1.1 General information
Sixty patients with peritoneal cancer who underwent HIPEC from June 2018 to June 2019 were selected and randomly divided into two groups of 30 patients each. One group was the control group, with intermittent intravenous administration of cisatracurium, and the other group was the experimental group, with continuous administration of cisatracurium. Inclusion criteria were as follows: ASA classification I–III, age 18–65 years, and signed informed consent form and agreement to be included in this study. Exclusion criteria were as follows: 1) presence of significant preoperative cardiopulmonary, hepatic, and renal insufficiency (including cardiac NYHA class II or higher, respiratory failure, Child-Pugh liver function class B or higher, and chronic renal insufficiency or ongoing dialysis); 2) presence of neuromuscular disorders; 3) presence of allergy to muscarinic drugs; and 4) recent use of drugs that affect neuromuscular conduction (including anticonvulsants, digitalis, diuretics, aminoglycoside antibiotics, and corticosteroids). The study was approved by the Ethics Committee of Beijing Shijitan Hospital, and all patients signed an informed consent form before the study.
All patients were routinely fasted from food and water before the surgery. After admission to the operating room, intravenous access was initiated, fluids were instituted, and ECG, invasive arterial pressure, oxygen saturation, and electroencephalographic bifrequency index (BIS) were monitored. Anesthesia was induced sequentially with sufentanil 0.4 ug/kg, propofol 2.0 mg/kg, and cisatracurium 0.2 mg/kg (for four-time 95% effective dose [ED], cisatracurium’s ED 95% was 0.05 mg/kg). After induction of anesthesia, the patient underwent tracheal intubation and was mechanically ventilated, and EtCO2 was maintained intraoperatively between 35 and 45 mmHg. Intravenous-inhalation combined anesthesia was chosen for the maintenance of anesthesia. Intraoperatively, sevoflurane inhalation anesthesia was administered with the concentration of volatilization pot output at 1.8–3% and the concentration of 1.8 L/min inhaled oxygen at 50%. Remifentanil was injected continuously at a rate of 0.1-0.2ug/kg/min. A BIS value of 45-55 was maintained. Cisatracurium was added at a rate of 0.1 mg/kg/h intermittently in the control group according to the commonly used clinical dose. Cisatracurium was pumped continuously at a rate of 1.5 ug/kg/min in the experimental group. Cisatracurium was discontinued 30 min before the end of surgery. Sevoflurane inhalation was discontinued 20 min before the end of surgery. Remifentanil was discontinued 10 min before the end of surgery. Sufentanil was added at 0.1 ug/kg. The maintenance dose of anesthetics was adjusted at any time during surgery according to the progress of surgery, changes in depth of anesthesia, and changes in hemodynamic indices.
At the end of the procedure, no muscarinic antagonist was administered. The patient was observed for recovery of muscle relaxation. After the patient regained consciousness and reached the tracheal extubation indication, the patient was extubated after the secretions were sufficiently aspirated in the oral cavity and trachea. Indications for extubation were as follows [25,26]: ① the patient was conscious and could respond to the call; ② cough and swallowing reflexes and muscle strength were restored, and the patient could keep the head raised for 5 s; ③ spontaneous breathing was restored, tidal volume reached 6 mL/kg, and regular respiratory rhythm was 12–20 cycles/min; and ④ oxygen saturation (SpO2) is > 97% 5 min after discontinuation of oxygen. The patients were sent to the postoperative ICU recovery unit (SICU) for continued observation after the vital signs stablized.
1.3 Observational indicators
1.3.1 General information of the patients, including gender, age, body mass index, ASA classification, and duration of anesthesia (min) and operation (min) were recorded. Intraoperative fluid rehydration and urine volume were recorded.
1.3.2 Patients’ vital signs (mean arterial pressure [MAP], heart rate [HR]) and respiratory indices (tidal volume [VT], respiratory rate [F], and SpO2) were recorded before anesthesia (T1) and at the time of tracheal tube removal (T2).
1.3.3 Total dosage of cisatracurium, time to return to 6 mL/kg of tidal volume for spontaneous breathing (t1), time to the ability to hold the head up for 5 s (t2), and time from the discontinuation of the inotropes to the removal of the tracheal tube (t3) were recorded. Arterial blood gases without oxygen were analyzed using a Gem Premier 3000 blood gas analyzer (IL, USA), and arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were measured before anesthesia, at the time of exit from the operating room, and at the time of transfer from SICU for the assessment of respiratory function.
1.3.4 For the recording of adverse reactions, patients were observed for adverse events such as skin rash, laryngospasm, bronchospasm, presence of cardiac arrhythmias, and intraoperative hypotension after intravenous cisatracurium injection. Postoperative follow-up was performed to assess whether the patient had intraoperative knowledge.
1.4 Statistical methods
SPSS 19.0 software was used for analysis. Normally distributed data were recorded as mean ± standard deviation, and independent samples t-test was used to compare the normally distributed data of the two groups, while chi-square test was used to compare the count data. P values <0.05 indicated statistical significance.