The ADRIB (Addition of Dexmedetomidine to Ropivacaine-induced supraclavicular Block) study was conducted in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement and the Declaration of Helsinki. Our study protocol was approved (28/09/2015) by the Guangzhou First People’s Hospital Research Ethics Board and was registered on clincaltrials.gov (NCT02630290; principal investigator: XR, date of registration: 15/12/2015). The protocol is available by request from the corresponding author. Written informed consent was obtained prior to study enrollment. Participants were recruited from Guangzhou First People’s Hospital, a tertiary teaching hospital affiliated with South China University of Technology. Adult patients aged 18–60 years with an American Society of Anesthesiologists (ASA) physical status 1 or 2 who were scheduled for elective forearm and hand orthopedic surgery were recruited. Written informed consent was obtained from each patient. Exclusion criteria were: taking antihypertensive drugs such as methyldopa, clonidine, and other α2 receptor agonists; peripheral neuropathy; coagulopathies; liver and kidney dysfunction; or history of allergy or hypersensitive reaction to any of the study medications.
Computer generated 1:1 ratio random numbers were used to randomly allocate the patients to an ultrasound-guided supraclavicular brachial plexus block with 20 mL 0.5% ropivacaine with or without 30 µg dexmedetomidine. The group allocation was concealed in sequentially numbered and sealed opaque envelopes. A nurse who was not involved in any other sections of the study obtained the envelopes before administration of the nerve block and prepared the treatment solutions by diluting 100 mg of ropivacaine (AstraZeneca AB, Sodertalje, Sweden) with or without 30 µg of dexmedetomidine (Hengrui Med, Jiangsu, China) in 0.9% sodium chloride in a final volume of 20 mL.
All the patients received 1.5 mg midazolam i.v. after peripheral intravenous access was secured. ECG, noninvasive arterial blood pressure, and pulse oximetry were monitored. An ultrasound-guided supraclavicular nerve block was performed according to a previously described technique . With the patient in the supine position and after skin disinfection, a linear ultrasound probe was positioned in the supraclavicular fossa inferomedially to identify the subclavian artery, the brachial plexus, and the pleura. The skin and the subcutaneous tissue were infiltrated with 3 mL 2% lidocaine, and a 20-gauge needle (0.90 × 90 mm) was inserted from lateral to medial using an in-plane technique until the tip of the needle was located deep between the subclavian artery and the first rib. A 5 mL volume of the treatment solution was injected, and the needle was redirected to the intermediate and superficial levels of the brachial plexus for a maximum spread of the rest treatment solution. All blocks were performed by a single trained investigator. The patients and the anesthesiologist performing the block were blinded to the study treatments.
Each patient’s heart rate (HR), noninvasive blood pressure, and oxygen saturation were recorded every 5 min until the end of the surgery and then again every 30 min up to 24 h postoperatively. The incidence of bradycardia (HR < 50 beats/min), hypotension (20% or more decrease in mean arterial pressure from baseline values), or hypoxemia (SpO2 < 90%) was noted. We assessed the sensory block using a 3-point pinprick scale (0 – 2, 0 = normal sensation, 1 = decreased pain sensation, 2 = loss of pain sensation) in the median, ulnar, radial, and musculocutaneous nerve locations every 5 min until 30 min after administration of the block. We evaluated the motor block in these 4 nerves using a thumb and second finger pinch, thumb and fifth finger pinch, finger abduction, and flexion of the elbow, respectively. We defined the onset time of the sensory block as the time from the local anesthetic injection until the loss of pain sensation in all 4 nerve territories and the onset time of the motor block as the time from the local anesthetic injection until the absence of movements in the hand and forearm. If the patient experienced pain in the surgical area, local anesthetic (2% lidocaine) infiltration was added by the surgeon. The need for supplementation of the block was at the discretion of the anesthesiologists.
Upon completion of the surgery, the patients were returned to surgical wards and monitored for 24 h by an investigator blinded to the group allocation. HR and blood pressure were recorded every hour for 6 h, then every 2 h until 12 h, and once more at 24 h postoperatively. Postoperative pain was assessed using a visual analog scale (VAS, 0–100, 0 = no pain, 100 = maximum imaginable pain) at the same time intervals. Tramadol (50 mg) was administered when the postoperative VAS>3, and was titrated up by 50 mg increments as needed for pain every 4 to 6 h, with the maximum total dose of 250 mg per day. The duration of analgesia was defined as time since local anesthetic injection until the report of postoperative pain at the surgical site, and the total analgesic requirement in first postoperative 24 h was also recorded. Incidences of postoperative nausea and vomiting (PONV) were managed with ondansetron. Any patient's self-reported abnormal sensation in the hand and/or forearm was recorded.
The primary outcome measure of this study was the duration of analgesia. The sample size calculation was based on a pilot study noting a mean value of 660 min and SD of 200 min for the duration of analgesia using a 2-sample t test with a 0.05 two-sided significance level and a power of 0.8. A 25% difference in the duration of analgesia was regarded as clinically relevant. We calculated that a minimum sample size of 27 patients was required in each group. This was increased to 30 patients to compensate for possible dropouts.
The independent 2-sample t test was used to compare normally distributed data and the Mann-Whitney U test was used to compare categorical or skewed data between the groups. Repeated-measures analysis of variance, followed by post hoc analysis with Bonferroni correction, was used to compare HR and blood pressure. The chi-square or Fisher's exact tests were used to compare the incidence of adverse effects. A value of P<0.05 was regarded as statistically significant.