Original contribution
Premedication with intravenous low-dose ketamine suppresses fentanyl-induced cough

https://doi.org/10.1016/j.jclinane.2006.05.021Get rights and content

Abstract

Study Objective

To evaluate the effect of low-dose ketamine on fentanyl-induced cough.

Design

Prospective, randomized, double-blind, placebo-controlled clinical trial.

Setting

Medical center hospital.

Patients

360 ASA physical status I-II patients aged 18 to 65 years, weighing between 40 and 80 kg, and scheduled for elective surgery during general anesthesia.

Interventions and Measurements

Patients were randomly assigned to receive either ketamine 0.15 mg/kg or placebo (equal volume of 0.9% saline) given intravenously over 10 seconds, one minute before administration of fentanyl (1.5 μg/kg IV, injected within 5 seconds), during induction of general anesthesia. Any episode of cough was classified as coughing and the onset time of cough (the time of the first episode of cough) was observed for one minute after fentanyl administration by a blinded observer. Severity of coughing was graded based on the number of episodes of coughing (mild, 1-2; moderate, 3-5; and severe, >5). Blood pressure, heart rate, and pulse oximetry oxygen saturation (Spo2) were recorded before giving ketamine or 0.9% saline and 1 minute after fentanyl injections.

Main Results

After the intravenous injection of fentanyl bolus, patients in the placebo group showed significantly higher frequency cough than those in the ketamine pretreatment group (21.6% vs 7.2%, P < 0.05), and onset time of the ketamine group was significantly longer than that of the control group (20 ± 8 vs 15 ± 10 seconds, P < 0.01). However, no difference in cough severity was observed between the two groups.

Conclusion

Low-dose ketamine (0.15 mg/kg IV) effectively reduces fentanyl-induced cough and delays the onset time of cough.

Introduction

Fentanyl is often used as a premedicant during induction of general anesthesia (GA) owing to its rapid onset, short duration, intense analgesia, reduced cardiovascular depression, and low histamine release [1], [2]. However, intravenous (IV) administration of fentanyl elicits cough, with frequency ranging from 28% to 65% [3], [4], [5], [6], [7], [8]. Coughing is undesirable during induction of anesthesia and is associated with adverse effects from elevated intracranial, intraocular, and intra-abdominal pressures [4], [5], [6], [7], [8], [9]. Tweed and Dakin [9] reported a case of explosive cough after peripheral IV injection of fentanyl that produced multiple conjunctival and periorbital petechiae. Prevention of fentanyl-induced cough is an important clinical implication.

A number of studies have been conducted to reduce the incidence of fentanyl-induced cough using readily available anesthetic adjuncts (eg, propofol, lidocaine, ephedrine, atropine, and midazolam, with varying success). Kamei et al reported that excitatory amino acids and N-methyl-d-aspartate (NMDA) receptor antagonists are capable of modulating the cough reflex [10]. Intravenous ketamine, an NMDA antagonist, has well-known potent analgesic and bronchodilatory effects [11], [12], [13], [14]. In our experience, the incidence of fentanyl-induced cough seems to be attenuated with ketamine. Thus, we conducted the present study to examine the effect of low-dose ketamine on fentanyl-induced cough.

Section snippets

Materials and methods

This study was approved by the Tri-service General Hospital's institutional review board. Written, informed consent was obtained from all patients before they were enrolled into this randomized, prospective, double-blind, placebo-controlled study. Three hundred sixty ASA physical status I and II patients aged between 18 and 65 years and scheduled for elective surgery during GA, were randomly assigned to one of two groups of 180 patients each, using computer-generated random numbers. Based on a

Results

There were no differences between the two groups in demographic data (Table 1). The hemodynamic data (BP, HR, and Spo2) were also similar and there was no significant difference between groups in baseline or after fentanyl injection (Table 2). After the IV fentanyl bolus injection, patients in the placebo group (39/180, 21.6%) showed a significantly higher frequency of cough than in the ketamine pretreatment group (13/180, 7.2%; P < 0.05), and the onset time of cough was significantly longer in

Discussion

The major finding in the present study is that pretreatment with ketamine 0.15 mg/kg IV reduced the frequency of fentanyl-induced cough from 21.6% to 7.2% and delayed the onset time of cough.

In our previous series, the frequency of fentanyl-induced cough in the placebo group was 18% at the fentanyl dose of 1.5 μg/kg, with an injection time of less than 5 seconds [15]; the frequency of fentanyl-induced cough in our control group was lower than the previously reported range of 28% to 65% [3], [4]

Acknowledgments

The authors thank Dr J. A. Lin for support in conducting this study.

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