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, observational study at http://www.chictr.org.cn (ChiCTR1800016163). A total of 58 parturients, aged 18–40 years, with a full-term (>37-week 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 combined spinal epidural (CSE) anesthesia between January 2019 and June 2019, were recruited. All study participants provided signed informed consent. The exclusion criteria were as follows: an 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 the cesarean surgery. The ultrasound measurements were performed with the parturient on the transfer bed in the post-anesthesia care unit 15 min 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 the transverse diameter and peak velocity of the RCFV (Fig. 1). A cardiac probe (SC-1; 5–1 MHz) was used to measure the anteroposterior diameter and peak velocity of the IVC (Fig. 1). Parturients were in a supine position when the ultrasound examination was performed. Measurement sequences for the transverse diameter of the RCFV, peak velocity of the RCFV, anteroposterior diameter of the IVC, peak velocity of the IVC were always applied to ensure that all examinations were completed within 15 min. The transverse diameters and peak velocities of the RCFV were measured 1 cm proximal to the confluence of the great saphenous vein into the common femoral vein during end expiration (Fig. 1). The cardiac probe was placed below the xiphoid. The anteroposterior diameters and peak velocities of the IVC were measured 2–3 cm below the IVC-right atrial junction during end expiration (Fig. 2). Transverse and anteroposterior diameters were measured by M-mode ultrasound, and the M-mode sample line was always adjusted to pass through the center of vessels to measure the diameters more precisely (Fig. 1A and Fig. 2A). All peak velocities were measured using the 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° (Fig. 1B and Fig. 2B). All the ultrasound recordings were performed by a board-certified ultrasound specialist; the 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 of 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 before delivery. Moreover, lactated Ringer’s solution, at an open, co-loaded infusion rate of 1 mL/kg/min, 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. Epidural boluses of 5 mL lidocaine were administered intermittently until satisfactory anesthesia was achieved.
Hypotension was defined as a drop in SAP by >20% from the baseline value before delivery. If hypotension occurred, a rescue phenylephrine bolus of 50 µg was administered by the anesthesiologist, and the 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 as well as the neonatal body weight were recorded. Further, 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 outcome was the peak velocity and anteroposterior diameter values of the IVC below the xiphoid, the peak velocity and transverse diameter values of the RCFV 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 IV fluid administered before delivery, total dose of phenylephrine and atropine, neonatal body weight, 1 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] 0.32–0.75, P = 0.0001) . A logistic regression OR of 2–2.5 (equal to an OR of 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 with a baseline prevalence of 40%, it was estimated that this study needed a minimal sample size of 52 parturients . Considering a dropout rate of 10%, a sample size of 58 was required.
The patient and obstetric characteristics are presented as mean ± standard deviation or median (interquartile range), 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.
The parameters of the IVC and RCFV, measured by ultrasound 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. Thereafter, the area under the receiver operating characteristic (ROC) curves was 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; Youden’s index was calculated as follows:
Youden’s index = sensitivity + specificity – 1
The perioperative hemodynamic parameters were assessed by two-way analysis of variance with the Bonferroni post hoc test.
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.