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      Effect of Intraoperative and Postoperative Infusion of Dexmedetomidine on the Quality of Postoperative Analgesia in Highly Nicotine-Dependent Patients After Thoracic Surgery : A CONSORT-Prospective, Randomized, Controlled Trial

      , MD, , MM, , MD, , MM, , MD, PhD, , MD, PhD

      Medicine

      Wolters Kluwer Health

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          Abstract

          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 (0.02 μg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02 μg/kg/h each, Group D1), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.04 μg/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 secondary outcome measures were pain intensity (numerical rating scale, NRS), level of sedation (LOS), Bruggrmann comfort scale (BCS), functional activity score (FAS), and concerning adverse effects.

          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 (0.04 μg/kg/h) and sufentanil (0.02 μg/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).

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          Most cited references 27

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          Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.

            (2008)
          Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers. We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039. All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053). Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.
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            Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials.

            Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia. The authors searched for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined. Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was -4.1 mg (95% confidence interval, -6.0 to -2.2) with clonidine and -14.5 mg (-22.1 to -6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia. Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.
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              Dexmedetomidine: an updated review.

              To review recent literature on the safety and efficacy of dexmedetomidine. Articles were identified through searches of MEDLINE (1966-January 2007). Key words included dexmedetomidine, medetomidine, alpha(2)-agonist, and sedation. References from selected articles were reviewed for additional references. Experimental and observational studies that focused on the safety and efficacy of dexmedetomidine in humans were selected. Dexmedetomidine is an alpha(2)-agonist for short-term sedation in critically ill patients. In postoperative patients, dexmedetomidine produced similar levels of sedation and times to extubation, with less opioid requirements compared with propofol. Dexmedetomidine has also been studied for sedation in critically ill medical and pediatric patients, as adjunct to anesthesia, and for procedural sedation. Hypotension, hypertension, and bradycardia are common adverse effects. Although dexmedetomidine is labeled only for sedation less than 24 hours, it has been administered for longer than 24 hours without apparent development of rebound hypertension and tachycardia. Dexmedetomidine is a safe and effective agent for sedation in critically ill patients. Further, well designed studies are needed to define its role as a sedative for critically ill medical, neurosurgical, and pediatric patients, as an adjunct to anesthesia, and as a sedative during procedures.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                August 2015
                14 August 2015
                : 94
                : 32
                Affiliations
                From the Department of Anaesthesiology (CR, FQ), Qilu Hospital of Shandong University, Jinan; and Department of Anaesthesiology (CR, XZ, ZL, CL, ZZ), Liaocheng People's Hospital, Liaocheng, China.
                Author notes
                Correspondence: Feng Qi, Qilu Hospital of Shandong University, No. 107, Wenhua West Road, Jinan, Shandong Province 250012, China (e-mail: 784253489@ 123456qq.com ).
                Article
                01329
                10.1097/MD.0000000000001329
                4616696
                26266376
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0

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