1. Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock
- Author
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Damian R. Handisides, George F. Tidmarsh, Laurence W. Busse, Harold M. Szerlip, Paul J Young, Marlies Ostermann, Shane W. English, Richard G. Wunderink, Lakhmir S. Chawla, Adam M. Deane, Rinaldo Bellomo, Timothy E Albertson, Michael T. McCurdy, and Ashish Khanna
- Subjects
Male ,medicine.medical_specialty ,Urology ,Vasodilatory shock ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Cardiovascular ,Medical and Health Sciences ,03 medical and health sciences ,0302 clinical medicine ,Catecholamines ,Interquartile range ,Clinical Research ,Sepsis ,Renin–angiotensin system ,medicine ,Humans ,ACE ,ACE dysfunction ,Proportional hazards model ,business.industry ,Septic shock ,Research ,Angiotensin II ,Hazard ratio ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Evaluation of treatments and therapeutic interventions ,030208 emergency & critical care medicine ,Shock ,lcsh:RC86-88.9 ,medicine.disease ,Emergency & Critical Care Medicine ,Confidence interval ,Shock (circulatory) ,6.1 Pharmaceuticals ,Female ,medicine.symptom ,Angiotensin I ,business - Abstract
Background In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Methods We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. Results Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls; P P P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels (P P P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P P = 0.003). In the placebo group, a baseline ANG I/II ratio P = 0.01) on unadjusted analyses. Conclusions Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. Trial registration ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.
- Published
- 2020