Transfusion Reduction in High-Bleeding-Risk Cardiac Surgery With Desmopressin

Summary

Rationale

Bleeding after cardiac surgery is a complication that might result in increased morbidity, mortality, and cost of cardiac surgery by 1.76 (confidence interval (CI), 1.64-1.90) times and a median increase in costs by Australian $33,338 (CI, $21,943-$38,415) \[1\]. Strategies and techniques to reduce postoperative bleeding in identified high-risk patients for bleeding after cardiac surgery might improve outcomes and resource utilization.

Desmopressin (DDAVP) is used as a hemostatic agent to prevent and treat bleeding in patients with mild hemophilia patients with von Willebrand's deficiency through stimulating the release of von Willebrand factor from endothelial cells.

Previous studies showed controversial results in terms of reduced transfusion requirements in patients with low risk for bleeding with post cardiopulmonary bypass (CPB) bleeding following prophylactic infusing desmopressin over 10 to 15 minutes after induction of anesthesia or protamine administration due to its positive effects on the coagulation system responsible for such bleeding. Contradictory, prophylactic desmopressin use demonstrated fewer transfusion requirements in patients treated with antiplatelets, which raises the need to examine its efficacy in high-risk cardiac surgery patients for perioperative bleeding. These controversial results might be attributed to delayed administration of desmopressin after evolving CPB-associated thrombocytopenia, platelet dysfunction, coagulation factor consumption and dilution, hyperfibrinolysis, and hypofibrinogenemia \[2\]

Concerns were raised about the associated transient decreases in systemic vascular resistance and blood pressure after desmopressin administration following discontinuing CPB and administering protamine, which might be related to the rapid infusion rate during the critical surgery stage.

The cost of a single dose of Desmopressin 0.3 ug/kg for a patient with an average weight of 70 Kg is about 82US$ which is cheaper than the alternative hemostatic agents proved to be effective in reducing bleeding and transfusion needs after cardiac surgery (e.g., fibrinogen concrete (average of 3 g = 1,167US$) and prothrombin complex concentrate (6,255US$ considering low fixed dosfixed-doseof 1040 IU F IX).

It is yet unclear if extended infusions of desmopressin started earlier before the development of CPB-associated coagulopathy and platelets dysfunction from anesthesia induction time and continued to the end of CPB before protamine administration would offer an "efficacy," "safety, and "cost-effective" benefits over placebo in patients with high risks for bleeding after cardiac surgery terms of the need for transfusion, cumulative postoperative 48-hour chest tube outputs, need for reoperation, thrombotic complications, 30-day mortality, hemodynamic stability, and urine output during and after completing infusion, and costs of the study drug and allogenic transfusion requirement. That raises the need to examine its impact on these crucial clinical outcomes.

Objective

The primary objective of this prospective multicentre randomized clinical trial (RCT) is, compared with placebo, to examine the impact of prolonged infusion desmopressin on reducing postoperative bleeding and the need for allogenic allogeneic transfusion in high-bleeding-risk cardiac surgery patients scheduled for elective cardiac surgical procedures using CPB. Secondary objectives include comparing placebo and desmopressin in terms of safety and cost-effectiveness.

Hypothesis

It is hypothesized that extended 'desmopressin' infusion compared to 'placebo' results in less postoperative bleeding and transfusion needs (more effective) and leads to less hemodynamic compromise (safer) and cheaper (cost-effective) in high-risk cardiac surgery patients.

Conditions

• Adult Patients Undergoing Cardiac Surgery
• High Bleeding Risks
• Planned Elective Cardiac Surgery Using CPB

Interventions

DRUG

Desmopresin

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Desmopressin 0.3 ug/kg of the patient's body weight will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

DRUG

Placebo

Before induction of anesthesia, patients will receive identical and similar clear study solutions in similar size transparent 50-cc bags, including Saline will be infused over five hours at a rate of 10 ml/hr. The local pharmacists who will not be involved in patients' care or data collection will prepare the study solution.

Sponsors & Collaborators

• Johns Hopkins Aramco Healthcare

  collaborator OTHER

• Imam Abdulrahman Bin Faisal University

  lead OTHER

Principal Investigators

• Mohamed R El Tahan, MD · Imam Abdulrahman Bin Faisal University

• Fahad Makhdoum, MD · Imam Abdulrahman Bin Faisal University

• Yasser F ElGhoneimy, MD · Imam Abdulrahman Bin Faisal University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-31

Primary Completion

2027-07-31

Completion

2027-08-31

Countries

• Saudi Arabia

Study Locations