Plasma Exchange in Acute Liver Failure
Plasma exchange should be used in critically ill acute liver failure patients who develop hyperammonemia (ammonia >150 μmol/L), as this represents the most current guideline-based recommendation, though the evidence quality remains limited. 1
Primary Indication: Hyperammonemia
The 2023 Critical Care Medicine guidelines provide a conditional recommendation for PLEX in ALF patients with hyperammonemia, specifically defined as ammonia levels >150 μmol/L. 1 This recommendation is based on the pathophysiology that hyperammonemia independently predicts both intracranial hypertension and hepatic encephalopathy in ALF patients, with 55% of patients developing intracranial hypertension when ammonia exceeds 200 μmol/L. 1
The rationale is that ALF patients, unlike those with acute-on-chronic liver failure, are not preconditioned to tolerate hyperammonemia and are therefore more vulnerable to cerebral edema and intracranial hypertension. 1
Evidence for Survival Benefit
Recent meta-analyses demonstrate significant mortality reduction with PLEX:
- At ≤60 days: 36% relative risk reduction (RR 0.64; 95% CI 0.51-0.80) 2
- At 90 days: 33% relative risk reduction (RR 0.67; 95% CI 0.50-0.90) 2
- The survival benefit appears particularly pronounced in single-etiology ALF studies (RR 0.53; 95% CI 0.37-0.74) 2
Specific Etiologies Where PLEX Should Be Considered
Wilson Disease
PLEX (or plasmapheresis) should be initiated immediately in Wilson disease-related ALF as a bridge to transplantation, as this presentation is uniformly fatal without transplant. 1 Treatment should include albumin dialysis, continuous hemofiltration, or plasma exchange to acutely lower serum copper and limit hemolysis. 1 Penicillamine should NOT be initiated in the acute setting due to hypersensitivity risk. 1
Acute Fatty Liver of Pregnancy
Studies including this etiology show pronounced survival benefit with PLEX (included in the single-etiology meta-analysis with RR 0.53). 2 However, expeditious delivery remains the primary treatment. 1
Rodenticidal Hepatotoxicity
This etiology demonstrates significant benefit from PLEX in cohort studies. 2
Important Caveats and Limitations
The guideline recommendation is conditional with low-quality evidence, meaning clinical circumstances and resource availability should heavily influence the decision. 1 The conditional nature reflects that while desirable effects probably outweigh undesirable effects, confidence is limited by evidence quality. 1
Contradictory Real-World Evidence
A 2025 UK multicentre study of 378 ALF patients found that while PLEX improved hemodynamic parameters (including significant reduction in noradrenaline requirements from 0.35 to 0.16 μg/kg/min), it did not improve overall survival (51.4% vs 62.6%, p=0.12) or transplant-free survival (42.6% vs 53.1%, p=0.24) compared to standard medical therapy. 3 This real-world data contradicts the meta-analysis findings and suggests the survival benefit seen in published literature may not translate to routine clinical practice. 3
Volume and Safety Considerations
- Survival benefit appears independent of plasma exchange volume utilized 2
- PLEX is generally safe, with the most common adverse effects being skin rash and allergic reactions (14% incidence) 4
- No major side effects directly attributable to PLEX have been reported in most studies 2
Clinical Algorithm
- Identify ALF patients with ammonia >150 μmol/L (threshold for hyperammonemia) 1
- Consider PLEX when available as adjunctive therapy to standard medical management 1
- Initiate immediately for Wilson disease regardless of ammonia level, as bridge to transplant 1
- Ensure simultaneous listing for liver transplantation in appropriate candidates, as PLEX is a bridge therapy, not definitive treatment 1
- Weigh resource availability and expertise given the conditional nature of the recommendation 1
What NOT to Use
Traditional therapies for chronic liver failure such as lactulose and rifaximin have not demonstrated benefit in ALF and should not be relied upon. 1