Methods
NRS pain, Resting pain, pain, impaired or retarded mental
INFILTRATION, RECRUITMENT, WEST, IMPAIRED RENAL FUNCTION, DRUG ALLERGY
This study was conducted at Queen Mary Hospital in Hong Kong, China. The study was approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18–176), and registered at clinicaltrial.gov prior to patient recruitment on 24/07/2018 (NCT03597997). All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was obtained from all patients participating in the trial.This study was prospective, double-blinded randomized controlled, conducted in accordance to the CONSORT guideline. All methods were carried out in accordance with Declaration of Helsinki. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy (left or right hepatectomy, segmentectomy, or wedge resection) were eligible. Exclusion criteria included the following: 1) known drug allergy to propofol, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors, paracetamol, ketamine; 2) alcohol or drug abuse; 3) impaired renal function, defined as preoperative serum creatinine level over 120 µmol/L; 4) impaired or retarded mental state; 5) body mass index (BMI) > 35 kg/mEligible patients were approached in the general ward before the operation for recruitment. The anaesthetic options were explained, and the patient was recruited into the study if s/he agreed. The patients were then randomized into one of two groups: i) SEVO group, anaesthetized by inhalational anaesthesia using sevoflurane; or ii) TIVA group, anaesthetized using propofol total intravenous anaesthesia. Patients recruited for hepatectomy were stratified in randomization. A computer-generated random sequence was used to select the allocation order, which was concealed in opaque envelopes, and opened at the time of intervention administration. Patients were not aware of the types of anaesthesia they received. A separate blinded investigator assessed the patients after the operation. The anaesthetist providing general anaesthesia was aware of the allocation, but s/he was not involved in data collection. Assessment was done at the general ward. Fasting for patients started at midnight before operation [On arrival to the operation theatre, a 20- or 22-gauge intravenous cannula was inserted. Standard monitoring with pulse oximeter, non-invasive blood pressure, and three lead electrocardiograms was applied prior to induction. For patients in the SEVO group, general anaesthesia was induced with propofol 1.5-3 mg/kg, remifentanil 0.5-1mcg/kg, and rocuronium 0.6-1 mg/kg or atracurium 0.5 mg/kg given intravenously (IV). Sevoflurane, air and oxygen was used for maintenance of general anaesthesia. FiOFor both groups of patients, morphine sulphate at a bolus dose of 0.1 mg/kg IV was given before skin incision. Additional 0.1 mg/kg of morphine sulphate IV could be given in divided doses when the surgery continued for more than 2 h at the discretion of the attending anaesthetist. Ketamine 0.5-1 mg/kg IV was given before skin incision. Patients received local wound infiltration with up to 2 mg/kg of levobupivacaine during wound closure [Resting pain scores were checked every 5 min in the PACU. Morphine sulphate at a dose of 2 mg IV was given every 5 min until the numerical rating scale (NRS) pain score was less than 4/10. Respiratory rate, oxygen saturation, Ramsay sedation scores, blood pressure and heart rate were monitored every 5 min in the PACU. Patient controlled analgesia (PCA) morphine was connected to the patient once the NRS pain score was less than 4/10. The following parameters were set for the PCA morphine machine: bolus 1 mg of intravenous morphine sulphate with each patient demand, lockout duration of 5 min, and maximum dose limit of 0.1 mg/kg of morphine sulphate per hour. When the patient resumed fluid diet in the ward on POD 0, regular oral dihydrocodeine was prescribed at a dose of 30 mg three times a day for two days. Afterwards, dihydrocodeine was given as needed. Breakthrough pain was treated by intramuscular/subcutaneous morphine 0.1 mg/kg every 4 h as needed starting from POD 0 [PCA morphine was given for at least 2 days. It was stopped on POD 2 if NRS pain scores during coughing were less than 4/10 and morphine consumption was low. PCA morphine was continued if NRS pain scores during coughing were equal or greater than 4. After discontinuation of PCA morphine, NRS pain scores (at rest and during coughing) and the dose and frequency of rescue analgesia used were recorded daily until patient discharge. Patient satisfaction with analgesia, where 0 corresponded to the least satisfaction, and 10 corresponded to the most satisfaction, was assessed on POD 1 [Various outcomes were also assessed at 3 and 6 months after surgery. This included the presence or absence of pain, and NRS pain scores at rest and with coughing [