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 end-point 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 mu moL/L, respectively; p < 0.001). Furthermore, medium ammonia was higher in hospital non-survivors than survivors (99 vs. 86 mu mol/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 mu moL/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 (R-2 = 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.

Automated summary

This study aimed to describe and assess the impact of serum ammonia variation on the outcomes of critically ill patients with cirrhosis. It was found that higher serum ammonia levels in the early stage of ICU admission were associated with higher hospital mortality. Therefore, the variation in serum ammonia may have prognostic value.