BJA Advance Access published online on May 16, 2007
British Journal of Anaesthesia, doi:10.1093/bja/aem125
The effect of ephedrine on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium
Department of Anaesthesiology, Kasturba Medical College, Manipal 576104, India
* Corresponding author. E-mail: hmkrishna20032002{at}yahoo.com
Accepted for publication April 3, 2007.
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Abstract |
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Background: We compared the effect of pre-treatment with ephedrine 75, 100, 150 µg kg–1 and saline on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium.
Methods: One hundred adult patients randomized into one of the four groups—PE 75, PE 100, PE 150, and saline (control) groups—were pre-treated with i.v. ephedrine 75, 100, 150 µg kg–1 or saline, respectively, 1 min before rapid tracheal intubation using propofol 2.5 mg kg–1 and rocuronium 0.6 mg kg–1. A blinded anaesthesiologist assessed the intubating conditions. Heart rate and mean arterial pressure were recorded before anaesthesia induction (baseline), post-induction, and every minute after intubation for 5 min. A 20% change in haemodynamic variables from baseline was regarded as clinically significant. Data were analysed using ANOVA test with post hoc Tukey's test and 
2 or Fisher's exact test. P<0.05 was regarded as significant.
Results: Patient characteristics, baseline heart rate, and mean arterial pressure were comparable between the groups. Intubating conditions were significantly better in the PE 75 (P=0.003) and PE 100 (P=0.001) groups. A significant increase in heart rate was observed in the PE 75 and PE 150 groups when compared with the saline group. A statistically significant difference in mean arterial pressure was noted between PE 75 and PE 150 groups and between PE 150 and saline groups at most of the time intervals. However, when considering the clinical significance of these, all groups were comparable (P>0.05).
Conclusions: Ephedrine either 75 or 100 µg kg–1 given before rapid tracheal intubation using propofol and rocuronium bromide improves the intubation conditions. It is not effective in preventing the hypotension which follows ensuing induction of anaesthesia.
Keywords: anaesthetics i.v., propofol; haemodynamics; heart, heart rate; induction, rapid sequence; intubation, intubating conditions; mean arterial pressure; neuromuscular block, rocuronium; premedication, ephedrine
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Introduction |
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Rocuronium is the currently preferred non-depolarizing neuromuscular blocking agent used as an alternative to succinylcholine for rapid tracheal intubation. Recognizing the problem of prolonged duration of action with larger doses, attempts were made to decrease the dose of rocuronium without compromising on its onset time or intubating conditions.1 Thus, the use of ephedrine during the induction of general anaesthesia has been described to accelerate the onset of action of rocuronium and improve the intubating conditions.23 It may also prevent hypotension associated with the use of propofol during induction of anaesthesia.4–6 However, various dosages of ephedrine have been recommended to achieve those objectives. It is desirable to use an appropriate dose of ephedrine to reap both these benefits without undue side-effects such as hypertension or tachycardia. In this study, we compared the influence of ephedrine 75, 100, 150 µg kg–1, and saline given before induction with propofol for rapid tracheal intubation using rocuronium bromide on (1) intubating conditions and (2) the accompanying haemodynamic changes (mean arterial pressure and heart rate).
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Methods |
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This prospective, randomized, double-blinded study was conducted after obtaining approval from the institutional review board. ASA physical status I patients of either gender aged 18–60 yr, weighing 35–75 kg undergoing elective surgical procedures requiring general tracheal anaesthesia were included. Exclusion criteria were: morbidly obese patients, anticipated difficult airway, pregnancy, drugs that influence induction agents or neuromuscular blocking agents, neuromuscular disorder, and history of known allergy to drugs used in the study. On the basis of our pilot study, we enrolled 100 patients into the study to provide a power of 80% (P=0.05).
The written informed consent of all the patients was taken. Randomization into one of the four groups was done by a computer-generated random number table and sealed envelope technique. The four groups were:
- PE 75 group;
- PE 100 group;
- PE 150 group; and
- Saline (control) group.
Patients were premedicated with oral diazepam 5 mg (if body weight <50 kg) or 10 mg (if body weight >50 kg) the night before the surgery and 2 h before the surgery. As per our hospital policy, patients were fasted 6 h for solid food and 2 h for clear fluids.
After transferring the patients into the operating room, standard monitoring (five lead ECG, Spo2, automated non-invasive arterial pressure by oscillometry) was instituted. I.V. access was obtained and infusion of lactated Ringer was started at a rate of 2 ml kg–1 h–1. All patients were preoxygenated with oxygen 100% for 3 min. An i.v. bolus of fentanyl 1 µg kg–1 rounded off to the nearest 5 µg was given 1 min after the start of preoxygenation. One minute after fentanyl injection, the study drug comprising of either ephedrine in the dosage of 75, 100, or 150 µg kg–1 in the groups PE 75, PE 100, and PE 150, respectively, rounded off to the nearest saline 0.5 mg, or saline 0.9% for the saline (control) group was injected. The study drug was prepared by an anaesthesiologist not involved in the study in an unlabelled 5-ml syringe, with the volume made to 5 ml using saline 0.9% as diluent.
After 3 min of preoxygenation, anaesthesia was induced with propofol 2.5 mg kg–1 rounded off to the nearest multiple of 10 mg in all the groups. Train-of-four (TOF) ratio monitoring in response to ulnar nerve stimulation was begun using TOF-GUARDTM. After induction of anaesthesia, rocuronium 0.6 mg kg–1 (rounded off to the nearest multiple of 5 mg) was given over 5 s in a running infusion. To each 10 ml of propofol 1% 1 ml of preservative-free lignocaine 2% was added in all the groups. Mask ventilation was not done till tracheal intubation, unless the oxygen saturation decreased to <95%.
An anaesthesiologist with at least 3 yr of experience, blinded to study drug, performed laryngoscopy and tracheal intubation with an appropriate sized Macintosh blade 60 s after administration of rocuronium. The anaesthesiologist also assessed the intubating conditions as per the intubation scoring system of the Consensus Conference on Good Clinical Research Practice in Pharmacodynamic Studies of Neuromuscular Blocking Agents, Copenhagen consensus.7 Oral tracheal tubes (7.0 and 8.0 mm, internal diameter) were used for female and male patients, respectively. The cuff was inflated with air until the disappearance of a palpable leak on positive pressure ventilation.
Patients' mean arterial pressure (as recorded by non-invasive monitoring), heart rate (as displayed by the electrocardiograph monitor), and oxygen saturation were recorded pre-induction (base line), just before intubation, and every minute thereafter for 5 min. A 20% change in haemodynamic variables from the baseline value was regarded as significant and managed by the concerned anaesthesiologist at their discretion. The duration of laryngoscopy (time from the insertion of the laryngoscope blade into the patient's mouth to its removal after successful intubation), TOF ratio (ulnar nerve stimulation; adductor pollicis response to supramaximal stimuli) at 60 s after rocuronium administration using TOF-GUARD, time for the disappearance of all four twitches on TOF count, and reaction of the patient to tracheal intubation were recorded.
Anaesthesia was maintained with oxygen 33%, nitrous oxide 66%, and halothane 1% after intubation for 5 min with positive pressure ventilation maintaining normocapnia. Care was taken to avoid any stimulus during the study period after intubation. Data were analysed using SPSS Version 9 for Windows. Duration of laryngoscopy, TOF ratio at 60 s, time for disappearance of all four twitches on TOF count, and haemodynamic variables were compared between the groups using ANOVA test and post hoc Tukey's test. Intubating conditions, and clinical significance of the haemodynamic changes, were compared among the groups using 2-test or Fisher's exact test as appropriate. A P-value <0.05 was regarded as significant.
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Results |
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Among the 100 patients recruited in the study none was excluded. Patient characteristics were comparable among the groups (Table 1). Duration of laryngoscopy was comparable among the groups (Table 2). Time for disappearance of all the four twitches on TOF count was comparable (P=0.635) (Table 2). TOF ratio at the end of 60 s after rocuronium administration was similar in the saline group when compared with the ephedrine-treated groups (P=0.284) (Table 2). Intubating conditions were significantly better in the PE 75 (P=0.003) and PE 100 (P=0.001) groups when compared with the saline group (Table 3). Baseline heart rate and mean arterial pressures were comparable between the groups. There was a significant increase in the heart rate in the PE 75 and PE 150 groups when compared with the saline group, which persisted until the end of the study period (Fig. 1). There was a statistically significant difference in the mean arterial pressure between groups PE 75 and PE 150, and between PE 150 and saline groups at most of the time intervals of the study period (Fig. 2). Considering a 20% change in haemodynamic variable from the baseline to be significant, all groups were comparable.
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Discussion |
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We found that ephedrine in the dosage of either 75 or 100 µg kg–1 given before rapid tracheal intubation with propofol 2.5 and rocuronium bromide 0.6 mg kg–1 improves intubation conditions. However, there was no clinically significant difference in mean arterial pressure and heart rate among the groups during the first 5 min after intubation.
Rocuronium used in the lower dose of 0.6 mg kg–1 for rapid tracheal intubation is known to provide suboptimal intubating conditions in 20–25% of patients.8 This could be as a result of a decrease in cardiac output caused by the induction agent resulting in slower onset of action at the laryngeal muscles and the diaphragm. The onset time of a neuromuscular blocking agent is partly determined by the speed with which the drug reaches the neuromuscular junction, a factor that appears to be proportional to cardiac output and muscle blood flow. Studies using induction agents that maintain cardiac output and arterial pressure (i.e. etomidate and ketamine) have suggested that the use of these drugs was associated with faster onset of action and better intubating conditions with rocuronium.910 Ephedrine, by increasing the cardiac output and tissue perfusion, and resulting in faster delivery of rocuronium to the laryngeal and diaphragmatic muscles might shorten the onset of action of rocuronium and improve the intubating conditions.311
On the basis of this hypothesis, ephedrine added to propofol during induction was found to improve the intubating conditions with rocuronium 0.6 mg kg–1.3 However, a fixed dosage of ephedrine (not based on the patient's body weight) was used and their observations were not substantiated with neuromuscular monitoring. The authors suggested the need for further studies to identify the ideal dose of ephedrine along with quantitative measurement of the onset of neuromuscular block.
In our study, ephedrine 75 and 100 µg kg–1 pre-treatment before propofol induction resulted in better intubating conditions, similar to the findings of the earlier study.3 An additional finding is that increasing the dosage of ephedrine from 100 to 150 µg kg–1 did not improve the intubating conditions. Probably, ephedrine in the excess dosages may produce vasoconstriction of blood vessels supplying laryngeal muscles, thus limiting the access of the relaxant to its site of action. The findings of neuromuscular monitoring in our study do not support the hypothesis that the ephedrine pre-treatment improves the intubating conditions by shortening the onset of action of rocuronium. The times for disappearance of all four twitches on TOF count and the TOF ratio at the end of 60 s of rocuronium injection were comparable among the groups. Most of the patients in all the groups had all four twitches to TOF stimuli even at 90 s. The lack of agreement between the blockade characteristics at the laryngeal muscles and the adductor pollicis is well demonstrated in the literature.12–15 However, as the site of monitoring was the same in all four groups, the results can still be compared for the difference in onset of neuromuscular block. The mechanism by which ephedrine improves the intubating conditions still remains obscure. Whether other inotropic agents that increase the cardiac output can also improve the intubating conditions needs to be studied.
Heart rate increased in all the ephedrine pre-treated patients in our study. This is similar to the findings of the earlier studies.56 There was, however, no significant difference among the ephedrine-treated groups. Thus, caution needs to be exercised in the subset of patients in whom ephedrine-induced tachycardia might be detrimental (e.g. patients with ischaemic heart disease). In such cases the risk of tachycardia has to be weighed carefully against the benefit of improved intubating conditions. Despite ephedrine pre-treatment, there was a decrease in mean arterial pressure in the immediate post-induction period. There was no clinically significant difference in mean arterial pressure and heart rate among the groups during the first 5 min after intubation (considering 20% change as clinically significant). Thus, prophylactic injection of ephedrine only attenuates, but does not completely abolish the decrease in arterial pressure associated with induction of anaesthesia using fentanyl and propofol.5
We performed rapid tracheal intubation with opioids, propofol, and rocuronium. Cricoid pressure was deliberately avoided. This procedure was standardized for all the groups. Despite these modifications, we believe that our results can be extrapolated for rapid sequence induction.
We conclude that pre-treatment with ephedrine either 75 or 100 µg kg–1 improves the intubating conditions during rapid tracheal intubation using propofol and rocuronium. However, it is not effective in preventing the hypotension which follows induction of anaesthesia.
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References |
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1 Magorian T, Flannery KB, Miller RD. Comparison of rocuronium succinylcholine and vecuronium for rapid sequence induction of anesthesia in adult patients. Anesthesiology (1993) 79:913–8.[Web of Science][Medline]
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