Comparison of the effects of ketamine or lidocaine on fentanyl-induced cough in patients undergoing surgery: A prospective, double-blind, randomized, placebo-controlled study

Curr Ther Res Clin Exp. 2010 Oct;71(5):289-97. doi: 10.1016/j.curtheres.2010.10.004.


Background: Fentanyl-induced cough is common but has not been viewed as a serious anesthetic problem. However, the cough may be explosive at times, may require immediate intervention, and may be associated with undesirable increases in intracranial, intraocular, and intra-abdominal pressures. Prevention of fentanylinduced cough in such situations is of paramount importance. Ketamine, at concentrations achieved with standard clinical doses, has a direct relaxant effect on airway smooth muscle.

Objective: This study was designed to assess the effects of ketamine or lidocaine on fentanyl-induced cough.

Methods: This double-blind, randomized, placebo-controlled study was conducted at the Erciyes University Medical School, Kayseri, Turkey. Consecutive adult patients aged 18 to 65 years and classified as American Society of Anesthesiologists physical status I or II who were undergoing elective surgery with general anesthesia were enrolled. Patients were randomly allocated equally into 3 groups to receive lidocaine 1 mg/kg, ketamine 0.5 μg/kg, or placebo intravenously 1 minute before fentanyl administration. Following intravenous fentanyl (1.5 μg/kg over 2 seconds) injection, an observer, unaware of the type of medication given to the patients, recorded the number of episodes of coughing, if any. Any episode of cough was classified as coughing and graded by investigators blinded to treatment as mild (1-2 coughs), moderate (3-4), or severe (≥5). Blood pressure, heart rate, pulse oximetry oxygen saturation (SpO2), and adverse effects (AEs) were recorded.

Results: A total of 368 patients were approached for inclusion; 300 patients met the inclusion criteria and were enrolled in the study. No patients in the ketamine group had cough. The frequency of cough was significantly lower in the lidocaine (11/100 [11%]; P = 0.024) and ketamine (0/100; P = 0.001) groups compared with the placebo group (23/100 [23%]). The intensity of cough was significantly lower in the lidocaine (mild, 7/100 [7%]; moderate, 4/100 [4%]; P = 0.037) and ketamine (0/100; P < 0.001) groups compared with the placebo group (mild, 10/100 [10%]; moderate, 12/100 [12%]; severe, 1/100 [1%]). Severe cough (≥5) was observed in 1 patient in the placebo group. Incidence and intensity of cough were significantly decreased in the ketamine group compared with the lidocaine group (incidence, P = 0.001; intensity, P = 0.003). There were no significant differences between groups with respect to systolic blood pressure, diastolic blood pressure, heart rate, SpO2, and AEs.

Conclusion: Intravenous ketamine (0.5 mg/kg) significantly reduced the reflex cough induced by fentanyl compared with lidocaine and placebo, and was well tolerated.

Keywords: coughing; fentanyl; ketamine; lidocaine.