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Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest—Results from the Prospective, Observational COMMUNICATE Trial

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Medical Communication and Psychosomatic Medicine, University Hospital Basel, 4031 Basel, Switzerland
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Emergency Department, University Hospital Basel, 4031 Basel, Switzerland
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Division of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland
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Intensive Care Unit, University Hospital Basel, 4031 Basel, Switzerland
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Department of Neurology, University Hospital Basel, 4031 Basel, Switzerland
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Faculty of Medicine, University of Basel, 4031 Basel, Switzerland
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Division of Internal Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
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Institute of Laboratory Medicine, Kantonsspital Aarau, 5001 Aarau, Switzerland
*
Author to whom correspondence should be addressed.
Equally contributing first authors.
J. Clin. Med. 2020, 9(12), 3815; https://doi.org/10.3390/jcm9123815
Received: 9 October 2020 / Revised: 8 November 2020 / Accepted: 19 November 2020 / Published: 25 November 2020
(This article belongs to the Section Emergency Medicine)
(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. View Full-Text
Keywords: metabolomics; arginine; asymmetric dimethylarginine (ADMA); symmetric dimethylarginine (SDMA); arginine/ADMA ratio; cardiopulmonary resuscitation; cardiac arrest; prognosis; outcome; mortality metabolomics; arginine; asymmetric dimethylarginine (ADMA); symmetric dimethylarginine (SDMA); arginine/ADMA ratio; cardiopulmonary resuscitation; cardiac arrest; prognosis; outcome; mortality
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MDPI and ACS Style

Keller, A.; Becker, C.; Nienhaus, K.; Beck, K.; Vincent, A.; Sutter, R.; Tisljar, K.; Schuetz, P.; Bernasconi, L.; Neyer, P.; Pargger, H.; Marsch, S.; Hunziker, S. Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest—Results from the Prospective, Observational COMMUNICATE Trial. J. Clin. Med. 2020, 9, 3815. https://doi.org/10.3390/jcm9123815

AMA Style

Keller A, Becker C, Nienhaus K, Beck K, Vincent A, Sutter R, Tisljar K, Schuetz P, Bernasconi L, Neyer P, Pargger H, Marsch S, Hunziker S. Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest—Results from the Prospective, Observational COMMUNICATE Trial. Journal of Clinical Medicine. 2020; 9(12):3815. https://doi.org/10.3390/jcm9123815

Chicago/Turabian Style

Keller, Annalena; Becker, Christoph; Nienhaus, Katharina; Beck, Katharina; Vincent, Alessia; Sutter, Raoul; Tisljar, Kai; Schuetz, Philipp; Bernasconi, Luca; Neyer, Peter; Pargger, Hans; Marsch, Stephan; Hunziker, Sabina. 2020. "Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest—Results from the Prospective, Observational COMMUNICATE Trial" J. Clin. Med. 9, no. 12: 3815. https://doi.org/10.3390/jcm9123815

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