A prospective, randomized, controlled study was performed to evaluate the feasibility of intraoperative auto-transfusion using an autologous-blood-recycling machine (BW-8200B, Wandongkangyuan, China) combined with a leukocyte-removing filter (Nanjing Shuangwei, China) filter for women undergoing caesarean section between July 2016 and May 2019. A total of 116 participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage (ICS) group or the control group. Figure 1 shows the schematic diagram of the trial. Preeclampsia was defined as a unique disorder of gestation and multiple systems associated with systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg as well as proteinuria > 1 (0.3 g per 24 h) and gestational age > 37 weeks. Placenta previa was defined as a condition where the placenta lies low in the uterus and partially or completely covers the cervix. Abnormally invasive placenta (AIP) was defined as a placenta that does not separate spontaneously at delivery.
Patient identification: After informed consent was obtained, a dedicated patient identification number (PID) was assigned to each patient for patient identification throughout the study process. According to the random number table generated by a computer, the research centre then performed random grouping. Then patients were grouped according to their assigned number. This clinical trial was approved by the Hospital Ethical Review Committee (No. 2016-XJS-003-01) and was registered (ChiCTR-ICC-15,007,096) on September 28, 2015. Details of the study can be found at http://www.chictr.org.cn/showproj.aspx?proj=11283.
Inclusion and exclusion criteria
Puerpera were enrolled in the study if they (1) were > 18 years old and diagnosed as American Society of Anaesthesiologists (ASA) Classification I-II; (2) had undergone elective or emergency caesarean section; and (3) had estimated intraoperative bleeding > 1000 mL. Puerpera were excluded if they (1) had preoperative Hb < 10 g/dL, preoperative platelets < 50 × 109/L, > 1.5 times prolonged PT and APTT before surgery, or body weight < 50 kg, (2) were Rh-negative or complicated with haematological diseases, autoimmune diseases, or acute fatty liver/HELLP syndrome; (3) had undergone preoperative anticoagulation therapy and accepted allogeneic blood transfusion within 3 months before the study, and participated in other clinical studies during pregnancy; (4) refused to accept allogeneic blood transfusion; and (5) had any diseases that could lead to inability to cooperate with the study, such as mental illness, language-comprehension disorders, etc.
Expected sample size
The expected sample size was calculated by referring to the studies on the effect of recovery autologous blood transfusion on the prognosis of orthopaedics and cardiac surgery patients with the smallest difference in haemoglobin index before and after selection as the basis for measuring the sample size, and setting β = 0.1 and ɑ=0.05 in the one-sided test method, level = 0.05 and a degree of power of 90%. The effective sample size calculated was 52 cases per group. Considering the drop rate of 10%, the final sample size was 58 cases per group.
Interventions
Allogeneic red blood cells or recovered autologous blood-washed red blood cells after filtration were transfused to patients with haemoglobin < 80 g/L in the control or ICS groups, respectively. In addition, transfused blood was supplemented with crystal or colloidal fluid for patients with bleeding blood volume < 500 ml.
For patients in the ICS group, an autologous blood recycling machine was installed before the operation. After delivery and placental separation, anticoagulant composed of 25,000 IU of heparin per 1000 ml of 0.9% NaCl solution was drip fed (1 drop/s) into the operation field and allowed to mix with the maternal blood spilt at the time of surgery into the operation field. The blood-saline solution (usually 800 mL) was then recovered using a separate special suction tube of an isolation suction system at a vacuum pressure of 20 KPa into a sterile reservoir [5] and centrifuged to allow larger, dense red blood cells (RBCs) to cling to the wall of the tube, while all other blood components were discarded directly to the waste bag. The RBCs were washed with and resuspended in sterile isotonic sodium chloride (0.9% NaCl) using a blood recycling machine and then infused back into the patient after passing through a white blood cell filter as soon as possible both during and after surgery. Autologous blood was required not to be stored for more than 6 h. During the operation, another suction unit was used to remove amniotic fluid. The technique had been previously standardized in our hospital. Infusion was stopped when the patient’s haemoglobin concentration reached 80 g/L. If the patient’s haemoglobin concentration was still < 80 g/dL, allogeneic red blood cells were infused until the haemoglobin concentration reached 80 g/L.
For patients in the control group, allogeneic red blood cells were infused when the haemoglobin concentration was < 80 g/L. When the patient’s haemoglobin concentration was ≥ 80 g/L, no blood cell transfusion was given. The amount of red blood cell transfusion depended on the bleeding amount and rate as well as the haemoglobin level.
Indications for the transfusion of other blood products
Intraoperative massive bleeding and massive autologous red blood cell transfusion are often accompanied by the loss of platelets and coagulation factors. In this case, other blood products, such as platelets, fresh frozen plasma and cryoprecipitate, should be appropriately infused. It is recommended that when the amount of bleeding exceeds 3500 mL, fresh frozen plasma (FFP) should be infused. If ordinary frozen plasma is infused, cryoprecipitate should be supplemented appropriately. If the amount of bleeding exceeds 2000 mL, platelet transfusion should be given. Patients were released from the operating room if their haemoglobin concentration was maintained at ≥ 80 g/L.
Anaesthesia and surgery
General or spinal anaesthesia was applied to all participants of the study by the responsible anaesthesiologist. The type, dose and management of anaesthetics, surgical procedure and ICU treatment were determined by the centre.
Blood transfusion management and data collection
In addition to intraoperative grouping, different blood transfusion methods were used after the operation. If the haemoglobin concentration was < 80 g/L, allogeneic blood was transfused until the patient’s haemoglobin concentration was ≥ 80 g/L. Perioperative treatments using other blood transfusions were also conducted following the existing guidelines. Blood loss during the operation was calculated by the research team to minimize variation.
Baseline visits
Patients participating in the study met all inclusion criteria and exclusion criteria and signed the informed consent form. The patient’s important underlying conditions, such as age, body weight, nulliparity, demographic data, weeks of gestation, comorbidities, caesarean section, placental position, intraoperative blood loss, eligibility criteria, and informed consent, were required to be included in the case report form (CRF). Haemoglobin, coagulation function and blood gas analyses were performed before surgery.
During surgery
During the surgery, vital signs, haemoglobin concentration, volume of allogeneic red blood cell transfusion, autologous blood recovery and transfusion, other blood product transfusion, fluid infusion, urine, type and dose of anaesthetics, and other drug dosages were monitored.
Clinical outcomes
The following clinical outcomes were recorded: (1) haemoglobin concentration at 30 min, 24 h, 3 d, and 7 d after surgery or at discharge (whichever was earlier); (2) coagulation function (PT/APTT) at 24 h, 3 d, and 7 d after surgery or at discharge (whichever was earlier); (3) results of blood gas analysis at 30 min and 24 h after surgery; (4) blood type antibody screened at 5 d after surgery; (5) in the case that the participants were transferred to the ICU, the cause for the transfer, ICU stay time and cost, use of mechanical ventilation and time; (6) use of allogeneic blood products during hospitalization; and (7) occurrence of amniotic fluid embolism (AFE), sepsis (Sepsis), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), pulmonary embolism (PE), complications of various organ systems and/or complications related to blood transfusion during the postoperative hospitalization; (8) hospitalization time and expenses; (9) complications during follow-up, and (10) completion of the clinical study, death (cause, time), withdrawal (cause) and rejection (cause).
Statistical analyses
Statistical analyses were performed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). The data distribution was tested for normality by visual inspection of histograms and the Kolmogorov-Smirnov test. Continuous variables are described using the mean ± standard deviation (SD). Normally distributed data were compared by the t-test or chi-square test according to the data type, and nonnormally distributed data were tested by nonparametric test. Time events were analysed by Kaplan-Meier curves. All statistical analyses were performed by bilateral tests. A P < 0.05 value was considered statistically significant.
