Materials and methods
After obtaining approval from the Research Ethics Committee of the International Peace Maternity and Child Health Hospital (Ethical number: GKLW 2017-85) and registering this prospective, double-blind study at http://www.chictr.org.cn (ChiCTR1800016163), were recruited 58 parturients aged 18–40 years, with a full-term (>37-weeks’ gestation) singleton pregnancy, a height of 156–170 cm, and an American Society of Anesthesiology (ASA) score of Ⅰ–Ⅱ who underwent elective cesarean delivery with CSE anesthesia during January 2019 to June 2019. All parturients provided signed informed consent. The exclusion criteria for the study included ASA score of Ⅲ–Ⅳ, contraindications to spinal anesthesia, prolonged pregnancy (>42 weeks), preexisting or pregnancy-induced hypertension or preeclampsia, placenta previa, placental abruption, multiple pregnancy, morbid obesity (body mass index [BMI] ≥36), fetal distress or fetal abnormalities, emergent cesarean delivery, and parturient refusal.
Parturients were instructed to fast for at least 6 hours before surgery. The ultrasound measurements were performed with the parturient on the transfer bed in the post-anesthesia care unit 15 minutes before anesthesia. An ultrasound device (EPIQ7; Philips, Ultrasound, Bothell, WA, USA) with a high frequency linear array probe L12-5 (5–12 MHz) was used for the measurement of transverse diameters and peak velocities of the RCFV and RCFA, and a cardiac probe SC-1 (5–1 MHz) was used for the measurement of anteroposterior diameters and peak velocities of the AA and IVC. Parturients were in a supine position when the ultrasound examination was performed. Measurement sequences for the transverse diameter of the RCFV and RCFA, peak velocity of the RCFV and RCFA, anteroposterior diameter of the IVC and AA, peak velocity of the IVC and AA were always applied to ensure all examinations finished within 15 minutes. The transverse diameter and peak velocity of the RCFV were measured 1 cm proximal to the bifurcation of the great saphenous vein flowing into the femoral vein. The transverse diameter and peak velocity of the RCFA were measured at 1 cm proximal to the distal bifurcation of the femoral artery. The cardiac probe was placed below the xiphoid. The anteroposterior diameter and peak velocity of the IVC were measured 2–3 cm below the IVC-right atrial junction during end expiration, and the anteroposterior diameter and peak velocity of the AA were measured 2 cm above the superior mesenteric artery. All peak velocities were measured using a pulsed-wave Doppler ultrasound mode. The Doppler sampling volume was placed in the center of the blood vessel, and the width of the sampling range gate was 2 mm. Doppler angle correction was performed when measuring velocity, with the calibration main line parallel to the direction of blood flow and at an angle of 50–60°. All transverse and anteroposterior diameters were measured by M-mode ultrasound. All ultrasound recordings were performed by a specified board-certified ultrasound specialist, and anesthesiologists and parturients were blinded to the examination results.
The parturient was then transferred to the operating room. After entering the room, an intravenous (IV) line was established with an 18-G IV catheter in the dorsum or wrist vein, on the right hand. Standard monitoring with electrocardiography, non-invasive blood pressure, and pulse oximetry were performed continuously. The cuff of the automated non-invasive blood pressure monitor was attached to the left arm. Systolic arterial pressure (SAP), heart rate (HR), and pulse oximetry were measured once per minute. The first two resting SAP and HR measurements with the parturient in the supine position were recorded and the average values were recorded as baseline SAP and HR measurements. If the baseline SAP was above 140 mmHg, the parturient was excluded from the study because of suspected hypertension. A CSE puncture was performed at the L3–4 level with the parturient in the right lateral decubitus position. After the cerebrospinal fluid was detected, 0.75% isobaric ropivacaine 12 mg with fentanyl 10 μg was injected intrathecally via a 27-G Whitacre needle and an epidural catheter was inserted via an 18-G Tuohy needle by advancing it 3 cm into the epidural space. The parturient was moved immediately to a supine position with left uterine displacement by placing a wedge under the right hip. Meanwhile, an open co-loaded infusion rate of 1 mL/kg/min of lactated Ringer’s solution was administered until delivery. Parturients were excluded from the study if they could still feel the pinprick sensation below the T6 level at the beginning of surgery.
Hypotension was defined as having a drop of SAP >20% from the baseline value before delivery. If hypotension happened, a rescue phenylephrine bolus of 50 µg was administered by the anesthesiologist, and a phenylephrine bolus was administered every time the parturient presented with hypotension before delivery. Bradycardia was defined as a HR below 50 beats per minute (bpm). If bradycardia was identified, 0.5 mg of atropine was administered. After delivery, the Apgar scores at 1 and 5 min and neonatal body weight were recorded. 1 mL of umbilical artery (UA) blood was collected by the obstetrician immediately after delivery, and blood gas assessments were performed using a blood gas analyzer (iSTAT1 Analyzer MN:300-G; Abbott Point of Care Inc., Princeton, NJ, USA) with an iSTAT CG4+ test cartridge.
The primary outcomes were the peak velocities and anteroposterior diameter values of the AA and IVC below the xiphoid and the transverse diameter and peak velocity values of the RCFV and RCFA, as measured by ultrasound before anesthesia, and the association between these measurements and post-spinal hypotension during cesarean delivery. Patient and obstetric characteristics such as age, weight, height, BMI, gravidity, parity, gestational weeks, induction-delivery interval, upper sensory level, total intravenous fluid before delivery, neonatal body weight, 1 min and 5 min Apgar scores, and the pH of UA blood were also recorded.
Statistical analysis and sample size calculation
Based on our previous study, the odds ratio (OR) of the association between the perfusion index (PI) on the right toe and post-spinal hypotension during cesarean delivery was 0.49 (95% confidence interval [CI] 0.32 to 0.75, P = 0.0001).8 A logistic regression OR = 2–2.5 (equal to an OR = 0.4–0.5) was assumed in this study. To measure the OR at a power of 0.9, a two-tailed α of 0.05, and a baseline prevalence of 40%, this study needed a maximal sample size of 52.9 Considering a dropout rate of 10%, a sample size of 58 was required.
The patient and obstetric characteristics were presented as mean ± standard deviation or median (interquartile range [IQR]), as appropriate, and were analyzed by an unpaired Student’s t-test, Fisher’s exact probability test, or Pearson’s Chi-Square test, as appropriate.
IVC, AA, RCFV, and RCFA measured in the supine position, were analyzed by multinomial logistic regression analysis to determine if they were independently associated with the incidence of post-spinal hypotension. Then, area under the receiver operating characteristic (ROC) curves were used to test the ability of the identified parameters to predict post-spinal hypotension, and the area under the curve (AUC) was calculated. The AUC is a measure of the accuracy of a parameter (AUC ≤ 0.5 indicates no predictive ability and AUC = 1.0 indicates the best possible prediction). The maximal value of Youden’s index was used as the criterion for selecting the optimum cut-off values of the predictive parameters, and the Youden’s index = sensitivity + specificity – 1.
All statistical analyses were performed using SPSS for Windows version 24.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was set at P <0.05.