Study population
This prospective observational study was approved by the Ethics Committee of Qilu Hospital of Shandong University (KYLL-2018-330). The study protocol was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants. All obtained data were treated confidentially. The parturients with massive blood loss in our study were taken care of as per the recommendation of the 2015 Postpartum hemorrhage: prevention and management (Green-top Guideline No. 52) by the Royal College of Obstetrician and Gynaecologists (RCOG).
A previous study showed that about 36% of parturients with placenta accreta developed hemodynamic instability during cesarean section, and vasoactive medication was used[37]. We studied 150 parturients with PPP undergoing elective cesarean section with general anesthesia in our center between January 2016 and December 2018, whose intraoperative blood loss≥1,000 mL. 42% of them developed hemodynamic instability. We assumed that the area under the receiver operating characteristic curve (AUROC) of hemodynamic indicators to diagnose hemodynamic instability was 0.80. The sample size calculation with PASS 15 software showed that at least 31 patients were needed to detect a difference of 0.30 between the AUROC of the hemodynamic indicators (0.80) and the null hypothesis (0.50), with a power of 0.9 and a two-tailed type I error of 0.05, assuming a hemodynamic instability incidence of 42% in parturients with PPP.
All eligible parturients with PPP who had an American Society of Anesthesiologists status of I to III, had an age of 18 to 49 years, and were undergoing elective cesarean section with general anesthesia from January 2019 to December 2020 were included in this study. The exclusion criteria were, severe aortic regurgitation, severe arrhythmia, left ventricular ejection fraction of <40%, pre-eclampsia, refusal to participate, emergency cases, and intraoperative blood loss <1,000 mL. The antepartum diagnosis of PPP was made clinically based on pelvic ultrasound or magnetic resonance imaging.
Perioperative management
Before surgery, the parturients were positioned supine with a 15° left lateral table tilt, two 18-gauge intravenous catheters were inserted, and intravenous hydration (1,000 mL) was commenced with non-pressurised infusion of lactated Ringers’ solution via intravenous cannulas. Two to four units of packed red blood cells were made immediately available.
Hemodynamic monitoring was initiated via a 22-gauge elastic catheter that was inserted into the radial artery and connected to a FloTrac (Version 3) sensor. SV and SVV were measured every 20 seconds according to the algorithm housed within the Vigileo monitor. Other routinely monitored parameters were continuous electrocardiography, pulse oximetry, end-tidal carbon dioxide, and arterial blood pressure. A central venous catheter was inserted into the internal jugular vein, and CVP was measured continuously during the perioperative period with a low-pressure transducer. The readings of HR, MAP, CVP, SVV, and SV were noted every 10 minutes throughout surgery. All raw data were recorded directly onto a computer for later statistical analysis.
A bilateral transversus abdominis plane block was performed prior to general anesthesia. The induction drugs for general anesthesia were propofol (2.0–2.5 mg · kg−1), remifentanil (1.0 μg · kg−1), and rocuronium (0.6 mg · kg−1). Anesthesia was maintained with remifentanil (0.2–0.25 μg · kg−1 · min−1) and propofol (4–6 mg · kg−1 · h−1). After fetal delivery, sufentanil (0.3–0.4 μg · kg−1) and midazolam (0.03–0.05 mg · kg−1) were injected to deepen the anesthesia. After general anesthesia induction, a laryngeal mask was inserted, and mechanical ventilation was adjusted to supply tidal volumes of 8 to 10 mL · kg−1 of standard body weight with volume-controlled ventilation, where standard body weight = (height − 70) × 60%. If a significant air leak occurred, endotracheal intubation was immediately performed. The respiratory rate was adjusted to maintain the end-tidal carbon dioxide pressure between 4.5 and 5.5 kPa. Respiratory settings were not changed throughout the measurements.
If significant and massive bleeding was present in the surgical field after placental delivery, rapid fluid infusions were initiated. Norepinephrine was administered when the MAP decreased to 60 mmHg and was adjusted to keep the MAP at 60 to 80 mmHg. Blood product transfusions were used according to blood gas analysis and laboratory test results. After confirming circulatory stability (hemodynamic indicators, especially a return of the SV to the approximate baseline level and maintenance of this level for >15 min) and a shift toward diuresis, the rate of fluid administration was immediately decreased to 1.5 mL · kg−1 · h−1 to avoid congestive heart failure secondary to overhydration. If CVP was maintained above baseline levels and the doctors believed that volume overload may be present, furosemide was administered. The decision regarding when to initiate or stop rapid fluid infusion and blood product transfusion was left to the discretion of the consultant anesthetist.
Patients were considered to have hemodynamic instability when MAP could not be maintained above 65 mmHg for longer than 10 seconds despite rapid fluid and blood transfusion after placenta delivery. Baseline hemodynamic values were defined as the preoperative average of 5 minutes of continuous measurements (MAP, HR, and SV) or values after general anesthesia induction (CVP and SVV). Placenta accreta was definitively diagnosed postoperatively based on pathologic examination or surgeons’ classification when separating the placenta. Blood loss was measured with reference to the blood collected in the suction bottle in the operating room and to the weight of the surgical swabs, excluding the volume of amniotic fluid.
Statistical Analysis
We calculated the mean and standard deviation for continuous variables with a normal distribution and the median with interquartile range for continuous variables with a non-normal distribution. Categorical variables are summarised as count and percentage. Continuous variables were analysed using the independent t-test or Mann–Whitney U test according to the results of the Shapiro–Wilk test for normality. Categorical variables were analysed by the chi-square test or Fisher’s exact test. Comparisons of hemodynamic indicators between different time points were performed using one-way reapeated measures ANOVA. The AUROC was calculated to measure the ability of the minimum/maximum indices to diagnose hemodynamic instability. The optimal cut-off value was determined by maximising the Youden index. All analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation), Free Statistics software version 1.4 (Beijing Free Clinical Medical Technology Co., Ltd.), and SPSS version 26 (IBM Corp., Armonk, NY, USA). Statistical significance was set at P < 0.05.
Data availability statement
The datasets generated during the current study are available from the corresponding author on reasonable request.