Both perfusion pressure and flow are critical in abdominal normothermic regional perfusion!

Abdominal normothermic regional perfusion (A-NRP) has emerged as a major advance in controlled donation after circulatory death (cDCD), improving organ utilization and post-transplant outcomes, especially in liver transplantation. Clinical series have shown lower rates of ischemic cholangiopathy and better graft outcomes when A-NRP is used instead of rapid recovery alone [1,2]. Yet, despite this progress, the hemodynamic monitoring of the reperfused abdominal compartment remains conceptually underdeveloped. In many settings, the adequacy of abdominal reperfusion is inferred mainly from extracorporeal pump flow and venous oxygen saturation sampled from the drainage line. We believe this is physiologically insufficient, because when it comes to tissue perfusion, arterial pressure is as important as blood flow. In this regard, during A-NRP, continuous arterial pressure monitoring of the reperfused compartment should be regarded as a critical requirement, because pressure, and not flow alone, is what makes organ perfusion effective [3,4].The rationale is grounded in fundamental hemodynamics. Organ blood flow is governed by the pressure gradient across the vascular bed and its resistance.Extracorporeal flow displayed by the pump is therefore only a circuit variable; it does not directly indicate whether an adequate driving pressure is being transmitted to the abdominal microcirculation. This issue is particularly relevant after death. During A-NRP, circulation is non-pulsatile, entirely pump-driven, and occurs in a vascular system that has lost autonomic regulation. Under these conditions, apparently acceptable circuit flow may coexist with inadequate arterial pressure if systemic vascular resistance is low. In such a situation, blood is moving through the circuit, but the pressure head required to perfuse ischemic tissues may be insufficient. In physiological terms, this corresponds to flow that is measurable, yet hemodynamically ineffective [4,5]. Misconceptions may therefore easily arise, such as assuming that high blood flow necessarily implies adequate systemic arterial pressure and effective tissue perfusion.The converse is also true: even with apparently sufficient pressure, low cardiac output respectively low circuit flow may still result in inadequate tissue oxygen delivery.The kidney illustrates why this distinction matters. Renal perfusion becomes pressuredependent below the autoregulatory range, and autoregulation itself is altered in shock states and cannot be assumed to be preserved after circulatory arrest and warm ischemia [4,6]. Thus, during A-NRP, a low arterial pressure in the reperfused abdominal compartment may translate directly into inadequate renal cortical perfusion despite apparently satisfactory extracorporeal flow. The same physiological concern likely extends to the liver and splanchnic organs, whose recovery after warm ischemia depends on restoration of effective tissue oxygen delivery rather than simply on the presence of circulating blood in the aorta. Preserved macroflow is not synonymous with restored organ perfusion [4][5][6].For the same reason, reliance on venous-line SvO2 is problematic. SvO2 is a global, flow-weighted average of oxygen extraction in the venous effluent reaching the sampling site. It is not an organ-specific perfusion marker. Low SvO2 is certainly concerning, but normal or elevated mixed SvO2 does not exclude regional hypoperfusion, heterogeneous flow distribution, impaired oxygen extraction, or microcirculatory shunting. This limitation has been emphasized repeatedly in critical care physiology. Venous oxygen saturation can remain normal despite persistent tissue hypoxia, a phenomenon described as "covert tissue hypoxia" [7,8]. This is particularly relevant when perfusion is unevenly distributed: well-perfused territories may dominate the venous signal and mask ongoing ischemia in more vulnerable organs.As illustrated in Figure 1, extracorporeal pump flow does not necessarily translate into effective abdominal organ perfusion. While pump flow reflects circuit blood flow and venous-line SvO2 reflects a global mixed venous signal, arterial pressure measured within the reperfused abdominal compartment more directly reflects the driving pressure for abdominal organ perfusion.Evidence from extracorporeal circulation supports this concern. During cardiopulmonary bypass, mixed venous oxygen saturation has been shown to correlate poorly with regional venous saturations. McDaniel and colleagues demonstrated that normal mixed venous saturation did not exclude marked regional venous desaturation during bypass [9]. Likewise, Lindholm et al. found that regional deoxygenation can occur despite normal mixed venous saturation [10]. Even more importantly, Dahn et al. showed that global venous oxygenation may coexist with depressed splanchnic venous oxygen saturation, illustrating that visceral hypoxia may be missed when only systemic venous oxygenation is monitored [11]. Although these studies were not performed in A-NRP donors, the physiological message is directly transferable: global venous oxygenation is an indirect and potentially misleading surrogate for abdominal organ reperfusion.what the organ bed receives. In addition, the interpretation of pump flow depends on circuit configuration, cannula size, and device-specific flow characteristics, which further limits its value as a stand-alone surrogate of effective organ perfusion [12]. If arterial pressure is low because resistance is low, a seemingly adequate flow can still fail to generate sufficient transorgan perfusion pressure. This is precisely why coherence between macrocirculation and microcirculation cannot be assumed. In critically ill states, correction of global hemodynamic variables does not reliably restore microvascular perfusion, and the same principle should apply even more strongly to organs that have just undergone warm ischemia and are being reperfused under nonphysiological extracorporeal conditions [5,13]. This physiological concern may be particularly relevant in donors who have already sustained an episode of global ischemia-reperfusion injury before WLST, such as after resuscitated cardiac arrest leading to hypoxic-ischemic brain injury. In such cases, abdominal organs may already be exposed to post-arrest low-flow states, vasoplegia, vasopressor-related maldistribution, and splanchnic hypoperfusion before the conventional DCD warm ischemic phase begins. This blind spot may be even more pronounced in uncontrolled DCD, where longer no-flow and low-flow periods, more severe metabolic derangement, and greater vascular dysfunction are expected at the time NRP is initiated. Indeed, uncontrolled DCD donors undergoing NRP have been shown to display more severe metabolic derangement than controlled DCD donors, often requiring more aggressive corrective treatment during reperfusion [14]. A-NRP is intended to recondition abdominal organs, not merely to re-establish circuit circulation.It is also important to recognize that, even at a constant pump flow, a fall in vascular resistance in one abdominal territory may redistribute flow toward that organ at the expense of others. For example, a drop in splanchnic vascular resistance may preferentially direct blood toward the liver while reducing effective perfusion of the kidneys. In this setting, total circuit flow alone cannot guarantee adequate and balanced reperfusion of all abdominal organs, because changes in regional resistance directly affect flow distribution and tissue perfusion.Continuous arterial pressure monitoring of the reperfused abdominal compartment addresses this blind spot. It provides direct information on the driving force available to perfuse the kidneys, liver, and gut, and it allows real-time adjustment of ECMO flow and vasopressors to achieve hemodynamically meaningful reperfusion. In practical terms, this pressure should ideally be measured directly within the reperfused abdominal arterial compartment, for example through a pressure-monitoring side port connected to the arterial return line or through an arterial catheter placed in the reperfused infradiaphragmatic arterial circulation. This approach is also consistent with broader NRP standardization efforts, which emphasize hemodynamic control and procedural reproducibility during abdominal NRP [3,4]. While the exact optimal pressure threshold still requires further refinement, published A-NRP protocols consistently support maintaining a mean arterial pressure in the range of 60-65 mmHg to ensure effective abdominal organ perfusion [15][16][17][18][19]. This is particularly important because accepted extracorporeal flow targets during NRP have largely been derived from protocolized experience and consensus documents, especially in liver preservation, and should not be interpreted in isolation from perfusion pressure [15][16][17][18]. Controlled and uncontrolled DCD are unlikely to require fundamentally different perfusion pressure targets; rather, uncontrolled DCD may require more aggressive hemodynamic support to achieve and maintain the same physiological goals because of more severe ischemia-reperfusion injury, metabolic derangement, and vascular dysfunction. needs to be defined more precisely, t Importantly, several of the currently accepted hemodynamic and perfusion targets used in controlled DCD liver preservation were initially informed by experience gained in uncontrolled DCD and by subsequent consensus recommendations [14][15][16][17][18]. The principle nevertheless remainsis straightforward: if arterial pressure iswe do not monitored arterial pressure within the reperfused compartment, we doone cannot be confident that truly know whether all abdominal organs are being effectively and adequately reperfused. This does not diminish the importance of adequate extracorporeal flow; rather, it emphasizes that flow must be interpreted together with pressure if reperfusion is to be assessed in physiologically meaningful terms.We are not claiming that compartmental arterial pressure monitoring has already been proven, in isolation, to improve graft or recipient survival. Rather, we argue that it is physiologically indispensable if the objective of A-NRP is true organ reperfusion rather than simple extracorporeal circulation. Flow is necessary, but pressure is what makes flow biologically relevant and appropriately distributed. In abdominal NRP, direct monitoring of arterial pressure within the reperfused compartment should therefore be considered a logical next step toward more rational, physiology-guided donor management.