovery. The development of good to excellent intubation conditions within 60 s after administration of succinylcholine does not depend on an adequate depth of anaesthesia. It is therefore not surprising that most rapid-sequence induction techniques using succinylcholine sacrifice depth of anaesthesia for speed of tracheal intubation and securing of the airway, despite the fact that tracheal intubation is more stressful than a surgical skin incision . In contrast to succinylcholine, all, even non-depolarizing, muscle relaxants with a fast onset of action (rocuronium and rapacuronium) rely more or less on an adequate depth of anaesthesia in order to attain consistently smooth intubation conditions within 60 s .
Succinylcholine has several undesirable and sometimes life threatening side-effects, many of which can be attenuated by pretreatment with a non-depolarising relaxant (precurarisation). Fasciculations and unco-ordinated muscle contractions of variable intensity are evident during the onset of action of succinylcholine and may result in an increase in intragastric pressure (to as much as 40 cmH2O in adults) and in the tone of the masseter muscle. The latter is maximal when the fasciculations cease and intubating conditions with succinylcholine will not be optimal until 20–30 s after cessation of fasciculations of facial muscles . Abdominal fasciculations are diminished by a defasciculating dose of a non-depolarizing muscle relaxant. In addition, the tone of the lower oesophageal sphincter is increased to a similar extent or more than intragastric pressure . Generally, regurgitation is not expected to occur before the increase in intragastric pressure exceeds 28 cmH2O. However, in several groups of patients (pregnant women, patients presenting with ascites, bowel obstruction or hiatus hernia and the elderly) the competence of the lower oesophageal sphincter may be diminished, and regurgitation of gastric content following succinylcholine may be a distinct possibility. Precurarization to prevent fasciculations or the use of a non-depolarizing relaxant are precautionary measures in these patients . Occasionally defasciculation as well as priming (see below) doses of non-depolarizing muscle relaxants may significantly influence neuromuscular function in sensitive individuals, particularly the elderly . Recent studies in human volunteers indicate that a train-of-four ratio of <0.9, which is achieved in sensitive individuals following priming, may weaken pharyngeal muscle function and airway protective mechanisms [11–13].
The short duration of action of succinylcholine in most patients is considered to be a unique advantage, notably in those rare situations of an unanticipated difficult intubation. However, in such situations hypoxia may not be prevented by waiting for some spontaneous ventilation to reappear but has to be averted by the early insertion of a laryngeal mask airway or other measures that are recommended in difficult airway algorithms. In addition, a mathematical model has predicted that critical haemoglobin desaturation (i.e. below 80%) will occur before neuromuscular function has recovered sufficiently following succinylcholine, particularly in patients with reduced oxygen reserves, such as the morbidly obese, children and critically ill patients .
Non-depolarizing muscle relaxants of intermediate onset of action for rapid-sequence induction
Atracurium and vecuronium were the first non-depolarizing muscle relaxants with an intermediate duration of action. The onset of action of twice an ED95 of these compounds was, however, still too slow to be suitable for rapid-sequence induction. The search for a non-depolarizing alternative to succinylcholine has led to three distinct techniques of using atracurium and vecuronium for rapid-sequence induction: (a) the use of large doses, (b) the priming principle and (c) the timing principle [1,15].
Higher doses of atracurium and vecuronium
Six times the ED95 of atracurium and vecuronium resulted in adequate (excellent to satisfactory) intubation conditions within 60 s . However, clinical duration after these doses of atracurium and vecuronium averaged 83 and 71 min, respectively. In addition, the high atracurium doses were associated with moderate hypotension due to histamine liberation.
In this technique a small, subparalytic ‘priming’dose is administered several minutes before the larger intubation dose is given. As a result the onset time is shortened and intubation can be performed earlier. This shortening in onset time could not be demonstrated by all investigators. With vecuronium a priming dose of 0.01 mg kg−1 followed 4 min later by an intubation dose of 0.1–0.14 mg kg−1 has been recommended. Occasionally the priming dose may cause subjective muscle weakness and even provoke aspiration. Priming may not be a safe approach particularly in elderly patients .
A single large bolus dose of a muscle relaxant is administered in this technique, followed by the induction agent as soon as the patient complains of weakness. The patient may perceive muscle weakness and shortness of breath if the hypnotic agent is not injected at the right moment or if the venous access is lost. In addition, the protective airway reflexes may be compromised. The timing principle has successfully been applied to achieve good intubation conditions with atracurium, vecuronium and, more recently, rocuronium.
Non-depolarizing muscle relaxants with a fast onset of action for rapid-sequence induction 
Rocuronium was the first non-depolarizing neuromuscular blocking agent with a fast onset of action (i.e. 1–2 min). The onset of block at the adductor pollicis muscle after rocuronium is about 2.5 times faster than after an equipotent dose of vecuronium or atracurium. In elective cases good or excellent intubation conditions are achieved within 60–90 s after rocuronium 0.6 mg kg−1 (2 × ED95) under various anaesthetic conditions in adults [17,18].
The laryngeal adductor muscles and the diaphragm are more resistant to the effects of rocuronium than the adductor pollicis muscle. Even when administered in large doses, the onset of action of rocuronium at the laryngeal muscles is slower than that of succinylcholine . Hence, when rocuronium is used in a classical rapid-sequence induction at a relatively light plane of anaesthesia, signs of incomplete neuromuscular block at the vocal cords, the diaphragm and other muscles may be observed more frequently than after succinylcholine.
A recent questionnaire revealed that the majority (97%) of obstetric anaesthetists in the United Kingdom do not use opioids (not even in small doses) as part of a rapid-sequence induction in elective Caesarean sections . In patients undergoing a Caesarean section the dose of thiopental had to be increased from 4 to 6 mg kg−1, and intubation was commenced at 80 s instead of 60 s in order to achieve good or excellent intubation conditions in 90% of patients after rocuronium 0.6 mg kg−1 . When anaesthesia is induced with thiopental alone in unpremedicated adult patients, intubation conditions produced by rocuronium 0.6 mg kg−1 are in fact less favourable than those produced by succinylcholine .
An anaesthetic technique including an opioid may therefore be essential when using rocuronium 0.6 mg kg−1 in order to achieve good intubation conditions within 60 s . In addition, there is good evidence that satisfactory intubation conditions after rocuronium 0.6 mg kg−1 can be achieved faster after propofol or ketamine than after thiopental or etomidate [22–24]. After rocuronium 0.6 mg kg−1, satisfactory intubation conditions in 90% of patients can be expected within 61 s and 101 s, respectively, using propofol 2.5 mg kg−1 or thiopental 5 mg kg−1 . Rocuronium ≥1 mg kg−1 should be administered to facilitate tracheal intubation in a ‘classical’ rapid-sequence setting in adults, i.e. using relatively light anaesthesia without an opioid or with only low doses of an opioid (e.g. fentanyl 1–2 µg kg−1) [25–29]. Doses of rocuronium up to 2 mg kg−1 were administered in a rapid-sequence setting without significant cardiovascular side-effects .
Whether rocuronium is a suitable alternative to succinylcholine in rapid-sequence induction is still a matter of debate, due mainly to its long duration of action in doses of 1 mg kg−1 or more [26,30–32]. Cademy strongly discourages using rocuronium for rapid-sequence induction and instead recommends using high doses of opioids such as alfentanil (20–60 µg kg−1) and propofol if it is desirable to avoid succinylcholine . Engbaek, in contrast, points out that the issue of a safe induction of anaesthesia in patients with an increased risk of pulmonary aspiration should not only address the question of rocuronium vs. succinylcholine, but also the judgement of the anaesthetist .
Rapacuronium has been in clinical use in the United States since the autumn of 1999. Like rocuronium, it is an aminosteroidal muscle relaxant with a fast onset of action, but its duration of action is shorter due to even lower potency than rocuronium (ED95 of about 0.75 mg kg−1) . The lower receptor specificity of muscle relaxants of low potency carries with it a greater likelihood of side-effects. Rapacuronium was shown to cause a moderate decrease in arterial pressure and a concomitant increase in heart rate due to vagolytic effects and calcium channel blocking properties. In contrast to rapacuronium, vecuronium has no, and rocuronium only mild, cardiovascular side-effects.
A range of different doses of rapacuronium has been evaluated for rapid tracheal intubation in paediatric, adult and elderly patients undergoing elective surgery. Under such conditions clinically acceptable intubation conditions may be achieved within 90 s in the majority of adult and elderly patients with rapacuronium in doses equal to or greater than 1.5 mg kg−1. The efficacy of 2–3 times the ED90 of rapacuronium in a rapid-sequence setting was evaluated in two large European studies [34,35]. The first of these two studies compared intubation conditions at 50 s following rapacuronium 1.5 mg kg−1 and succinylcholine 1 mg kg−1 during rapid-sequence induction in adult patients undergoing elective surgery . Clinically acceptable intubation conditions were achieved less frequently after rapacuronium in this study, the overall frequency of acceptable (good and excellent) conditions being 89.4% and 97.4% after rapacuronium and succinylcholine, respectively (P < 0.001). In a second study, which was based on the results of the first study, rapacuronium 2.0 and 2.5 mg kg−1 were compared to succinylcholine during rapid-sequence induction with thiopental and fentanyl in 602 patients, including 109 emergency cases . Intubation conditions were clinically acceptable in 91.8% of patients given succinylcholine, and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg−1, respectively.
The main problem with using rapacuronium in high doses is a relatively high incidence of pulmonary side-effects (bronchospasm and/or increased airway pressure). Heart rate also increased significantly during the first 5 min after tracheal intubation when rapacuronium was used [34,35]. Pulmonary side-effects of rapacuronium seem to be dose-dependent and were observed in 10.7–18.5% of patients after rapacuronium 1.5–2.5 mg kg−1, compared to a 4% incidence after succinylcholine [34,35]. A light plane of anaesthesia predisposes to bronchospasm following tracheal intubation. In the study by Blobner and colleagues, patients were unpremedicated and received thiopental and relatively small doses of fentanyl for induction of anaesthesia . This anaesthetic technique may have contributed to the relatively high incidence of pulmonary side-effects observed after rapacuronium. In contrast, after rocuronium the cardiovascular response to intubation under thiopental anaesthesia supplemented with alfentanil 10 µg kg−1 was not dependent on dose, which ranged from 0.4 to 2 mg kg−1, i.e. up to about seven times its ED95 . In addition, there is no evidence in anaesthetic literature for pulmonary side-effects following the administration of rocuronium in a rapid-sequence setting.
Succinylcholine or rocuronium, rather than rapacuronium, should be considered as the preferred muscle relaxants during rapid-sequence induction. 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.
Rocuronium, when administered in large doses (i.e. ≥1 mg kg−1), appears to be a drug that can be used instead of succinylcholine in a classical rapid-sequence induction situation, i.e. under relatively light anaesthesia. It might be argued that the long duration of rocuronium could be a disadvantage in the case of an unexpectedly difficult intubation. However, a preoperative assessment of the airway is mandatory in any patient and may indicate other intubation techniques, which do not rely on the use of any muscle relaxant, including succinylcholine.
With respect to rapid tracheal intubation, the timing and priming principles offer no advantage over the use of rocuronium in doses of twice its ED95 in combination with an appropriate induction technique (i.e. including an opioid) or the use of larger doses of rocuronium under relatively light anaesthesia.
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