Abstract
Background
Priming is a well-known method to accelerate the onset of action of nondepolarizing neuromuscular-blocking agents. It consists of administration of a small dose of neuromuscular blocking agent several minutes before the principal dose is given. Ephedrine has been shown to improve the intubating conditions of rocuronium following its priming with a small dose. However, the potential effects of ephedrine on intubating conditions using atracurium after its priming with a small dose have not yet been studied. Since rocuronium is not available in Iran, atracurium is widely used as an alternative.
Methods
We studied two groups of patients, each group consisting of 32 patients. One group received ephedrine after priming (PE) and the other received placebo following priming (P). There were no significant differences between the two groups in age, sex, physical status (assessed using the American Society of Anesthesiologists classification), baseline mean arterial pressure and baseline heart rate. Patients with anticipated difficult airway, hypertension, obesity, any evidence of neuromuscular, cardiovascular, respiratory, hepatic, or renal disease, as well as those taking medications known to interact with atracurium or ephedrine were excluded. The anesthesiologist, the physician responsible for recording the results, and the statistician interpreting them were blinded to group allocations. Intubating conditions were graded according to Cooper's criteria. A clinically acceptable outcome was defined as good or excellent intubating conditions, represented by overall scores of 6–7 and 8–9, respectively.
Results
Intubating conditions were clinically acceptable in 22 patients in the PE group and 15 patients in the P group (p = 0.13). Vocal cord position and jaw relaxation scores during intubation and response to intubation did not differ significantly between the two groups. The mean arterial pressure showed significant differences over the course of time between the two groups (p < 0.01). Heart rate exceeded 120 bpm more frequently in the PE than in the P group (p < 0.01).
Conclusion
The effects of ephedrine on improving intubating conditions following atracurium priming were not statistically significant. Given the risk of exacerbation of coronary ischemia by tachycardia, and the negative results on intubating conditions in our study, we cannot recommend the use of ephedrine for improving intubating conditions following priming with atracurium.
Keywords
atracurium; ephedr; ineintubation, intratracheal;
1. Introduction
Priming, a popular method to accelerate the onset of non-depolarizing neuromuscular-blocking agents, is to administer a fraction of the paralyzing dose of neuromuscular blocking drug several minutes before the principal dose is given for intubation.1 The onset time of a drug may be shortened if an agent that can increase cardiac output is given simultaneously.2 Ephedrine, an indirect sympathomimetic agent, has been used for this purpose.3−9 Indeed, it has been shown that ephedrine improves intubating conditions following priming with rocuronium.10
Since the availability of rocuronium is limited in Iran, atracurium is widely used. For this reason, we decided to evaluate the effects of ephedrine on intubating conditions using atracurium following its priming in a triple-blinded, randomized clinical trial.
2. Methods
Sixty-four patients (29 females), aged 15−70 years, undergoing elective surgery under general anesthesia were included in the study. All patients were of ASA physical status I or II.11 All patients gave their informed consent and the study protocol was approved by the local ethics committee. Exclusion criteria were an anticipated difficult airway, hypertension, taking medications known to interact with atracurium or ephedrine, obesity (body mass index > 30 kg/m2 ), and evident neuromuscular, cardiovascular, respiratory, hepatic, or renal disease.
All patients were premedicated with midazolam 0.03 mg/kg and fentanyl 1.5 μg/kg. Atracurium at 0.04 mg/kg was used for priming. Two minutes and 45 seconds after priming, patients were given propofol 2.5 mg/kg plus either ephedrine 70 μg/kg (PE group) or placebo (normal saline) 70 μg/kg (P group). Each group included 32 patients and allocation of patients to groups was carried out by randomization. Intubation was performed 30 seconds after the patients were given the intubating dose of atracurium (0.5 mg/kg). Noninvasive arterial blood pressure and heart rate were recorded at baseline (immediately prior to the priming dose), immediately after intubation, and at 1, 2, and 5 minutes afterwards.
Tracheal intubation was performed and assessed by a single anesthesiologist who was blinded to the group allocation and not involved in the assessment. The physician responsible for recording the results and the statistician interpreting them were also ignorant of the allocation. Intubating conditions were graded according to Cooper’s criteria,12 which com prises jaw relaxation, vocal cord position, and response to intubation. A clinically acceptable outcome was defined as good or excellent intubating conditions, represented by an overall score of 6−7 or 8−9, respectively (Table 1). Further details of the methods can be found elsewhere.10
The χ2 and Student’s t tests were used for comparisons between the two groups, where appropriate. Repeated measures analysis of variance (ANOVA) was used to compare the groups with respect to mean arterial pressure and heart rate changes over time. Data were analyzed using SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). A p value < 0.05 was considered statistically significant.
3. Results
There were no significant differences between the two groups in age, sex and ASA physical status (Table 2). Two patients (6%) in the PE group and three patients (9%) in the P group failed to have intubation within 20 seconds after the intubating dose of atracurium was given (p= 0.5). Intubating conditions were clinically acceptable in 22 patients (69%) in the PE group and in 15 patients (47%) in the P group (p= 0.13). Vocal cord position and jaw relaxation scores during intubation and response to intubation did not show statistically significant differences between the groups (p= 0.30, p= 0.20, and p= 0.06, respectively) (Table 3).
There was no significant difference between the two groups in baseline mean arterial pressure or heart rate (p= 0.12 and p= 0.49, respectively). Mean arterial pressure differed significantly over the course of time between the two groups (p< 0.01), with an in crease immediately after intubation in the PE group. Heart rate, however, was similar over the course of time in both groups (Table 4). During the priming interval, no patient showed any signs of discomfort, palpebral ptosis, blurred vision, respiratory difficulty or hypoxia. During the study period, heart rate exceeded 120 bpm in 15 (46.9%) and four (12.5%) patients in the PE and P groups, respectively (p< 0.01). Tachycardia was uneventful in these 19 patients.
4. Discussion
This study was carried out in two closely similar groups, each consisting of 32 patients. The effects of ephedrine on improving the intubating conditions following atracurium priming were not statistically significant (p= 0.13). The increase and decrease in mean arterial pressure over time was significant in the PE group, corresponding with the sympathomimetic effect of ephedrine. Heart rate exceeded 120 bpm more frequently in the PE than in the P group (p< 0.01).
It has been shown in a recent study that ephedrine improves intubating conditions following priming with rocuronium.10 The study consisted of four groups of patients (31 patients each), i.e. groups PE (priming + ephedrine), P (priming only), E (ephedrine), and NPE (no priming, no ephedrine). The authors concluded that ephedrine in combination with propofol significantly improved clinical intubating conditions 30 seconds after priming with rocuronium compared with priming without ephedrine and ephedrine with out priming. Although we had a comparable sample size and used the same protocol (except atracurium was used instead of rocuronium) for PE and P patients, our results failed to show any statistically significant differences, which we believe was due to insufficient power. One limitation with our study was the lack of neuromuscular monitoring data for a more precise evaluation of the effects of ephedrine on intubating conditions.
Rocuronium is not available in Iran, and atracurium remains the mainstay of neuromuscular blocking for intubation. Therefore, it is not rational to apply the results of studies using rocuronium as a generalization. Tachycardia, even though uneventful in our study, is a potentially important problem. Given the risk of exacerbation of coronary ischemia by tachycardia as a consequence of ephedrine use, and the failure of our results to show a statistically significant difference in intubating conditions, we cannot recommend the use of ephedrine for improving intubating conditions following priming with atracurium.