Participants
This study was approved by the Ethics Committee of Anqing Hospital Affiliated with Anhui Medical University. The study was prospectively registered in the Chinese Clinical Trial Registry on November 4, 2019 (ChiCTR1900027185). Before surgery, each patient signed an informed consent form. The study was conducted at Anqing Hospital Affiliated with Anhui Medical University from November 2019 to October 2020.
Female or male uremia patients aged 18 and 65 years old of American Society of Anesthesiologists (ASA) physical status IV scheduled to undergo total parathyroidectomy were eligible. Patients were excluded if they had refusal to participate,platelet abnormalities, coagulation abnormalities, anticoagulation, serious cardiovascular and cerebrovascular diseases, hypertension (predialysis diastolic blood pressure, DBP > 110 mmHg), hyperkalemia (serum K+ concentration > 5.5 mmol/L), amino-amide local anesthetic allergy, local sepsis, and diaphragmatic motion abnormality. Diaphragmatic motion was evaluated using M mode sonography, and unilateral diaphragmatic motion was classified as normal, paretic, akinetic,and paradoxical [14].
The study was a randomized, double-blind, controlled clinical trial. All eligible participants were randomized to the BSCPB group or the CON group with a 1:1 allocation using computer-generated random numbers. Group assignments were kept in sealed envelopes, and only the nurse responsible for preparing the local anesthetic was allowed to open the envelope and the assigned drug. The assigned drugs according to group assignments in syringes had no difference in appearance. The patients and data collectors (anesthesiologists) did not know the drugs used for BSCPB. All the patients were nil per os (NPO)approximately 6 h before surgery.
Study protocol
All surgeries were performed by three experienced surgeons. The patients were not given any preoperative medication. Dialysis was performed routinely within 24 h before surgery. The arteriovenous fistula of long-term dialysis patients were protected by medical staff during surgery. Noninvasive blood pressure (NBP), heart rate (HR), electrocardiogram (ECG) and peripheral pulse oximeter (SPO2) values were monitored using a multiparameter monitor (Philips MX500, Boeblingen, Germany). An intravenous catheter was inserted into the forearm without arteriovenous fistula, and Ringer’s solution was intravenously administered through the catheter at a rate of 3 ml/kg/h.
As described by Gürkan et al. [15], all bilateral blocks were performed by the attending anesthesiologist who experienced techniques including ultrasound and nerve block before the induction of anesthesia. Patients were lying supine, and their heads were rotated to the opposite side of the block. The ultrasound probe and the skin of the blocked area were routinely sterilized. A high-frequency linear ultrasonic probe (SonoSite Turbo; SonoSite Inc., Bothell, Wash, USA) was placed on the posterior margin of the sternocleidomastoid (SCM) muscle at the level of fourth cervical vertebra(C4). At the posterior corner of the SCM muscle, the superficial cervical plexus was visualized as a hypoechoic structure (Fig. 1). The 22-gauge needle was inserted under the SCM muscle using the in-plane technique. The needle position and location were confirmed by injecting 0.5–1 ml of solution after negative aspiration of no blood and air, 7.5 ml ropivacaine 0.5% was administered on each side in the BSCPB group, while equal amount of 0.9% normal saline was administered in the CON group (Fig. 1). After being administered, no block-related side effects, such as anesthetic toxicity, epidural block anesthesia, total spinal block anesthesia, recurrent laryngeal nerve blockade, phrenic nerve blockade or Horner’s syndrome, were confirmed, and general anesthesia was induced.
General anesthesia was induced with midazolam (0.02 mg/kg), propofol (2.0 mg/kg), sufentanil (0.3 μg/kg) and cisatracurium (0.15 mg/kg). After adequate muscle relaxation, an endotracheal tube containing surface electrodes (NIM-Response Nerve Integrity Monitoring, Medtronics) was inserted using a video laryngoscope (Youyi Medical,Zhejiang,China),and surface electrodes were positioned at the glottic level in contact with both true vocal folds [16]. All patients were ventilated with an Aspire View anesthetic machine (GE Healthcare, Madison, WI, USA) in volume control mode. In the two groups, the tidal volume (VT) was maintained at 8–10 ml/kg, respiratory rate (RR) was fixed at 10–12 breaths/min, inspiratory-to-expiratory-time ratio (I:E) was 1:2 and inspired oxygen fraction (FiO2) was 0.5 (balanced with air) throughout the anesthesia period. After administration of induction doses of muscle relaxants, no muscle relaxants were administered during surgery. Anesthesia was maintained with target-controlled infusions of propofol (effect-site concentration, Ce 2–4 μg/ml) and remifentanil (Ce 2–8 ng/ml) using closed-loop titration guided by bispectral index (BIS, GE Healthcare, Madison, WI, USA) [17]. BIS values was maintained between 45–60 to prevent the occurrence of intraoperative awareness. The medication was administered manually or switched to manual infusion during surgery if required. Experienced surgeons preserved the anatomical integrity of motor nerves by visual identification and exposure of both the external branch of the superior laryngeal nerve and the recurrent laryngeal nerve. Additionally, the recurrent laryngeal nerve prevented injury by intraoperative neuromonitoring during parathyroidectomy.
IV bolus infusion of tolansetron 4 mg was used to prevent postoperative nausea or vomiting (PONV) at the end of surgery. All patients retained the endotracheal tube and were transferred to the postanesthesia care unit (PACU). The endotracheal tube was removed after full recovery of consciousness and spontaneous ventilation, and the train-of-four ratio was at least 0.9. If the Steward recovery score was >4 points [18], the patient escorted back to the ward from the PACU. The administration of postoperative routine analgesia was IV bolus infusion of parecoxib sodium 40 mg at the end of surgery, followed by an IV bolus infusion of parecoxib sodium 40 mg every 12 h for the next 24 h. If the visual analog scale (VAS) scores was at least 3 or the patient requested analgesia, IV bolus infusion of tramadol 50 mg was given as a rescue analgesic.
Data collection
Demographic and clinical characteristics, including age, height, weight,gender, HGB (hemoglobin, preoperative and within 10 min after surgery), PLT (platelets), APTT (activated partial thromboplastin time), PT (prothrombin time), TT (thrombin time), and Fib (fibrinogen), were recorded. Additionally, the duration of anesthesia and surgery was documented. Intraoperative fluid input was recorded. Intraoperative blood loss was recorded and evaluated by the HGB value, which was measured preoperatively and within 10 min after surgery [19]. Each patient was assessed using the global QoR-40 score [20] on the day before surgery and POD1. The QoR-40 includes five dimensions: emotional state (9 items), physical comfort (12 items), physical independence (5 items), psychological support (7 items) and pain (7 items). Each item is assessed using a 5-point numerical rating scale. The QoR-40 score ranges from 40 to 200. The recovery state is proportional to the score (40 = extremely poor recovery, 200 = excellent recovery). The total consumption of remifentanil was recorded. For the first time to required rescue analgesia, number of patients requiring rescue analgesia and total consumption of tramadol during the first 24 h after surgery were recorded. The total number of patients who vomited and the number of vomits were recorded. The occurrence of PONV was assessed by the PONV Intensity Scale, and PONV Intensity Scale score of 50 was defined as clinically significant PONV [21]. The VAS scores at 2, 4, 8, 12 and 24 h after surgery were rated using a 10-cm visual analog scale (VAS: 0 = no pain, 10 = the most pain imaginable). Block-related side effects were observed.
Statistical analysis
The calculation of sample size was based on the global QoR-40 score. A change of 10 points or more on the QoR-40 signifies a clinically important difference. In our pilot study, an overall standard deviation of 13 points was estimated, and with an α of 0.05, 37 patients would be required in each group (assuming a power of 80%). Anticipating a study drop-out rate of 10%, we included 41 patients per group.
Data analysis was performed using SPSS version 23.0 (SPSS Inc., Chicago, IL). Shapiro-Wilk test was used to evaluated the normal distribution of data. Continuous variables were presented as the mean (standard deviation, SD). Normally distributed variables were compared using Student’s t-test. Nonnormally distributed variables were presented as the median (interquartile range, IQR), and compared using the Mann–Whitney U test. VAS scores was compared using repeated- measures analysis of variance, and post hoc multiple comparisons was performed with Bonferroni correction. Qualitative data was presented as number or percentage, and compared using the chi-square test. P values of less than 0.05 was considered to be statistically significant.