Several studies have demonstrated the usefulness of opioids for preventing cough. The antitussive effect of opioids is primarily central, and maintaining a certain effect site opioid concentration with TCI is considered reliable. Remifentnil is an ultrashort-acting opioid that is a suitable agent for this purpose, because its effect quickly and predictably disappears after cessation without delayed recovery from anesthesia.[22,23] In several studies, a TCI of remifentanil during anesthetic emergence was reported to allow patients to recover from general anesthesia without coughing or hemodynamic instability,[8,23,24] and several studies extrapolated the effective Ce of remifentanil for preventing airway reflexes during anesthetic emergence.[7–10]
In the up-and-down sequential allocation design, there are several methods for estimating EC: the Dixon method, logistic/probit regression, and isotonic regression. Among these methods, we adapted the isotonic regression method for estimating the EC of remifentanil. Because the Dixon method is a simplified design focusing on EC50, extrapolation to higher quartiles such the EC95 calculated in an up-and-down sequential allocation design may impose great bias and cannot be a reliable value. The estimated EC95 of remifentanil to prevent cough cannot be readily applied to clinical practice and should be confirmed in a properly designed study for determining EC95, like a biased coin design that can directly estimate EC at any quartile.
This study has several limitations. First, we did not measure real plasma concentrations of remifentanil from patient blood sampling. However, because the Minto pharmacokinetic model, used for remifentanil TCI, has been commonly used with acceptable bias and accuracy in clinical situation, this predicted EC of remifentanil can be used reliably in clinical practice. Second, the study population was limited to females between 20 and 65 years of age. Gender may affect opioid effect; males are less sensitive to the analgesic effects of opioid than females and older patients are more sensitive to opioids. These factors should be considered when interpreting the data.
. Jun N, Lee J, Song J, et al. Optimal effect-site concentration of remifentanil
for preventing cough during emergence from sevoflurane-remifentanil
anaesthesia. Anaesthesia 2010;65:930–5.
. Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand 2005;49:1088–91.
. Park SH, Han SH, Do SH, et al. Prophylactic dexamethasone decreases the incidence of sore throat and hoarseness after tracheal extubation with a double-lumen endobronchial tube. Anesth Analg 2008;107:1814–8.
. Sumathi P, Shenoy T, Ambareesha M, Krishna H. Controlled comparison between betamethasone gel and lidocaine jelly applied over tracheal tube to reduce postoperative sore throat, cough, and hoarseness of voice. Br J Anaesth 2008;100:215–8.
. Tagaito Y, Isono S, Nishino T. Upper airway reflexes during a combination of propofol and fentanyl anesthesia
. Anesthesiology 1998;88:1459–66.
. Mendel P, Fredman B, White PF. Alfentanil suppresses coughing and agitation during emergence from isoflurane anesthesia
. J Clin Anesth 1995;7:114–8.
. Lee B, Lee JR, Na S. Targeting smooth emergence: the effect site concentration of remifentanil
for preventing cough during emergence during propofol–remifentanil
anaesthesia for thyroid surgery. Br J Anaesth 2009;102:775–8.
. Choi EM, Park WK, Choi SH, et al. Smooth emergence in men undergoing nasal surgery: the effect site concentration of remifentanil
for preventing cough after sevoflurane-balanced anaesthesia. Acta Anaesthesiol Scand 2012;56:498–503.
. Lee JH, Choi SH, Choi YS, et al. Does the type of anesthetic agent affect remifentanil
effect-site concentration for preventing endotracheal tube-induced cough during anesthetic emergence? Comparison of propofol, sevoflurane, and desflurane. J Clin Anesth 2014;26:466–74.
. Choi SH, Min KT, Lee JR, et al. Determination of EC95 of remifentanil
for smooth emergence from propofol anesthesia
in patients undergoing transsphenoidal surgery. J Neurosurg Anesthesiol 2015;27:160–6.
. Knoll H, Ziegeler S, Schreiber JU, et al. Airway injuries after one-lung ventilation: a comparison between double-lumen tube and endobronchial blocker. Anesthesiology 2006;105:471–7.
. Nishino T, Kochi T, Ishii M. Differences in respiratory reflex responses from the larynx, trachea, and bronchi in anesthetized female subjects. Anesthesiology 1996;84:70–4.
. Nishino T. Physiological and pathophysiological implications of upper airway reflexes in humans. Jpn J Physiol 2000;50:3–14.
. Sant’Ambrogio G, Remmers JE, de Groot WJ, et al. Localization of rapidly adapting receptors in the trachea and main stem bronchus of the dog. Respir Physiol 1978;33:359–66.
. Sant’Ambrogio G. Afferent pathways for the cough reflex. Bull Eur Physiopathol Respir 1987;23(suppl 10):19s–23s.
. Tatar M, Sant’Ambrogio G, Sant’Ambrogio FB. Laryngeal and tracheobronchial cough in anesthetized dogs. J Appl Physiol 1994;76:2672–9.
. Pisarri TE, Jonzon A, Coleridge HM, Coleridge JC. Vagal afferent and reflex responses to changes in surface osmolarity in lower airways of dogs. J Appl Physiol 1992;73:2305–13.
. Minto CF, Schnider TW, Egan TD, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil
. I. Model development. Anesthesiology 1997;86:10–23.
. Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics 2002;58:171–7.
. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia
research. Anesthesiology 2007;107:144–52.
. Dilleen M, Heimann G, Hirsch I. Non-parametric estimators of a monotonic dose-response curve and bootstrap confidence intervals. Stat Med 2003;22:869–82.
. Glass PS, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil
(GI87084B). Anesth Analg 1993;77:1031–40.
. Nho JS, Lee SY, Kang JM, et al. Effects of maintaining a remifentanil
infusion on the recovery profiles during emergence from anaesthesia and tracheal extubation. Br J Anaesth 2009;103:817–21.
. Lee JH, Koo BN, Jeong JJ, et al. Differential effects of lidocaine and remifentanil
on response to the tracheal tube during emergence from general anaesthesia. Br J Anaesth 2011;106:410–5.
. Dahan A, Kest B, Waxman AR, Sarton E. Sex-specific responses to opiates: animal and human studies. Anesth Analg 2008;107:83–95.
. Soh S, Park WK, Kang SW, et al. Sex differences in remifentanil
requirements for preventing cough during anesthetic emergence. Yonsei Med J 2014;55:807–14.
. Hohlrieder M, Tiefenthaler W, Klaus H, et al. Effect of total intravenous anaesthesia and balanced anaesthesia on the frequency of coughing during emergence from the anaesthesia. Br J Anaesth 2007;99:587–91.
. Hamaya Y, Dohi S. Differences in cardiovascular response to airway stimulation at different sites and blockade of the responses by lidocaine. Anesthesiology 2000;93:95–103.
. Nishino T, Anderson JW, Sant’Ambrogio G. Effects of halothane, enflurane, and isoflurane on laryngeal receptors in dogs. Respir Physiol 1993;91:247–60.
. Nishino T, Anderson JW, Sant’Ambrogio G. Responses of tracheobronchial receptors to halothane, enflurane, and isoflurane in anesthetized dogs. Respir Physiol 1994;95:281–94.
. Hans P, Marechal H, Bonhomme V. Effect of propofol and sevoflurane on coughing in smokers and non-smokers awakening from general anaesthesia at the end of a cervical spine surgery. Br J Anaesth 2008;101:731–7.
. Batra YK, Ivanova M, Ali SS, et al. The efficacy of a subhypnotic dose of propofol in preventing laryngospasm following tonsillectomy and adenoidectomy in children. Paediatr Anaesth 2005;15:1094–7.
. McKeating K, Bali IM, Dundee JW. The effects of thiopentone and propofol on upper airway integrity. Anaesthesia 1988;43:638–40.
. Brown GW, Patel N, Ellis FR. Comparison of propofol and thiopentone for laryngeal mask insertion. Anaesthesia 1991;46:771–2.
. Mertens MJ, Engbers FH, Burm AG, Vuyk J. Predictive performance of computer-controlled infusion of remifentanil
anaesthesia. Br J Anaesth 2003;90:132–41.