Ethics
The study was approved by the ethics committee of Huzhou Maternity & Child Care Hospital (Ethical Committee number 201801; Chairperson Ping-ya He) and written informed consent was provided by all patients prior to enrollment in the study.
Study design and patient population
A total of 80 patients with repeat cesarean section, aged 23-36 years (weight 56-90 kg, American Society of Anesthesiologists levels I and II ) were involved in the study. The patients were randomly placed in either the intravenous remifentanil-assisted epidural group (group R) or the epidural group (group E).
Criteria for inclusion and exclusion
Patients undergoing repeat cesarean section, with full-term, singleton pregnancies, who had arranged for epidural anesthesia, were included in this study. Patients with contraindications for epidural anesthesia, history of allergy to bupivacaine or opioids, history of spinal surgery, or intrauterine hypoxia were excluded from this study. Patients with epidural anesthesia puncture failure, poor effect of epidural anesthesia, or intraoperative hemorrhea were also excluded from the analysis.
Preoperative preparations and anesthesia protocol
All patients fasted for 6 h and discontinued fluid intake 2 h before repeat cesarean section. Intravenous access was established, 5 L/min oxygen was administered, and Ringer’s lactate 8 ml/kg was preloaded after patients entered the operating room. Electrocardiography, noninvasive arterial pressure, respiratory rate, and pulse oximetry were routinely monitored for all parturients.
Before epidural anesthesia was administered, patients were placed in the left lateral decubitus position. The epidural space was cannulated at the L2-3 interspace with the midline approach, using an 18-gauge Tuohy needle. A loss-of-resistance to the saline technique was used to affirm the puncture; then, a 20-gauge epidural catheter was advanced 3 cm cephalad. Three milliliters 1.5% lidocaine with 10 μg adrenaline was injected through the epidural catheter as a test dose. Epidural administration of 0.75% ropivacaine was performed in two groups until the epidural anesthesia level of all parturients reached T6. In group R, remifentanil was continuously intravenously infused at a rate of 0.05 μg·kg-1·min-1 at the beginning of the operation. The intravenous infusion rate of remifentanil was increased by 0.025 μg·kg-1·min-1 if patients complained of discomfort or pain. The maximum speed of intravenous infusion did not exceed 0.15 μg·kg-1·min-1. If excessive sedation or respiratory depression occurred, intravenous infusion of remifentanil was reduced 0.025 μg·kg-1·min-1 until infusion was completely discontinued. In group E, if the patients complained of discomfort or pain, 0.75% epidural ropivacaine was administered as needed. Intravenous infusion of ketamine was administered as needed, or general anesthesia was performed if the discomfort or pain were not relieved.
If the saturation of pulse oxygen (SpO2) was<95% or respiratory rate (RR) was<8 times/min (i.e., respiratory depression was observed), the parturient was awakened and oxygen was administered with a pressure mask. If the heart rate (HR) was <50 beats/min, intravenous atropine 0.5 mg was administered. If hypotension (a systolic blood pressure (SBP) reduction of >30% or a value of <90 mmHg) occurred, intravenous ephedrine 5-10 mg was administered. All anesthesia procedures were performed by the same senior anesthesiologist and all data were recorded by an anesthesia nurse. Patients in both groups were excluded from this study if the anesthetic block level did not reach T10, or if they were changed to general anesthesia 15 min after epidural administration.
Measurements
The following parturient data were recorded: age, body mass index (BMI), weight, ASA status, dose of ropivacaine, gestational weeks, dose of remifentanil, and epidural anesthesia block level (counted from the sacral vertebra[11]) were recorded. SpO2, mean arterial pressure (MAP), HR, and RR were recorded before anesthesia (T0), as well as at skin incision (T1), delivery of baby (T2), uterine suture (T3), and intraoperative traction (T4) in all parturients. The visual analogue scale (VAS) score was recorded at T1, T2, T3, and T4; the maximum VAS score during surgery was also recorded. The degree of comfort during surgery was assessed using the numerical rating scale ( NRS, 0 = least comfort imaginable, 10 = very comfortable ). The use of intraoperative oxytocin was recorded in both groups. Incidences of intraoperative respiratory depression (RR<8 times/min), bradycardia, hypotension, and postoperative adverse reactions were recorded for both groups; Apgar scores were recorded at 1and 5 min after birth for both groups, as were the numbers of neonatal resuscitations and the pH value of neonatal umbilical arterial blood.
The comfort scores during surgery was the primary outcome measure of the study; the secondary outcomes were the maximum VAS score, and maternal and newborn adverse effects during surgery.
Statistical analysis
In a preliminary trial of 20 patients, the comfort scores during surgery were 8.9±0.9 and 7.8±1.6 in groups R and E, respectively. Based on the preliminary trial, 26 patients were required per group to detect a 15% increase of comfort score for 90% power and an α level of 0.05, with a drop-out rate of 15%. Data are expressed as mean ± standard deviation (SD), or numbers of patients, as appropriate. Statistical analyses were performed using independent t-tests, the chi-squared test, Fisher’s exact test, and repeated measures analysis of variance, as appropriate. All statistical analyses were performed using SPSS version 22.0 (SPSS Inc., Chicago, IL, USA). p< 0.05 was considered to indicate statistical significance.