**3. Techniques for establishing normothermic regional perfusion in donation after circulatory death**

While NRP relies on extracorporeal membrane oxygenation (ECMO) technology, its clinical application is, in general, less complex than that of therapeutic ECMO. A venous cannula is placed to derive blood from the donor inferior vena cava or right atrium, which is then pumped through a membrane oxygenator and a heat exchanger before returning to the donor arterial bed (aorta or iliac or femoral artery). An in-line reservoir may be included in the circuit, as well, to allow for replacement of volume prior to circuit failure in the event of volume loss or inadequate venous return due to severe vasoplegia (particularly relevant in the setting

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*Normothermic Regional Perfusion in Solid Organ Transplantation*

**3.1 Abdominal normothermic regional perfusion**

of uDCD). The precise positioning of occlusion balloon catheters or clamps used to exclude other vascular beds is what determines whether NRP is either thoracoab-

In uDCD, cannulation for the establishment of abdominal NRP is performed post-mortem after death is declared, typically in the emergency department. In cDCD, in contrast, cannulation for abdominal NRP may be performed either prior to the withdrawal of life support (pre-mortem) or following the declaration of death. Pre-mortem cannulation may be performed either percutaneously or via femoral cut-down in a variety of settings (intensive care unit, radiology suite, operating room). Post-mortem cannulation, on the other hand, is most often done in open abdomen in the operating room, though some centers have used femoral artery and vein catheters or guidewires placed prior to withdrawal of care to access and thereby

cannulate the femoral vasculature following the declaration of death [12].

primed NRP circuit, the supraceliac aorta is clamped, and NRP is initiated.

**3.2 Thoracoabdominal normothermic regional perfusion**

For uDCD donors and cDCD donors with pre-mortem cannulation, a bolus of heparin is administered, and cannulation of unilateral femoral vessels is performed either via open femoral cutdown and isolation of the femoral artery and vein or percutaneously using Seldinger technique [11]. Cannulae are left clamped and connected to the tubing of the primed NRP circuit. The contralateral femoral artery is also cannulated with an aortic occlusion balloon catheter, which is left deflated in the case of cDCD and advanced into the supraceliac aorta under radiographic control. Following the withdrawal of life support and the declaration of death in cDCD, the aortic occlusion balloon is inflated, and the abdominal NRP circuit is initiated (**Figure 2**). Proper positioning of the balloon excluding the aortic arch vessels is confirmed by chest radiograph and absence of flow measured in a left radial

For cDCD donors undergoing open post-mortem cannulation, once death has been declared, the surgical team performs midline laparotomy to cannulate the abdominal aorta immediately proximal to and the infrarenal inferior vena cava immediately distal to their respective bifurcations. Cannulae are connected to the tubing of the

Blood is sampled at baseline and every 30 minutes during abdominal NRP to determine biochemical, hematological, and acid-base parameters. In general, pump flow is

globin >7 g/dL. Hepatic transaminases should remain stable throughout NRP; levels >3× the upper limit of normal at baseline and/or >4× the upper limit of normal at the end of NRP may be considered relative contraindications for recovery of the liver and pancreas [10, 11]. In general, NRP is run for a minimum of 1 hour and a maximum of 4 hours to allow adequate reconditioning of the abdominal organs and recovery of energy substrates without provoking additional end-organ injury [4, 5, 7, 8, 13, 14].

While the circuit for abdominal NRP may be established pre-mortem, cannulation to establish a complete thoracoabdominal NRP circuit is done post-mortem in the operating room. After the declaration of death, the chest is entered through a midline sternotomy, and the pericardium is opened. A bolus of heparin is injected into the heart directly, an arterial cannula is inserted into the distal ascending aorta/aortic arch, and a venous cannula is inserted into the right atrium. Cannulae are connected to the tubing of the primed NRP circuit, the aortic arch vessels are

, temperature 35–37°C, PaO2 100–150 mmHg, and hemo-

*DOI: http://dx.doi.org/10.5772/intechopen.84771*

dominal or abdominal only.

arterial catheter.

maintained >1.7 L/min/m2

clamped, and NRP is initiated.

*Advances in Extracorporeal Membrane Oxygenation - Volume 3*

**donation after circulatory death**

viability prior to recovery [10, 11].

**2. Principles behind the use of normothermic regional perfusion in** 

**3. Techniques for establishing normothermic regional perfusion in** 

*During ischemia, the concentrations of adenine nucleotides (ATP, ADP, AMP) and nucleosides (adenosine, inosine) progressively decline. Also, the concentrations of nucleotide breakdown products (xanthine, hypoxanthine) increase, thereby leading to the production of oxygen free radicals upon reperfusion. Normothermic regional perfusion is capable of reversing these processes and increases the concentrations of endogenous antioxidants, effectively recharging and reconditioning organs in the abdomen and chest prior to* 

While NRP relies on extracorporeal membrane oxygenation (ECMO) technology, its clinical application is, in general, less complex than that of therapeutic ECMO. A venous cannula is placed to derive blood from the donor inferior vena cava or right atrium, which is then pumped through a membrane oxygenator and a heat exchanger before returning to the donor arterial bed (aorta or iliac or femoral artery). An in-line reservoir may be included in the circuit, as well, to allow for replacement of volume prior to circuit failure in the event of volume loss or inadequate venous return due to severe vasoplegia (particularly relevant in the setting

**donation after circulatory death**

During warm ischemia, ATP degradation leads to the progressive accumulation of xanthine and hypoxanthine, important sources of superoxide radical at organ reperfusion [3]. A period of post-ischemic NRP in DCD donors is useful to restore cellular energy substrates [4], reduce levels of nucleotide degradation products [5], improve the concentrations of endogenous antioxidants [6], and even stimulate processes of cellular repair prior to graft recovery [7] (**Figure 1**). An experimental study demonstrates that by blocking the A2 receptors of adenosine, the beneficial effects of NRP are abolished, indicating that NRP mediates its effect, at least in part, through adenosine as a form of ischemic preconditioning [8]. Post-ischemic NRP may also be useful to reduce the vasoconstrictive effects of cold graft washout with the static cold storage solution [9] and offers an opportunity to assess organ

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**Figure 1.**

*recovery for transplantation.*

of uDCD). The precise positioning of occlusion balloon catheters or clamps used to exclude other vascular beds is what determines whether NRP is either thoracoabdominal or abdominal only.
