1. Respiratory Support and Ventilation

Advanced hepatic encephalopathy in DILI-induced acute liver failure (ALF) often mandates airway protection and controlled ventilation to prevent aspiration, manage intracranial pressure (ICP), and minimize ventilator-induced lung injury (VILI).

Indications for Intubation

• Grade III–IV encephalopathy (Glasgow Coma Scale ≤8) with loss of airway reflexes
• Significant risk of aspiration or evidence of elevated ICP

Ventilator Strategy

• Tidal Volume: 4–6 mL/kg ideal body weight (lung-protective strategy).
• Permissive Hypercapnia: Target PaCO₂ of 40–55 mm Hg if ICP is monitored; avoid aggressive hyperventilation (PaCO₂ <30 mm Hg) which can cause cerebral vasoconstriction.
• PEEP: Start at 5–8 cm H₂O, balancing oxygenation needs with effects on venous return and ICP.
• Plateau Pressure: Maintain <30 cm H₂O to prevent barotrauma.

Sedation and Monitoring

Use short-acting sedatives like propofol or fentanyl to facilitate daily sedation interruptions and neurologic checks. Neuromuscular blockade may be considered for refractory ICP spikes or severe patient-ventilator asynchrony.

2. Hemodynamic Support

Hypotension in ALF is common, driven by systemic vasodilation, capillary leak, and relative intravascular volume depletion. The goal is to maintain mean arterial pressure (MAP) for adequate organ perfusion while carefully managing fluid balance to prevent worsening cerebral and pulmonary edema.

Vasopressor Therapy

• Indication: MAP <65 mm Hg despite initial fluid resuscitation (20–30 mL/kg isotonic crystalloid) or signs of hypoperfusion (e.g., rising lactate).
• First-Line Agent: Norepinephrine, started at 0.05–0.1 mcg/kg/min and titrated to a target MAP of 65–75 mm Hg.
• Adjunct Agent: Vasopressin at a fixed dose of 0.03 units/min can be added to reduce the required norepinephrine dose.
• Monitoring: An invasive arterial line is essential for continuous blood pressure monitoring. Monitor lactate clearance (target ≥10%/h) and urine output (target ≥0.5 mL/kg/h) as markers of improved perfusion.

3. Pharmacotherapy for Complication Prevention

Critically ill patients with DILI require prophylactic therapies to prevent common ICU complications, including venous thromboembolism (VTE) and stress-related mucosal bleeding.

A. VTE Prophylaxis

Despite coagulopathy (elevated INR), patients with ALF are often in a prothrombotic state due to deficiencies in anticoagulant proteins and endothelial dysfunction. Pharmacologic prophylaxis is recommended unless significant contraindications exist.

B. Stress-Related Mucosal Bleeding Prophylaxis

Prophylaxis is indicated for patients at high risk of stress ulcers, such as those on mechanical ventilation or with profound coagulopathy.

4. Infection Control and Iatrogenic Organ Dysfunction

Patients with ALF have significant immune dysregulation, placing them at high risk for infection. Furthermore, the use of invasive devices and necessary medications can lead to iatrogenic complications. A proactive approach is essential.

Key Strategies

• Antibiotic Stewardship: Use empiric broad-spectrum antibiotics only for clear signs of septic shock. De-escalate therapy within 48–72 hours based on culture results.
• Device Bundles: Strictly adhere to central line and ventilator-associated pneumonia (VAP) bundles, including daily review of line necessity, chlorhexidine care, and head-of-bed elevation.
• Medication Review: Perform a daily review of all medications to identify and discontinue or dose-adjust potentially nephrotoxic or hepatotoxic agents. Monitor drug levels (e.g., vancomycin troughs) closely.
• VILI Prevention: Consistently apply a lung-protective ventilation strategy (low tidal volume, plateau pressure <30 cm H₂O) to all ventilated patients.

5. Multidisciplinary Goals-of-Care Conversations

When DILI-ALF is severe or refractory to initial supportive care, structured, team-based discussions are critical to align treatment with patient values and establish realistic goals, including evaluation for liver transplantation.

Triggers for a Formal Meeting

• Progressive ALF despite maximal support (e.g., MELD score >30, worsening encephalopathy).
• Need to formally evaluate for liver transplantation candidacy.
• Consideration of extracorporeal support (e.g., MARS, Prometheus).

Communication and Team Approach

The core team should include critical care, hepatology, transplant surgery, palliative care, nursing, and social work. Regular family meetings (every 48–72 hours) should be scheduled to provide consistent updates, discuss prognosis using objective scores (like MELD), and clarify the patient’s wishes and advance directives. Early involvement of palliative care can significantly reduce moral distress for both the family and the clinical team and facilitate shared decision-making.