Impact of intra-operative cell salvage on blood coagulation in high-bleeding-risk patients undergoing cardiac surgery with cardiopulmonary bypass: a prospective randomized and controlled trial

This study was approved by the Ethics Committee of the Zhejiang Provincial People’s Hospital (RCT ID: ChiCTR-TRC-13003268). Patients were enrolled in the study after written informed consent was signed. Inclusion and exclusion criteria were shown in Table 1 [3, 7, 8]. One hundred and ten eligible patients were randomly assigned into two groups according to a randomization list: cell salvage group (Group CS) and control group (Group C). Patients in Group CS were treated with intra-operative CS while those in Group C without.

Tranexamic Acid (AMCHA, 30 mg/kg) was infused in all patients after anesthesia induction [9]. The CPB was performed using a HL20 heart–lung machine (MAQUET, Israel) with an OCTOPUS4 extracorporeal membrane oxygenation (Medtronic, USA). The volume of fluid primed was 1.8 L, the main ingredient was ringer’s lactate solution, along with a small amount of albumin and mannitol. Anticoagulation was achieved with heparin to maintain an activated clotting time (ACT) above 480 s. After separation from CPB, heparin was reversed by protamine to a target-ACT of range from 90 to 110 % of base value.

In Group CS, shed blood from wound and mediastina were sucked into the cell saver reservoir (Haemonetics, USA, volume of disposable centrifuge bowl is 125 mL) after anticoagulated by heparin saline during the period of non-heparinization (Fig. 1). The heparinised saline contain 25,000 IU of heparin in 1 L of 0.9 % saline at a rate of 100 mL/h. At the end of CPB, residual blood in the CPB circuit was directly sucked into the reservoir. After being filtrated, centrifugated, washed and concentrated, the recovered blood turned into autologous blood (autologous red blood cell suspension), which was transfused back to the patient immediately. The washing program used in the CS involved a 5:1 ratio between the 0.9 % saline wash and collection of blood from the operating field. All of the autologous blood was transfused back to the patients by the end of surgery. In Group C, shed blood from wound and mediastina during the period of non-heparinization (Fig. 1) were sucked into suction apparatus and were discarded. In Group C, at the end of CPB residual blood in the CPB circuit were sucked into suction apparatus and were discarded. Patients’ bleeding during the period of heparinization (Fig. 1) in two groups were sucked into the CPB circuit.

After heparin was reversed by protamine, allogeneic red blood cell (RBC) was used if hemoglobin (HB) was lower than 8 g/dL in Group C [3]. In Group CS, allogeneic RBC was used only if HB was still lower than 8 g/dL after transfused all of the autologous blood. Allogeneic fresh-frozen plasma (FFP) and PLT transfusion was used during peri-op according to the protocol (showed in the seventh and eighth line in Fig. 2 [3, 16, 19]. Patients with excessive bleeding during post-op, which was defined as the rate of bleeding greater than 300 mL in the first hour after surgery or greater than 2 mL/kg/h for 3 consecutive hours, were treated according to the same protocol (Fig. 2).

Basal and operative characteristics: including age, gender, BSA, type of surgery, complications, CPB time, surgical time, tracheal intubation time, length of ICU stay, length of hospital stay, the volume of residual blood in CPB circuit, the volume of intra-operative blood loss, the volume of mediastina tube drainage (MTD) in 6 and 24 h after surgery, intra-operative dosage of heparin and protamine. The volume of intra-operative blood loss was calculated as the volume sucked into cell saver reservoir minus the volume of heparin saline for anticoagulation in Group CS or the volume sucked into suction apparatus in Group C.

Volume of blood transfusion during peri-op: including the volume of autogenous blood in Group CS, the volume of allogeneic blood (RBC, PLT and FFP) in two groups.

Hematological parameters during peri-op: including general parameters and parameters related to blood coagulation. General parameters included RBC and HB. Parameters related to blood coagulation included TEG parameters (Haemonetics, USA), PLT and FIB. TEG parameters included R value (R-TEG and R-h-TEG), MA and LY 30. R (reaction time, normal range from 10 to 19 min) represents the time to initiation of clot formation. R-TEG and R-h-TEG are the R value of test of kaolin-activated sample and heparinase-modified kaolin-activated sample, respectively; MA (maximum amplitude, normal range from 54.5 to 72.5 mm) represents the maximum clot strength; LY30 (lysis rate-30, normal range from 0 to 7.5 %) represents the rate of cloth lysis 30 min after MA. Venous blood was tested at the following four time points or anytime when excessive bleeding occurred during post-op: at the time of after anesthesia induction and 5 min before beginning of surgery (T₁), 5 min after heparin was reversed by protamine during surgery (T₂), at the end of surgery (T₃) and at 24 h after end of surgery (T₄) (Fig. 1).

Impairment of blood coagulation during peri-op: impairment of blood coagulation was diagnosed according to the test results of hematological parameters related to blood coagulation (showed in the seventh and eighth line in Fig. 2). Impairment of blood coagulation were classified into five types: heparin residual, coagulopathy due to low PLT (decreasing of PLT results in hypocoagulability), coagulopathy due to low FIB (shortage of FIB results in hypocoagulability), coagulopathy due to low coagulation factors (shortage of other coagulation factors except for factor results in hypocoagulability) and hyperfibrinolytic (showed in the seventh and eighth line in Fig. 2) [17, 19]. The sum of above five types was total impairment of blood coagulation.

Adverse events during post-op: including excessive bleeding, resternotomy, cardiovascular failure, severe arrhythmias, myocardial infarction, infection, renal failure, respiratory failure, epileptic syndrome, cognitive decline and death.

Data are presented as mean (standard deviation, SD) for continuous parametric values, or as numbers with percentage for categorical data. For continuous data, the two-sample two-sided Student’s t test or the Wilcoxon Rank-Sum two-sample two-sided test was used. For categorical data, the χ ² test or Fisher’s exact-test was used. Considering some variables may influence relevant clinical outcomes potentially, the logistic regression model was used to analyze the outcomes in Table 4. Odds ratios (ORs) resulting from logistic regression analysis were used to estimate relative risk (RR) ratios. Data analysis was performed using SAS statistical software (version 9.1; SAS Institute Inc., Cary, NC, USA). P value of less than 0.05 was considered as statistically significant.

Of the total 110 patients randomized between April 2013 and September 2014, 55 were allocated to Group CS and 55 to Group C (Fig. 3). There was no difference between two groups in the listed variables (Table 2).

The mean volume of autologous blood transfusion in Group CS was 4.13 U (0.31 U). The proportion of allogeneic RBC transfusion during peri-op was 41.51 % in Group CS versus 78.00 % in Group C. The mean volume of allogeneic RBC transfusion during peri-op was 2.66 U in Group CS versus 5.40 U in Group C. Both the proportion and volume of allogeneic RBC transfusion during peri-op were significantly lower in Group CS than in Group C (Table 3).

The incidences of heparin residual at T₃ and during post-op were significant higher in Group CS (15.09 and 13.21 %) than in Group C (4.00 and 2.00 %), with p value as 0.024 and 0.010, respectively (Fig. 4). Similarly, the incidences of total impairment of blood coagulation at T₃ and during post-op were significant higher in Group CS (32.08 and 26.42 %) than in Group C (18.00 and 12.00 %), with p value as 0.043 and 0.040, respectively (Fig. 4). The RR value of CS with heparin residual was 6.10. CS was associated with an increase in the RR for heparin residual (p = 0.034) (Table 5).

The incidence of excessive bleeding during post-op were significantly higher in Group CS (32.08 %) than in Group C (16.00 %) (Table 4). The RR value of CS with excessive bleeding was 4.58. CS was associated with an increase in the RR for excessive bleeding (p = 0.049) (Table 5).