Table 1.
Summary of primary trial design, methods, randomization, and outcome measures
| Feature | Details |
|---|---|
| Design | RCT with three treatment arms |
| Setting | Aretaieio University Hospital, Athens, Greece |
| Inclusion criteria | ASA I–II, age: 30 and 70 years, scheduled for abdominal hysterectomy or myomectomy without preoperative pain |
| Exclusion criteria | Patient’s refusal or contraindication to the use of local anesthetics, body mass index > 35 kg/m2, cardiovascular disease, significant renal/hepatic impairment, insulin-dependent diabetes mellitus, central nervous system or psychiatric disease, chronic use of opioids/steroids/clonidine/other α2 agonist/analgesics or any drugs acting on the central nervous system during the previous 2 weeks, drug/alcohol abuse, language/communication barrier or inability to comprehend the pain assessment scale and/or the use of a patient-controlled analgesia (PCA) pump |
| Ethical approval and study registration |
Institutional Review Board (Protocol ID: EE-2/04/31-01-2017-Chairman Dr I. Vassileiou). Study approval was obtained for short- (0-48 h) and long-term (3, 6, and 12 months) follow-up, according to the submitted protocol ClinicalTrials.gov (ID: NCT03363425) |
| Ethical standards and guidelines followed |
1964 Declaration of Helsinki and its later amendments The Consort Guidelines for reporting Randomized Controlled Trials All patients signed a written informed consent to participate in the study and the follow-up period, according to protocol |
| Sample size calculation |
Calculated after the recruitment of 50 patients (DEX: 16, LIDO: 17, CONTROL: 17), by analyzing the data of 44 (four dropouts in the DEX group and two dropouts in the CONTROL group) The study was powered for a reduction of 20% in NRS at rest at 24 h postoperatively. Approximately 26 patients were needed per group to achieve a statistical power of 0.80. A total number of at least 30 patients per group was planned to compensate for possible future dropouts |
| Randomization/allocation | Eligible patients were randomly allocated to one of the three study groups, dexmedetomidine (DEX), lidocaine (LIDO) or sodium chloride (NaCl) 0.9% (CONTROL) with the help of a computer-generated list (https://www.randomizer.org) |
| Concealment and outcome assessment during the initial 48-h period |
Solutions and syringes were prepared according to group allocation by an independent nurse who did not further participate in the study To mask intervention, identical 50-ml syringes were prepared for infusion by an automatic pump. Solution volumes (50 ml), appearance and infusion rates (0.9 ml/kg/h loading and 0.15 ml/kg/h maintenance) were identical in all groups A blinded researcher assessed postoperative outcomes |
| Interventions |
Type of surgery: Abdominal hysterectomy or myomectomy Type (concentration) of iv infusion: dexmedetomidine (4 μg/ml) or lidocaine (10 mg/ml) or placebo (sodium chloride 0.9%) |
| Infusion rates | |
| Preoperatively |
0.9 ml/kg/h for 10 min (Corresponding to: 0.6 μg/kg dexmedetomidine 1.5 mg/kg lidocaine) |
| Intraoperatively |
0.15 ml/kg/h, until the final stitch (Corresponding to: 0.6 μg/kg/h dexmedetomidine 1.5 mg/kg/h lidocaine) |
| Primary outcome measures | Cumulative morphine consumption and pain scores at 24 h |
| Secondary outcome measures |
Acute pain: Cumulative morphine consumption and pain scores at the Post Anesthetic Care Unit, 2 h, 4 h, 8 h, and 48 h Patient’s subjective sedation feeling (0–10 scale) Nausea (0–10 scale) Sevoflurane consumption (grams) Time (hours after extubation) to first passage of flatus/stool Time of getting up from bed (hours after extubation) Sleep quality (0–10 scale) Patient satisfaction (0–10 scale) at 24 h and 48 h Discharge time Need for rescue analgesia and rescue antiemetic Drug side effects and complications associated with the interventions Chronic pain: Chronic pain (NRS) at 3, 6, and 12 months Neuropathic pain or neuropathic elements (DN4 scores) at 3, 6, and 12 months |
| Recruitment | 91 female patients (31 in DEX, 30 in LIDO, and 30 in CONTROL group) recruited from June 2017 to January 2020 |
| Patients assessed for CPP and neuropathic pain | 81 female patients/12-month follow-up |