Warm Perfusion and Machine Perfusion

Machine perfusion keeps a procured organ connected to a circuit that pumps a preservation fluid through its vessels during storage, rather than holding it static on ice. It spans a temperature range: hypothermic machine perfusion maintains cold flow, while normothermic (warm) perfusion holds the organ near body temperature so it can metabolize and even function outside the body.

Definition

Machine perfusion is a preservation method in which a donor organ is connected to a circulating perfusate during storage; in hypothermic perfusion the organ is kept cold while flow is maintained, and in normothermic (warm) perfusion the organ is held near physiologic temperature so that metabolism and function are sustained ex vivo.

Scope

The topic covers the rationale for perfusing rather than statically storing an organ, the distinction between hypothermic and normothermic approaches, and what each is intended to achieve (limiting injury, enabling assessment of marginal grafts). It is a reference overview and does not direct device selection, perfusion settings, or clinical use for any organ or patient.

Core questions

• What does maintaining flow add beyond keeping an organ cold and static?
• How do hypothermic and normothermic perfusion differ in aim and mechanism?
• Can perfusion allow a marginal organ to be assessed before the decision to transplant?

Key concepts

• Hypothermic machine perfusion
• Normothermic (warm) machine perfusion
• Ex vivo organ assessment
• Marginal and extended-criteria donors
• Continuous perfusate circulation
• Reconditioning of grafts

Mechanisms

Maintaining flow through an organ during storage is intended to limit the metabolic and microvascular derangements that accumulate during static ischemia and are unmasked on reperfusion (Eltzschig & Eckle, 2011). Hypothermic machine perfusion keeps the organ cold while circulating perfusate, aiming to wash out metabolites and support the cold-storage benefit with ongoing flow (Moers et al., 2009). Normothermic perfusion instead restores near-body temperature and oxygenated flow so the organ resumes metabolism, which both reduces cold-ischemic time and creates an opportunity to observe how the graft functions before implantation (Nasralla et al., 2018).

Clinical relevance

Machine perfusion is most discussed in the context of marginal and circulatory-death donors, where the margin for ischemic injury is narrow, and it bears on how such grafts are evaluated and selected. This entry summarizes the concepts and trial evidence; it does not recommend a device, a temperature, or a perfusion strategy for any case.

Evidence & guidelines

Randomized trials anchor this topic. In deceased-donor kidney transplantation, hypothermic machine perfusion was compared with static cold storage (Moers et al., 2009). In liver transplantation, normothermic preservation was tested against cold storage in a randomized trial (Nasralla et al., 2018), and hypothermic oxygenated machine perfusion was evaluated in donation-after-circulatory-death liver grafts in a separate randomized trial (van Rijn et al., 2021).

History

Pulsatile hypothermic perfusion of kidneys was explored decades ago but was largely displaced by simple cold storage once effective preservation solutions appeared. The expansion of donor pools to include marginal and circulatory-death organs revived interest, and randomized trials in kidney (Moers et al., 2009) and liver transplantation (Nasralla et al., 2018; van Rijn et al., 2021) moved both hypothermic and normothermic perfusion from concept toward clinical practice.

Debates

Hypothermic versus normothermic perfusion

Hypothermic perfusion preserves the metabolic-slowing benefit of cold storage while adding flow, whereas normothermic perfusion restores function ex vivo and permits graft assessment; which approach is preferable depends on organ and donor type and remains an active question informed by trial data.

Key figures

• Folkert Belzer
• Constantin Coussios

Seminal works

• moers-2009
• nasralla-2018
• van-rijn-2021

Frequently asked questions

What is the difference between hypothermic and normothermic machine perfusion?

Hypothermic perfusion keeps the organ cold while circulating fluid through it, combining cold storage with flow. Normothermic perfusion warms the organ to near body temperature so it metabolizes and functions outside the body, which also allows its function to be assessed before transplantation.

Why might machine perfusion matter more for marginal organs?

Marginal and circulatory-death organs tolerate ischemia less well, so the additional flow and, in the normothermic case, the chance to evaluate the graft before implantation are of particular interest. Randomized trials have examined these benefits in kidney and liver transplantation.