The study was approved in July 2014 by the local Institutional Review Board of Ewha Womans University Hospital, Seoul, Republic of Korea (EUMC 2014-05-032-007) and registered with the Clinical Trial Registry of Korea (https://cris.nih.go.kr) under the trial ID KCT0002514. Written informed consent was obtained from all patients. A prospective randomized, double-blind study was performed at term pregnancy scheduled for elective cesarean section. Parturients with pregnancy-induced hypertension, multiple pregnancies, placenta previa, cardiac diseases, or contraindications to regional anesthesia were excluded. A total of 40 parturients were randomized to receive CSEA with either the double-space technique (double group, n = 20) or single-space technique (single group, n = 20). The random allocation sequence was created by an anesthesiologist who did not participate in the study using a computer-generated randomization schedule (www.randomization.com). On arrival at the operating room, all parturients were rapidly infused with 10 ml kg-1 of lactated Ringer’s solution. Oxygen was administered at a flow rate of 3 l min-1 through a nasal cannula. Electrocardiogram, noninvasive blood pressure and pulse oximetry monitoring were performed, and baseline values were recorded. After taking the right lateral position, preprocedural ultrasound scanning was performed in a nonsterile manner. Using a 2–5 MHz curved probe (M-TurboTM; SonoSite Canada Inc., Canada), the sacrum was identified first; then, the transducer was moved cephalad, and the intervertebral level was marked with a skin marker. All parturients received local anesthetic infiltration at the L1–2 and L3–4 interspaces using 1% lidocaine prior to CSEA.
In the double group, an 18-gauge Tuohy needle (Perifix®; B. Braun, Melsungen, Germany) was introduced, using a loss of resistance to air to confirm the epidural space. Dural puncture was performed at the L3–4 interspace with a 25-gauge Quincke tip spinal needle (Tae Chang Industrial Co., Ltd., Kongju, Korea). Next, 0.5% hyperbaric bupivacaine 6 mg mixed with fentanyl 25 μg was given intrathecally after the free flow of cerebrospinal fluid was observed. A 20-gauge epidural catheter was inserted through the epidural needle, 3–4 cm into the epidural space. After the Tuohy needle had been removed, the catheter was firmly fixed and covered with gauze so that the level of catheter entry could not be distinguished. For the epidural test dose, 3 ml of 0.375% levobupivacaine with epinephrine (1:200,000) was injected.
In the single group, the procedure was performed at the L3–4 interspace. An 18-gauge Tuohy needle (Espocan®; B. Braun, Melsungen, Germany) was introduced using a loss of resistance to air, and the dura was punctured with a 27-gauge Sprotte needle using the needle-through-needle technique. When free flow of cerebrospinal fluid was observed, 0.5% hyperbaric bupivacaine 6 mg and fentanyl 25 μg were administered. After withdrawal of the spinal needle, a 20-gauge epidural catheter was inserted through the epidural needle, 3–4 cm into the epidural space. The Tuohy needle was removed, and epidural catheter fixation and an epidural test dose injection were performed in the same manner as in the double group.
CSEA was performed by one investigator (YJK). The parturients and the investigator (EHC) were unaware of which group they had been assigned to, and the investigator (EHC) performed all assessments.
The primary outcome measures for this study were time spent on the procedure, time to readiness, and sensory block level. The secondary outcomes included the failure of the block, the incidence of side effects (e.g., hypotension, bradycardia, nausea, dizziness), neonatal outcomes, parturient satisfaction scores (0–10, 0 = unsatisfied, 10 = satisfied; at the end of the procedure, upon arrival at the postanesthesia care unit (PACU), and 48 h postoperatively) and variables associated with postoperative recovery (e.g., pain scores, motor blockade, and sensory level). The total procedure time was defined as the time interval between local infiltration to the skin and the intrathecal injection. Time to readiness was defined as the time from intrathecal injection to the T4 sensory block. The point of intrathecal injection was taken as time 0 min in both groups. Maternal blood pressure was recorded every minute for 10 min and at 5-min intervals for the remaining time. Hypotension was defined as a 20% or greater decrease below the preinduction level or a systolic pressure below 95 mmHg, which was treated immediately with ephedrine 5 mg, i.v., and repeated whenever necessary. Bradycardia (heart rate < 50 bpm) was treated with 0.5 mg of atropine.
At the end of surgery, parturients received an epidural bolus injection: 10 ml of a solution of ropivacaine 0.2% with morphine sulfate 1 mg. Postoperative analgesia was provided with an epidural infusion at 5 ml h-1 of a solution containing ropivacaine 2 mg ml-1 and fentanyl 4 μg ml-1.
The sensory block was tested every minute for 10 min and 1, 6, 12, 24, and 48 h after the operation. The motor block was checked 1 and 6 h after the operation. Sensory levels were checked by cold sensation using an alcohol sponge, and the motor block was assessed using a modified Bromage scale (0 = no block; 1 = weak or absent hip flexion, able to move knees and ankles; 2 = unable to move hips or knees, able to move ankles; and 3 = unable to move any joint). Postoperative pain scores using numeric rating scales (NRS) (0–10; 0 = no pain, 10 = the most severe pain imaginable) were recorded postoperatively at 1, 6, 12, 24, and 48 h.
It was recorded when the patients started urination after foley catheter removal and when the patients observed the first flatus. The time to start walking was also recorded independently.
Statistical comparisons of the continuous variables between the two groups were analyzed with Student’s t-test, and sensory and motor block variables were compared using the Mann-Whitney U test. Differences between the two groups in the incidences of side effects such as hypotension, pain, nausea and vomiting and dizziness were analyzed with chi-square tests and Fisher’s exact test when appropriate. A repeated measures analysis of variance was used to test the difference between the two groups in blood pressure. P < 0.05 was considered to be statistically significant. SPSS (ver. 18.0, Chicago, IL, USA) was used for the statistical analysis. The data are expressed as numbers, percentages, and medians [range] or means ± standard deviation. From our experience and a previous study , using a two-sided design at a significance level of 5% with a power of 80%, an estimated 16 parturients per group were needed to detect a sufficient effect size. Assuming a 20% dropout rate, we designed the study with 20 parturients in each group.