Effect of Intraoperative and Postoperative Infusion of Dexmedetomidine on the Quality of Postoperative Analgesia in Highly Nicotine-Dependent Patients After Thoracic Surgery

Smoking is one of the most common addictions in the world. Nicotine inhalation could increase the risk of cardiorespiratory diseases. However, the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed. This CONSORT-prospective, randomized, double-blinded, controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine (Fagerstrom test of nicotine dependence 6)-dependent patients after thoracic surgery. One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014, and a total of forty-nine were excluded. One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double-blind, randomized study: sufentanil (0.02mg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02mg/kg/h each, Group D1), or sufentanil (0.02mg/kg/h) plus dexmedetomidine (0.04mg/kg/h) (Group D2). The patient-controlled analgesia (PCA) program was programmed to deliver a bolus dose of 2 ml, with background infusion of 2 ml/h and a lockout of 5 min, 4-hour limit of 40 ml, as our retrospective study. The primary outcome measure was the cumulative amount of self-administered sufentanil; the sec, Zhong Liu, MD, C MM, , and Feng Qi, MD, PhD The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery (P< 0.05), whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4, 8, and 16 hours after surgery (P< 0.05). Compared with S group, the NRS scores at rest at 1, 4, and 8 hours after surgery and with coughing at 4, 8, 16, and 24 hours after surgery were significantly lower in D2 group (P< 0.05). However, compared with D1 group, the NRS scores both at rest and with coughing at 4 and 8 hours after surgery were significantly lower in D2 group (P< 0.05). The NRS scores both at rest and with coughing show that there were no significant differences between D1 group and S group at each time point after surgery (P> 0.05). LOS of group D2 was higher than S and D1 groups at 1 hour after surgery (P< 0.05), BCS of group D2 was higher than S and D1 groups at 4, 8, and 16 hours after surgery (P< 0.05), and FAS of group D2 was higher than S and D1 groups at 48 and 72 hours after surgery (P< 0.05). The number of rescue analgesia during 72 hours after surgery in D2 group was lower than S and D1 groups (P< 0.05). There were no significant differences among the 3 groups in terms of baseline clinical characteristics and postoperative adverse effects except for itching (P> 0.05). Among the tested patient-controlled analgesia options, the addition of dexmedetomidine (0.04mg/kg/h) and sufentanil (0.02mg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for highly nicotine-dependent patients during the initial 72 hours after thoracic surgery. Trial Registration: chictr.org (ChiCTR-TRC-14004191). (Medicine 94(32):e1329) Abbreviations: ASA = American Society of Anesthesiologists, BCS = Bruggrmann comfort scale, BIS = bispectral index, BMI = body mass index, FAS = functional activity score, FTND = Fagerstrom test of nicotine dependence, HR = heart rate, ICU = intensive care unit, LOS = level of sedation, MAP = mean arterial pressure, NRS = numerical rating scale, PACU = postanesthesia care unit, PCA = patient-controlled analgesia, SpO2 = pulse oxygen saturation, SRD = serious respiratory depression. INTRODUCTION Smoking is one of the most common addictions worldwide. As patients with tobacco addiction required to stop smoking before thoracic surgery for at least 4 weeks, previous data had been focused on the association between smoking and postoperative outcomes. Nicotine inhalation could increase the risk diseases, which require postoperative U) care or longer admission. However, ved postoperative analgesia for nicotinewww.md-journal.com | 1 dependent, especially highly nicotine-dependent, patients undergoing thoracic surgery has not been specifically addressed. The thoracotomy wound often generates severe postoperative pain, which is considered one of the most severe forms and is difficult to control. It is particularly important to optimize postoperative analgesia in highly nicotine-dependent patients undergoing thoracic surgery. First of all, these patients may be experiencing higher incidence of associated comorbidities and abnormal pulmonary function than nonsmokers because of preexisting long-term smoking before surgery. Second, poor analgesia after surgery usually contributes to further deterioration. Lots of systemic and regional methods of analgesia have been developed for post-thoracotomy pain. Dexmedetomidine, a more favorable pharmacokinetic profile than clonidine—a2:a1 specificity ratio, 1600:1 versus 200:1; plasmatic half-life T1/2, 2–2.5 versus 9–12 hours; protein binding, 94% versus 50%; and lipophilic action, 3.5-fold of that of clonidine—has been used for sedation/analgesia in ICU and during surgery or other procedures such as endoscopy. It also shows superior analgesia and opioid-sparing effects when used as an adjuvant agent after the postoperative period. Our previous study had proved that patients with different levels of nicotine dependence require different amounts of postoperative opioid analgesia. The aim of this prospective, randomized, controlled trial was to evaluate whether dexmedetomidine added to patient controlled analgesia (PCA) sufentanil could afford enhanced analgesic effect, while reducing the adverse effects related to PCA sufentanil administration for highly nicotine-dependent patients during the initial 72 hours after thoracic surgery. At the same time, the adverse effects related to the dexmedetomidine–sufentanil mixture were also investigated.