Association of intra-operative red blood cell transfusion on the systemic immune index and recovery in patients undergoing cesarean section: a large propensity score-matched study

Study design and statement of ethics

After obtaining approval from the Shanghai First Maternity and Infant Hospital Institutional Review Board. We retrospectively collected data from 1426 patients who underwent a cesarean section between January 2016 and June 2020.

The inclusion criteria were pregnant women with elective term single pregnancy. Exclusion criteria were as follows: emergency cesarean section; twin pregnancy; use of anti-inflammatory drugs or immunosuppressants for > 1 month prior to the cesarean section; chronic inflammatory diseases; and incomplete medical records. The pregnancy characteristics, medical history, operative details, and post-operative course were extracted from the medical records.

All pregnant women, or a relative as appropriate, provided informed consent for the use of their clinical data for research prior to the cesarean section. This study was reviewed and approved by the Shanghai First Maternity Ethics Committee (protocol: #2020–049).

Primary outcome

The primary outcome of this study was the LOS, defined as the time from the date of the cesarian section to the date of discharge.

Secondary outcomes

The secondary endpoints included peri-operative systemic inflammation indicators, the rate of post-operative complication, wound complications, the fatigue severity score, the admission rate to the intensive care unit (ICU), and the 30-day all-cause readmission rate. The systemic inflammatory indicators included neutrophil, lymphocyte, monocyte, and platelet counts recorded 3 days prior to the cesarian section and on post-operative days (POD) 1 and 3. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and the neutrophil-to-lymphocyte ratio (SII). Complications were evaluated using the Clavien-Dindo classification which is suitable to describe the incidence and grade the severity of surgical complications, as follows: grade I, any deviation from the expected post-operative course without the need for pharmacological treatment or surgical, endoscopic, and radiological intervention; grade II, complications require pharmacological treatment with drugs other, than those allowed for grade I complications, blood transfusion, and total parenteral nutrition; grade III, complications require surgical endoscopic or radiological intervention; grade IV, life-threatening complication; and grade V, patient death.

Exposure variable

The exposure variable is the use of blood transfusion with the following criteria used as clinical indicators for the need for transfusion: intra-operative blood loss volume > 500 ml and an intra-operative decrease in Hb level < 8 g/dl. The type of blood products used—red blood cells or fresh frozen plasma—and the number of units transfused were recorded.

Anesthesia care

Upon entering the operating room, a pre-operative pregnancy screening was performed as per the American Society of Anesthesiologists (ASA) standards. Spinal anesthesia is the first choice for cesarean sections in patients without contraindications to this type of anesthesia. For spinal anesthesia induction, patients were placed in the right recumbent position and the subarachnoid puncture was performed at the L3–L4 or L2–L3 inter-vertebral space. After observing the free flow of cerebrospinal fluid at the puncture site, 0.5% hyperbaric ropivacaine, consisting of 2 mL of 0.75% hyperbaric ropivacaine in 1 mL of saline, was administered. An epidural indwelling catheter, 4 cm in length, was placed in the epidural space. At 5-min post-induction, the extent of anesthesia was evaluated at the T4 to T6 level. When the anesthetic effect was unsatisfactory, an additional 5 ml of 0.5% ropivacaine was injected into the epidural space. For patients with contraindications to spinal anesthesia, such as coagulation dysfunction, lumbar disease, or physiological shock, general anesthesia was administered. General anesthesia was induced using propofol (target-controlled infusion, effect-site concentration 3.0–4.0 µg/ml), remifentanil (0.3–0.5 µg/kg), and rocuronium (0.6 mg/kg). After induction, endotracheal intubation was performed and general anesthesia was maintained using propofol, sufentanil, and remifentanil. Repeated bolus injections of sufentanil and rocuronium were administered throughout the surgery.

Statistical analysis

Continuous variables were reported as the mean ± standard deviation and categorical variables as frequencies and percentages. To control for the effects of selection bias, propensity score matching was performed, and differences in study outcomes between groups “with” (BT) and “without” (NBT) intra-operative blood transfusion were evaluated for the matched groups. Matching was performed using a 5-to-1 digit greedy match algorithm. On univariate analyses, between-group differences were evaluated using the chi-square test or Fisher’s exact test, as appropriate, for categorical variables and the independent samples t-test or Wilcoxon signed-rank test, as appropriate, for continuous variables. Statistical analyses were performed using SPSS software (version 28.0; SPSS Inc., Chicago, IL, USA), with significance set at a P-value < 0.05.

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