Effect of Acute Normovolemic Haemodilution, Retrograde Autologous Priming and Antifibrinolytic Therapy Applied as Multimodal Blood Conservation Strategy on Perioperative Blood Loss in Cardiac Surgery- A Randomized Control Study

A prospective randomized control study will be conducted on patients undergoing open heart surgery at the Department of Cardiothoracic Surgery unit of KLE’s Prabhakar Kore Hospital & Medical Research Centre Belgaum.

A total of 150 elective patients for open heart surgery on cardiopulmonary bypass will be considered for the study. Patients will be randomized and allocated into two groups by computer generated randomization table :

MMBC GROUP: In whom multimodal blood conservation protocols will be strictly adhered and,

CONTROL GROUP: In whom adherence to multimodal blood conservation protocols won’t be followed.

Baseline patient demographic, clinical and biochemical data like age, height, weight, body surface area, sex, type of surgery, preop antiplatelet or anticoagulant medications, comorbidities, hemogram along with haematocrit, liver, coagulation, and renal functions will be noted for all patients.

After shifting the patient into the operating theatre, the American Society of Anaesthesiology standard monitors such as the pulse oximeter, non-invasive blood pressure cuff, and electrocardiogram will be attached, and the baseline vitals will be noted. A wide-bore (16G) intravenous cannula and 20g radial intra-arterial line will be secured under local anaesthesia. A vigilant anaesthetic induction respecting hemodynamics will be done after analysis of the arterial gas sample and pre-oxygenating patient with 100% oxygen for 3 minutes. Intravenous midazolam (0.1 mg/kg), fentanyl (8-10 mcg/kg), propofol (0.5-1 mg/kg), and pancuronium (0.15mg/kg) will be used to induce anaesthesia and the airway will be secured with an appropriate sized endotracheal tube. Anesthesia will be maintained using fentanyl, isoflurane and muscular relaxation with vecuronium.

The blood conservation strategies that will be applied in MMBC group will be as follows:

1. Use of synthetic antifibrinolytic agent, tranexamic acid intraoperatively (Antifibrinolytic injection Tranexamic acid 20mg/kg intravenous will be given in all patients before the incision and 10mg/kg along with protamine during heparin reversal)

2. Acute normovolemic haemodilution: -

In the MMBC group as per the multimodal blood conservation strategy, in patients with baseline haematocrit value of more than 40%, autologous blood will be drawn from patients to achieve acute normovolemic haemodilution. The volume of blood withdrawn will be calculated using the following equation

 Autologous blood Volume (ml) = EBV (ml) * (HCTInitial – HCTBefore CPB)/HCTInitial.

Where,

 HCTBefore CPB = HCTTarget × (EBV(ml)  +1200)/EBV(ml)

where,

HCT is haematocrit (%)

HCTBefore CPB: haematocrit after autologous blood withdrawal, immediately before initiation of cardiopulmonary bypass.

HCTTarget: A desired haematocrit just after initiation of CPB and following the haemodilution caused by the addition of the priming volume will be fixed as 30% to limit the drop in nadir haematocrit during the conduct of CPB below 24%. This value is fixed keeping in mind the expected blood loss during the conduct of CPB, (i.e. during initiation, maintenance, delivery of cardioplegia and termination of CPB).

EBV: Estimated patient’s blood volume (65ml/kg for females,70ml/kg for males)

1200ml: CPB circuit priming volume

HCTInitial: Baseline haematocrit value obtained from ABG in the operating room before the withdrawal of autologous blood.

 Mean arterial pressure will be maintained above 65mmhg during withdrawal by infusing a balanced crystalloid solution of 1.5-2:1(balanced crystalloid solution: blood) ratio. The calculated autologous blood volume will be collected in a standard blood collection bag containing CPDA (Citrate Phosphate Dextrose Adenine) solution. Bags will be filled while resting on an electronic scale to ensure proper filling and maintenance of the proper ratio of blood to citrate-phosphate-dextrose (450 g of blood per bag). Bags will be stored in a wrapped sterile drape and will be kept at room temperature with gentle agitation.In the control group, patients will be heparinized with conventional dosing of heparin that is 4mg/kg, and in the MMBC group patients are heparinized using a heparin dose-response curve to achieve a target ACT (activated clotting time) of 480 seconds. Before initiating cardiopulmonary bypass, retrograde autologous priming will be done in which the patient’s blood will be used to displace the priming volume from both arterial and venous lines retrogradely with careful monitoring of hemodynamics. Packed cell transfusion will be done in patients when the haematocrit value drops below 24% on cardiopulmonary bypass. After termination of CPB, once the heparin reversal protocol is fulfilled, in control group reversal will be done with 0.8mg of protamine for each mg of heparin and in MMBC group the dose of protamine will be decided based on the heparin dose-response curve. Those patients in the MMBC group whose autologous blood was collected will be transfused back to patients once they are off bypass and heparin reversal is complete. Cardiopulmonary bypass time will be noted in both groups. Post cardiopulmonary bypass PRBC will be transfused only if the haematocrit value drops below 27% (Hb 9gm/dl) or depending upon the clinical condition of the patient as per the guideline recommendations (EACTS 2019). Total intraoperative blood loss will be noted in each group. Postoperatively patients will be observed for the clinical outcome. The outcome will be divided as “Good”, “Poor” or “Worst” based on standard variables used to define the postoperative outcome.

Outcome Variable

Post-operative Clinical Outcome

|Good

Poor

Worst

|Duration of Mechanical Ventilation

<24 hours

24 hours

          Perioperative Mortality

  |Vasoactive Inotropic Score

<20 for at least 6 hours

20 for at least 6 hours

|Length of ICU Stay

<7 days

7 days

|Use of Mechanical cardiovascular support

No

Yes

|·       Perioperative Organ Dysfunction – (1. Acute Kidney Injury, 2. Cerebrovascular event, 3. Hepatic Injury, 4. Respiratory Failure.)

 No

Yes

|·       Perioperative sepsis

No

Yes

 Also, the total expenditure in the intensive care unit will be noted for all the patients.