Abstract
(1) Background: In patients with shock, the L-arginine nitric oxide pathway is activated, causing an elevation of nitric oxide, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels. Whether these metabolites provide prognostic information in patients after out-of-hospital cardiac arrest (OHCA) remains unclear. (2) Methods: We prospectively included OHCA patients, recorded clinical parameters and measured plasma ADMA, SDMA and Arginine levels by liquid chromatography tandem mass spectrometry (LC-MS). The primary endpoint was 90-day mortality. (3) Results: Of 263 patients, 130 (49.4%) died within 90 days after OHCA. Compared to survivors, non-survivors had significantly higher levels of ADMA and lower Arginine and Arginine/ADMA ratios in univariable regression analyses. Arginine levels and Arginine/ADMA ratio were significantly associated with 90-day mortality (OR 0.51 (95%CI 0.34 to 0.76), p < 0.01 and OR 0.40 (95%CI 0.26 to 0.61), p < 0.001, respectively). These associations remained significant in several multivariable models. Arginine/ADMA ratio had the highest predictive value with an area under the curve (AUC) of 0.67 for 90-day mortality. Results for secondary outcomes were similar with significant associations with in-hospital mortality and neurological outcome. (4) Conclusion: Arginine and Arginine/ADMA ratio were independently associated with 90-day mortality and other adverse outcomes in patients after OHCA. Whether therapeutic modification of the L-arginine-nitric oxide pathway has the potential to improve outcome should be evaluated.
Highlights
Cardiac arrest is a critical condition, associated with a mortality rate of almost 90% [1]
Arginine serves as the only source for nitric oxide (NO), which is synthesized through nitric oxide synthase (NOS) [4,5]
Clinical and laboratory shock markers were significantly higher in non-survivors
Summary
Cardiac arrest is a critical condition, associated with a mortality rate of almost 90% [1]. OHCA leads to severe cardiogenic shock with activation of several biochemical pathways. Recent studies have shown Arginine and its metabolites from the NO pathway to be associated with outcome among different diseases, such as endothelial dysfunction (e.g., hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis and renal failure) [10,11,12,13,14,15], cardiovascular disease [16,17,18,19], conditions of the respiratory system (e.g., asthma, pneumonia and chronic obstructive pulmonary disease [COPD]) [20,21], critical illness [22,23,24], shock [25] and multiple organ failure in sepsis [26]
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