Jesper Kjaergaard1, Niklas Nielsen2, Matilde Winther-Jensen3, Michael Wanscher4, Tommaso Pellis5, Michael Kuiper6, Jakob Hartvig Thomsen3, Jørn Wetterslev7, Tobias Cronberg8, John Bro-Jeppesen3, David Erlinge9, Hans Friberg10, Helle Søholm3, Yvan Gasche11, Janneke Horn12, Jan Hovdenes13, Pascal Stammet14, Matthew P Wise15, Anders Åneman16, Christian Hassager3. 1. Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: Jesper.kjaergaard.05@regionh.dk. 2. Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden. 3. Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 4. Department of Cardiothoracic Anesthesiology RT, The Heart Centre, Copenhagen University Hospital, Denmark. 5. Department of Intensive Care, Santa Maria degli Angeli, Pordenone, Italy. 6. Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, The Netherlands. 7. Copenhagen Trial Unit, Centre of Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark. 8. Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden. 9. Department of Cardiology, Skåne University Hospital, Lund, Sweden. 10. Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden. 11. Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland. 12. Department of Intensive Care, Academic Medical Centrum, Amsterdam, The Netherlands. 13. Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 14. Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg. 15. Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom. 16. Department of Intensive Care, Liverpool hospital, Sydney, New South Wales, Australia.
Abstract
AIM: Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. METHODS: In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. RESULTS:Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. CONCLUSION: Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C.
RCT Entities:
AIM: Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC. METHODS: In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days. RESULTS: Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM. CONCLUSION: Time to ROSC remains a significant prognostic factor in comatose OHCApatients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C.
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