Glenn M Eastwood1, Antoine G Schneider2, Satoshi Suzuki3, Leah Peck4, Helen Young5, Aiko Tanaka6, Johan Mårtensson7, Stephen Warrillow8, Shay McGuinness9, Rachael Parke10, Eileen Gilder11, Lianne Mccarthy12, Pauline Galt13, Gopal Taori14, Suzanne Eliott15, Tammy Lamac16, Michael Bailey17, Nerina Harley18, Deborah Barge19, Carol L Hodgson20, Maria Cristina Morganti-Kossmann21, Alice Pébay22, Alison Conquest23, John S Archer24, Stephen Bernard25, Dion Stub26, Graeme K Hart27, Rinaldo Bellomo28. 1. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: glenn.eastwood@austin.org.au. 2. Service de Médecine Intensive Adult Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Electronic address: Antoine.Schneider@chuv.ch. 3. Department of Anesthesiology and Resuscitology, Okayama University Hospital, Okayama, Japan. Electronic address: Suzuki-s@mtc.biglobe.ne.jp. 4. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: leah.peck@austin.org.au. 5. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: helen.young@austin.org.au. 6. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: aiko.tanaka@austin.org.au. 7. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: johan.martensson@austin.org.au. 8. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: stephen.warrillow@austin.org.au. 9. Cardiothoracic and Vascular Intensive Care Unit Auckland City Hospital, Auckland, New Zealand. Electronic address: ShayMc@adhb.govt.nz. 10. Cardiothoracic and Vascular Intensive Care Unit Auckland City Hospital, Auckland, New Zealand. Electronic address: RParke@adhb.govt.nz. 11. Cardiothoracic and Vascular Intensive Care Unit Auckland City Hospital, Auckland, New Zealand. Electronic address: EGilder@adhb.govt.nz. 12. Cardiothoracic and Vascular Intensive Care Unit Auckland City Hospital, Auckland, New Zealand. Electronic address: LianneM@adhb.govt.nz. 13. Department of Intensive Care Monash Medical Centre, Victoria, Australia. Electronic address: Pauline.Galt@monashhealth.org. 14. Department of Intensive Care Monash Medical Centre, Victoria, Australia. Electronic address: Gopal.Taoiri@monashhealth.org. 15. Department of Intensive Care Monash Medical Centre, Victoria, Australia. Electronic address: Suzanne.Eliott@monashhealth.org. 16. Department of Intensive Care Eastern Health, Victoria, Australia. Electronic address: tammy.lamac@easternhealth.org.au. 17. Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address: michael.bailey@monash.edu. 18. Department of Intensive Care Royal Melbourne Hospital, Victoria, Australia. Electronic address: Nerina.harley@rmh.org.au. 19. Department of Intensive Care Royal Melbourne Hospital, Victoria, Australia. Electronic address: Deborah.barge@mh.org.au. 20. Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University Physiotherapy Department, The Alfred Hospital, Melbourne, Australia. Electronic address: carol.hodgson@monash.edu. 21. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Barrow Neurological Institute at Phoenix Children's Hospital, and Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, USA. Electronic address: Cristina.morganti-kossmann@monash.edu. 22. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia. Electronic address: bay@unimelb.edu.au. 23. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia. Electronic address: alison.conquest@unimelb.edu.au. 24. Department of Medicine The University of Melbourne, Victoria, Australia. Electronic address: jarcher@unimelb.edu.au. 25. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address: S.Bernard@alfred.org.au. 26. Department of Cardiology, Alfred Hospital, Victoria, Australia. Electronic address: d.stub@alfred.org.au. 27. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: graeme.hart@austin.org.au. 28. Department of Intensive Care Austin Hospital, Victoria, Australia. Electronic address: rinaldo.bellomo@austin.org.au.
Abstract
BACKGROUND: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. METHODS: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) andS100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. RESULTS:We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). CONCLUSIONS: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.
RCT Entities:
BACKGROUND: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. METHODS: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. RESULTS: We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMHpatients had good functional recovery compared with 18 (46%) TNpatients. Hospital mortality occurred in 11 (26%) TTMHpatients and 15 (37%) TNpatients (p=0.31). CONCLUSIONS: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.
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