What is the recommended drug dosing approach for Donation after Circulatory Death (DCD) scenarios?

Recommended Drug Dosing Approach for Donation after Circulatory Death (DCD) Scenarios

The recommended drug dosing approach for DCD scenarios should include administering heparin prior to withdrawal of life-sustaining therapy (WLST) at a dose of 100-300 units/kg or a fixed dose of 30,000 units to ensure adequate circulation and minimize organ damage. 1

Prewithdrawal Medication Administration

Heparin Administration

• Administer heparin prior to WLST rather than at the onset of the agonal phase 1
  • Dosing options:
    • Weight-based: 100-300 units/kg
    • Fixed dose: 30,000 units
  • Timing: Immediately before WLST to ensure adequate circulation
  • Rationale: Reduces odds of primary non-function following DCD liver transplantation and improves graft survival 1, 2

Additional Medications

• Consider administration of alpha-blockers or other vasodilators prior to withdrawal:
  • Phentolamine may enhance organ blood flow and lower incidence of delayed renal graft function 1
  • Specific informed consent should be obtained for these antemortem medications 1

Thrombolytic Protocols for Liver Grafts

Tissue Plasminogen Activator (tPA) Options

• Option 1: Inject tPA (0.5 mg per 100g liver weight) into donor hepatic artery on back table 1

  • Keep hepatic artery clamped for 10-15 minutes after portal reperfusion
  • Unclamp before arterial anastomosis to allow excess tPA to back-bleed

• Option 2: Inject 2 mg of tPA after 5 mg of verapamil into donor hepatic artery after portal vein anastomosis 1

• Option 3: Inject tPA (100 μg/kg donor body weight) into donor hepatic artery before portal vein anastomosis 1

• Option 4: Mix 100 mg of tPA with 1L of room temperature normal saline and administer via donor aorta as initial flush solution during organ recovery 1

Normothermic Regional Perfusion (NRP) Protocols

Types of NRP

• Abdominal NRP (A-NRP): Limited to abdominal organs 1
• Thoracoabdominal NRP (TA-NRP): Includes in situ coronary perfusion for heart recovery 1

Implementation of NRP

• Duration: Typically 1-4 hours for organ assessment 1
• Monitoring: Collect and analyze hemodynamic and laboratory data during perfusion 1
• Benefits:
  • Improves organ utilization rates 1, 3
  • Reduces primary non-function and early allograft dysfunction 1
  • Improves 1-year patient and graft survival 1, 3
  • Reduces biliary complications in liver transplants 1

Monitoring and Documentation Requirements

Critical Time Points to Document

• Time of WLST
• Time at which heparin is given
• First minute when oxygen saturation (SpO2) drops to <70%
• First minute when systolic blood pressure (sBP) drops to <50 mmHg
• Time of circulatory arrest determination
• Time of incision
• Time of cold flush
• Time of cross-clamp
• Time of NRP initiation and termination (if applicable)
• Time of organ removal 1

Arterial Line Placement

• Routinely place an arterial line prior to WLST to:
  • Accurately determine loss of circulation
  • Monitor duration of functional donor warm ischemia time (f-DWIT)
  • Ensure lack of brain perfusion when using NRP 1

Practical Considerations and Pitfalls

Common Pitfalls to Avoid

1. Delayed heparin administration: Administering heparin during the agonal phase rather than before WLST may reduce its effectiveness due to poor circulation 1

2. Inadequate monitoring: Failure to place an arterial line can lead to inaccurate assessment of circulatory arrest and warm ischemia time 1

3. Excessive waiting time: Waiting periods longer than 5 minutes after circulatory arrest unnecessarily increase warm ischemia time 1

4. Terminology confusion: Using ambiguous terms like "donor warm ischemia time" without specifying the exact definition can lead to miscommunication 1

5. Bleeding risk with thrombolytics: While thrombolytic protocols have shown promising results, the risk of excessive bleeding should not be underestimated, especially in patients with coagulopathy, fibrinolysis, or thrombocytopenia 1

Organ-Specific Considerations

• Liver: Most sensitive to warm ischemia; consider thrombolytic protocols to prevent ischemic cholangiopathy 1
• Kidneys: Benefit from NRP with excellent 1-year graft survival 1
• Heart: TA-NRP can significantly expand the donor pool for heart transplantation 1, 4
• Lungs: Can exhibit primary function with appropriate DCD protocols 3

Conclusion

The standardization of drug dosing and organ preservation protocols in DCD scenarios is essential for maximizing organ viability and transplant outcomes. The evidence strongly supports premortem heparin administration, careful monitoring of hemodynamic parameters, and consideration of advanced preservation techniques like NRP to improve graft function and survival. These protocols must be implemented by experienced surgical teams familiar with both the technical aspects and ethical considerations specific to DCD organ recovery.