Tufanogullari 2008.

Methods	RCT, 4 parallel groups
Participants	Number: 80 men (n = 19) and women (n = 61) Country: USA Surgery: laparoscopic bariatric surgery (gastric banding or gastric bypass), general anaesthesia, elective Age: 22 to 66 years ASA: II or III Other inclusion criteria: none reported Exclusion criteria: allergy to alpha‐2 adrenergic agonists or sulpha drugs; uncontrolled hypertension; heart block greater than first degree; alcohol or drug abuse; neurological, cardiovascular, renal, hepatic or gastrointestinal disease; opioid analgesic medication within 24 hours; pregnancy or breast‐feeding; inability to speak and read English
Interventions	DEX 0.2 group: dexmedetomidine 0.2 µg/kg/h (n = 20) vs DEX 0.4 group: dexmedetomidine 0.4 µg/kg/h (n = 20) vs DEX 0.8 group: dexmedetomidine 0.8 µg/kg/h (n = 20) vs Control group: saline infusion (n = 20) For all groups, an intravenous infusion started before induction for anaesthesia and throughout surgery, and no bolus All participants: Premedication: midazolam 20 µg/kg, celecoxib 400 mg orally Anaesthesia and during surgery: propofol 1.25 mg/kg, lidocaine 0.75 mg/kg. Rocuronium 0.6 mg/kg. Desflurane. Crystalloid solution 25 mL/kg for gastric bypass and 10 mL/kg for gastric banding. Neostigmine 40 µg/kg and glycopyrrolate 5 µg/kg After surgery: ondansetron 4 mg when the laparoscope was withdrawn. Before wound closure, bupivacaine 0.25% was infiltrated at the fascial level of all portals
Outcomes	Amount of 'rescue' analgesia: Fentanyl, 25 to 50 µg boluses during initial time in PACU, given by personnel until PCA morphine was possible PCA morphine on postoperative day 1 (initiated when verbal response scale (VRS) pain score was < 7 and after recovery from anaesthesia) Hydromorphone (2,5 mg/mL)–acetaminophen (167 mg/mL) orally on postoperative day 1 VRS pain 0 to 10 after 1 day PO Number of participants needing 'rescue' opioid after 1 day PO Number of participants with nausea during stay in PACU Number of participants with vomiting during stay in PACU Number of participants requiring antiemetics during stay in PACU (intravenous promethazine 6.25 mg administered if VRS nausea score > 3 on 2 consecutive evaluations) VRS nausea scores 0 to 10 at 30‐minute intervals until PACU discharge Time to passing flatus (participants making a diary note) Time to ambulation without assistance Number of participants with post‐interventional complications or side effects: Hypertension and/or tachycardia requiring 'rescue' beta‐blocker (after increased anaesthesia) Hypotension requiring rescue phenylephrine (after reduction in anaesthesia and 200 mL fluid)
Notes	Study authors contacted for supplementary information about 'rescue' analgesia regimen and details about PONV, without reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...a computer‐generated random number table" Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote: "The study medication was prepared by the operating room (OR) pharmacist in identical 60‐mL syringes. DEX 0, 200, 400, or 800 µg was added to saline to achieve a total volume of 40 mL... for the 4 study groups...An infusion of the study medication was started at 0.04 mL/kg/h" Quote: "The investigators, attending anaesthesiologists, OR, recovery and ward nurses, as well as the patients were blinded to the computer‐generated randomization schedule" Comment: probably done
Blinding of participants and personnel (performance bias) Pain, 'rescue' analgesia, postoperative sedation	Low risk	Quote: "The investigators, attending anaesthesiologists, OR, recovery and ward nurses, as well as the patients were blinded to the computer‐generated randomization schedule" Comment: probably done
Blinding of participants and personnel (performance bias) PONV	Low risk	Same as above
Blinding of participants and personnel (performance bias) Time to first passage of flatus or stool	Low risk	Same as above
Blinding of participants and personnel (performance bias) Time to first out‐of‐bed mobilization	Low risk	Same as above
Blinding of participants and personnel (performance bias) Post‐interventional complications or side effects	Low risk	Same as above
Blinding of outcome assessment (detection bias) Pain, 'rescue' analgesia, postoperative sedation	Low risk	Same as above
Blinding of outcome assessment (detection bias) PONV	Low risk	Same as above
Blinding of outcome assessment (detection bias) Time to first passage of flatus or stool	Low risk	Same as above
Blinding of outcome assessment (detection bias) Time to first out‐of‐bed mobilization	Low risk	Same as above
Blinding of outcome assessment (detection bias) Post‐interventional complications or side effects	Low risk	Same as above
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Three patients (one from each of the DEX 0.2, 0.4, and 0.8 groups) were admitted to the intensive care unit from the postsurgical ward because of surgical complications at the gastrointestinal anastomosis site (e.g., bleeding, obstruction) and their postoperative data were excluded from the final analysis" Comment: As participants were excluded for surgical reasons and were equally distributed, risk of bias was probably low
Selective reporting (reporting bias)	Unclear risk	The published article was in line with the protocol, which was available, but outcomes were described in very general terms only. Two outcomes seemed to be added post hoc (number of participants discharged on postoperative day 1 and number of days until discharge), but they showed no significant differences between groups
Other bias	High risk	Comment: Criteria for the use of analgesia were not clearly described, even though participants went through a complex 3‐step rescue analgesia regimen. As VRS pain scores were collected only in the PACU and on postoperative days 1 and 2, one might suspect some irregularities in the way analgesia was administered. Information given to participants on how to administer the analgesia at home was not described. One might suspect lack of control of participant compliance at home, leading to high risk of bias Quote: "This investigator–initiated, Food and Drug Administration‐approved study was supported, in part, by an unrestricted educational grant from Hospira, Inc.a (Lake Forest, IL), endowment funds from the Margaret Milam McDermott Distinguished Chair in Anesthesiology, and the White Mountain Institute, a non‐profit private foundation (Paul F. White, President)" Quote (from authors' conclusion): "Our findings would suggest that the modest anaesthetic‐sparing effect was of little (if any) clinical significance because dexmedetomidine failed to facilitate a faster emergence from desflurane anaesthesia after bariatric surgery. (…) the primary benefit of Dex in this study appeared to be related to its ability to reduce emetic sequelae by decreasing the need for the desflurane during the operation and fentanyl immediately after surgery" Comment: The potential conflict of interest is of unclear importance. The conclusion of the study authors seem modest and reasonable, but it is not stated in what way the grant was 'unrestricted' (e.g. if Hospira owned the data or needed to approve of the manuscript)