1 Département d'Anesthésie et de Réanimation and 2 Département de Chirurgie Maxillo-Faciale, Centre Hospitalo-Universitaire Nord, Marseille, France. 3 Department of Anesthesiology, Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, Missouri, USA
* Corresponding author. E-mail: marc.leone{at}ap-hm.fr
Accepted for publication June 17, 2004.
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Abstract |
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Methods. In a randomized prospective study, 81 patients were enrolled to determine which of three target remifentanil blood concentrations was required to blunt coughing during intubation, cuff inflation, and tracheal suctioning. Anaesthesia was achieved with propofol at a steady effect-site concentration of 3.5 µg ml1. The target blood remifentanil concentrations were 5, 10, or 15 ng ml1. These concentrations were maintained for 12 min before intubation.
Results. There was no cough response to intubation in more than 74% of patients and no significant difference in the incidence of coughing with intubation between the three groups. Significant difference in coughing, diminishing with increasing remifentanil target concentration, was observed with cuff inflation (P=0.04) and tracheal suctioning (P=0.007). Bradycardia and hypotension was more frequent with the remifentanil target concentration of 15 ng ml1. Tracheal suctioning resulted in more coughing than intubation (P=0.01) or cuff inflation (P=0.004).
Conclusion. Target remifentanil blood concentrations of 5, 10, and 15 ng ml1 associated with a 3.5 µg ml1 propofol target blood concentration provided good intubating conditions and absence of cough about 75% of the time. Higher target remifentanil concentrations were associated with less coughing during tracheal tube cuff inflation and tracheal suctioning.
Keywords: analgesic techniques, i.v. ; analgesics opioid, remifentanil ; intubation, tracheal ; lung, trachea, suction
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Introduction |
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Our objective was to determine the most appropriate target concentration of remifentanil required to blunt the cough response, whilst maintaining a steady effect-site concentration of propofol, during three procedures that typically induce a cough reflex.
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Methods |
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Statistics
The hypothesis of this study was that there would be a clinically meaningful difference in the incidence of coughing during intubation among the three groups according to remifentanil target blood concentrations. In order to detect a decrease in the cough response from 50 (the highest incidence) to 10% (the lowest incidence), 25 patients would be required in each of the three groups with a power of 80% and a P-value of 0.05.
Descriptive statistics, means and SD, were calculated for continuous variables, and frequencies for qualitative variables. Comparative statistics used included, 2 or Fisher's tests to compare qualitative variables, and Student's t-test or non-parametric tests to compare quantitative variables. The level of significance was set at 0.05.
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Results |
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Tracheal suctioning resulted in more coughing than intubation (43 vs 21%, P=0.01) and cuff inflation (43 vs 19%, P=0.004). No significant difference in coughing was observed between intubation and cuff inflation. If we excluded the subgroup of patients requiring lidocaine spray, the absence of coughing was achieved in 62% of patients during tracheal suctioning compared with 87% during intubation (P=0.005) and 84% during cuff inflation (P=0.01). In the same subgroup of patients, who did not receive lidocaine, a significant association between the target blood concentration of remifentanil and coughing during tracheal suctioning was shown (P=0.007). This association was not found for intubation and cuff inflation.
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Discussion |
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The optimal target blood concentration of remifentanil for blunting coughing during procedures such as intubation, cuff inflation, and tracheal suctioning appears to be at least 10 ng ml1. A target blood concentration of 5 ng ml1 does not blunt the cough reflex in about 30% of patients during procedures but this was improved at 10 ng ml1. This is comparable with a previous study, which concluded that an effect-site concentration of remifentanil 8 ng ml1 with an effect-site concentration of propofol 3 µg ml1 provides satisfactory conditions for intubation.10 The intubation in that study10 occurred 4 min after the induction of anaesthesia, whereas a 12-min period was chosen in the present study. This longer time interval was chosen to allow both drugs to reach a steady state at the time of intubation.8 Rapid injection of propofol produces significantly higher peak arterial propofol concentrations.11 The different rate of drug injection may explain the higher concentrations required in the present study to achieve a similar rate of good conditions during intubation. Moreover, a target of 3.5 µg ml1 is in agreement with the reported propofol concentration at which consciousness was lost in 50% of the patients, 3.4 µg ml1.12 Although a computer simulation suggested that the optimal blood propofol and remifentanil concentrations with respect to satisfactory intraoperative anaesthetic conditions were 2.0 µg ml1 and 6.3 ng ml1, respectively, such concentrations, in our clinical experience, do not prevent a cough response to powerful stimuli like intubation and tracheal suctioning.1
Remifentanil has been recommended for neurosurgery,2 and is widely used for eye and ear surgery.4 During such delicate surgery, the inhibition of coughing is recommended to avoid surgical complications.4 Tracheal suctioning, a powerful stimulus for coughing, may occasionally be indicated during anaesthesia. When coughing is stimulated during eye surgery, complications such as suprachoroidal haemorrhage may occur.13 Our study suggests that tracheal suctioning is a stronger cough-inducing stimulus than intubation or cuff inflation, as remifentanil 5 ng ml1 was associated with coughing in 66% of patients, whereas there was no cough reflex with tracheal suctioning in 73% of patients with a 15 ng ml1 target blood concentration. Such target concentrations induce hypotension and bradycardia. This is consistent with the finding that opioids blunt somatic and autonomic responses to tracheal stimulation in a concentration-dependent manner.14
The present study has several limitations. The use of lidocaine in patients with closed or moving vocal cords could have resulted in a decreased cough reflex. However, the results in this study were the same for all end points whether or not the patients who received lidocaine were included in the analysis. The target concentrations are based on mathematical pharmacokinetic models, and actual plasma concentrations were not measured. We did not assess the vocal cord damage and postoperative hoarseness. A recent study15 showed that the quality of tracheal intubation contributes to laryngeal morbidity; good intubating conditions are less frequently associated with postoperative hoarseness and vocal cord damage. Adding atracurium to a propofolfentanyl induction regimen significantly improved the quality of tracheal intubation and decreased postoperative hoarseness and vocal cord damage.15 Our results suggest that induction without neuromuscular blocking agents may not provide optimal conditions for intubation in a large propoprtion of patients, even with the highest target remifentanil concentration (15 ng ml1).
In conclusion, a suitable target remifentanil concentration to decrease the likelihood of a cough reflex during intubation may be at least 10 ng ml1, with a propofol target concentration of 3.5 µg ml1. This combination is associated with coughing in 30% of patients during tracheal suctioning. The addition of a neuromuscular blocking agent, or possibly a higher target propofol concentration, is advisable when the cough reflex could induce surgical complications.
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Appendix |
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A remifentanil infusion of 0.2 µg kg1 min1 during 12 min in 70 kg male adults typically results in blood concentrations of 5 ng ml1, and a 0.6 µg kg1 min1 infusion typically results in blood concentrations 15 ng ml1 of remifentanil. A blood concentration of 15 ng ml1 may be achieved in 4 min with a 1.5 µg kg1 bolus for 1 min followed by 1 µg kg1 min1 infusion until the fourth minute.
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Acknowledgments |
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References |
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