John Bro-Jeppesen1, Jesper Kjaergaard2, Pascal Stammet3, Matthew P Wise4, Jan Hovdenes5, Anders Åneman6, Janneke Horn7, Yvan Devaux8, David Erlinge9, Yvan Gasche10, Michael Wanscher11, Tobias Cronberg12, Hans Friberg13, Jørn Wetterslev14, Tommaso Pellis15, Michael Kuiper16, Niklas Nielsen17, Christian Hassager2. 1. Department of Cardiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. Electronic address: jbj@dadlnet.dk. 2. Department of Cardiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. 3. Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg. 4. Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom. 5. Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 6. Department of Intensive Care, Liverpool Hospital, Sydney, New South Wales, Australia. 7. Department of Intensive Care, Academic Medical Centrum, Amsterdam, The Netherlands. 8. Laboratory of Cardiovascular Research, Luxembourg Institute of Health, Luxembourg. 9. Department of Cardiology, Lund University, Lund, Sweden. 10. Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland. 11. Department of Cardiothoracic Anesthesiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. 12. Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden. 13. Department of Anesthesia and Intensive Care, Lund University, Lund, Sweden. 14. Copenhagen Trial Unit, Centre of Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark. 15. Department of Intensive Care, Santa Maria degli Angeli, Pordenone, Italy. 16. Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, The Netherlands. 17. Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden.
Abstract
AIM: Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation, however data on the prognostic value of inflammatory markers is sparse. We sought to investigate the importance of systemic inflammation, assessed by interleukin-6 (IL-6) in comatose survivors of out-of-hospital cardiac arrest. METHODS: A total of 682 patients enrolled in the Target Temperature Management (TTM) trial, surviving >24h with available IL-6 data were included. IL-6 was measured on days 1, 2 and 3 after return of spontaneous circulation. Severity of PCAS was assessed daily by the Sequential Organ Failure Assessment score. Survival status was recorded at 30 days. RESULTS:High levels of IL-6 at day 1-3 (all p<0.0001) were independently associated with severity of PCAS with no interaction of target temperature (all p=NS). IL-6 levels did not differ between temperature groups (p(interaction)=0.99). IL-6 levels at day 2 (p<0.0001) and day 3 (p<0.0001) were associated with crude mortality. Adjusted Cox proportional-hazards analysis showed that a two-fold increase of IL-6 levels at day 2 (HR=1.15 (95% CI: 1.07-1.23), p=0.0002) and day 3 (HR=1.18 (95% CI: 1.09-1.27), p<0.0001) were associated with mortality. IL-6 levels at day 3 had the highest discriminative value in predicting mortality (AUC=0.66). IL-6 did not significantly improve 30-day mortality prediction compared to traditional prognostic factors (p=0.08). CONCLUSIONS: In patients surviving >24h following cardiac arrest, IL-6 levels were significantly elevated and associated with severity of PCAS with no significant influence of target temperature. High IL-6 levels were associated with increased mortality. Measuring levels of IL-6 did not provide incremental prognostic value.
RCT Entities:
AIM: Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation, however data on the prognostic value of inflammatory markers is sparse. We sought to investigate the importance of systemic inflammation, assessed by interleukin-6 (IL-6) in comatose survivors of out-of-hospital cardiac arrest. METHODS: A total of 682 patients enrolled in the Target Temperature Management (TTM) trial, surviving >24h with available IL-6 data were included. IL-6 was measured on days 1, 2 and 3 after return of spontaneous circulation. Severity of PCAS was assessed daily by the Sequential Organ Failure Assessment score. Survival status was recorded at 30 days. RESULTS: High levels of IL-6 at day 1-3 (all p<0.0001) were independently associated with severity of PCAS with no interaction of target temperature (all p=NS). IL-6 levels did not differ between temperature groups (p(interaction)=0.99). IL-6 levels at day 2 (p<0.0001) and day 3 (p<0.0001) were associated with crude mortality. Adjusted Cox proportional-hazards analysis showed that a two-fold increase of IL-6 levels at day 2 (HR=1.15 (95% CI: 1.07-1.23), p=0.0002) and day 3 (HR=1.18 (95% CI: 1.09-1.27), p<0.0001) were associated with mortality. IL-6 levels at day 3 had the highest discriminative value in predicting mortality (AUC=0.66). IL-6 did not significantly improve 30-day mortality prediction compared to traditional prognostic factors (p=0.08). CONCLUSIONS: In patients surviving >24h following cardiac arrest, IL-6 levels were significantly elevated and associated with severity of PCAS with no significant influence of target temperature. High IL-6 levels were associated with increased mortality. Measuring levels of IL-6 did not provide incremental prognostic value.
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