Activation of the kynurenine pathway predicts mortality and neurological outcome in cardiac arrest patients: A validation study

Nina Loretz; Christoph Becker; Seraina Hochstrasser; Kerstin Metzger; Katharina Beck; Jonas Mueller; Sebastian Gross; Alessia Vincent; Simon A Amacher; Raoul Sutter; Kai Tisljar; Philipp Schuetz; Luca Bernasconi; Peter Neyer; Hans Pargger; Stephan Marsch; Sabina Hunziker

doi:10.1016/j.jcrc.2021.09.025

Activation of the kynurenine pathway predicts mortality and neurological outcome in cardiac arrest patients: A validation study

J Crit Care. 2022 Feb:67:57-65. doi: 10.1016/j.jcrc.2021.09.025. Epub 2021 Oct 18.

Authors

Nina Loretz¹, Christoph Becker², Seraina Hochstrasser³, Kerstin Metzger⁴, Katharina Beck⁵, Jonas Mueller⁶, Sebastian Gross⁷, Alessia Vincent⁸, Simon A Amacher⁹, Raoul Sutter¹⁰, Kai Tisljar¹¹, Philipp Schuetz¹², Luca Bernasconi¹³, Peter Neyer¹⁴, Hans Pargger¹⁵, Stephan Marsch¹⁶, Sabina Hunziker¹⁷

Affiliations

¹ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
² Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland; Emergency Department, University Hospital Basel, Petersgraben 2, 4051 Basel, Switzerland. Electronic address: [email protected].
³ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁴ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁵ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁶ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁷ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁸ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland. Electronic address: [email protected].
⁹ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland; Intensive Care Unit, University Hospital Basel, Petersgraben 4, 4051 Basel, Switzerland. Electronic address: [email protected].
¹⁰ Intensive Care Unit, University Hospital Basel, Petersgraben 4, 4051 Basel, Switzerland; Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: [email protected].
¹¹ Intensive Care Unit, University Hospital Basel, Petersgraben 4, 4051 Basel, Switzerland. Electronic address: [email protected].
¹² Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland; Division of Internal Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland. Electronic address: [email protected].
¹³ Institute of Laboratory Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland. Electronic address: [email protected].
¹⁴ Institute of Laboratory Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland. Electronic address: [email protected].
¹⁵ Intensive Care Unit, University Hospital Basel, Petersgraben 4, 4051 Basel, Switzerland; Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: [email protected].
¹⁶ Intensive Care Unit, University Hospital Basel, Petersgraben 4, 4051 Basel, Switzerland; Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: [email protected].
¹⁷ Department of Medical Communication and Psychosomatic Medicine, University Hospital Basel, Klingelbergstrasse 23, 4056 Basel, Switzerland; Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: [email protected].

PMID: 34673332
DOI: 10.1016/j.jcrc.2021.09.025

Abstract

Purpose: Activation of the kynurenine pathway (KP) has been shown to predict outcome in cardiac arrest (CA) patients. We validated these findings in a Swiss cohort.

Methods: We measured admission tryptophan and kynurenine levels in 270 consecutive CA patients (38 in-hospital CA) and investigated associations with in-hospital mortality and neurological outcome at hospital discharge.

Results: 120 of 270 (44%) patients died in the hospital. Compared to survivors, non-survivors showed higher median initial kynurenine levels (5.28 μmol/l [IQR 2.91 to 7.40] vs 3.58 μmol/l [IQR 2.47 to 5.46]; p < 0.001) and a higher median kynurenine/tryptophan ratio (0.10 μmol/l [IQR 0.07 to 0.17] vs 0.07 μmol/l [IQR 0.05 to 0.1]; p < 0.001). In a model adjusted for age, gender and comorbidities, kynurenine (OR 1.16, 95% CI 1.05 to 1.27; p = 0.001) and kynurenine/tryptophan ratio (OR 1.19, 95% CI 1.08 to 1.31; p = 0.003) were significantly associated with mortality. Results were similar for neurological outcome.

Conclusions: Our findings validate a previous study and show associations of the activation of the KP with unfavorable outcomes after CA. Future studies should evaluate whether therapeutic modulation of the KP may impact clinical outcomes after CA.

Keywords: Cardiac arrest; Intensive care medicine; Kynurenine; Post-cardiac arrest syndrome; Prognostication; Tryptophan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Heart Arrest* / therapy
Hospital Mortality
Humans
Kynurenine* / metabolism
Tryptophan

Substances

Kynurenine
Tryptophan