Use of Lactulose to Treat Hyperammonemia in ICU Patients Without Chronic Liver Disease or Significant Hepatocellular Injury

Objectives: To review ICU patients with elevated ammonia without a clear hepatic etiology, to compare outcomes between those who received lactulose and those who did not. Design: Retrospective observational study. Setting: Medical, surgical, and subspecialty intensive care units at Wake Forest Baptist Medical Center, Winston-Salem, North Carolina between December 2012 and August 2016. Patients: Adults with ammonia levels above 50 μmol/L, excluding those with known chronic liver disease, inborn error of metabolism, active use of valproic acid, total bilirubin ≥ 2 μmol/L, or alanine aminotransferase ≥ 100 units/L. Interventions: Comparison in ICU length of stay (LOS), hospital LOS, in-hospital mortality, and mortality at 30 and 90 days. Measurements and Main Results: Criteria for inclusion were met in 103 cases. Mean ammonia level was 75 μmol/L, with undetermined etiology in the majority of subjects. Lactulose was given in 48 cases (46.6%), with a median of 9.5 doses given. There were no significant differences in outcomes between the lactulose and non-lactulose groups. Among subjects with multiple data points, lactulose did not have a dose-dependent effect on ammonia level, and was not associated with faster ammonia normalization compared to non-lactulose. When analyzed separately, patients with moderate hyperammonemia (60-99 μmol/L) who received lactulose had longer hospital and ICU length of stay compared to non-lactulose (417.8 hours vs. 208.4 hours, P = 0.003, and 229.2 hours vs. 104.7 hours, P = 0.025; respectively), though confounders were present. Conclusions: Routine use of lactulose to treat mild to moderate hyperammonemia in this patient population was not associated with improved outcomes.