**2.4.4 Infections**

*Infections* occur in ALF from functional immunosuppression. Patients are susceptible to overwhelming bacterial and fungal sepsis, although clinical signs of infection may be absent. Empiric antibacterial and antifungal therapy should be considered in the setting of advanced hepatic encephalopathy, shock, or for patients listed for transplantation. Associated sepsis and septic shock are managed with broad-spectrum antibiotics, vasoactive agent support and high-dose corticosteroids.

### **2.4.5 Pulmonary complications**

*Respiratory disturbances,* including acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), are frequent manifestations of ALF. In the setting of ALI and ARDS, lungprotective strategies with low tidal volume (6 cc/kg ideal body weight) ventilator settings and mild permissive hypercapnea are recommended. Hypoxemic respiratory failure portends a poor prognosis and is treated supportively. Severe hypercapnea, bronchoscopy, and patient-ventilator asynchrony can exacerbate intracranial hypertension; titration of the set respiratory rate to compensate for hypercapnea, as well as adequate sedation and analgesia to improve synchrony, are imperative. Neuromuscular-blocking paralytic agents may be necessary if patient-ventilator asynchrony persists despite adequate sedation.

#### **2.4.6 Metabolic derangements**

*Metabolic derangements* result both from impaired hepatic metabolic function and resulting multi-organ failure. Consequences include lactic acidosis and disturbances in arterial pH, glucose, and electrolytes. Hypoglycemia results from impaired gluconeogenesis and glycogenolysis, and is managed via dextrose infusion and frequent glucose monitoring. Electrolyte disturbances include hyponatremia, hypokalemia, hypomagnesemia, and hypophosphatemia, and should be corrected when recognized. However, the appearance of hypophosphatemia may indicate a favorable prognosis due to intracellular phosphorus consumption and hepatic regeneration. Finally, the high metabolic demands in ALF create a generalized catabolic state with resultant high nutritional needs. Enteric nutrition is recommended over parental routes to reduce gastrointestinal bacterial translocation and bleeding from stress ulceration.
