Donor management and optimization

Donor management and optimization refers to the intensive-care physiologic support of a deceased organ donor in the interval between authorization for donation and surgical organ recovery, undertaken with the goal of preserving organ function and maximizing the number and quality of organs that can be transplanted.[1][2] After death is declared by neurologic criteria (see Donation after brain death), the body's normal homeostatic control is lost, and a series of predictable physiologic derangements threatens every transplantable organ. Active management to counter these derangements, sometimes called "donor optimization", is delivered by the intensive-care team in partnership with the organ procurement organization (OPO), and the practice has been shown in observational studies to increase the number of organs transplanted per donor.[2][3]

Major professional societies have issued consensus guidance on this phase of care. In the United States, the most widely cited synthesis is the 2015 multidisciplinary consensus statement of the Society of Critical Care Medicine (SCCM), the American College of Chest Physicians, and the Association of Organ Procurement Organizations.[1] The standardized physiologic targets that organize this care are commonly called donor management goals (DMGs).[3]

Physiology after brain death

Brain death triggers a cascade of pathophysiologic changes that destabilize the donor.[1][4] The terminal brainstem ischemia (herniation) produces a transient "autonomic storm," a massive catecholamine surge that causes severe hypertension, tachycardia, and myocardial stress.[4] This is followed by collapse of central sympathetic outflow, with loss of vasomotor tone and profound vasodilatory (distributive) shock.[1][4] Additional derangements include:

• Diabetes insipidus, from loss of posterior-pituitary antidiuretic hormone, producing massive dilute urine output, hypovolemia, and hypernatremia.[4]
• Cardiovascular instability and myocardial dysfunction, partly from the catecholamine surge ("myocardial stunning") and partly from loss of vascular tone.[1][4]
• Neurogenic pulmonary edema and a systemic inflammatory response that injure the lungs.[1][4]
• Hypothermia, from loss of hypothalamic thermoregulation.[1][4]
• Coagulopathy, including disseminated intravascular coagulation and thrombocytopenia, from release of tissue factor from necrotic brain.[4]
• Endocrine failure, including reductions in circulating thyroid hormone, cortisol, and antidiuretic hormone.[1][4]

Left untreated, these processes lead to progressive organ injury and loss of otherwise transplantable organs.[1][2]

Donor management goals (DMGs)

Donor management goals are a bundle of standardized physiologic targets, typically spanning cardiovascular, pulmonary, renal, and endocrine endpoints, that the donor is managed toward before organ recovery.[3] Representative targets cited in reviews and protocols include a mean arterial pressure (MAP) above 60 mmHg, central venous pressure of roughly 6-8 mmHg, heart rate of 60-120 beats per minute, urine output of about 1-3 mL/kg/hr, serum sodium below approximately 155 mEq/L, core temperature of 36-38 °C, and, for potential lung donors, a ratio of arterial oxygen tension to inspired oxygen fraction (P/F ratio) above 300 on standardized ventilator settings.[2][3] Potential cardiac donors are additionally assessed for left-ventricular ejection fraction (commonly a target above 45%).[2]

Multiple OPO-based studies have linked the DMG bundle to better yield. In a prospective study across eight OPOs in United Network for Organ Sharing (UNOS) Region 5, meeting at least seven of nine donor management goals before organ recovery was an independent predictor of four or more organs transplanted per donor (odds ratio 2.34), yet the goals were met at the time of authorization in only a minority of donors, evidence of a gap that earlier, more aggressive management could close.[3] These findings underpin the DMG Registry and the broad adoption of bundle-based donor care across United States OPOs.[3]

Hemodynamic management

Restoring an adequate circulating volume is the first priority, because hypovolemia from diabetes insipidus and pre-donation fluid losses is common.[1][4] Isotonic crystalloids and colloids such as 5% albumin are used; hydroxyethyl-starch solutions are generally avoided because of associations with renal injury and delayed graft function.[4] When perfusion targets are not met by fluid alone, vasopressors and inotropes are added.[1][4] Vasopressin is frequently favored because it simultaneously supports vascular tone in vasodilatory shock and treats diabetes insipidus; other agents (for example, dopamine, norepinephrine, or phenylephrine for vasodilation, and dobutamine or epinephrine for pump failure) are selected according to the hemodynamic pattern.[1][4] The aim is to meet perfusion targets while minimizing the cumulative vasopressor burden, since high pressor requirements are themselves associated with reduced organ yield.[3][4]

Hormone replacement therapy

Hormonal resuscitation therapy (HRT), variously combining a corticosteroid, vasopressin, thyroid hormone (triiodothyronine, T3, or levothyroxine, T4), and insulin for glycemic control, is used in many protocols for hemodynamically unstable donors and for marginal cardiac donors.[1][4] Corticosteroids are also given to blunt the systemic inflammatory response.[1][4]

The evidence base for HRT is mixed and the practice is contested. Large retrospective OPO analyses have reported associations between combined hormonal therapy and increased organ yield, but the SCCM consensus statement and subsequent reviews note that high-quality randomized data are limited and that recommendations rest substantially on observational evidence and expert opinion.[1][4] The role of routine thyroid hormone in particular is disputed; some analyses have raised concern about an association with adverse cardiac-graft outcomes.[4] Readers should treat HRT components as an area of ongoing debate rather than settled practice.[1][4]

Lung-protective ventilation and recruitment

Because the lungs are especially vulnerable after brain death and are recovered from only a minority of donors, ventilator management has shifted from historical high tidal volumes toward a lung-protective strategy adapted from acute respiratory distress syndrome care: tidal volumes of roughly 6-8 mL/kg of predicted body weight, moderate positive end-expiratory pressure (PEEP, commonly 8-10 cm H2O), periodic recruitment maneuvers, conservative fluid balance, and routine bronchoscopy to clear secretions and assess the airway.[1][4] These measures, combined with structured donor management, have been associated with substantial increases in lung utilization.[3][4]

Glycemic, electrolyte, temperature, and transfusion management

Hyperglycemia is treated with insulin to maintain glucose control.[1][4] Hypernatremia, common because of diabetes insipidus, is corrected (often to below about 155 mEq/L) before recovery because elevated donor sodium has been associated with liver-graft dysfunction.[4] Normothermia (36-38 °C) is maintained with active warming to limit cold-induced coagulopathy and arrhythmia.[1][4] Anemia and coagulopathy are corrected with red-cell and other blood-product transfusion as needed, which also supports intravascular volume.[1][4]

DCD-specific considerations

In donation after circulatory death (DCD), the donor does not meet neurologic death criteria; death is declared on circulatory criteria after planned withdrawal of life-sustaining treatment.[5] DCD donors are therefore managed differently: the focus is on optimizing the candidate before withdrawal and on minimizing the warm-ischemia interval between circulatory arrest and cold perfusion, rather than on the prolonged post-brain-death support described above.[1][5] Heparin and other pre-mortem interventions, and the no-touch observation period after arrest, are governed by local protocol and ethics review (see Organ procurement (recovery surgery)).[5]

Roles and setting

Donor management takes place in the intensive care unit and is a shared responsibility.[1][2] The treating ICU team continues physiologic support, while the OPO assumes coordination of donation, typically through an organ procurement (or donation) coordinator who directs goal-directed management, orders donor-specific testing and consultations, and works toward the DMGs in conjunction with organ-specific evaluation (see Donor evaluation and infectious disease testing).[1][2][3] This management phase ends when the donor is transported to the operating room for recovery.[2]

See also

• The donation pathway
• Donation after brain death (DBD)
• Donation after circulatory death (DCD)
• Organ procurement (recovery surgery)
• Donor evaluation and infectious disease testing

References

• Kotloff RM, Blosser S, Fulda GJ, et al. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/CCM.0000000000000958. PMID: 25978154.
• Hwang HP, Kim JM, Shin S, et al. Organ procurement in a deceased donor. Korean J Transplant. 2020;34(3):134-150. doi:10.4285/kjt.2020.34.3.134. PMID: 35769061. PMCID: PMC9186815.
• Malinoski DJ, Patel MS, Daly MC, Oley-Graybill C, Salim A; UNOS Region 5 DMG Workgroup. The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study. Crit Care Med. 2012;40(10):2773-2780. doi:10.1097/CCM.0b013e31825b252a. PMID: 22846779.
• Clarke C. Management of the brain-dead organ donor. Indian J Thorac Cardiovasc Surg. 2021;37(Suppl 3):395-400. doi:10.1007/s12055-021-01224-y. PMID: 34548770. PMCID: PMC8445737.
• American Society of Transplant Surgeons. Position Statement on a 5-Minute Observation Period for Donation After Circulatory Death. https://www.asts.org/docs/default-source/position-statements/asts-position-statement-on-a-5-minute-observation-period.pdf