This study was approved by the human research review committee at the southwest hospital of third military medical university. The protocol was registered prospectively with Chinese Clinical Trial Registry (ChiCTR-IOR-16008099) on March 15th，2016. The principal investigator was Bin Yi. The study took place at the Department of Anesthesia, Southwest Hospital, the Third Military Medical University, Chongqing, from 25 August 2016 to 14 August 2017.
Patients scheduled for elective lower limbs surgery in the Southwest Hospital and desiring LPBs and SNBs were offered enrollment. Written informed consent was obtained from the participants for publication of this article and any accompanying tables. A copy of the written consent was available for review by the Editor of this journal. Inclusion criteria were as following: willingness to participate in the study (written informed consent), ASA classification of I to III, elder than 18 years old. Exclusion criteria were as following: refusal to participate, history of neurological diseases, coagulopathy and infection at the site of block, allergy to local anesthetics(LAs), and any contraindication to peripheral nerve blockade noted by the attending anesthesiologist. All patients were randomly allocated to Group U (ultrasound-guidance), Group N (nerve stimulator-guidance) or group M(combined-guidance) by random number table, respectively.
Blinding
The anesthesiologist performed the blockade was strictly blinded to patients’ group assignment before the procedure. Only when the anesthesiologist commenced with the blockade, a prepared sealed opaque envelope containing the patient’s group assignment was opened. Then the anesthesiologist completed the blockade with the indicated technique. The investigator blinded to the technique used during the procedure was present in the block area to assess procedure-related outcomes. To ensure the blindness of the patient to the anesthesia method preferred, all procedures performed behind an opaque screen and investigators were required not to say anything about the technique in use. Another investigator assessing block quality was blinded to the group allocation and remained outside the block area after completion of the nerve blockade. Finally, a statistician blinded to the blockade procedure or data collection did statistic analysis, with group data labeled only as numbers until all analyses were completed.
Block preparation
All nerve block procedures were performed preoperatively by 1 of 3 attending anesthesiologists who were skilled in peripheral nerve blockade with both US and NS guidance. Meanwhile all of them had been in clinical practice with an effort on regional anesthesia for at least 5 years. After arriving the operating room, patients were placed in the lateral decubitus position with the surgical limb uppermost and were monitored continuously via electrocardiography, SpO2 measurement, and noninvasive blood pressure monitoring during nerve blockade and surgery. Both the ultrasound and nerve stimulation systems were prepared and positioned conventionally in each group. The ultrasound machine and nerve stimulator were turned on, and a grounding lead was placed on the lateral aspect of the leg being blocked for each group. Patient’s group allocation was given to the anesthesiologist performing the block only after preparation of both systems was completed and just before the block procedure. Patients were pretreated with 0.05mg/kg midazolam and 50 to 200 ug of fentanyl. The injection site was prepared with chlorhexidine gluconate. 5 ml of 0.5% lidocaine was injected subcutaneously at the site of needle insertion. The LA mixture was made up of 0.4% ropivacaine and 0.4% lidocaine. The total volume of the mixture was 50ml. The total amount of LAs used was determined by the dosage of ropivacaine needed, namely 3mg/kg. Patient and researcher assessing the block were kept away from seeing both the block procedure itself and the sonographic display by an opaque screen. According to group allocation, patients received their nerve blocks under one of the following two techniques.
Nerve stimulation technique
In the operating room, LPB was performed using the chayen’s approach [13, 14]. The puncture site was located 4-5 cm lateral from posterior midline along the intercristal line. A 110-mm, 22-G stimulating needle connected to a nerve stimulator (Stimuplex HNS 11, B. Braun) was advanced perpendicular to skin. The nerve stimulator was set to a pulse duration of 0.1 ms, current intensity of 1.0 mA, and frequency of 2 Hz. When the stimulating intensity was progressively reduced to 0.4 mA or less while maintaining the twitch in the quadriceps distribution. LAs were given half the amount according to the weight of patients for LPB and SNB respectively. When the correct needle position was achieved based on evoking the desired motor response, the amount of LAs described above was injected. SNB was performed using the classic Labat’s approach[15]. The needle was inserted 5 cm below the midpoint of a line connecting the posterior superior iliac spine and the greater trochanter. After an appropriate stimulus was localized in the sciatic distribution, LAs described above was injected.
Ultrasound-guided technique
We chose "Shamrock Method” for LPBs[16]. A sterile cover was put on a 3MHz low-frequency ultrasound probe (LOGIQe 4C-RS, GE Inc, USA). The ultrasound transducer was positioned on the line connecting subcostal margin and iliac spine and adjusted until a clear view of psoas, erector muscle and quadratus lumborum appeared. The hyperechoic structure located in the posterior internal quadrant of psoas was lumbar plexus. The puncture site was beneath the probe and 4-5cm lateral from the vertebral body. We chose subgluteal approach for SNBs[17]. The ultrasound transducer was positioned perpendicular to the skin on the line connecting the ischial tuberosity and greater trochanter, and a clear transverse image of the hyperechoic sciatic nerve between the ischial tuberosity and greater trochanter was obtained. For LPBs and SNBs, the needle placement and spread of LAs were confirmed with ultrasound visualization. After the proper needle placement was confirmed, incremental injection of the same LA solution in the same volume occurred as described previously until circumferential spread around the nerve was obtained. The needle was redirected, when required, to achieve this goal. As for group M, initially, needle-to-nerve guidance was applied
according to group U. Maintaining the needle nerve position, the nerve stimulator was set as described for group N. When the correct needle position was achieved based on evoking the desired motor response, LAs described above was injected.
Block evaluation
Evaluation of nerve block was performed by an investigator blinded to those who administered the blockade. The motor and sensory response in the nerve distribution area were assessed every 5 minutes until complete motor and sensory effects were achieved. If it took more than 30 minutes to achieve sensory loss in both distributions after the end of injection with LAs, we identified that it was failed block. The attending anesthesiologist had the right to perform general anesthesia, rescue blockade, or supplementation with a local field block when came across with a failed block. The motor block was assessed with a modified Bromage Scale; 2, full motor strength, 1, decrased strength; and 0, no strength. Similarly, the sensory block was evaluated with ice: 2, full sensation (no change): 1, decreased sensation; and 0, no sensation.
Postoperative follow-ups were performed in the post-anesthesia care unit and by telephone within 72 hours after the procedure by clinical personnel in addition to study-related procedures.
Outcomes
The primary outcome was the incidence of the LAST. LAST can present with both central nervous system (CNS) and cardiovascular system (CVS) clinical manifestations. The CNS symptoms were including tongue numbness, tinnitus, light-headedness, metallic taste, nystagmus, confusion, tremors, agitation, seizures, coma, and respiratory arrest[18]. The CVS symptoms include tachycardia, arrhythmias, hypertension, and later toxic symptoms such as bradycardia, cardiac depression, cardiovascular collapse, and asystole[18]. The secondary outcomes were the quality of the nerve block and associated risk factors. The quality of the block included number of needle redirections, motor and sensory block onset and restoration times in the lumbar and sciatic nerve distributions. The associated factors included age, gender and comorbidities. Needle redirections were counted as the number of times in which the needle was withdrawn of at least 10mm with subsequent forward movement. The upper limit of redirections was 20, but if necessary the needle was allowed to redirect as many times as possible to achieve proper placement as described previously. The onset of motor and sensory block was assessed by the modified Bromage scale as mentioned above for the distributions of both the lumbar plexus and sciatic nerves. The onset time was measured between final LA injection and the first observation of a 0 score. During the phone follow-up, patient provided time of first return of sensation and block-related complications on post-operative day 1. The block duration time was defined as interval between block completion and first return of sensation. Any reported complications were recorded.
Statistical analysis
The statistical analyses were performed using Statistical Package for the Social Sciences (Windows Software, version 19.0; SPSS Inc, Chicago, IL) and Power Analysis and Sample Size(Windows Software, version 11.0;NCSS Inc, Utah).
Demographic and perioperative data were expressed as the means and standard deviations. Parametric and non-parametric Kolmogorov–Smirnov tests were applied to assess normality. The primary outcome (incidence of LAST) and potential risk factors were compared by c2 test or Fisher exact test when appropriate (n<5 in any field). In the c2 test, we tested whether there were differences in the incidence of the LAST and the odds ratios of potential risk factors among different groups. The demographic and secondary outcomes were compared among the three groups by one-way ANOVA, following by multiple comparisons using LSD test or Welch and Dunett’s T3 test for unequal variances. In the one-way ANOVA, we tested whether there were differences in the patients’ characteristics and block quality among the three groups. This analysis was followed by 95% CIs with Bonferroni correction to adjust for multiple comparisons (three different methods for nerve block for motor and sensory onset and restoration time data and demographic data) to minimize the chance of a type error I (0.05). For all comparisons, 2-tailed P <0.05 was considered statistically significant.
In the current study, there were 319 patients randomly allocated into the three groups. Finally, data from 100 patients for each group was analyzed. We did a test for the power of test regarding the primary outcome after experiment. We calculated the effect size (0.182) in the software PASS. Then we set the significant level as 0.05. Referring to the result, we found that when the total sample size was 300, the power(1-β) of the test was 0.81.