1. Weaning and De-escalation of Intensive Therapies

As graft function stabilizes following treatment for acute rejection, the focus shifts to methodically reducing intensive therapies. This gradual de-escalation is critical to balance ongoing rejection prevention with the need to mitigate ICU-related complications such as infection, delirium, and prolonged mechanical ventilation.

A. Immunosuppression Taper Protocols

The initial high-dose steroid pulse (e.g., methylprednisolone 500–1,000 mg IV daily for 3 days) is transitioned to an oral prednisone equivalent, typically starting at 1 mg/kg/day. This is followed by a slow taper, often reducing the dose by 0.1 mg/kg every 5 to 7 days until a maintenance dose of approximately 5 mg/day is reached. For calcineurin inhibitors like tacrolimus, trough targets are cautiously lowered by 2–4 ng/mL every two weeks, contingent on stable spirometry and no signs of infection. Close monitoring is essential during this period, including:

• Graft Surveillance: Frequent spirometry, donor-specific antibody (DSA) levels, and donor-derived cell-free DNA testing.
• Drug Levels: Tacrolimus troughs should be checked twice weekly during the taper, then weekly once at maintenance dose.
• Infection Markers: Regular surveillance for CMV via PCR and monitoring of inflammatory markers like procalcitonin.

B. Sedation and Analgesia Weaning

A structured approach to weaning sedation and analgesia, incorporating daily awakening trials, is crucial to reduce delirium and ICU-acquired weakness. The choice of agent and taper strategy depends on the drug’s pharmacology.

For analgesia, converting from IV opioids to enteral alternatives is a key step. For example, IV fentanyl can be transitioned to oral methadone by first calculating the 24-hour IV morphine equivalent dose and then converting to methadone at a 1:1.5 ratio. Multimodal adjuncts like acetaminophen and gabapentinoids should be used to facilitate opioid reduction. When using methadone, QTc interval monitoring is mandatory, and a bowel regimen is essential.

C. Ventilator Liberation

Daily assessment for readiness to wean from mechanical ventilation is standard practice. Once a patient meets readiness criteria, a spontaneous breathing trial (SBT) should be performed.

• Readiness Criteria: Hemodynamic stability (minimal vasopressors), FiO₂ ≤ 0.4, PEEP ≤ 8 cm H₂O, and adequate cough and mental status.
• SBT Protocol: A 30–120 minute trial on a T-piece or with minimal pressure support (≤ 8 cm H₂O). Success is determined by stable respiratory rate, adequate tidal volume, and a Rapid Shallow Breathing Index (RSBI) ≤ 105 breaths/min/L.
• Post-extubation Support: High-flow nasal cannula or noninvasive ventilation may be used to prevent reintubation in at-risk patients.

2. Conversion from IV to Enteral Medications

As gastrointestinal function returns, transitioning medications from intravenous to enteral routes is a critical step toward patient mobilization and discharge. This conversion requires careful consideration of drug bioavailability, formulation, and administration technique to ensure therapeutic equivalence.

A. Pharmacokinetic Considerations

Oral bioavailability can be highly variable. Tacrolimus bioavailability averages 25-30% but can range from 5% to over 90% between individuals. Mycophenolate mofetil is more predictable with ~94% bioavailability, but its absorption can be impaired by GI dysmotility. Therapeutic drug monitoring (TDM) is mandatory after any formulation change to ensure drug exposure remains within the target range.

B. Conversion Guidelines

The following table provides general guidance for common IV-to-enteral conversions in transplant recipients. Dosing must be individualized and confirmed with TDM.

3. Post-ICU Syndrome (PICS) Prevention

Post-ICU Syndrome (PICS) is a constellation of new or worsened impairments in physical, cognitive, and mental health that arise after critical illness. Patients recovering from severe rejection are at high risk due to prolonged mechanical ventilation, deep sedation, and high delirium burden. Proactive implementation of the ABCDEF bundle is the cornerstone of PICS prevention.

4. Medication Reconciliation and Discharge Planning

A safe transition from the ICU to the ward and ultimately to home hinges on meticulous medication reconciliation and patient education. The complexity of post-transplant regimens makes this process especially high-stakes.

A. Comprehensive Medication Review

Before discharge, a pharmacist-led review is essential to verify the doses, timing, and formulations of all medications. This includes immunosuppressants, prophylactic antimicrobials, PPIs, and antihypertensives. The goal is to identify and resolve any duplications, omissions, or discrepancies that may have arisen from ICU-initiated therapies.

B. Discharge Counseling

Effective patient and caregiver education is paramount to ensuring adherence and preventing post-discharge complications. Key strategies include:

• Teach-Back Method: Ask the patient or caregiver to explain the dosing schedule, storage requirements, and key signs of rejection in their own words.
• Written Materials: Provide clear, low-literacy written instructions, including a color-coded medication calendar.
• Adherence Aids: Recommend pillboxes and smartphone app reminders to help manage the complex regimen.

C. Coordination and Follow-Up

A warm handoff to the outpatient transplant coordinator, primary care physician, and any home health services is crucial. A post-discharge clinic visit should be scheduled within 7 days to check graft function and therapeutic drug levels. Any changes made to the medication regimen during hospitalization must be clearly communicated to all outpatient providers to ensure continuity of care.