BACKGROUND: The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome. METHODS AND RESULTS: Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification. CONCLUSIONS: KP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome.

Early Activation of the Kynurenine Pathway Predicts Early Death and Long-term Outcome in Patients Resuscitated From Out-of-Hospital Cardiac Arrest / G. Ristagno, R. Latini, J. Vaahersalo, S. Masson, J. Kurola, T. Varpula, J. Lucchetti, C. Fracasso, G. Guiso, A. Montanelli, S. Barlera, M. Gobbi, M. Tiainen, V. Pettilä, M. Skrifvars. - In: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE. - ISSN 2047-9980. - 3:4(2014 Aug), pp. e001094.1-e001094.10. [10.1161/JAHA.114.001094]

Early Activation of the Kynurenine Pathway Predicts Early Death and Long-term Outcome in Patients Resuscitated From Out-of-Hospital Cardiac Arrest

G. Ristagno;
2014-08

Abstract

BACKGROUND: The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome. METHODS AND RESULTS: Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification. CONCLUSIONS: KP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome.
brain; cardiac arrest; kynurenine; shock; survival; tryptophan
Settore MED/41 - Anestesiologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
JAHA2014_KP in Finnresusci.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 800.5 kB
Formato Adobe PDF
800.5 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/620363
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 28
  • ???jsp.display-item.citation.isi??? 30
social impact