1. ICU-Level Respiratory and Cardiovascular Support

Severe pulmonary GVHD can present as bronchiolitis obliterans or diffuse alveolar damage leading to hypoxemic respiratory failure; cardiovascular involvement may manifest as myocarditis or vasoplegia. Early, targeted support improves outcomes.

A. Indications for Invasive Mechanical Ventilation

• PaO₂/FiO₂ < 150 mm Hg on optimized noninvasive support
• Respiratory rate > 35 breaths/min or accessory muscle use
• Rising PaCO₂ with respiratory acidosis
• Signs of respiratory muscle fatigue (e.g., paradoxical breathing)

B. Lung-Protective Ventilator Strategy

• Tidal volume 6 mL/kg predicted body weight
• Plateau pressure < 30 cm H₂O
• PEEP per ARDSnet tables to maintain adequate oxygenation
• Prone positioning or recruitment maneuvers if PaO₂/FiO₂ remains < 100 mm Hg

C. Indications for Hemodynamic Support

• Mean Arterial Pressure (MAP) < 65 mm Hg after fluid resuscitation guided by dynamic indices (pulse pressure variation, stroke volume variation)
• Evidence of end-organ hypoperfusion (lactate > 2 mmol/L, oliguria)

D. Vasopressors and Inotropes

• Norepinephrine: First-line agent, titrated to maintain MAP ≥ 65 mm Hg.
• Dobutamine: Add at 2–10 mcg/kg/min if cardiac index is < 2.2 L/min/m² on monitoring.
• Utilize bedside echocardiography or pulse-contour analysis to tailor therapy.

2. Prevention of ICU-Related Complications

Immunosuppressed patients with GVHD are at a heightened risk for thromboembolism, stress ulcers, and hospital-acquired infections. A structured approach to prophylaxis and strict infection control are critical components of their ICU care.

3. Management of Immunosuppressive Toxicities

Calcineurin inhibitors (CNIs), steroids, and antiproliferative agents are cornerstones of GVHD therapy but carry significant risks of nephrotoxicity, neurotoxicity, and cytopenias. Early detection, vigilant monitoring, and prompt dose adjustment are essential to mitigate harm.

4. Nutritional and Symptom Support

GI GVHD and treatment-related mucositis severely impair oral intake. Proactive nutritional support and aggressive symptom control are vital to support healing, maintain gut integrity, and reduce complications.

A. Enteral vs. Parenteral Nutrition

• Enteral Nutrition (EN): Preferred method. Initiate trophic feeds (10–20 mL/h) early unless contraindications exist (e.g., ileus, severe mucositis, shock).
• Parenteral Nutrition (PN): Initiate if EN meets < 60% of energy needs for ≥ 7 days.
• Monitoring: Monitor electrolytes, liver function, and glucose closely. Advance calories gradually to prevent refeeding syndrome.

B. GI Symptom Management

• Mucositis: Sucralfate 1 g four times daily; 0.5% viscous lidocaine rinse.
• Pain: Scheduled acetaminophen; opioids as needed (e.g., hydromorphone 0.2–0.5 mg IV q4h prn).
• Diarrhea: Loperamide (initial 4 mg, then 2 mg after each loose stool; max 16 mg/day).
• Nausea: 5-HT₃ antagonists or NK1-receptor antagonists per institutional protocol.

5. Multidisciplinary Goals-of-Care

The use of high-risk or experimental interventions in severe GVHD demands clear, patient-centered discussions and a robust ethical framework for decision-making.

A. Ethical Framework

• Weigh the anticipated benefits and burdens of intensive or investigational therapies.
• Apply the core principles of autonomy, beneficence, nonmaleficence, and justice in all decisions.

B. Communication Strategies

• Schedule regular, interdisciplinary family meetings, using structured communication approaches (e.g., SPIKES).
• Clearly document goals of care, code status, and advance directives in the electronic medical record.

C. Palliative Care Integration

• Engage the palliative care team early for expert symptom management and psychosocial support for both the patient and family.
• Facilitate a smooth transition to hospice care when curative or life-prolonging intent is no longer aligned with patient goals.