The efficacy and safety of intrathecal dexmedetomidine for parturients undergoing cesarean section: a double-blind randomized controlled trial

This trial was approved by the ethics committee of Feng Xian People’s Hospital and the Affiliated Hospital of Xuzhou Medical University. Written informed consent was obtained from all enrolled participants. This manuscript adheres to the applicable CONSORT guidelines. This study was a two-centers, prospective, double-blind, randomized controlled trial, and the two centers are the Affiliated Hospital of Xuzhou Medical University and Feng Xian People’s Hospital. Patient recruitment and data collection were started in April 2019 and ended in July 2019. The inclusion criteria of our study were: (1) Full-term pregnant women undergoing elective cesarean section under spinal anesthesia; (2) Age: 20 ~ 35 years; (3) ASA physical status II ~ III; The exclusion criteria were: (1) Multiple pregnancies; (2) Cardiovascular disease (e.g., pre-eclampsia and hypertension); (3) Serious hepatic dysfunction (Child-Pugh class C); (4) serious renal dysfunction (undergoing dialysis before surgery); (4) History of alcohol or opioid addiction; (5) Contraindication to spinal anesthesia; (7) Refusing to sign informed consent.

According to the random number generated by computer, parturients were randomly allocated into three equal groups to receive either DEX, fentanyl or normal saline in combination with bupivacaine. The randomization sequence was placed in serially numbered opaque envelopes. Before the start of spinal anesthesia, an anesthesiologist prepared relevant drugs according to the randomization sequence and the anesthesiologist would not participate in the data collection, follow-up, and analysis.

All parturients included in the study routinely fasted for 6–8 h before surgery, and none of them received pre-medication. When parturients were admitted into the operating room, standard monitoring for pulse oxygen saturation (SpO₂), heart rate (HR), electrocardiogram (ECG), and noninvasive blood pressure (NIBP) was carried out. All parturients were given a supplementation of 3 L/min O₂ through the nasal catheter. Then an intravenous 18-G cannula was inserted and patients were preloaded with ringer lactate 10 ml/kg 15–20 min before anesthesia.

With the parturients in the left lateral position, spinal anesthesia was performed at the L3-L4 interspace with a 25 G spinal Quincke-tip needle and study drugs were injected slowly within 15 s after the cerebrospinal fluid flowing out. The three groups were scheduled to receive drugs as follows: bupivacaine group (group B): 9 mg (1.2 ml) of 0.75% bupivacaine, with 1.0 ml of normal saline. Bupivacaine + fentanyl group: (group FB): 9 mg (1.2 ml) of 0.75% bupivacaine, with 20 μg of fentanyl in 1.0 ml of normal saline. Bupivacaine + DEX group (group DB): 9 mg (1.2 ml) of 0.75% bupivacaine, with 5 μg of DEX in 1.0 ml of normal saline. After removing the spinal needle, parturients were in the position with a 15-degree tilt to the left side immediately. All spinal anesthesia procedures were performed by experienced anesthesiologists. The sensory block level was tested by the pinprick method using a blunt 25-G needle. Assessment of the dermatomal level was done every 1 min until the peak sensory block level was achieved. Subsequently frequent testing every 10 min was performed until regression to S1 dermatome. The motor block was assessed by the modified Bromage scale (MBS, 0 = no paralysis,1 = inability to raise the leg, 2 = inability to flex the knee, and 3 = inability to flex the ankle) [14]. Surgery was allowed to commence once the sensory block level reached T6 [15]. Any patient showing moderate pain (visual analog score (VAS) ≥3) was administered intravenous 0.5 mg/kg ketamine. If hypotension (systolic blood pressure (SBP) < 90 mmHg or descending baseline values by 30%) persisted, intravenous 6 mg of ephedrine was administered; If bradycardia (HR < 50 bpm) occurs, intravenous 0.5 mg of atropine was administered. Repeat if necessary. Intraoperative ephedrine and atropine consumption were recorded. After surgery, all patients underwent patient-controlled intravenous analgesia (PCIA) with 2 μg/kg of sufentanil and 10 mg of tropisetron.

The primary outcome of our study was the duration of sensory block, which was defined as time taken from intrathecal injection to sensory regression to S1 dermatome. The secondary outcomes of our study were as follows: the onset time of sensory block, which was defined as time taken from intrathecal injection to the maternal feeling of lower extremities temperature increment or numbness [16]; the onset time of motor block, which was defined as time taken from intrathecal injection to MBS > 1; the duration of motor block, which was defined as time taken from intrathecal injection to MBS = 0; the peak sensory block level; the blood gas analysis for PH, PaO₂, and PaCO₂ of the umbilical artery (UA) and umbilical vein (UV) blood samples of the newborn, which was performed immediately after collection; the plasma concentration of DEX in the UA and UV, which was determined by High-Performance Liquid Chromatography Tandem Mass Spectrometry methods [17]; Apgar scores, which were assessed at 1st and 5th min by the obstetrician who was blinded to the study; the hemodynamic parameters of parturient including BP, HR, which were evaluated at: baseline values (T0), immediately after blockcade (T1), 5 min (T2), 10 min (T3), 15 min (T4) and 20 min (T5) after blockcade. BP and HR at T0 were defined as the average values measured for 3 consecutive times at rest after entering the operating room.

The recovery quality of parturients within 24 h after surgery was assessed by obstetric quality of recovery-11 score [18] (ObsQoR-11, score from 0 to 10 in each term, where 0 = strongly agree and 10 = strongly disagree, the higher of the score, the higher of recovery quality), which was designed for parturients and presented by Ciechanowicz S; intra-and postoperative adverse events including nausea, vomiting and shivering, time to the first analgesic request and total sufentanil comsumption at 24 h after surgery were also recorded. Parturients were contacted by telephone for a post-operative 30 days following discharge to determine whether nerve injury occurred, including any new onset of back, buttock or leg pain or paresthesia. All of these evaluations were performed by an anesthesiologist blind to any other aspect of the trial.

The sample size was calculated using PASS 15.0 software (NCSS, LLC, Kaysville, USA). The sample size calculation was based on the primary outcome, the duration of sensory block. According to our pilot trial results, the duration of sensory block was 114.3 ± 28.5 min for group B, 120.1 ± 29.4 min for group FB, 128.8 ± 29.5 min for group DB. A total of 80 patients were required to achieve 80% power with an alpha error of 5% based on the module of analysis of variance (ANOVA) in PASS. Considering a lost-to-follow-up rate of about 15%, 94 patients are required for each group. Finally, a total of 100 parturients were recruited in our study.