25.1 Solid Organ Transplant Recipients & Deceased Donor Management
Key Takeaways
Azoles, macrolides, and non-dihydropyridine calcium-channel blockers raise calcineurin inhibitor levels sharply, while rifampin and phenytoin lower them, so levels must be rechecked whenever such drugs change.
Hyperacute hepatic artery thrombosis after liver transplantation presents with rapidly rising transaminases and is diagnosed with urgent Doppler ultrasound.
Primary graft dysfunction after lung transplantation presents within 72 hours as diffuse infiltrates with hypoxemia and is managed with lung-protective ventilation and ECMO when needed.
Donor management after brain death targets a mean arterial pressure of at least 60 to 65 mmHg with vasopressin for diabetes insipidus and hormone replacement including levothyroxine and methylprednisolone.
After withdrawal in donation after circulatory death, death is declared following a 2 to 5 minute observation period of absent circulation, and procurement begins only after that interval.
Immunosuppression: What Drives ICU Problems
| Agent | Key toxicity | Interactions |
|---|---|---|
| Tacrolimus and cyclosporine (calcineurin inhibitors) | Nephrotoxicity, hypertension, hyperkalemia with a low bicarbonate, hypomagnesemia, tremor, seizures, PRES, thrombotic microangiopathy, diabetes | Raised by azoles, macrolides, diltiazem and verapamil, protease inhibitors, grapefruit; lowered by rifampin, phenytoin, carbamazepine |
| Mycophenolate | Myelosuppression, diarrhea | Reduced by antacids and cholestyramine |
| Azathioprine | Myelosuppression | Allopurinol and febuxostat cause life-threatening marrow suppression |
| Sirolimus and everolimus | Impaired wound healing, pneumonitis, proteinuria, mouth ulcers, thrombocytopenia | CYP3A4 interactions |
| Corticosteroids | Hyperglycemia, infection, myopathy, psychiatric effects | Adrenal suppression: stress dosing |
| Belatacept | Post-transplant lymphoproliferative disease in EBV-naive patients | |
| Antithymocyte globulin and alemtuzumab | Cytokine release, prolonged lymphopenia |
Rule: whenever a critically ill transplant recipient starts or stops an azole, macrolide, rifamycin, or anticonvulsant, recheck the calcineurin inhibitor level within a day or two. Never stop immunosuppression abruptly without transplant team input, even in severe sepsis; it is usually reduced rather than stopped.
Graft-Specific Emergencies
| Organ | Early complications | Clues and management |
|---|---|---|
| Kidney | Renal artery or vein thrombosis, urine leak, ureteral obstruction, lymphocele, acute rejection, calcineurin toxicity, BK nephropathy | Sudden anuria with graft tenderness suggests vascular thrombosis: urgent Doppler ultrasound and surgical exploration. Biopsy distinguishes rejection from toxicity |
| Liver | Hepatic artery thrombosis (rapidly rising transaminases, needing urgent Doppler and revascularization or retransplantation), portal vein thrombosis, biliary leak or stricture, primary nonfunction, small-for-size syndrome | Postoperative coagulopathy, hypoglycemia, and encephalopathy point to graft failure |
| Lung | Primary graft dysfunction within 72 hours (diffuse infiltrates with hypoxemia, graded like ARDS), airway anastomotic dehiscence, phrenic nerve injury, pleural complications, hyperacute and acute rejection, CMV and Aspergillus infection | Lung-protective ventilation, conservative fluids, ECMO for severe dysfunction; bronchoscopy for anastomotic assessment and for diagnosis of rejection |
| Heart | Right ventricular failure from donor-recipient mismatch or pulmonary hypertension, bradyarrhythmia (denervated heart), acute rejection, tamponade | The denervated heart does not respond to atropine: use isoproterenol, dobutamine, or pacing; inhaled pulmonary vasodilators and inotropes for RV failure |
| Pancreas and intestine | Graft thrombosis, anastomotic leak, rejection with high rejection rates for intestine | Monitor glucose for pancreas graft function; endoscopy for intestinal rejection |
Distinguishing rejection from infection is the central ICU problem: both cause fever and graft dysfunction, and the treatments are opposite. Biopsy and pathogen testing (including CMV PCR, respiratory viral panels, galactomannan, and beta-D-glucan) should be pursued before committing to escalating immunosuppression.
Post-Transplant Infection and Malignancy
- Follow the timeline framework (see the immunocompromised host section): nosocomial in the first month, opportunistic from 1 to 6 months, and community-acquired beyond 6 months, modified by prophylaxis and net immunosuppression.
- Prophylaxis typically includes trimethoprim-sulfamethoxazole for Pneumocystis, valganciclovir for CMV in at-risk pairings, and antifungal prophylaxis in lung and liver recipients.
- Post-transplant lymphoproliferative disease: EBV-driven, presenting with fever, adenopathy, and organ masses; reduce immunosuppression and give rituximab-based therapy.
- Hemophagocytic lymphohistiocytosis and thrombotic microangiopathy are immunosuppression-associated syndromes that mimic sepsis.
Deceased Donor Management After Brain Death
Once death by neurologic criteria is declared and authorization obtained, the goal shifts to organ preservation. The organ procurement organization directs management, often with "rule of 100s" style targets.
| Problem | Target and therapy |
|---|---|
| Hemodynamics | Mean arterial pressure at least 60 to 65 mmHg; volume repletion first, then vasopressin (which also treats diabetes insipidus) and norepinephrine; avoid excessive catecholamines, which harm the heart graft |
| Diabetes insipidus | Occurs in most donors: desmopressin or a vasopressin infusion, with free water replacement; keep sodium below about 155 mEq/L to protect liver grafts |
| Hormone replacement | Methylprednisolone (which improves lung and other graft outcomes), levothyroxine for hemodynamic instability, insulin for glucose 140 to 180 mg/dL |
| Lungs | Lung-protective ventilation with PEEP, recruitment, head elevation, aspiration prevention, and bronchoscopy; a conservative fluid strategy |
| Temperature | Normothermia; poikilothermia is common. Therapeutic mild hypothermia (34 to 35 °C) in donors reduced delayed graft function in kidney recipients |
| Coagulopathy and anemia | Transfuse to maintain oxygen delivery; correct coagulopathy for procurement |
| Monitoring | Arterial line, central access, echocardiography for cardiac assessment, serial laboratory tests |
Family support and clear separation of the clinical team from the donation request remain essential (see the ethics section).
Donation After Circulatory Death (DCD)
- Setting: a patient with devastating, non-survivable illness who does not meet neurologic criteria for death, whose surrogate has independently decided to withdraw life-sustaining treatment.
- Process:
- The decision to withdraw is made first and independently of donation.
- Withdrawal occurs in a setting (operating room or ICU) that allows timely procurement, with comfort-focused care provided throughout.
- After circulation ceases, a hands-off observation period of 2 to 5 minutes (program-specific) elapses before death is declared. Procurement begins only afterward.
- If death does not occur within a predefined window (commonly 60 to 120 minutes), donation is cancelled and the patient continues to receive comfort care.
- Premortem interventions (such as heparin or cannula placement) require consent and are governed by local policy.
- Normothermic regional perfusion (NRP) restores circulation to abdominal or thoracoabdominal organs after death is declared, with the cerebral circulation excluded by aortic arch vessel occlusion or clamping. It improves graft function, and the ethical debate centers on whether restoring circulation is consistent with the permanence standard of death; practice and policy vary by jurisdiction and institution.
- Machine perfusion (hypothermic and normothermic ex situ) is increasingly used to assess and improve marginal grafts, including after DCD.
A 54-year-old kidney transplant recipient on tacrolimus is admitted with invasive aspergillosis and started on voriconazole. Three days later he has tremor, a creatinine rise from 1.2 to 2.4 mg/dL, potassium of 5.9 mEq/L, and magnesium of 1.1 mg/dL. What is the most likely explanation?
Acute rejection requiring pulse corticosteroids
Voriconazole inhibition of CYP3A4 raising the tacrolimus level
Tacrolimus underexposure causing antibody-mediated injury
Aspergillus invasion of the renal allograft
A 62-year-old woman is 36 hours after bilateral lung transplantation. She has diffuse bilateral infiltrates, a PaO2/FiO2 of 120, normal left ventricular function, a pulmonary artery wedge pressure of 10 mmHg, and negative cultures and bronchoscopy. Which diagnosis and management are correct?
Hyperacute rejection requiring plasma exchange and immediate retransplantation
Cardiogenic pulmonary edema requiring aggressive diuresis and inotropes
Primary graft dysfunction managed with lung-protective ventilation, conservative fluids, and ECMO if severe
Cytomegalovirus pneumonitis requiring intravenous ganciclovir
A family has independently decided to withdraw life-sustaining treatment from a patient with devastating brain injury who does not meet criteria for death by neurologic criteria, and has authorized donation after circulatory death. Which statement about the process is correct?
Organ procurement may begin immediately when the arterial line shows no pulsatility
Death is declared after a hands-off observation period of 2 to 5 minutes of absent circulation, and procurement begins only then
The patient must be given vasopressors during withdrawal to preserve organ perfusion
If the patient does not arrest within 2 hours, life-sustaining treatment must be resumed and donation continues
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