Abstract: Objective: Fentanyl-induced cough (FIC) is a common complication with a reported incidence from 18.0% to 74.4% during general anesthesia induction. FIC increases the intrathoracic pressure and risks of postoperative nausea and vomiting, yet available treatments are limited. This study was designed to investigate whether administering fentanyl via a slow intravenous fluid line can effectively alleviate FIC during induction of total intravenous general anesthesia. Methods: A total number of 1200 patients, aged 18–64 years, were enrolled, all of whom were American Society of Anesthesiologists (ASA) grade I or II undergoing scheduled surgeries. All patients received total intravenous general anesthesia, which was induced sequentially by midazolam, fentanyl, propofol, and cisatracurium injection. Patients were randomly assigned to receive fentanyl 3.5 μg/kg via direct injection (control group) or via a slow intravenous fluid line. FIC incidence and the severity grades were analyzed with the Mann-Whitney test. Other adverse reactions, such as hypotension, hypertension, bradycardia, tachycardia, hypoxemia, vomiting, and aspiration, during induction were also observed. The online clinical registration number of this study was ChiCTR-IOR-16009025. Results: Compared with the control group, the incidence of FIC was significantly lower in the slow intravenous fluid line group during induction (9.1%, 95% confidence interval (CI):6.7%–11.4% vs. 55.9%, 95% CI: 51.8%–60.0%, P=0.000), as were the severity grades (P=0.000). There were no statistical differences between the two groups with regard to other adverse reactions (P>0.05). Conclusions: The administration of fentanyl via a slow intravenous fluid line can alleviate FIC and its severity during induction for total intravenous general anesthesia. This method is simple, safe, and reliable, and deserves clinical expansion.

全麻诱导期经静脉输液管缓慢滴注和快速输注芬太尼对该药诱发呛咳的影响

[1]Agarwal, A., Azim, A., Ambesh, S., et al., 2003. Salbutamol, beclomethasone or sodium chromoglycate suppress coughing induced by iv fentanyl. Can. J. Anaesth., 50(3):297-300.

[2]Cheng, X.Y., Lun, X.Q., Li, H.B., et al., 2016. Butorphanol suppresses fentanyl-induced cough during general anesthesia induction: a randomized, double-blinded, placebo-controlled clinical trial. Medicine, 95(26):e3911.

[3]Cinelli, E., Bongianni, F., Pantaleo, T., et al., 2013. Suppression of the cough reflex by α2-adrenergic receptor agonists in the rabbit. Physiol. Rep., 1(6):e00122.

[4]de Graaff, J.C., Bijker, J.B., Kappen, T.H., et al., 2013. Incidence of intraoperative hypoxemia in children in relation to age. Anesth. Analg., 117(1):169-175.

[5]el Baissari, M.C., Taha, S.K., Siddik-Sayyid, S.M., 2014. Fentanyl-induced cough—pathophysiology and prevention. Middle East J. Anaesthesiol., 22(5):449-456.

[6]Faruqi, S., Murdoch, R.D., Allum, F., et al., 2014. On the definition of chronic cough and current treatment pathways: an international qualitative study. Cough, 10(1):5.

[7]Firouzian, A., Emadi, S.A., Baradari, A.G., et al., 2015. Can low dose of propofol effectively suppress fentanyl-induced cough during induction of anaesthesia? A double blind randomized controlled trial. J. Anaesthesiol. Clin. Pharmacol., 31(4):522-525.

[8]Gecaj-Gashi, A., Nikolova-Todorova, Z., Ismaili-Jaha, V., et al., 2013. Intravenous lidocaine suppresses fentanyl induced cough in children. Cough, 9(1):20.

[9]He, G., Li, L.I., Guan, E., et al., 2016. Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo. Oncol. Lett., 12(1):563-571.

[10]Joseph, V., Paul, E.M., 2008. Perioperative hypertension management. Vasc. Health. Risk. Manag., 4(3):615-627.

[11]Jung, H.J., Kim, J.B., Im, K.S., et al., 2011. Effects of a priming dose of fentanyl during anaesthesia on the incidence and severity of fentanyl-induced cough in current, former and non-smokers. J. Int. Med. Res., 39(6):2379-2384.

[12]Kamei, J., Nakanishi, Y., Asato, M., et al., 2013. Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways. Cough, 9(1):3.

[13]Kalezic, N., Stojanovic, M., Ladjevic, N., et al., 2013. Risk factors for intraoperative hypotension during thyroid surgery. Med. Sci. Monit., 19:236-241.

[14]Karbasy, S.H., Derakhshan, P., 2016. The effect of low dose fentanyl as a premedication before induction of general anesthesia on the neonatal Apgar score in cesarean section delivery: randomized, double-blind controlled trial. Med. J. Islam. Repub. Iran, 30:361.

[15]Kinsella, S.M., Tuckey, J.P., 2001. Perioperative bradycardia and asystole: relationship to vasovagal syncope and the Bezold-Jarisch reflex. Br. J. Anaesth., 86(6):859-868.

[16]Kurokochi, N., 2001. Age-corrected intraoperative tachycardia correlates with postoperative electrocardiographic alterations. J. Anesth., 15(1):11-16.

[17]Li, Y.H., Xu, J.H., Yang, J.J., et al., 2005. Predictive performance of ‘Diprifusor’ TCI system in patients during upper abdominal surgery under propofol/fentanyl anesthesia. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 6(1):43-48.

[18]Lim, K.J., Lee, S.K., Lee, H.M., et al., 2013. Aspiration pneumonia caused by fentanyl-induced cough—a case report. Korean J. Anesthesiol., 65(3):251-253.

[19]Lin, J.A., Yeh, C.C., Lee, M.S., et al., 2005. Prolonged injection time and light smoking decrease the incidence of fentanyl-induced cough. Anesth. Analg., 101(3):670-674.

[20]Liu, H.L., An, L.J., Su, Z., et al., 2015. Magnesium sulphate suppresses fentanyl-induced cough during general anesthesia induction: a double-blind, randomized, and placebo-controlled study. Int. J. Clin. Exp. Med., 8(7):11332-11336.

[21]Mukherjee, A., Kundu, A.K., Ghosh, S., et al., 2011. Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level. J. Anaesthesiol. Clin. Pharmacol., 27(4):489-494.

[22]O'Shaughnessy, M.A., Adams, J.E., 2015. Perioperative management of hypertension in hand surgery patients. J. Hand. Surg. Am., 40(8):1684-1687.

[23]Park, K.B., Ann, J., Lee, H., 2016. Effects of different dosages of oxycodone and fentanyl on the hemodynamic changes during intubation. Saudi Med. J., 37(8):847-852.

[24]Peringathara, B., Robinson, S., 2016. Fentanyl-induced cough is a risk factor for postoperative nausea and vomiting. Br. J. Anaesth., 117(2):269.

[25]Peter, V.D., 2011. Cough: an unmet clinical need. Br. J. Pharmacol., 163(1):116-124.

[26]Rozé, H., Lafargue, M., Ouattara, A., 2011. Case scenario: management of intraoperative hypoxemia during one-lung ventilation. Anesthesiology, 114(1):167-174.

[27]Saleh, A.J., Zhang, L., Hadi, S.M., et al., 2014. Priming dose of intravenous ketamine-dexmedetomidine suppresses fentanyl-induced coughing: a double-blind, randomized, controlled study. Ups. J. Med. Sci., 119(4):333-337.

[28]Sedighinejad, A., Naderi Nabi, B., Haghighi, M., et al., 2013. Propofol is effective to depress fentanyl-induced cough during induction of anesthesia. Anesthesiol. Pain Med., 2(4):170-173.

[29]Solanki, S.L., Doctor, J.R., Kapila, S.J., et al., 2016. Acupressure versus dilution of fentanyl to reduce incidence of fentanyl-induced cough in female cancer patients: a prospective randomized controlled study. Korean J. Anesthesiol., 69(3):234-238.

[30]Walsh, M., Devereaux, P.J., Garg, A.X., et al., 2013. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology, 119(3):507-515.

[31]Xu, Y., Zhu, Y., Wang, S., et al., 2015. Dezocine attenuates fentanyl-induced cough in a dose-dependent manner—a randomized controlled trial. Int. J. Clin. Exp. Med., 8(4):6091-6096.

[32]Yu, H., Yang, X.Y., Zhang, X., et al., 2007. The effect of dilution and prolonged injection time on fentanyl-induced coughing. Anaesthesia, 62(9):919-922.