Following the approval by the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College, we obtained the written informed consent from all the participants for this randomized prospective clinical trial. This prospective, double-blind, randomized controlled study has been registered prior to patient enrollment at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/; Principal investigator: Fangjun Wang, Date of registration: July 28 2016, Registration number：ChiCTR-INR-16008933 ).
This is a clinical, controlled, and randomized trial. 150 parturients at term, all of the participants were primigravida. American Society of Anesthesiologists (ASA) grade I or II, single birth, and undergoing optional cesarean section, were included in this study. Exclusion criteria included: a history of hypersensitivity to the drugs used, contraindications for regional block(such as infection of the puncture site, anatomic deformities, or coagulation disorders), diagnosis of acute or chronic fetal distress, prior administration of opioids and other central nervous system depressants, Rhesus immunization, pregnancy-induced hypertension syndrome, body mass index (BMI) > 35 kg/m2, and intraoperative blood loss >800ml. The patients were randomized into three groups by use of sealed envelopes (50 patients each) to receive epidural block (EPB group), subarachnoid block (SAB group), or epidural block combined with caudal block (EAC group).
All the parturients were assessed preoperatively by history, physical examination, and laboratory evaluations (liver function, renal function tests, and complete blood picture). The day before surgery, the study protocol, including EPB, SAB and EAC procedures were explained to each parturient. All parturients were made familiar with the use of a numeric rating scale (NRS) identifying 1 as unsatisfactory and 5 as the excellent. The parturients were fasted for 8 hours and had not been given any preanesthetic medication. Monitoring in the operating room included electrocardiography (ECG), pulse oxygen saturation (SpO2), urine volume, and non-invasive blood pressure (NIBP). Baseline NIBP, respiratory rate, ECG and SpO2 were recorded. After a good IV access secured, all parturients were administered 500 ml of Ringer's lactic acid solution intravenously before anesthesia. The 6 L/min oxygen was provided to all participants by a facemask until the end of the operation. All blocks isolated from gynecologists were performed by the same group of anesthesiologists who were proficient in intravertebral anaesthesia and had more than 10 years experience in anaesthesia.
Patients in three groups were placed with a left lateral position, and local anesthesia of skin and subcutaneous tissues were performed at puncture site under aseptic technique with 2% lidocaine hydrochloride 2-3mL. The epidural puncture site was at the L2-3 intervertebral space in EPB group and T11-T12 intervertebral space in EAC group. The epidural space was localized and confirmed with the sudden disappearance of resistance and the appearance of negative pressure. Then an epidural catheter was inserted 4.5cm into epidural space in a cephalic direction and gently withdrawing either no cerebrospinal fluid or blood. In EAC group, a 22-gauge needle was inserted into the sacral hiatus using ultrasound to guide accurate placement of the needle, after prior negative blood aspiration, a caudal injection of 0.25% ropivacaine 20ml administered in <30 s was performed, then any untoward effect was observed for 5-10 minutes. In SAB group, the 18G Tuohy needle was used to identify epidural space by loss of resistance to air technique at L2-3 or L3-4 intervertebral space, and a 25G pencil point spinal needle was inserted through the 18G Tuohy needle and once free flow of cerebrospinal fluid was obtained hyperbaric 0.5% ropivacaine 15 mg (3 ml) was injected intrathecally over 30 seconds, then epidural catheter was inserted 4.5 cm into epidural space and fixed without withdrawing CSF or blood through it in SAB group. After the epidural catheter being secured to skin surface, the caudal injection and intrathecal injection, women were repositioned with left uterine displacement by keeping a wedge beneath the right half of lower back and a pillow was placed below the head and shoulders. Thereafter, 3 mL of 2% lidocaine hydrochloride solution was administered as a test dose and any untoward effect was observed for in EPB group and EAC group. After 5–8 minutes of institution of the test dose, EPB group and EAC group were received epidural anesthesia with 15 mL and 10 mL of 0.75% ropivacaine respectively. Surgical procedures were initiated only after the anesthetic level was completely established minimum until T10 or 20 min had pasted after completion of spinal or epidural anesthetic. Participants were required to compare the sensation of cool inducted by evaporating of alcohol on the cervical skin to the sensation at lower dermatome levels. The alcohol cotton ball was moved from caudad to cephalad direction starting at the L2 dermatome, and the testing of sensory level was performed every two minutes after administration of the spinal or epidural anesthetic untill 30 min had passed. Patients were asked to indicate when the sensation of alcohol felt the same as on the forehead. Motor block using a modified Bromage motor scales(MBS) (1=Complete block, unable to move feet or knees; 2 =Almost complete block, able to move feet only; 3 = Partial block, just able to move knees; 4 = Detectable weakness of hip flexion while supine, full flexion of knees; 5 =No detectable weakness of hip flexion while supine)13 was also recorded at the same intervals. The following variables were recorded: time to initial onset of cryanaesthesia at T10, maximal sensory block level, time to attain maximum motor blockade, and time for complete regression of motor block. Maternal hemodynamic parameters included NIBP (both systolic and diastolic), ECG, heart rate, SpO2 and respiratory rate, were monitored continuously. Recordings were made every 1 minute until 30 minutes after the local anesthetic administered and at 5-minute intervals thereafter up to the end of surgery. Hypotension (defined as systolic falling more than 20% before anesthesia or systolic values lower than 80 mmHg) was treated with ephedrine 6 mg intravenous bolus immediately. Bradycardia (defined as heart < 55 beats/minute) was treated with 0.3 mg of injection atropine.
During the surgical procedure, Intravenous fluids were given as per the body weight and operative loss requirement with none requiring blood transfusion. Intraoperative adverse events like nausea, vomiting, maternal bradycardia or hypotension were recorded. Nausea and/or vomiting were treated with ondansetron 4 mg intravenous. During at the end of surgery, the quality of anesthesia was judged by the parturients and the gynecologist on a numeric rating scale (NRS) from 1 (unsatisfactory: the parturients feel pain and the gynecologist felt tension in the patient's abdominal muscles, general anesthesia required to complete the cesarean section) to 5 (excellent: the parturients feel painless and the gynecologist felt relaxant in the patient's abdominal muscles). All patients returned to the maternity ward and received epidural analgesia after cesarean section. In order to avoid PDPH, patients in group SAB were positioned supine for at least 4 hours after surgery, whereas patients in group EPB and EAC did not need to be so. The quality of postoperative comfort was judged by the parturients 12h after operation on a numeric rating scale (NRS) from 1 (unsatisfactory: with a headache, moveless and numbness legs, be in a uncomfortable position while breastfeeding) to 5 (excellent: no headache, free movement of legs and without numbness, be in a comfortable position while breastfeeding). All the indicators were assessed and recorded by a research assistant who was unware of the grouping of clinical trials.
A comparison of the satisfaction rate of patients was the primary outcome of this study. In the preliminary experiment, we found that the satisfaction rates of patients in the spinal anesthesia group, epidural block group and epidural block combined with caudal block group were 65%, 75% and 85% respectively. We assumed that 10% decrease in satisfaction rate of patients would be clinically relevant and calculated that a sample size of 48 patients would be needed in each group (type I error of 0.05, power of 0.9). Considering a 10% dropout rate, 53 patients in each group were necessary.
The statistic software SPSS (version 19.0) was used for all statistical analysis. One-sample Kolmogorov-Smirnov test was applied to analyze the distribution of the data, and each group of data was taken a homogeneity test for variance in multiplicate samples by the means of Levene. One-way analysis of variance was used to examine the differences of quantitative data between groups. The Kruskal-Wallis H(K) was performed to analyze the ordered variables, such as time to cryanaesthesia at T10, maximal sensory blockade spinal segments, time to maximum motor block, time for complete regression of motor block and apgar scores. The incidences of maternal bradycardia, hypotension, nausea, vomiting, postoperative headache, quality of anesthesia and postoperative comfort among the three groups were compared with Chi-Square test. A p value<0.05 was considered statistically significant.