The following is a summary of “Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study,” published in the August 2024 issue of Critical Care by Mortensen et al.

Patients with critical care illness require an optimal balance between macro and micro-circulation, which is necessary for optimal organ perfusion. Nitric oxide (NO), a regulator of vascular hemostasis and tone, is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NO substrates arginine and homoarginine.

Researchers conducted a retrospective study to investigate the changes in plasma concentrations of ADMA, SDMA, arginine, and homoarginine during 1-5 days of intensive care unit (ICU) admission and to assess the association between the change in concentration for days 1–3 and 30-day all-cause mortality.

They measured ADMA, SDMA, arginine, and homoarginine (NO-biomarkers) on days 1-5 of patients with critical care from the ICU at Copenhagen University Hospital, North Zealand. The changes were determined in NO-biomarkers for days 1–5 with linear mixed models, and subsequently, how the changes in NO-biomarkers for days 1–3, were associated with 30-day all-cause mortality. Post-hoc association between plasma concentration at admission and 30-day all-cause mortality was also investigated. 

The results showed that 577 patients had plasma samples from days 1–5. Plasma concentrations of ADMA and arginine increased from days 1–5, while SDMA concentrations rose from days 1–2 and then declined from days 2–5. No change in homoarginine concentrations was observed from days 1–3, but there was a slight increase from days 3–5. Of the 512 patients alive 3 days after ICU admission, a 2fold increase in ADMA concentration from days 1–3 was associated with decreased mortality in multivariate analysis (HR 0.45; 95% CI 0.21–0.98; P=0.046). Increases in SDMA, arginine, or homoarginine were not linked to mortality. Post-hoc analysis revealed that a 2fold increase in ADMA or SDMA concentrations at admission was associated with higher mortality (HR 1.78; 95% CI 1.24–2.57; P=0.0025, and HR 1.41; 95% CI 1.05–1.90; P=0.024, respectively).

They concluded that while increasing ADMA concentrations on days 1–3 are inversely associated with mortality, admission concentrations of ADMA and SDMA are more promising predictors and potential therapeutic targets in patients admitted to ICU.

Source: annalsofintensivecare.springeropen.com/articles/10.1186/s13613-024-01362-7