A rapid-sequence induction (RSI) of anaesthesia is recommended when the risk of pulmonary aspiration of gastric content is increased. For years this technique has included the combined use of a fast acting hypnotic and the depolarizing neuromuscular blocking agent succinylcholine. Because the use of succinylcholine is associated with the potential occurrence of serious complications associated with its depolarizing effect, a fast acting non-depolarizing alternative has been needed. The onset of rocuronium is more rapid than any other commercial available non-depolarizing neuromuscular blocking agents, but for a RSI it has been recommended to use higher doses of rocuronium (0.9-2.3 mg kg−1) than the normal 0.6 mg kg−1 to obtain intubating conditions equivalent to those of succinylcholine 1.0 mg kg−1 [1-4]. Such doses will produce long lasting muscle paralysis, which may be undesirable from a clinical point of view. However, the quality of the intubating conditions is not only determined by muscle relaxation, but also by the quality of anaesthesia and the suppression of the laryngeal reflexes by the induction agents [5,6]. Thus, it has been suggested that pretreatment with a fast acting opioid as alfentanil may improve intubating conditions after rocuronium .
The intubating conditions of rocuronium and succinylcholine with the RSI technique have so far mainly been evaluated among elective patients [1,2,7-11]. In subjects scheduled for emergency procedures there is only scanty knowledge of intubating conditions after rocuronium [7,10]. Whether rocuronium can replace succinylcholine in the emergency situation, under which induction regimen and at which dose is still under much debate .
We therefore, decided to compare the overall intubating conditions of standard doses of rocuronium 0.6 mg kg−1 and succinylcholine 1.0 mg kg−1 during a strict RSI regimen including propofol and alfentanil in patients scheduled for emergency surgery with increased risk of pulmonary aspiration of gastric content.
The local Ethics Committee (The Scientific Ethical Committees of Copenhagen and Frederiksberg, Sundhedsforvaltningen, Sjællandsgade 40, 2200 København N, Denmark) approved the study. Patients were recruited from two centres after obtaining written informed consent. Inclusion criteria were age older than 17 yr, ASA I-III and emergency abdominal or gynaecological surgery necessitating a RSI technique with succinylcholine because of an increased risk of pulmonary aspiration of gastric content. Patients were excluded in case of pregnancy, contraindications to succinylcholine, predisposition to malignant hyperthermia, known atypical plasma cholinesterase, anatomical conditions in head or neck indicating difficult intubation conditions, rheumatoid arthritis involving the cervical spine, neuromuscular disease or medication influencing neuromuscular transmission. Furthermore, patients with a Mallampati score of 4 or a Mallampati score of 3 and an atlanto-occipital extension angle below 50 degrees were excluded, as both circumstances predict a difficult airway .
Patients were offered premedication with an intramuscular injection of morphine (18-55 yr: 10 mg, 56-70 yr: 5 mg and >70 yr: 2.5 mg) given 30 min before induction of anaesthesia. In the operating theatre the patient was allocated by the concealed envelope method to receive either succinylcholine 1 mg kg−1 or rocuronium 0.6 mg kg−1. The patients were placed in the supine position with their head elevated about 10 cm on a pillow (the sniffing position) and preoxygenated with 100% oxygen for 3 min via the anaesthetic breathing circuit and a facemask. One member of the study group induced anaesthesia with alfentanil 10-20 μg kg−1 and propofol 2-3 mg kg−1 given within 5 and 20 s, respectively in a fast running saline infusion and followed immediately by either rocuronium 0.6 mg kg−1 or succinylcholine 1.0 mg kg−1 over 5 s. Cricoid pressure was applied immediately after injection of the drugs. The bolus doses of alfentanil and propofol were chosen to be within the given range and according to patients' general preoperative conditions.
Another anaesthesiologist (a senior member of the study group) blinded to the muscle relaxant and concealed in a room next to the operation theatre until 40 s after its administration, hereby preventing him from seeing fasciculations after succinylcholine, commenced laryngoscopy with a MacIntosh blade number 3, 50 s after muscle relaxant administration, aiming at tracheal intubation exactly 60 s after the end of muscle relaxant injection. The anaesthesiologist, who did the intubation, subsequently evaluated the intubating conditions according to an established guideline using five variables: ease of laryngoscopy, position of vocal cords, movement of vocal cords, movement of limbs and coughing during tracheal intubation and inflation of the cuff. Each variable was scored as good, acceptable or poor . A 7.5 mm endotracheal tube was used for female and an 8.5 mm endotracheal tube for male, all with a plastic covered metallic stylet in the tube according to Danish tradition during RSI and as recommended in textbooks . The stylet did not protrude from the tracheal end of the tube. Subsequent management of anaesthesia was at the discretion of the anaesthetist. Intubation conditions were considered as clinically acceptable if all variables were either excellent or good. Intubation conditions were clinically unacceptable, if any of the variables were poor. Intubating conditions were graded as failed if tracheal intubation was not completed within 30 s. The heart rate (HR), systolic and diastolic blood pressure (BP) were measured non-invasively before induction of anaesthesia (control), immediately after administration of the induction and neuromuscular blocking agents and 1 and 2 min after endotracheal intubation. For each patient maximal change in HR and mean arterial blood pressure (MAP) as percent of control were calculated. Signs of histamine release (bronchospasm, bronchial secretion, erythema, and oedema) were evaluated 2 min after the endotracheal intubation. The anaesthesiologist blinded to the muscle relaxant also evaluated whether the changes in pulse rate, BP or histamine release had any clinical significance. The patients were visited the next day by an anaesthesiologist and specifically screened for awareness and muscle pain.
We decided that less than 9% difference in the clinically acceptable intubating conditions was of no clinical interest and calculated with a significance level P < 0.05 (2α = 0.05) and a β of 0.1 that 107 patients were required in each group . We included 222 patients to compensate for patients later being excluded from the analysis. The patient characteristics and haemodynamic data are given as medians (inter-quartile range [2.5-97.5 percentile]).
The number of patients with clinically acceptable or unacceptable intubation conditions in the two study groups were compared using the Χ2 test and the Fisher's exact test. The BP and HR change was tested using analysis of variance (ANOVA) with post hoc Tukey test (SPSS 11.0).
Two hundred and twenty two patients were randomized to the study, but only 209 patients were included in the final analysis. The operation was cancelled before study drug administration in three patients (all succinylcholine group), two patients (one in each group) were randomized a second time for a subsequent eligible procedure but only included once (the first randomization) and eight patients (seven in the rocuronium group and one in the succinylcholine group) were excluded because of a major protocol violation (not emergency patients but a RSI was needed, e.g. due to oesophageal sphincter insufficiency). The eight patients received study drug and were treated exactly according to protocol except from not being emergency patients. The patient characteristics and doses of alfentanil and propofol of the remaining 209 patients are given in Table 1 and the indications for the operations in Table 2. Among the patients with intestinal obstruction, five in the rocuronium group and 11 in the succinylcholine group had their gastric content aspirated with a tube before induction of anaesthesia.
All patients with dentures had them removed before endotracheal intubation, except one patient in each group. The frequency of dentures was not different between the two groups. The distributions of the intubating conditions are given in Table 3. The proportion of patients with clinically acceptable intubation conditions was 93.5% and 96.1% for the succinylcholine and rocuronium groups, respectively. The difference between the groups (rocuronium minus succinylcholine) was 2.6% (95% confidence interval: −3.39 to 8.63%).
Although all patients were intubated, more patients in the rocuronium group coughed in relation to the tracheal intubation (29 vs. 12, Fisher's exact test: P = 0.0028). Tracheal intubation failed within 30 s. in five patients in the succinylcholine group and in two patients in the rocuronium group, respectively. In these patients tracheal intubation was successful either in the second, third or fourth attempt.
A second statistical analysis was performed including the data of the 10 patients excluded from the study. There was still no statistically significant difference between the intubation conditions of the two muscle relaxants.
The changes in HR and MAP are shown in Table 4. HR remained unchanged in both groups throughout the study period (ANOVA, P = 0.405). The maximal HR change (median (interquartile interval [2.5-97.5 percentile])) after induction of anaesthesia and administration of the neuromuscular blocking agent and until 2 min after tracheal intubation was 1.1% (−10.8 to 11.6 [−21.5 to 39.9]) in the succinylcholine group and 0.0% (−12.6 to 13.5 [−26.1 to 41.7]) in the rocuronium group. Only one patient (succinylcholine group) required treatment of dysrhythmias. A persistent atrial fibrillation with a ventricular rate of 118-132 was treated with verapamil and sotalol after induction of anaesthesia. A statistically significant decrease in MAP was observed after induction of anaesthesia in both groups (ANOVA, P < 0.0005). The maximal change in MAP was −23.6% (−35.4 to −11.6 [−52.0 to 27.3]) in the succinylcholine group and −25.4% (−36.6 to −15.8 [−47.8 to 18.6]) in the rocuronium group. Eighteen patients in the succinylcholine group and 17 patients in the rocuronium group received treatment with ephedrine, volume and/or Trendelenburg's position due to a decrease in BP. In four patients in the succinylcholine group depth of anaesthesia was increased after tracheal intubation due to an increase in BP. Neither for HR nor for MAP was there a statistically significant difference between treatment groups and the anaesthesiologist judged none of the changes in HR or BP as having clinical consequences for the patients. Signs of histamine release (erythema) were seen in two patients in the succinylcholine group, not necessitating any treatment.
At the postoperative visit after 24 h, five patients in the succinylcholine group and two in the rocuronium group, reported muscular pain. None of the patients reported signs of awareness.
This study is the first to show, that in emergency patients with a genuine risk of aspiration of gastric content to the lungs, there is no clinically significant difference in the intubating conditions of rocuronium 0.6 mg kg−1 or succinylcholine 1.0 mg kg−1 during a RSI regimen with alfentanil and propofol.
Our findings of clinically acceptable intubating conditions during RSI in 95.4% of the patients with rocuronium 0.6 mg kg−1 are in accordance with some of the early studies of rocuronium [1,7,9]. However, other more recent findings have suggested that larger doses of 0.9-1.2 mg kg−1 of rocuronium are necessary to match the intubating conditions of succinylcholine [2,8,10]. The discrepancy between these later results and our findings are probably explained by the fact that we decided to add a fast acting opioid (alfentanil) to the induction regimen with propofol to attenuate the laryngeal response to intubation. Propofol suppresses the laryngeal reflexes more than thiopental , but whether propofol in itself improves intubating conditions is questionable [6,7]. However, tracheal intubation without a muscle relaxant has been accomplished reliably with propofol and alfentanil though with alfentanil doses considerably larger than the one used in the present study . Also, pretreatment with alfentanil 20 μg kg−1 as part of a RSI regimen with thiopentone or propofol has been shown to improve intubating conditions after rocuronium . These findings indicate that alfentanil may add further to the quality of the intubating conditions from neuromuscular blockade and explain the discrepancies between our results and the general impression that rocuronium 0.6 mg kg−1 is too small a dose to be used in patients needing RSI.
Many of the previous RSI studies are based on more or less modified RSI techniques in elective patients and so far only a few studies have included a minor number of emergency patients in their study groups [2,10]. As pointed out in a recent review on this topic  more systematic information about the intubating conditions is needed from emergency patients undergoing emergent RSI. Our results seem to indicate that during such procedures only clinically unimportant differences in the intubating conditions exist between rocuronium and succinylcholine.
The findings that intubation failed in 5% and 2% after succinylcholine and rocuronium, respectively are a little higher than the findings of Andrews and colleagues  (1% for both rocuronium and succinylcholine). We carefully evaluated the patients preoperatively to minimize the risk of a difficult airway and in all of the patients with a first attempt intubation failure we managed to insert the endotracheal tube at the second, third or fourth attempt. The differences between our findings and those of Andrews and colleagues may be explained by the fact that we restricted the period of the intubating attempt to 30 s. The use of a stylet during RSI is recommended in Miller's Anaesthesia  and is a common practice in Denmark. We cannot exclude the possibility that this may have influenced the overall intubating conditions, but as a stylet was used in all patients, it is likely that the effect was similar in both groups.
The doses of succinylcholine and rocuronium used in this study are standard doses for tracheal intubation. The onset of peripheral rocuronium block from this dose is delayed compared to that of succinylcholine [18-21]. Furthermore, twitch depression of the adductor pollicis muscle after 60 s. does not adequately reflect central muscle paralysis [18,22]. Therefore, we decided to carry out tracheal intubation based on time (60 s) and not on monitoring of peripheral neuromuscular block.
Even with a dose of only 0.6 mg kg−1, rocuronium has a predicted spontaneous duration of block which is about 5 times longer than that of succinylcholine. This has to be taken into account when deciding which agent to be used in clinical practice.
Among the variables of intubation in our study, coughing with the diaphragm seemed to be more pronounced in the rocuronium group, though still clinically acceptable. Similar observations were made by Sparr and colleagues . The more pronounced reaction of the diaphragm to intubation and cuff inflation is readily explained by the delay of rocuronium onset in this muscle compared to succinylcholine .
The HR in the two treatment groups was unaffected by both induction of anaesthesia and tracheal intubation, while median decrease in MAP during the procedure was 25%. In thirty-nine patients the changes in arterial pressure caused the anaesthetist to use simple corrective measures like ephedrine, volume therapy, Trendelenburg position or increasing anaesthesia and in no patient was the cardiovascular changes judged to have clinical consequences. It is well known that the use of propofol for induction of anaesthesia is associated with more hypotension and less increase in HR than occurs with thiopental and this effect is more pronounced in higher ASA classes [24,25]. We used propofol and alfentanil to reduce the laryngeal reflexes but had concern about their combined depressant effect on the cardiovascular system during a RSI in emergency patients. It is known that alfentanil in combination with thiopental does have a suppressing effect on HR, systolic BP and systemic vascular resistance even with a relatively small dose like 15 μg kg−1 as used in our study [26,27]. In the elderly and in the hypertensive patient attenuation of the cardiovascular response to laryngoscopy and intubation is not complete with alfentanil 10 μg kg−1 before propofol [28,29]. Yet our results indicate that the combination of propofol and alfentanil as used in this study does not have serious cardiovascular effects during a RSI in ASA class I-III patients.
From the results of this study we conclude that during a RSI regimen with alfentanil and propofol, rocuronium 0.6 mg kg−1 or succinylcholine 1.0 mg kg−1 both provide clinically acceptable intubation conditions in 60 s with differences that are without clinical relevance in patients scheduled for emergency surgery. The findings show that under the conditions of this regimen rocuronium may be a substitute for succinylcholine.
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