類鴉片成癮性止痛劑Fentanyl引發之乾咳與氣道過度反應之研究

Fentanyl-induced Coughing and Airway Hyperresponsiveness

背景：類鴉片止痛劑，諸如morphine等藥物，具有鎮咳之藥理作用，此鎮咳之藥理機轉可能與鴉片接受器有關。有趣的是，某些類鴉片止痛劑也具有引發乾咳的作用；在有限文獻紀載中，使用諸如fentanyl等類鴉片止痛劑做為臨床麻醉誘導，甚至可高達有40％以上病患產生乾咳。由於咳嗽機轉包括週邊、中樞、及傳入傳出途徑等標的，本臨床研究針對週邊機轉，亦即病患之氣道反應性，作一與fentanyl誘發咳嗽之相關性研究。方法：採用性別、年齡配對之個案對照研究。受試者必須簽署受試者同意書。選取26位曾經於麻醉誘導中，因給與fentanyl而引發乾咳之病患為實驗組，同時另外配對選取26位於同一期間亦接受麻醉，而無fentanyl引發乾咳之病患，作為對照組。選取或排除病患之條件皆事先訂出。凡有可能影響實驗結果之介入因素，皆予以控制、分析。先取得每位參與實驗病患之基礎呼吸功能參數。呼吸道反應性則以methacholine激發試驗取得之PC20或支氣管擴張試驗為評估依據。結果：實驗組與對照組發生氣道過度反應的比例分別為30.77％及19.23％。配對比較後，McNemar檢驗顯示，兩組之差別並未達到統計上顯著水準(P = 0.257)。結論：統計結果無法證實類鴉片止痛劑fentanyl引發之乾咳與氣道過度反應之間有顯著的相關性。

Background: The tussive effect of fentanyl, in sharp contrast to the antitussive effect that common opioids have, is not rarely seen in clinical anesthesia. Pretreatment with β2 agonist inhalation could dramatically suppress fentanyl-induced coughing. We hypothesized that airway hyperresponsiveness might exist in large proportion of the subjects who had experienced fentanyl-induced coughing during previous anesthesia. Methods: We designed a case-controlled matching study to investigate the correlation between fentanyl-induced coughing and airway hyperresponsiveness. Twenty-six consecutive subjects (ASA I-III), who experienced fentanylinduced coughing during anesthesia in our hospital from 1999 to 2000, were enrolled in this study as the fentanylcough group. In all the subjects baseline spirometry was first obtained. Airway responsiveness was evaluated with either PC20 of methacholine challenge test or bronchodilator test. After matching age and sex, another 26 subjects without history of fentanyl-induced coughing during previous anesthesia were also enrolled in the study as the control group. Results: The proportion of airway hyperresponsiveness in fentanyl-cough group and control group was 30.77% and 19.23% respectively. After pairing of these two groups, McNemar test revealed no significant difference in the proportion of airway hyperresponsiveness between these two groups (P = 0.257). Conclusions: From the analysis of the present study, we cannot prove that there is a direct correlation between fentanyl-induced coughing and airway hyperresponsiveness.