Yonsei Med J.  2014 May;55(3):807-814. 10.3349/ymj.2014.55.3.807.

Sex Differences in Remifentanil Requirements for Preventing Cough during Anesthetic Emergence

• Soh S
• Park WK
• Kang SW
• Lee BR
• Lee JR

• KMID: 2068695
• DOI: http://doi.org/10.3349/ymj.2014.55.3.807

Abstract

PURPOSE
Target-controlled infusion (TCI) of remifentanil can suppress coughing during emergence from general anesthesia; nevertheless, previous studies under different clinical conditions recommend significantly different effective effect-site concentrations (effective Ce) of remifentanil for 50% of patients (EC50). The differences among these studies include type of surgery and patient sex. In recent years, study of sex differences in regards to anesthetic pharmacology has drawn greater interest. Accordingly, we attempted to determine the effective Ce of remifentanil for preventing cough for each sex under the same clinical conditions.
MATERIALS AND METHODS
Twenty female and 25 male ASA physical status I-II grade patients between the ages of 20 and 46 years who were undergoing thyroidectomy were enrolled in this study. The effective Ce of remifentanil for preventing cough was determined for each sex using the isotonic regression method with a bootstrapping approach, following Dixon's up-and-down method.
RESULTS
Isotonic regression with a bootstrapping approach revealed that the estimated EC50 of remifentanil for preventing coughing during emergence was significantly lower in females {1.30 ng/mL [83% confidence interval (CI), 1.20-1.47 ng/mL]} than in males [2.57 ng/mL (83% CI, 2.45-2.70 ng/mL)]. Mean EC50 in females was also significantly lower than in males (1.23+/-0.21 ng/mL vs. 2.43+/-0.21 ng/mL, p<0.001). Mean arterial pressure, heart rate, and respiratory rate over time were not significantly different between the sexes.
CONCLUSION
When using remifentanil TCI for cough prevention during anesthetic emergence, patient sex should be a considered for appropriate dosing.

Keyword

Sex difference; effect-site concentration; general anesthesia; remifentanil; target-controlled infusion; cough prevention

MeSH Terms

Adult
Anesthesia, General/*adverse effects
Cough/*prevention & control
Female
Humans
Male
Middle Aged
Piperidines/*administration & dosage/*therapeutic use
Sex Factors
Young Adult
Piperidines

Figure

• 

  Fig. 1 Assessment of success or failure of smooth emergence over the predetermined concentration of remifentanil based on consecutive patients by Dixon's up-and-down method. Mean EC50 for smooth emergence was calculated from cross-over pairs from failure (open circle) to success (closed circle) in 25 male patients (A) and 20 female patients (B). EC50, effective effect-site concentration (Ce) of remifentanil for suppression of emergence cough in 50% of patients.

• 

  Fig. 2 Pooled-adjacent-violators algorithm response rate in female (▲) and male (●) groups. EC50 of remifentanil in females was 1.30 ng/mL (83% CI, 1.20-1.47 ng/mL) and 2.57 ng/mL (83% CI, 2.45-2.70 ng/mL) in males. EC95 in females was 1.86 ng/mL (95% CI, 1.56-1.96 ng/mL) and 2.96 ng/mL (95% CI, 2.77-2.98 ng/mL) in males. Both EC50 and EC95 were significantly lower in the female group than in the male group. EC50, effective Ce of remifentanil for suppression of emergence cough in 50% of patients; EC95, effective Ce of remifentanil for suppression of emergence cough in 95% of patients; CI, confidence interval.

• 

  Fig. 3 MAP, HR, and RR were not significantly different in females (▲) and males (●) over time (p-values for MAP, HR, and RR=0.351, 0.082 and 0.277, respectively). The female MAP was significantly higher than that of males at the end of the surgery, 10 min after extubation, and before transfer out from the postanesthetic care unit (p=0.012, p<0.001, and p<0.001, respectively). With regard to HR, there was no significant difference at any time point. RR increased continuously from each prior time point in both males and females: just after extubation to 5 min after extubation (p<0.001), 5 min after extubation to10 min after extubation (p<0.001), and 10 min after extubation to before transfer out from the post-anesthetic care unit (p<0.001). MAP, mean arterial pressure; HR, heart rate; RR, respiratory rate; bpm, breaths per min.

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