Early serum ammonia variation in critically ill patients with cirrhosis: A multicentre cohort study

Background: Serum ammonia variation in critically ill patients with cirrhosis has been poorly studied. Aim: To describe and assess the impact of serum ammonia variation in these patients' outcomes. Methods: We studied patients ≥18 years old admitted to the intensive care units (ICUs) at University of Alberta Hospital (Edmonton, Canada) and Curry Cabral Hospital (Lisbon, Portugal; derivation cohort, n = 492) and Northwestern University Hospital (Chicago, USA; validation cohort, n = 600) between January 2010 and December 2021. Primary exposure was ICU days 1–3 serum ammonia. Primary endpoint was all-cause hospital mortality. Results: In the derivation cohort, 330 (67.1%) patients were male and median (IQR) age was 57 (50–63) years. On ICU day 1, median ammonia was higher in patients with grade 3/4 hepatic encephalopathy (HE) than those with grade 2 HE or grade 0/1 HE (112 vs. 88 vs. 77 μmoL/L, respectively; p < 0.001). Furthermore, medium ammonia was higher in hospital non-survivors than survivors (99 vs. 86 μmol/L; p < 0.030). Following adjustment for significant confounders (age, HE, vasopressor use and renal replacement therapy delivery), higher ICU day 2 ammonia was independently associated with higher hospital mortality (adjusted OR per each 10 μmoL/L increment [95% CI] = 1.11 [1.01–1.21]; p = 0.024). In the validation cohort, this model with serial ammonia (ICU days 1 and 3) predicted hospital mortality with reasonably good discrimination (c-statistic = 0.73) and calibration (R² = 0.19 and Brier score = 0.17). Conclusions: Among patients with cirrhosis in the ICU, early serum ammonia variation was independently associated with hospital mortality. In this context, serial serum ammonia may have prognostic value.