Expanding the Pool: The Critical Care of the "Marginal" or Extended Criteria Donor

Dr Neeraj Manikath , claude.ai

Abstract

The persistent global shortage of transplantable organs has necessitated a paradigm shift toward accepting donors that fall outside traditional "ideal" criteria. Extended criteria donors (ECD) represent a heterogeneous population that, with judicious selection and aggressive critical care optimization, can significantly expand the donor pool without compromising recipient outcomes. This review explores the medical strategies employed by intensivists to assess, resuscitate, and optimize organs from marginal donors, with particular emphasis on organ-specific management, emerging ex vivo perfusion technologies, and the ethical framework underpinning these decisions.

Introduction

Approximately 17 people die daily in the United States awaiting organ transplantation, while thousands more suffer progressive organ failure on transplant waiting lists worldwide¹. This critical mismatch between organ supply and demand has catalyzed increasing acceptance of extended criteria donors (ECD)—donors previously deemed unsuitable due to advanced age, comorbidities, or organ dysfunction. Modern critical care management has transformed many of these "marginal" organs into viable grafts, challenging the intensivist to function simultaneously as resuscitator, organ steward, and prognosticator.

The acceptance of ECD organs represents a calculated risk-benefit analysis: while these organs may carry higher rates of delayed graft function or reduced longevity, they often provide survival advantages over remaining on the waiting list². Understanding how to optimize these donors requires sophisticated critical care expertise and represents one of the most impactful contributions an intensivist can make to transplant medicine.

Defining "Extended Criteria": Understanding the Risk-Benefit Analysis

Historical Context and Evolution

The term "extended criteria donor" originated in kidney transplantation, initially defined by the United Network for Organ Sharing (UNOS) in 2002 as donors aged ≥60 years or donors aged 50-59 years with at least two of the following: cerebrovascular accident as cause of death, serum creatinine >1.5 mg/dL, or history of hypertension³. However, this binary classification has evolved toward more nuanced, organ-specific risk assessment tools.

Organ-Specific Definitions

Kidney Transplantation: The Kidney Donor Profile Index (KDPI) has replaced the ECD designation, providing a continuous scale from 0-100% that predicts post-transplant graft survival⁴. Donors with KDPI >85% represent the highest risk category. Donation after circulatory death (DCD) kidneys, particularly from Maastricht category III donors (controlled withdrawal of life-sustaining therapy), demonstrate higher rates of delayed graft function (30-50%) but comparable long-term outcomes to standard criteria donors when warm ischemia time is minimized⁵.

Pearl: DCD kidneys with warm ischemia time <30 minutes have outcomes approaching DBD (donation after brain death) kidneys. Aggressive donor management during the agonal phase is critical.

Liver Transplantation: Steatotic livers represent a significant ECD category, with macrovesicular steatosis >30% associated with increased primary non-function⁶. Age >70 years, split livers, and DCD livers also carry elevated risk. The Donor Risk Index (DRI) and the Balance of Risk (BAR) score help quantify these risks⁷. However, in experienced centers, carefully selected steatotic livers (30-60% steatosis) can be successfully transplanted with acceptable outcomes.

Hack: Request immediate frozen section biopsy for suspected steatotic livers. Intraoperative assessment remains the gold standard, as imaging often underestimates fat content.

Heart Transplantation: Traditional upper age limits of 40-45 years have expanded to >55 years in selected donors⁸. Left ventricular hypertrophy, prolonged inotrope dependence (>7 days), and elevated troponins represent relative contraindications requiring careful evaluation. Donor-recipient size mismatch (predicted heart mass ratio <0.86) increases mortality risk⁹.

Lung Transplantation: ECD lungs include those with age >55 years, smoking history >20 pack-years, PaO₂/FiO₂ ratio <300 mmHg, abnormal chest radiograph, or purulent secretions¹⁰. Despite these factors, many such lungs perform adequately post-transplant when properly assessed.

The Risk-Benefit Calculus

The fundamental question is not whether ECD organs have inferior outcomes to ideal donors—they do—but whether they provide superior outcomes compared to remaining waitlisted. For many recipients with high Model for End-Stage Liver Disease (MELD) scores or prolonged dialysis duration, accepting an ECD organ offers significant survival advantages²,¹¹.

Oyster: Beware of "futile" transplants where predicted recipient survival is worse than remaining waitlisted. Tools like the Survival Outcomes Following Liver Transplantation (SOFT) score help identify these scenarios.

Advanced Organ-Specific Optimization

Hemodynamic Management

Aggressive hemodynamic optimization forms the cornerstone of donor management. Traditional goals include mean arterial pressure (MAP) >65 mmHg, central venous pressure 6-10 mmHg, and urine output >1 mL/kg/hr¹². However, emerging data suggests higher MAP targets (70-80 mmHg) may improve renal perfusion in potential kidney donors¹³.

Hormone Replacement Therapy: The hemodynamic collapse following brain death results from hypothalamic-pituitary dysfunction. The controversial "thyroid hormone protocol" involves administering T3 or T4, methylprednisolone, vasopressin, and insulin¹⁴. While not universally adopted, some centers report improved cardiac function and increased organ yield, particularly in hemodynamically unstable donors.

Pearl: Early vasopressin (0.5-4 units/hr) can reduce catecholamine requirements and may improve cardiac and renal function through V1a and V2 receptor effects.

Pulmonary Management

Lung-protective ventilation is paramount: tidal volumes 6-8 mL/kg predicted body weight, PEEP 8-10 cmH₂O, and plateau pressure <30 cmH₂O minimize ventilator-induced lung injury¹⁵. For marginal lungs, aggressive pulmonary toilet, recruitment maneuvers, and prone positioning may salvage organs initially deemed unsuitable.

Donor lung apnea testing causes significant atelectasis and hypoxemia. Performing apnea testing with continuous positive airway pressure (CPAP) at 10 cmH₂O can minimize these deleterious effects¹⁶.

Managing Acute Kidney Injury in Donors

Approximately 20% of potential donors develop acute kidney injury (AKI)¹⁷. The intensivist faces a critical decision: can these kidneys be rehabilitated for transplantation?

Optimization strategies include:

• Volume resuscitation guided by dynamic indices (pulse pressure variation, stroke volume variation)
• Maintaining euvolemia to optimize renal perfusion without causing pulmonary edema
• Minimizing nephrotoxic medications
• Treating hypernatremia gradually (decrease Na⁺ by ≤10 mEq/L per 24 hours)
• Early initiation of vasopressin to reduce norepinephrine requirements

Hack: Terminal serum creatinine matters less than trajectory. A donor with improving creatinine from 3.0 to 2.0 mg/dL may yield better kidneys than one with stable creatinine of 1.8 mg/dL.

Kidneys from donors with AKI demonstrate higher rates of delayed graft function but comparable long-term outcomes, particularly when warm ischemia is minimized and recipient factors are favorable¹⁸.

Metabolic and Endocrine Management

Hyperglycemia (target 120-180 mg/dL) and diabetes insipidus management are crucial. Desmopressin (1-4 mcg IV q6-12h) treats central diabetes insipidus while potentially improving coagulation through von Willebrand factor release¹⁹.

The Role of Ex Vivo Machine Perfusion

Ex vivo machine perfusion represents perhaps the most transformative technology in modern transplantation, converting previously non-transplantable organs into viable grafts through assessment, preservation, and therapeutic intervention.

Liver Perfusion

Normothermic machine perfusion (NMP) maintains donor livers at 37°C with oxygenated blood or perfusate, allowing real-time functional assessment²⁰. Lactate clearance, bile production quality, perfusate pH, and vascular resistance provide objective metrics of liver viability.

Clinical Applications:

• Extended preservation times (up to 24 hours)
• Functional assessment of DCD and steatotic livers
• Delivery of therapeutic interventions (defatting therapies, gene therapy)
• Hepatitis C virus-positive donor liver treatment with direct-acting antivirals

The multicenter Consortium for Organ Preservation in Europe (COPE) trial demonstrated that NMP reduced organ discard rates from 29% to 19% and decreased early allograft dysfunction²¹.

Pearl: Lactate clearance on NMP is highly predictive. Livers failing to achieve lactate <2.5 mmol/L after 2 hours of perfusion have poor post-transplant outcomes.

Hypothermic oxygenated perfusion (HOPE) at 4-10°C offers a simpler, more widely applicable alternative, reducing ischemia-reperfusion injury and improving outcomes in ECD liver transplantation²².

Heart Perfusion

The Organ Care System (OCS) Heart provides warm perfusion at 34°C, enabling functional assessment and extended preservation²³. This technology has facilitated increased utilization of DCD hearts and extended geographic sharing.

The DCD Heart Trial demonstrated that DCD hearts preserved with OCS yielded similar outcomes to standard DBD heart transplants, effectively expanding the donor pool by an estimated 30%²⁴.

Hack: Lactate trends during OCS perfusion predict cardiac function. Rising lactate suggests myocardial injury and should prompt careful consideration before transplantation.

Kidney Perfusion

Hypothermic machine perfusion (HMP) for kidneys improves outcomes compared to static cold storage, particularly for ECD and DCD kidneys²⁵. Perfusion parameters including renal resistance and flow help predict post-transplant function.

Normothermic regional perfusion (NRP) in DCD donors—restoring circulation to abdominal organs while maintaining cardiac arrest—may reduce warm ischemia injury and improve kidney outcomes²⁶. However, ethical concerns about brain reperfusion have limited NRP adoption in some jurisdictions.

Future Horizons

Emerging technologies include:

• Subnormothermic perfusion (20-34°C) optimizing preservation while permitting metabolism
• Xenoperfusion using animal organs as biological support systems
• Pharmacologic reconditioning (e.g., mesenchymal stem cells, gene therapy)
• Artificial intelligence-driven perfusion parameter analysis

Oyster: Machine perfusion is not salvage therapy for obviously unsuitable organs. Patient selection and organ assessment remain paramount.

Informed Consent for the Recipient

The decision to accept an ECD organ involves complex risk stratification and shared decision-making. Intensivists contribute vital information about donor management and organ quality that informs these discussions.

Key Elements of Informed Consent

Recipients must understand:

1. Specific risk factors (donor age, comorbidities, organ dysfunction)
2. Expected outcomes compared to standard criteria donors
3. Alternative options (remaining waitlisted, accepting only standard donors)
4. Waitlist mortality risk and anticipated waiting time
5. Center-specific experience with ECD organs

Pearl: Frame the discussion around survival benefit, not graft longevity. A 60-year-old recipient may achieve full life expectancy even if an ECD kidney functions for only 12-15 years.

Quantifying Risk

Risk calculators provide objective data:

• Kidney: Estimated Post-Transplant Survival (EPTS) score matched with KDPI
• Liver: MELD-Plus, BAR score, SOFT score
• Heart: Donor-specific antibodies, Index of Organ Quality (IOQ)

The "Kidney Allocation System" in the US prioritizes matching high-KDPI kidneys to high-EPTS recipients, optimizing organ utility while minimizing waste²⁷.

Cultural and Individual Considerations

Recipient willingness to accept ECD organs varies significantly based on cultural factors, prior experiences, health literacy, and individual risk tolerance. Some patients prioritize immediate transplantation to escape dialysis or improve quality of life, while others prefer waiting for "perfect" organs despite mortality risks.

Hack: Involve social workers and transplant coordinators early. Their relationships with patients facilitate difficult conversations about risk acceptance.

The Intensivist's Role as a Steward

Intensivists occupy a unique position in transplantation, simultaneously advocating for potential donors, protecting recipient safety, and optimizing societal organ utility.

Ethical Framework

The primary ethical principle is non-maleficence: first, do no harm. Transplanting a marginally functional organ that results in immediate graft failure, recipient death, or complications exceeding waitlist morbidity violates this principle.

Competing obligations include:

• Donor family respect: Honoring wishes for organ donation
• Recipient autonomy: Supporting informed decision-making
• Justice: Fair allocation and maximizing organ utility
• Beneficence: Providing life-saving transplantation when appropriate

Decision-Making Under Uncertainty

Not all ECD organ decisions are clear-cut. When facing uncertainty:

1. Consult multidisciplinary teams: Surgeons, transplant physicians, pathologists
2. Use objective data: Biopsy results, perfusion parameters, laboratory trends
3. Consider recipient factors: Age, comorbidities, waitlist position
4. Document thoroughly: Rationale for acceptance or decline decisions
5. Learn systematically: Review outcomes to refine future decisions

Oyster: Avoid premature closure. An initial impression of organ unsuitability may be revised with additional information (improving kidney function, favorable biopsy, excellent perfusion parameters).

Quality Improvement and Outcome Tracking

Centers should systematically track ECD organ outcomes to inform future acceptance decisions. Key metrics include:

• Delayed graft function rates
• Primary non-function rates
• 1-year and 5-year graft survival
• Patient survival
• Quality of life measures

Pearl: Establish center-specific protocols for ECD organ evaluation. Standardization improves decision consistency and facilitates quality improvement.

The Evolving Landscape

As technologies advance and experience grows, yesterday's "marginal" organ becomes today's standard. Hepatitis C-positive organs, once universally declined, are now routinely transplanted with antiviral treatment²⁸. HIV-positive to HIV-positive transplantation is increasingly accepted²⁹. The intensivist must remain current with evolving evidence and adapt practice accordingly.

Conclusion

Extended criteria donors represent an indispensable and expanding component of modern transplantation. Through sophisticated critical care management, objective risk assessment tools, revolutionary ex vivo perfusion technologies, and thoughtful ethical stewardship, intensivists can transform marginal organs into life-saving grafts.

The intensivist's role extends beyond traditional resuscitation to encompass organ optimization, quality assessment, and contribution to complex risk-benefit analyses. As technologies evolve and experience accumulates, the boundary between "standard" and "extended" criteria will continue to shift, driven by the unwavering imperative to save lives languishing on transplant waiting lists.

The most profound contribution an intensivist can make may be recognizing that the "marginal" donor represents not a limitation, but an opportunity—an opportunity to expand life-saving transplantation to those who would otherwise die waiting.

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References

1. Hart A, et al. OPTN/SRTR 2019 Annual Data Report: Kidney. Am J Transplant. 2021;21(S2):21-137.

2. Merion RM, et al. Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA. 2005;294(21):2726-2733.

3. Metzger RA, et al. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3(S4):114-125.

4. Rao PS, et al. A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation. 2009;88(2):231-236.

5. Summers DM, et al. Kidney donation after circulatory death (DCD): state of the art. Kidney Int. 2015;88(2):241-249.

6. McCormack L, et al. Use of severely steatotic grafts in liver transplantation. Ann Surg. 2007;246(6):940-948.

7. Dutkowski P, et al. Are there better guidelines for allocation in liver transplantation? Ann Surg. 2011;254(5):745-754.

8. Khush KK, et al. Donor selection in the modern era. Ann Cardiothorac Surg. 2018;7(1):126-131.

9. Kransdorf EP, et al. Predicted heart mass is the optimal metric for size match in heart transplantation. J Heart Lung Transplant. 2019;38(2):156-165.

10. Orens JB, et al. International guidelines for the selection of lung transplant candidates. J Heart Lung Transplant. 2006;25(7):745-755.

11. Schaubel DE, et al. Survival benefit-based deceased-donor liver allocation. Am J Transplant. 2009;9(4p2):970-981.

12. Kotloff RM, et al. Management of the potential organ donor in the ICU. Crit Care Med. 2015;43(6):1291-1325.

13. Pennefather SH, et al. Haemodynamic goals in donor management. Transplant Rev. 2019;33(3):149-154.

14. Rosendale JD, et al. Hormonal resuscitation yields more transplanted hearts with improved early function. Transplantation. 2003;75(8):1336-1341.

15. Mascia L, et al. Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation. JAMA. 2010;304(23):2620-2627.

16. Levesque S, et al. Prospective evaluation of the Transplant Quebec Standardized Donor Management Protocol. Can J Anaesth. 2013;60(12):1178-1185.

17. Boffa C, et al. Acute kidney injury in deceased donors. Transplantation. 2020;104(6):1145-1156.

18. Heilman RL, et al. Increasing the use of kidneys from unconventional and high-risk deceased donors. Am J Transplant. 2016;16(11):3086-3092.

19. Fitzgerald RD, et al. DDAVP in the management of diabetes insipidus and platelet dysfunction in the organ donor. Anaesth Intensive Care. 1996;24(6):703-709.

20. Nasralla D, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50-56.

21. van Rijn R, et al. Hypothermic machine perfusion in liver transplantation. Curr Opin Organ Transplant. 2018;23(2):235-243.

22. Dutkowski P, et al. First comparison of hypothermic oxygenated perfusion versus static cold storage of human donation after cardiac death liver transplants. Ann Surg. 2015;262(5):764-771.

23. Ardehali A, et al. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II). Lancet. 2015;385(9987):2585-2591.

24. Dhital KK, et al. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death. Lancet. 2015;385(9987):2577-2584.

25. Moers C, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19.

26. Hessheimer AJ, et al. Normothermic regional perfusion in controlled donation after circulatory death. Transplantation. 2021;105(11):2371-2379.

27. Stewart DE, et al. Diagnosing the decades-long rise in the deceased donor kidney discard rate in the United States. Transplantation. 2017;101(3):575-587.

28. Goldberg DS, et al. Trial of transplantation of HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;376(24):2394-2395.

29. Durand CM, et al. HIV-1-positive kidney transplant candidates and HIV-1-positive donors. Curr Opin Organ Transplant. 2019;24(4):416-423.

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