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Sex-Related Differences in the Effect-Site Concentration of Remifentanil for Preventing QTc Interval Prolongation Following Intubation in Elderly Patients with a Normal QTc Interval

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Abstract

Background

Female sex and age more than 65 years are common risk factors for the development of torsades de pointes in association with heart rate-corrected QT (QTc) interval prolongation, which can be induced by tracheal intubation during general anaesthesia. However, the administration of remifentanil can prevent intubation-induced QTc interval prolongation. We compared sex-related differences in the effect-site concentration (Ce) of remifentanil for preventing QTc interval prolongation among elderly patients.

Methods

Twenty-two female and 22 male patients older than 65 years were enrolled. Anaesthesia was induced with remifentanil and propofol using a target-controlled infusion. The Ce of remifentanil for maintaining a QTc interval prolongation <15 ms following intubation was determined for each sex using the isotonic regression method and a bootstrapping approach following Dixon’s up-and-down method.

Results

The Ce of remifentanil for preventing QTc interval prolongation following intubation in 50 % of the population (EC50) and 95 % of the population (EC95) were significantly lower in females than in males. Isotonic regression revealed that the EC50 (83 % confidence interval) of remifentanil was 3.50 (2.95–4.08) ng/mL in females and 4.38 (4.08–4.63) ng/mL in males. The EC95 (95 % confidence interval) of remifentanil was 4.43 (4.25–4.48) ng/mL in females and 4.94 (4.78–4.98) ng/mL in males.

Conclusions

Target-controlled infusion of remifentanil is effective in attenuating QTc interval prolongation after intubation among elderly patients and the Ce of remifentanil is lower in females than in males.

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Acknowledgments

The authors thank the biostatisticians of the Department of Research Affairs for their statistical comments and analysis as well as Dong-Su Jang, MFA, medical illustrator, Medical Research Support Section, Yonsei University College of Medicine, for his help with the figures.

Conflict of interest

This study was supported by a new faculty research seed money grant for 2013 from Yonsei University College of Medicine (8-2013-0016).

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Correspondence to D. W. Han.

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Clinical Trials registry number: NCT01720498.

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Kim, S.Y., Song, M.K., Kim, MS. et al. Sex-Related Differences in the Effect-Site Concentration of Remifentanil for Preventing QTc Interval Prolongation Following Intubation in Elderly Patients with a Normal QTc Interval. Drugs Aging 31, 695–702 (2014). https://doi.org/10.1007/s40266-014-0198-9

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