Study design
After approval by the Ethics Committee of the Second Affiliated Hospital, Harbin Medical University, China and obtaining informed consents, 75 ASA grade Ι and II patients were enrolled in this prospective, randomized, double-blind controlled trial. The participants, aged between 18 to 60 years old, were scheduled for forearm or hand surgery through the ultrasound-guided axillary BPB. The exclusion criteria included: patients with a history of allergy to the study medication, peripheral neuropathy, central nervous system disease, puncture site infection, a history of severe hepatic, renal, cardiac or pulmonary disease, coagulation disorder, alcohol or opioid abuse, chronic pain, severe/morbid obesity, pregnant or lactating women.
Patients were randomly allocated into three groups (n=25) using a sealed envelope technique and all patients were administered 33 mL of the investigated solutions:
Group R received 30 mL of 0.25% ropivacaine (75 mg) plus 3 mL 0.9% NaCl;
Group RL received 15 mL of 0.25% ropivacaine (37.5 mg) and 15 mL of 0.5% lidocaine (75 mg) plus 3 mL of 0.9% NaCl;
Group RLD received 15 mL of 0.25% ropivacaine (37.5 mg) and 15 mL of 0.5% lidocaine (75 mg) plus 3 mL of dexmedetomidine (0.75 µg/kg).
Monitoring
Insertion of 18-gauge intravenous catheter in a peripheral vein of the lower extremity was performed and 5 mL/kg/h infusion of lactated Ringer’s solution was started. Oxygen (3 L/min) was delivered to the patients through a face mask without any sedative medication. Standard monitoring was established for non-invasive systolic arterial pressure (SAP) and diastolic arterial pressure (DAP), heart rate (HR), the respiratory rate (RR), the peripheral oxygen saturation (SpO2) and the bispectral index (BIS) values. The axillary BPB was performed by an anesthesiologist unaware of which agents were being used. The patients were placed in the supine position with the upper arm in 90° abduction and the elbow in 110° flexion. After preparation and disinfection of the injection site, the axillary artery and axillary vein were visualized under the ultrasound-guidance (Terason 2000+, America, 14 MHz) and the median, ulnar and radial nerves were explicitly identified. A 22-gauge needle was advanced with real-time guidance closely approach to the nerve. After repeated aspiration to avoid intra-vascular injection, each nerve was observed surrounded by 11mL of the LA solutions tested.
Assessment
Blocks were assessed at 30-sintervals until a confirmation of fully block was achieved since the onset time was exceedingly short. After the surgery, we performed the block evaluation every 30 min until complete recovery of the sensation and motor function. The sensory block was assessed by a 3-scale pinprick test (0=normal sensation; 1=blunt sensation; 2=no sensation). The motor block was evaluated by a 3-scale system (0=normal motor ability; 1=capable of moving fingers only; 2=no motor ability).
The onset time of the sensory and motor block, the duration of the sensory and motor block, and the analgesic time were recorded. The onset time of sensory block was defined as the time from the end of injection to the disappearance of pain sensation in the three nerve territories (score 2). The interval from the sensory onset time to the normal sensation (score 0) was denoted as durations of the sensory block. The motor onset time was defined as the period from the end of the injection to achieving only movement of any finger (score 1). The motor block duration was determined as the time from the motor onset time to the complete motor recovery of the hand and forearm (score 0). The end of the administration of the solutions to the first analgesics request after the operation was considered as the analgesic time.
Supplementary Protocol
Flurbiprofen 50 mg was intravenously (IV) administered one time to the patients if they complained of pain and how many times of rescue analgesia for a period of 48h were recorded. The anesthesiologist who evaluated the block responses and the patients were blinded to the solution used. The patients who were not completely blocked 30 min after the injection were excluded from the study. If patients suffered pain during the operation, they received IV fentanyl 1 µg/kg plus midazolam 0.02 mg/kg and the block was considered failure. These patients were also excluded from the trial.
SAP, DAP, HR and SpO2 were recorded at baseline and 5, 10, 15, 30, 45 and 60 min after the injection of LAs. The BIS values were registered at baseline, as well as 5, 10, 15, 20, 25, 30, 45 and 60 min post-injection. Bradycardia and hypotension were defined when the values decreased by 20% from their baseline levels. Hypertension was present when mean arterial pressure (MAP) increased by more than 20% over the baseline values. SpO2 less than 90% was considered to indicate respiratory depression. The incidences of other side effects, such as nausea, vomiting, dizziness, dry mouth were also recorded.
Statistical analysis
The duration of analgesia was considered the primary outcome variable. To show a 30% increase in the value of the variable and to detect power of 0.9 and a level of the significance of 0.05, we calculated the respective values of at least 19 patients for each group.
Statistical analysis was conducted with SAS9.13(SAS Institute Inc., Cary, NC). Demographic and time datawere analyzed by t test. The hemodynamic data and the BIS values were subjected to repetitive measure analysis of variance (ANOVA), followed by single effect analysis. To identify gender heterogeneity between the groups, x2 test was used. P<0.05 was considered statistically significant.