Ethics approved and registration
This prospective, single-center, randomized, controlled trial was approved by the Ethics Committee of Shanghai Sixth People’s Hospital affiliated to Shanghai Jiao Tong University and written informed consent was obtained from parents or guardians. The protocol was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, Principal investigator: Hui Zhang, Registration number: ChiCTR-INR-17011525, Date of registration: 30/05/2017) and published [14]. The study complied with the Declaration of Helsinki and was monitored by the Good Clinical Practice (GCP) Unit at Shanghai Sixth People’s Hospital affiliated to Shanghai Jiao Tong University. The study was conducted from May 2017 to February 2020in Shanghai Sixth People’s Hospital affiliated to Shanghai Jiao Tong University.
Inclusion and exclusion criteria
We screened a total of 126 children, aged 1 to6yr with the ASA physical status I or II scheduled for osteotomy for developmental dislocation of the hip. Exclusion criteria included contraindication for lumbar plexus block, developmental delays, neurological or psychiatric disease, local infection at the needle entry point, coagulopathy, nerve injury, allergy to anesthetics and study medications, and lack of parental consent for the child’s participation in the study.
Randomization and blinding
Randomization was based on computer-generated allocation and a randomization number was concealed in an opaque envelope. All participants were randomly assigned to either ultrasound-guided lumbar plexus block group (Group Block) or control group (Group Control) at a 1:1 allocation ratio after induction of general anesthesia. Anesthesiologist who performed intraoperative anesthetic care knew the assignment. Patients, parents, surgeons, assessment investigators, the medical staff who provided postoperative care in the post-anesthesia care unit (PACU), data collectors, and statisticians were all blinded to the group allocation. The nerve block details were recorded, kept in a sealed envelope and opened when medically necessary and at the beginning of statistical analysis.
Conduct of the study
Standard monitoring including electrocardiograph (ECG), non-invasive blood pressure (NIBP), pulse oximetry (SpO2), end tidal carbon dioxide (ETCO2), and temperature were applied after all participants entered the operating room. Anesthesia induction was carried out using midazolam (0.1mg·kg−1), fentanyl (2μg·kg−1), propofol (3mg·kg−1)and vecuronium (0.1mg·kg−1) administered intravenously. Patients were intubated endotracheally after the induction, and ETCO2 was aimed at 35 to 40mmHg.
Patients in Group Control received a bolus injection of fentanyl 1μg·kg−1 intravenously before skin incision.
Patients in Group Block received ultrasound-guided lumbar plexus block before skin incision. Ultrasound scans of lumbar plexus were carried out using the S-NerveTM Ultrasound System (Sonosite Inc., Bothell, WA, USA) in patients assigned to Group Block. A linear array (6~13MHz) transducer was used to perform lumbar plexus block with the longitudinal approach. All nerve blocks in this study were performed by the same experienced anesthesiologist, who was qualified for ultrasound-guided lumbar plexus block. After induction, every patient assigned to Group Block was placed in the lateral decubitus position with the operative side upwards and the hips and knees flexed in order to enlarge interspinous spaces and provide better image of lumbar plexus. When transducer was placed 1.5~2 cm lateral to the midline of the patient’s back and parallel to the long axis of the spine at the level L3-4, the lumbar transverse processes produced a ‘trident sign’[15]. Because the psoas major muscle is anterior to the transverse processes, the lumbar plexus was distinguished within the major psoas muscle. With ultrasound guidance, the block needle was advanced cautiously perpendicular to the skin until the needle tip was located 1-1.5 cm below the space between the transverse processes. All patients received 0.2% ropivacaine 1ml·kg−1 (Naropin 10mg·ml−1, Astrazeneca, Wilmington, DE, UAS)[16]. The maximum dose of ropivacaine was limited to 20 ml[16].
The success of lumbar plexus block was defined as follows:(i) visualization of the needle tip in the right position, the spread of local anesthetic around the lumbar plexus nerve;(ii)an increase of no more than 15% in heart rate, blood pressure in response to the skin incision;(iii)an increase of no more than 25% in heart rate, blood pressure during the operation[17]. Patients in Group Block were considered as failed blocks once one of the above criteria could not be met. The surgery was performed at least 15 min after the nerve block.
Anesthesia was maintained with 60% nitrous oxide, 40% oxygen and 2% end-tidal sevoflurane. The concentration of sevoflurane was added by 0.5% if the values of heart rate, blood pressure increased more than 15% from the baseline values during the operation. Conversely, the concentration of sevoflurane was reduced by 0.5% if the values of heart rate, blood pressure decreased more than 15% from the baseline values. If the increase was more than 25% from the baseline values, additional bolus of fentanyl 1μg·kg−1was administered. Patients recorded as a failure or a inadequate lumbar plexus block were followed up. Intention-to-treat analysis was used to analyze data including failed block.
Intraoperative anesthetic management and postoperative assessments
During the operation, if the heart rate reduced to less than 50 beats per min, atropine 10μg·kg−1 was used. Ephedrine 0.1mg·kg−1 was used to treat hypotension when blood pressure decreased more than 25% from the baseline value. At the end of the operation, sevoflurane and nitrous oxide were discontinued and oxygen flow was increased to 6l·min−1. Patients were transferred to PACU and monitored until the end of the study.
Intraoperative data collection included heart rate, blood pressure, respiratory rate, concentration of sevoflurane, and fentanyl dose. The average value of end-tidal sevoflurane concentration (EtSev%) was calculated from all values recorded every 5 min throughout the operation.
After extubation and emergence, a blinded well-trained observer performed all assessments. EA was assessed by PAED scale[18] at 0, 5, 10, 20, and 30 min after emergence. We defined EA as PAED score≥10[18, 19]. Severe EA was defined as PAED score≥13[18] and treated with a bolus of fentanyl 0.5μg·kg−1 [8,18]. The primary outcome was the incidence of EA 30 min after emergence from anesthesia. Postoperative pain at 0, 5, 10, 20, and 30 min after emergence was evaluated by the CHEOPS scale[20]. Patient with CHEOPS>7 was treated with a bolus of fentanyl 0.5μg·kg−1 [8,18].
Emergence time (from discontinuation of sevoflurane to the first response to a simple verbal command), extubation time (from the end of anesthesia to extubation), intraoperative collective fentanyl rescue dose, adverse effects and complications were recorded.
At the end of study, that is, 30 min after emergence, the patients were given nurse controlled analgesia (NCA) with morphine. Bolus dose is 10 μg·kg−1, lockout interval 30 min and background infusion is 10 μg·kg−1·h−1.
Statistical Analysis
The incidence of EA for pediatric hip surgery was approximately 42% in our pilot study. Therefore, a minimum sample size of 60 patients in each group would have 90% power to detect an absolute reduction of 15% in the incidence of EA in the intervention group at a significance level of 0.05, considering a possible dropout rate of 10%.
Categorical variables such as the incidence of EA and severe EA were expressed as frequencies (percentage) and analyzed with Chi-square test or Fisher’s exact test. One-way Repeated-measures ANOVA or Generalized estimated equation (GEE)was applied to analyze data for PAED and CHEOPS according to the test for normality and homogeneity of variance. Continuous variables with a normal distribution were summarized with mean (standard deviation, SD) and were analyzed with an independent-sample t test.
The level of significance for each test was set at α=0.05, 2 tailed. All data were subjected to the Kolmogorov-Smirnov test for normality. All data were analyzed with SPSS 23.0 (IBM SPSS Statistics for Windows, Version 23.0; IBM Corp., Armonk, NY). Intention-to-treat strategy was performed in every case.