What is warm ischemia time in liver transplantation?

Warm Ischemia Time in Liver Transplantation

Warm ischemia time in liver transplantation refers to the period when the liver graft experiences warm ischemic injury, with different definitions depending on the donation type, and should be limited to less than 90 minutes to minimize complications and improve outcomes. 1

Definition and Types of Warm Ischemia Time

• In liver transplantation, warm ischemia time (WIT) can be divided into two main categories depending on the type of donation:

  • Donor warm ischemia time (dWIT) - occurs in donation after circulatory death (DCD) donors and is generally defined as the time from extubation to cross-clamp 1
  • Recipient warm ischemia time (rWIT) - occurs during implantation of the liver graft 2

• In DCD liver transplantation, donor warm ischemia time can be further categorized into:

  • Agonal phase - begins when blood pressure or oxygen saturation drops below certain thresholds (70-80 mmHg in systolic pressure, 50-60 mmHg in MAP, or 60-80% in SpO2) 1
  • Asystolic phase - from cardiac arrest to the start of cold perfusion 3
  • Functional warm ischemia time - starts when either SpO2 or blood pressure drops below a certain threshold and lasts until the start of cold perfusion 4

• A newer concept called combined warm ischemia time has been introduced, defined as the sum of donor warm ischemia time and recipient warm ischemia time 3

Impact on Graft Function and Outcomes

• Warm ischemia time exceeding 90 minutes is associated with decreased graft survival in HCV patients 1

• True warm ischemia time (interval between significant ischemic insult, such as a drop in mean arterial pressure below 60 mmHg, and initiation of perfusion) longer than 20-30 minutes is associated with increased complications in DCD liver transplantation 1

• Total warm ischemia time (interval between discontinuation of mechanical ventilation and initiation of perfusion) longer than 30-45 minutes is associated with increased complications in DCD liver transplantation 1

• Combined warm ischemia time should ideally not exceed 60 minutes to minimize the risk of severe acute kidney injury after DCD liver transplantation 3

• Prolonged warm ischemia time reduces the cold preservation limits of liver grafts:

  • 10 minutes of warm ischemia reduces cold preservation limit to 20 hours
  • 20 minutes of warm ischemia reduces cold preservation limit to 12 hours
  • 30 minutes of warm ischemia reduces cold preservation limit to 6 hours 5

Strategies to Minimize Warm Ischemia Time

• Expeditious donor surgery is essential to minimize warm ischemia time in DCD liver transplantation 6

• Time from incision to cross-clamp is the only surgically modifiable period to shorten donor warm ischemia 1

• Premortem heparin administration (30,000 units) is used in >90% of DCD donors to prevent thrombus formation, though this practice may be ethically controversial 1

• Careful donor and recipient selection is crucial when considering DCD liver transplantation 6

• Ex vivo machine perfusion techniques are being investigated as potential strategies to mitigate the effects of warm ischemia, though these are currently considered investigational 1

Clinical Recommendations

• Cold ischemia time should be kept under 8 hours and warm ischemia time should not exceed 90 minutes to optimize outcomes 1

• For DCD liver transplantation, the following time frames should not be exceeded:

  • True warm ischemia time: 20-30 minutes
  • Total warm ischemia time: 30-45 minutes
  • Cold ischemia time: 8-10 hours 1

• Combined warm ischemia time should be kept under 60 minutes to reduce the risk of acute kidney injury 3

• Expeditious, in situ biliary flush should be performed to minimize bile-induced epithelial damage in DCD liver donors 1

• The use of DCD livers with longer ischemia times or from older donors should be limited to reduce the risk of biliary complications 1