This prospective clinical observational study was approved by the Institutional Scientific Research and Clinical Trials Ethics Committee of the First Affiliated Hospital of Zhengzhou University (ref.: 2019- KY-120) and registered at chictro.org (ref.: ChiCTR1900024352; July 6, 2019).
Patients who were classified as American Society of Anesthesiologists (ASA) physical status I-II, aged between 18-65 years, all genders, BMI 18 to 28 kg/m2, and scheduled to undergo laparoscopic nephrectomy under general anaesthesia, agree to use postoperative analgesia pump for 48h after surgery, agreed to cooperate and signed the informed consent were recruited.
Patients with the following conditions were excluded: severe heart, lung and metabolic diseases, hepatic or renal dysfunction, a history of neuromuscular system disease, mental illness, and a tendency to malignant hyperthermia, preoperative existing pain, long-term use of sedative and analgesic drugs (> 3 months), drug or alcohol abusers, or severe hypertension, poor understanding or communication difficulty, failed venous cannulation, changed in surgical approach (from laparoscopic to open surgery, the operative time over than 3 h, failed to complete the data collection.
Preoperative pain assessment
An anaesthetist visited the patients the day before surgery, described the visual analogue scale (VAS) for them and instructed on the use of PCIA bump. On the day of surgery, an experienced nurse inserted a peripheral venous catheter (B. Braun Melsungen AG, Germany ) with a standard-size(1.1 × 3.2 mm inner diameter) into a superficial vein on the back of the patient’s hand in the preoperative preparation room. The patients were asked to estimate, on a horizontal VAS ruler, their maximum pain intensity associated with this procedure, recorded to one decimal point (0.0-10.0). Then the nurse recorded the VAS score estimated (on a horizontal VAS ruler, their maximum pain score associated with this procedure) by the patients, and dichotomized the patients into low response group (VCP score < 2.0 VAS units) or high response group (VCP score ≥ 2.0 VAS units). The nurse was aware of whether the patient was to take part in the study.
All patients were anaesthetized by anaesthetists who were blinded to study and did not participate in data collection. Once in the operating room, the standardized monitoring of ECG, SpO2, noninvasive blood pressure was established. Before the induction of anaesthesia, the patients were given IV Penehyclidine Hydrochloride 0.5 mg, and a loading dose of dexmedetomidine with 0.5 μg kg-1 was infused over 10 minutes. The bispectral index (BIS) was used to monitor the depth of anaesthesia. Then anaesthesia was induced with midazolam 2 mg, sulfentanil 0.5 μg kg-1, etomidate 2-3 mg kg-1. Cisatracurium 0.2 mg kg-1 was given to facilitate endotracheal intubation. Anaesthesia was maintained with sevoflurane (1-2%), remifentanil 0.1-0.3 μg kg-1 min-1. The cisatracurium was used to provide a satisfactory level of muscle relaxation. The BIS value was maintained between 40 to 60. The pneumoperitoneum pressure with carbon dioxide was set at 13-15 mmHg, and the EtCO2 was maintained at 35 to 45 mmHg. Thirty minutes before the end of the surgery, sulfentanil 10 μg and flurbiprofen axetil 100 mg were given as postoperative analgesia, and tropisetron 5 mg was given to prevent postoperative nausea and vomiting. At the end of the surgery, sevoflurane and remifentanil were stopped. Immediately after surgery, the PCIA pump was attached to the peripheral venous line by the anaesthetist. Then the patients were sent to the post anaesthetic care unit for anaesthetic resuscitation. All patients were sent to the general ward after being fully awake. Upon arrival in the general ward, all the patients were once again instructed on the use of the PCIA pump and VAS.
Postoperative analgesia regimen
The PCIA with sulfentanil regimen was applied to 48 h after surgery. The PCIA regimen consisted of sulfentanil 3.0 μg kg-1 and 5 mg tropisetron, mixed with 0.9% normal saline to a total volume of 150 ml. The PCIA was programmed to deliver a 2 ml bolus on demand, with a lock-out interval of 10 min, and a background infusion rate of 2 ml h-1. In the ward, patients pressed PCA when VAS score at rest > 3.0. If patients still reported pain or the VAS scores ≥ 4.0, supplemental rescue boluses of intravenous flurbiprofen axetil injection of 50 mg were administered. The complete history of continuous infusion, bolus infusion, and bolus demand for the PCIA device was downloaded after surgery.
Outcome variables measures and data collection
The study outcomes variables and the vital parameters were recorded at 2, 4, 8, 12 and 24 hours after surgery. During the studied period, pain intensity, sulfentanil consumption, pressing times of the PCIA, and the number of rescue analgesia were recorded at above time points. Overall satisfaction index of the patients was recorded at 24 h. Pain intensity was assessed with VAS at rest and during coughing.
The primary outcome was maximum postoperative pain scores at rest and during coughing within the first 24 h. The secondary outcome was effective times of pressing, additional consumption of sulfentanil and satisfaction index at 24 h. Also, the number of rescue analgesia within the first 24 h was also measured.
Postoperative data collector was blinded to the preoperative peripheral venous cannulation-induced pain score of the patients.
Sample size and statistical analyses
The sample size was based on a pilot experiment of 20 cases resulted in our observation that patients with VCP score ≥ 2.0 VAS units was present in 8 out of 20 patients and that mean maximum postoperative pain score (VAS) at rest within 24 hours after surgery was 3.9 (± 1.3) . Therefore, in order to show a 20% difference between the patients with VCP score ≥ 2.0 VAS units and the patients with VCP score ≥ 2.0 VAS units, the number of patients in each group was expected to be 41 (α=0.05, β=0.8). Since the groups are unequal, assuming a 40% of patients with VCP score ≥ 2.0 VAS units, and allow for up to 15% dropouts, a total of 120 patients (48 patients with VCP score ≥ 2.0 VAS units and 72 patients with VCP score < 2.0 VAS units ) would be sufficient to test our hypothesis.
The IBM SPSS version 22.0 software packages were used for statistical analyses. The normality of the continuous data was tested by the Shapiro-Wilk test. Normally distributed continuous variables were expressed as mean ± SD and compared between groups using a two-sample Student t-test. IF the distribution was not normal, the median with inter-quartile range (IQR) were expressed, and a Mann–Whitney U-test was used. Categorical data were expressed as frequency (n) and percentage (%) and were statistically tested using the chi-square or Fisher’s exact test. Correlations between variables were assessed with Spearman’s rank correlation coefficients. Logistic regression analysis was used to evaluate the predictive abilities of cannulation-induced pain intensity. All P values < 0.05 were considered to be statistically significant.