Copeptin as a marker of outcome after cardiac arrest: a sub-study of the TTM trial

Joachim Düring,Homa Rafi Nikoukhah,Johan Undén,Niklas Nielsen,Michael Jaeger Wanscher,Janneke Horn,Michael Kuiper,Josef Dankiewicz,Hans Friberg,Matt Wise,Pascal Stammet,Jesper Kjaergaard,Christian Hassager,Martin Annborn,Yvan Devaux,Tobias Cronberg

doi:10.1186/s13054-020-02904-8

Abstract

BackgroundArginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest.MethodsSerial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score.ResultsSix hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06–1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01–1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02–1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12–0.27], p < 0.001.ConclusionCopeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure.Trial registrationClinical Trials, NCT01020916. Registered November 26, 2009.

Highlights

Hypoxic ischemic encephalopathy (HIE) is the major determinant of outcome after out-of-hospital cardiac arrest (OHCA) [1]
Death is biphasic after OHCA with early death (1–3 days) to a large degree related to circulatory failure, while later death (> 3 days) is mainly related to withdrawal of life-sustaining therapy (WLST) due to assumed severe HIE [2]
The incidence of death was independently associated with log2transformed copeptin, hazard ratio (HR) 1.17 [1.06– 1.28], p = 0.001(Fig. 3); for samples at 24 h, significance was lost at 48 h, p = 0.471, while 72-h samples were trending towards significance, HR 1.11 [1.00–1.23], p = 0.054

Summary

Introduction

Hypoxic ischemic encephalopathy (HIE) is the major determinant of outcome after out-of-hospital cardiac arrest (OHCA) [1]. Existing prognostication models are targeted at neurologic functional outcome. Patients with a presumed high risk of circulatory-related death may benefit from extended hemodynamic monitoring and support. This is relevant for patients without signs of severe HIE and a potential good long-term outcome. A surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest

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Conclusion