Nitric oxide biomarkers and circulatory failure in critical illness: A cohort study

Arterial hypotension is frequently observed in critically ill patients. Nitric oxide (NO) is pivotal in vasodilation. We investigated the associations between NO-biomarkers (asymmetrical dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and homoarginine) and treatment with norepinephrine and plasma lactate on ICU days 1-3.

A prospective cohort study of 527 adult ICU patients with NO-biomarkers at admission. Associations with norepinephrine treatment were analyzed in logistic regressions on the first three days of ICU admission. Associations with the highest daily plasma lactate were analyzed with linear mixed models.

Increasing ADMA and arginine were associated with decreased norepinephrine treatment (ICU day 1: OR 0.36 pr 1 μmol/L ADMA, 95 % CI 0.17-0.78; p = 0.009, and OR 0.85 pr 10 μmol/L arginine; 95 % CI 0.79-0.92; p < 0.001). An increase in homoarginine of 1 μmol/L was associated with an increase in plasma lactate of 6 % (95 % CI -2 % to 15 %) from ICU days 1-2 and 4 % (95 % CI -4 % to 13 %) from ICU days 2-3. SDMA was not associated with either outcome.

Increased ADMA and arginine at admission are associated with decreased norepinephrine treatment on the first three days of ICU admission. Increased homoarginine concentrations are associated with increasing plasma lactate.