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Original Papers

Choice of the hypnotic and the opioid for rapid-sequence induction

Lavazais, S.; Debaene, B.

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European Journal of Anaesthesiology: November 2001 - Volume 18 - Issue - p 66-70



Rapid-sequence induction of anaesthesia, sometimes referred to as ‘crash’ induction, is mainly used to protect the airway when there is a risk of aspiration of gastric contents. This technique is thus used widely in obstetric anaesthesia for Caesarean section, and also during emergency procedures. It may also be used in non-emergency patients when there is a risk of aspiration, as in cases of obesity, gastro-oesophageal reflux, or diabetes mellitus. The technique of rapid-sequence induction involves preoxygenation, administration of a hypnotic, application of cricoid pressure and avoidance of positive pressure ventilation prior to securing the airway with a cuffed tracheal tube. Thus, the time interval between the loss of consciousness and the correct placement of the tracheal tube remains a high-risk period of aspiration. The major goals of the anaesthetic protocols in these situations are to reduce this period of time and to have excellent intubating conditions. A neuromuscular blocking agent with a short onset of action is usually administered to obtain good quality intubating conditions. An anaesthetic agent suitable for use for rapid-sequence induction should induce loss of consciousness within 60 s, produce apnoea of only a short duration in case of unexpected difficult intubation, inhibit laryngeal reflexes, not induce any bronchospasm, laryngospasm or muscle rigidity, show minimal interindividual variability, and cause no haemodynamic instability.

Choice of hypnotic and opioid for rapid-sequence induction without muscle relaxants

Thiopental alone was shown to provide adequate intubating conditions as long ago as 1948 [1]. However, propofol appears to suppress the pharyngeal and laryngeal reflexes more effectively [2], 12 of 20 intubations being reported to be smooth and easy following premedication with diazepam and droperidol, and propofol 2.5 mg kg−1 [3]. However, this technique may be associated with suboptimal intubating conditions and undesirable haemodynamic responses in some patients, necessitating the use of adjuvants. In a double-blind study comparing four different combinations (propofol 2.5 mg kg −1 + saline, propofol 2.5 mg kg −1 + alfentanil 20 µg kg−1, propofol 2.5 mg kg −1 + alfentanil 30 µg kg−1 and propofol 2.0 mg kg −1 + alfentanil 30 µg kg−1), the combination of alfentanil 30 µg kg−1 and propofol 2.5 mg kg−1 allowed satisfactory intubating conditions in 79% of patients and completely prevented the cardiovascular response to intubation [4]. Premedication with temazepam and administration of lidocaine 1 mg kg−1 2 min before propofol and alfentanil improves conditions further, due mainly to reduction in the incidence of coughing [5]. While it is generally accepted that intubating conditions are better with propofol, some studies have shown that thiopental rather than propofol in combination with alfentanil may provide more favourable intubating conditions [6]. However, the conditions are more effective with a combination of thiopental, alfentanil and succinylcholine [7]. Therefore, a low dose of alfentanil without lidocaine could not be recommended for rapid-sequence induction without using a muscle relaxant.

The dose of propofol used at induction can be decreased if the dose of alfentanil is increased; however, such a protocol may result in haemodynamic side-effects such as bradycardia and hypotension. Intubating conditions were not significantly different using propofol 2.0 mg kg−1 with alfentanil 40 µg kg−1 and lidocaine 1 mg kg−1 compared with thiopental 4 mg kg−1 and succinylcholine 1.0 mg kg−1 [8]. However, arterial pressure decreased significantly compared with preinduction values and remained lower even after intubation. Using etomidate 0.3 mg kg−1 instead of propofol with the same doses of alfentanil and lidocaine, intubating conditions are comparable, but with a lesser decrease in arterial pressure. Tracheal intubation was attempted 90 s after injection of anaesthetic, which may be somewhat lengthy for a rapid-sequence induction. Increasing the dose of alfentanil to 50 µg kg−1 with propofol 2 mg kg−1 provides acceptable intubating conditions in premedicated patients, even without lidocaine, but results in a 30% decrease in mean arterial pressure [9]. This technique may therefore not be appropriate for elderly or hypovolaemic patients or those with cardiovascular or cerebrovascular disease.

Remifentanil is a new opioid with a rapid onset of effect and a short half-life and in contrast to alfentanil the time to recovery is not influenced greatly by the dose. Thus, the clinical advantages of remifentanil in rapid-sequence induction are obvious. A recent study has compared the intubating conditions at 60 s and haemodynamic effects following propofol 2.5 mg kg−1 preceded by remifentanil 3–4 µg kg−1 or alfentanil 30 µg kg−1 following diazepam premedication [10]. All patients received atropine 0.01 mg kg−1 immediately before induction of anaesthesia. The frequency of excellent intubation conditions was significantly higher in patients receiving remifentanil 4 µg kg−1 compared to alfentanil (55 vs. 20%). However, many patients exhibited movement. Despite the use of atropine, heart rate remained lower after tracheal intubation than before induction but no patient manifested signs of opioid-induced rigidity, probably due to a slow injection rate of opioids, premedication with benzodiazepine and administration of propofol soon after the opioids. In another study the rate of excellent intubating conditions was found between 95 and 100% following propofol 2.0 mg kg−1 and remifentanil 3 or 4 µg kg−1 [11]. The difference may be due to remifentanil being administered as a slow infusion over 90 s, propofol being injected over 5 s instead of 20 s and laryngoscopy being attempted 90 s after propofol injection in this latter study. However, this does not represent a true rapid-sequence induction and the intubating scoring system used was also different. The duration of apnoea was less than 5 min irrespective of the dose of remifentanil used, being comparable to that of succinylcholine.

It is not surprising that the intubating condition 60 s following propofol is not always excellent or acceptable. As the T½ ke0 of propofol is approximately 2.7 min, the effect site concentration 60 s after propofol injection would be 4 µg mL−1 or less, which is inadequate to obtain a depth of anaesthesia consistent with clinically acceptable intubating conditions in all the patients. It seems logical to recommend the use of a premedicant such as midazolam [12]. Thus, propofol 2.5 mg kg−1 with lidocaine 1–1.5 mg kg−1 and alfentanil 30 µg kg−1 may provide acceptable intubation conditions without deleterious haemodynamic side-effects when intubation is carried out without a muscle relaxant. Alternatively, propofol may be used with remifentanil.

Choice of hypnotic and opioid for rapid-sequence induction using succinylcholine

The aims of using a hypnotic and opioid when succinylcholine is used to facilitate intubation during rapid-sequence induction are to avoid awareness, to blunt haemodynamic side effects and to enhance the quality of intubation. As the effects of succinylcholine are apparent well within 60 s, the hypnotics and opioids have a much smaller influence on the intubating conditions.

Do we need opioids during rapid-sequence induction facilitated with succinylcholine? A study has examined the haemodynamic responses to tracheal intubation after the induction of anaesthesia with thiopental 4 mg kg−1, etomidate 0.3 mg kg−1 or propofol 2.5 mg kg−1, with or without fentanyl 2 µg kg−1 and using succinylcholine 1.5 mg kg−1. Tracheal intubation was performed 60 s after the relaxant had been injected: arterial pressure after thiopental and fentanyl was significantly lower just prior to intubation than after thiopental alone [13]. Arterial pressure after tracheal intubation following thiopental and fentanyl increased to a similar extent to that following thiopental alone but it did not exceed preinduction values. Similar patterns were also observed after etomidate–fentanyl and propofol–fentanyl combinations. It was concluded that the use of fentanyl was associated with reductions in arterial pressures and heart rate, cf. the other groups where fentanyl was not used, and the responses to laryngoscopy and intubation were not blunted.

Fast-onset opioids, e.g. alfentanil and remifentanil, may be more effective for preventing or treating perioperative episodes of autonomic stimulation. Recently it has been demonstrated that alfentanil 30 µg kg−1 provided complete attenuation of cardiovascular and catecholamine response to tracheal intubation in healthy premedicated patients anaesthetized with thiopental 4 mg kg−1 and succinylcholine 1.5 mg kg−1 [14]. Increasing the alfentanil dose beyond 30 µg kg−1 was no better and could be deleterious due to a decrease in arterial pressure. The combination of alfentanil and propofol may also be useful in attenuating the increase in intraocular pressure following intubation facilitated with succinylcholine [15].

More recently, it has been demonstrated that a single bolus of remifentanil of 1.0 or 1.25 µg kg−1 was able to control the haemodynamic response to tracheal intubation during rapid-sequence induction in unpremedicated patients receiving thiopental 5–7 mg kg−1 and succinylcholine 1.0 mg kg−1 [16]. However, 35% of patients receiving the 1.25 µg kg−1 dose of remifentanil suffered reduced systolic arterial pressures, <90 mmHg, at some time during the study; one patient also developed bradycardia <50 beat min−1.

Therefore it seems logical to recommend the use of opioids during rapid-sequence induction when succinylcholine is administered. Thus, in unpremedicated patients, alfentanil 30 µg kg−1 with thiopental 4 mg kg−1, alfentanil 30 µg kg−1 with propofol 2 mg kg−1 or thiopental 5–7 mg kg−1 followed by remifentanil 1.0 µg kg−1 injected as a bolus over 30 s are appropriate. The influence of hypnotic agents on intubating conditions at 60 s is less clear when succinylcholine is used because complete paralysis occurs with its use in the laryngeal muscles within 60 s [17]. Agents such as midazolam are unsuitable as induction agents for rapid-sequence induction in obstetrics because they cause severe neonatal depression and have a slow onset of action [18].

Choice of hypnotic and opioid for rapid-sequence induction with non-depolarizing muscle relaxants

Two non-depolarizing muscle relaxants, rocuronium and rapacuronium, have been proposed to replace succinylcholine in rapid-sequence induction. The degree of block at 60 s (the usual time for intubation during rapid-sequence induction) is more pronounced after rapacuronium than after rocuronium. Therefore, the influence of anaesthetic agents on intubating conditions is much more marked when rocuronium is used. Several studies have addressed this issue when using rocuronium in a moderate dose of 0.6 mg kg−1. Using ketamine 1.5 mg kg−1 as the induction agent, the intubating conditions were scored as ‘excellent’ or ‘good’ in 20/20 patients undergoing Caesarean section, this rate being significantly higher than with thiopental 5 mg kg−1 [19]. No opioids were administered and tracheal intubation was carried out at 45 s at 50% paralysis of the adductor pollicis muscle. Similar results were obtained in another study in patients undergoing elective surgery [20]. The frequency of excellent intubating conditions at 60 s in unpremedicated patients has been found to be significantly higher (94 vs. 75%) following propofol 2.5 mg kg−1 than after etomidate 0.3 mg kg−1 [21]. The conditions with etomidate improved by the addition of alfentanil 10 µg kg−1 [22]. The diaphragmatic response to intubation was significantly lower after etomidate and alfentanil compared with thiopental and alfentanil (44 vs. 80%), due probably to a more rapid onset of rocuronium block when using etomidate [23]. Addition of alfentanil 20 µg kg−1 also improves the intubating conditions with propofol and thiopental [24].

Increasing the dose of rocuronium to 1.0 mg kg−1 improves the quality of intubations because the degree of block obtained at 60 s is more pronounced compared with a lower dose. Thus the rate of clinically acceptable intubating conditions was not significantly different compared with succinylcholine when anaesthesia was induced with propofol 2.5 mg kg−1 alone [25] or with a combination of thiopental 5 mg kg−1 and fentanyl 1–2 µg kg−1 [26].

Intubating conditions following rapacuronium 1.5 mg kg−1 or succinylcholine 1.0 mg kg−1 have been compared following induction of anaesthesia with fentanyl 2–3 µg kg−1 and thiopental 3–6 mg kg−1 or alfentanil 20 µg kg−1 and propofol 1.5–2 mg kg−1 [27], and fentanyl 2–5 µg kg−1 and propofol 1–3 mg kg−1 [28]. The frequency of clinically acceptable intubating conditions was not influenced by anaesthetic drugs used for induction. The intubating conditions using a higher dose of rapacuronium (2.0 or 2.5 mg kg−1) were only marginally better at 60 s [29].

A problem with the use of rapacuronium is the occurrence of respiratory side-effects, e.g. an increase in the airway pressure or bronchospasm. Fleming and colleagues [28] observed this is in 3% of patients in their study, while it was reported in 10% of patients in the study by Sparr and colleagues [27]; the frequency increased alarmingly after higher doses (13.5% and 18.5% after 2.0 and 2.5 mg kg−1 doses) [29]. The design of none of these studies allowed the exact cause of respiratory side effects to be determined although it appears that these are more common during rapid-sequence induction and in smokers or those with irritable airways. It is likely that rapacuronium will not be recommended for use during rapid-sequence induction.


In conclusion, the choice of hypnotics and opioids for rapid-sequence induction, and the use of premedication, is guided by the choice of the muscle relaxant. The influence of anaesthetic agents on the quality of intubation is important when rapid-sequence induction is attempted without a muscle relaxant. Under these circumstances, premedication is useful and short-acting opioids such as alfentanil (30–40 µg kg−1) or remifentanil (up to 4 µg kg−1) need to be used with the hypnotic agent; lidocaine i.v. helps to improve the intubating conditions further. The choice of the anaesthetic agents depends on the speed of onset of the muscle relaxant, when one is used. A small dose of opioid, e.g. alfentanil 10–20 µg kg−1, is perhaps necessary when using an agent such as rocuronium in a modest dose (0.6 mg kg−1). Acceptable intubating conditions may be obtained even without opioids when using succinylcholine or rapacuronium, or rocuronium in a higher dose. However, the addition of opioids helps to attenuate undesirable haemodynamic effects.


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ANAESTHESIA; INTRATRACHEAL; rapid-sequence induction; ANAESTHETICS; intravenous; thiopental; propofol; NEUROMUSCULAR BLOCKING AGENTS; succinylcholine; rocuronium; rapacuronium; OPIOIDS; alfentanil; remifentanil

© 2001 European Society of Anaesthesiology