Rocuronium Versus Succinylcholine

Are They Equally Effective During Rapid-Sequence Induction of Anesthesia?

Abstract

The purpose of our study was to assess the onset and quality of muscle paralysis and intubation conditions with succinylcholine (Sch) or rocuronium (Roc) during rapidsequence induction.Patients were randomly assigned to receive thiopental (5 mg/kg) and Sch (1.5 mg/kg) or thiopental (5 mg/kg) and Roc (1.2 mg/kg). The anesthesiologists performing the endotracheal intubation were blinded by standing with their back to the patient. Thirty seconds after drug administration, laryngoscopy was performed. Intubating conditions were scored, the clinical onset of apnea was noted, and a train-of-four monitor recorded data. All patients were ASA physical status I-III and scheduled for emergency procedures; both groups were demographically similar. Thirteen patients received Roc and 13 received Sch. There was no significant difference between the two groups in the number of patients receiving excellent intubating scores (P = 0.41) or in the combined number of patients receiving good and excellent scores (P = 1.0). There was no significant difference in time of onset of apnea for Sch (22 +/- 13 s) versus Roc (16 +/- 8 s). The return of the first twitch response was significantly faster with Sch (5.05 +/- 2.5 min) compared with Roc (17.3 +/- 21.7 min) (P = 0.0001). Implications: In pediatric patients scheduled for emergency surgery, thiopental 5 mg/kg and rocuronium 1.2 mg/kg provided conditions for the completion of intubation in <60 s comparable to those provided by thiopental 5 mg/kg and succinylcholine 1.5 mg/kg. We conclude that rocuronium is a reasonable substitute for succinylcholine in children for rapidsequence intubation when a rapid return to spontaneous respiration is not desired.

(Anesth Analg 1998;87:1259-62)

Serious adverse effects, such as hyperkalemia and malignant hyperthermia, are more frequently reported in children ^[1,2] when succinylcholine (Sch) is administered to facilitate rapid-sequence endotracheal intubation (RSI). However, no other drug has been shown to provide a comparably fast onset of neuromuscular blockade. Non-depolarizing drugs, such as pancuronium and vecuronium, have a relatively fast speed of onset if given in large doses ^[3,4], particularly in children ^[5], but their onset of action even at these doses is still slower than Sch. Rocuronium (Roc) is suitable for RSI in adults and has a shorter onset of action than previously available depolarizing drugs ^[6]. The purpose of our study was to compare, in a randomized fashion, the efficacy of Roc versus Sch during RSI in a pediatric population.

Methods

After approval of the study by our institutional review board and informed parental consent, children aged 2-15 yr, ASA physical status I-III, were enrolled in the study. All patients were scheduled for emergency procedures that called for RSI. All patients had a normal airway on physical examination. Patients were randomized using a random numbers Table toreceive either Roc 1.2 mg/kg or Sch 1.5 mg/kg. All investigators except the one designated to dispense the study drug were blinded to the choice of muscle relaxant.

Routine monitors were used, and a train-of-four (TOF) monitor-electrode (TOF-GUARD[trade mark sign]; Organon Technical, Turnhout, Belgium) was attached to the adductor pollicis before the induction of anesthesia. All patients were preoxygenated with 100% O₂ using four vital capacity breaths or four crying breaths. After atropine (0.01 mg/kg) was given, anesthesia was induced with thiopental (5 mg/kg), and the muscle relaxant was given. All drugs were injected through a series of stopcocks located 6 in. from the IV cannula, and the IV tubing was rapidly flushed with 5 mL of isotonic sodium chloride solution from an adjacent stopcock after each drug. The time taken to inject and flush all the drugs was <10 s. No other sedatives or analgesics were administered before induction. TOF monitoring was started immediately after the injection of the thiopental, and a stimulus was applied every 15 s. The time of onset of clinical apnea was noted from loss of respiratory effort. All events were timed with a stopwatch.

The investigators performed the laryngoscopies but were blinded to the relaxant by standing with their back to the patient during the induction so that they could not detect fasciculations. Twenty-five seconds after the administration of the muscle relaxant, they turned toward the patient, and exactly 30 s after the administration of the muscle relaxant, this individual attempted laryngoscopy and intubation, then scored the intubation according to Table 1. The time taken from the administration of the muscle relaxant to the completion of intubation was recorded. After intubation, anesthesia was maintained with either halothane or isoflurane in 30% oxygen. Narcotics were administered as indicated by the surgical procedure.

Table 1: Intubation Scoring System

The disappearance of TOF, return of any twitch, and time of return of the first response of the TOF to 25% of the response before neuromuscular blockade (25% of TOF) were recorded. Statistical analysis of the data was performed by using unpaired t-tests, Fisher's two-tailed exact test, and Levene's test for equality of variance when appropriate.

Results

Twenty-six patients were enrolled in the study (18 male, 8 female); 13 received Roc and 13 received Sch. There was no significant difference in mean +/- SD age or weight between the groups (6.4 +/- 4.2 and 6.8 +/- 2.4 yr; 26.8 +/- 16.4 and 29.2 +/- 14.2 kg for Sch and Roc, respectively).

At laryngoscopy, normal airway anatomy was confirmed, and the vocal cords of all patients were easily visualized, including those of a patient with a peritonsillar abscess. The arterial oxygen saturation did not decrease in any patient before intubation. The time to onset of apnea was similar in both groups (Table 2). There was no significant difference between the groups in the time to completion of intubation after the administration of the muscle relaxant (Table 2).

Table 2: Times from Muscle Relaxant Administration to the Onset of Various Clinical Indicators

For acceptable intubating conditions (those rated good or excellent by the intubator), there was no significant difference between the two groups (P = 1.0) (Figure 1). For excellent intubating conditions, there was also no significant difference (P = 0.41). When intubation conditions were not considered excellent, the reason was usually movement of the vocal cords. No patient moved their extremities. One patient in the Roc group received a low intubation score because of moving vocal cords and severe coughing and bucking after insertion of the endotracheal tube. In this patient, precipitation of drug was noticed in the IV tubing due to inadequate flushing between the administration of thiopental and the administration of Roc. One patient in the Sch group also received a low intubation score because of poor jaw relaxation and moving vocal cords, but there was no apparent technical reason in this patient. In both groups, a successful return to spontaneous respiration was easily accomplished at the end of the procedure.

Figure 1: Intubation conditions were scored as excellent = 9, good = 6-8, fair = 5-6, and poor = 0-2.

Discussion

RSI and intubation in pediatric patients is a concern because of the rare, but potentially fatal, side effects of Sch, such as hyperkalemic cardiac arrest, malignant hyperthermia, and rhabdomyolysis ^[1,2], especially in boys <6 yr of age ^[7]. The pediatric product labeling for Sch has been revised to state that succinylcholine is indicated for "emergency intubation or instances where immediate securing of the airway is necessary, e.g., laryngospasm, difficult airway, full stomach or for IM use when a suitable vein is inaccessible" ^[8]. As a result, an alternative muscle relaxant suitable for RSI that has the same advantage of rapid onset as Sch but fewer side effects is desirable ^[9-11].

Most studies evaluating alternative muscle relaxants for RSI, including pediatric studies, consider a 60-s onset of action adequate ^[6,12-15]. These studies, however, all used simulated RSI with the added effects of other anesthetic drugs, which may not accurately reflect patient responses during RSI. We compared the two drugs during actual RSI in emergently scheduled patients. Our study suggests that Roc 1.2 mg/kg and Sch 1.5 mg/kg are comparable for laryngoscopy and tracheal intubation within <60 s.

Children are more susceptible to hypoxemia during apnea than adults ^[16]. Children presenting for emergency surgery requiring RSI may be particularly vulnerable to hypoxemia after the onset of apnea secondary to decreased functional residual capacity from abdominal pathology, an increase in metabolic rate due to fever or sepsis, or difficulty in preoxygenating crying or combative children ^[17,18]. This is of particular concern in younger children, in whom a duration of apnea of >or=to60 s before initiating laryngoscopy could lead to profound arterial oxygen desaturation ^[19,20]. Because we used actual conditions of RSI in our study, we attempted intubation exactly 30 s after the administration of the thiopental and muscle relaxant combination to accomplish intubation in <1 min to avert arterial oxygen desaturation.

Roc has a faster onset time and shorter duration than the previously available drugs pancuronium and vecuronium ^[6,12,21,22]. Studies in children have shown that Roc 0.6-0.9 mg/kg with thiopental 5 mg/kg and alfentanil 10 [micro sign]g/kg provides intubating conditions comparable to those of Sch within 60 s ^[14]. Roc 1.2 mg/kg after premedication with midazolam and thiopental 2-7 mg/kg is a suitable alternative to Sch for RSI in adults ^[6]. Because we wanted to accomplish intubation within 60 s and did not wish to use any narcotic that may obtund laryngeal reflexes before induction, we chose a dose of Roc of 1.2 mg/kg (4 times the 95% effective dose) ^[23].

In our study, we found that intubating conditions were considered excellent or good in most patients in both groups. The reason for a good, rather than an excellent, score was usually vocal cord movement, which did not impede passage of the endotracheal tube. Only one patient in the Roc group and one patient in the Sch group were considered to have fair or poor intubating conditions; in the patient receiving Roc, this was due to a technical error in injecting the drug. With such results, for a power analysis to have an 80% chance of detecting a difference in intubating conditions between the two groups with a 95% confidence would require that the sample be infinitely large. For this reason, we did not continue the study beyond this cohort of patients. Even if 2 of 13 patients, rather than the actual 1 of 13 patients in the Roc group had had unsatisfactory intubating conditions, it would still have required a sample size of 524 patients to demonstrate a significant difference between the two drugs.

The duration of the surgical procedure must also be considered, as the longer-acting muscle relaxant may outlast the duration of the procedure. In our patients, the procedure was expected to be long enough that the muscle relaxant would have time to wear off in both groups.

Intubating conditions can be influenced by the choice of anesthetic and the use of adjuvant drugs, such as narcotics, sedatives, or lidocaine ^[24]. Because propofol and etomidate depress pharyngeal and laryngeal reactivity more than thiopental ^[15,25], we selected thiopental to minimize enhancement of muscle relaxation. If propofol or etomidate had been selected, one would expect that intubating conditions would be improved. We did not administer any sedatives or analgesics in the immediate preoperative period to maintain the clarity of assessment.

TOF monitoring of the adductor pollicis was used to determine the time of loss of twitch and the time to return of 25% of TOF. However, because good intubating conditions are present with Roc before neuromuscular blockade of the adductor pollicis muscle ^[12,26-28], we also recorded the onset of apnea and the intubation score, because these measurements are most valid in a clinical setting.

The speed and technique of IV injection can also alter the time to onset of apnea and the intubating conditions ^[21]. Therefore, a series of stopcocks was used, rather than injecting the drugs into a T connector at the IV site, which can be difficult to perform rapidly in a struggling child. To prevent precipitation of drugs in the IV tubing and to ensure rapid delivery of the drug to the patient, each drug was flushed with 5 mL of isotonic sodium chloride solution from an in-line stopcock. The total time taken to inject and flush all drugs in each patient was <10 s. In one patient, the thiopental was not adequately flushed before the administration of Roc, which led to visible precipitation in the line. The resulting intubating conditions were poor in this patient.

We conclude that, in our population of pediatric patients scheduled for emergency surgery, Sch and Roc provide comparable conditions for accomplishing intubation within <60 s of administration. Our data suggest that Roc can be substituted for Sch during RSI in pediatric patients in whom a rapid return to spontaneous respiration is not desired.