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Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
Glenn Eastwood1, Alistair D Nichol1, Carol Hodgson1
1From the Departments of Intensive Care (G.E., L.P., R.B.) and Neurology (J.A.), Austin Hospital, the Australian and New Zealand Intensive Care Research Centre (G.E., A.D.N., C.H., S.M., G.C., M.J.B., E.P., B.A., T.T., R.B.), the School of Public Health and Preventive Medicine, Monash University (S.B., D.S.), the Departments of Intensive Care (C.H., S.B., T.T.) and Cardiology (D.S.), Alfred Hospital, the Division of Critical Care (C.H., R.B.) and the Departments of Medicine (J.A.) and Critical Care (A.D.), University of Melbourne, the Department of Intensive Care, Royal Melbourne Hospital (A.D., R.B.), and the Department of Intensive Care, Northern Hospital (A.G.), Melbourne, VIC, the Division of Critical Care, George Institute for Global Health, Sydney (C.H.), and the Intensive Care Unit, Princess Alexandra Hospital, and the School of Medicine, University of Queensland, Brisbane (J.W.) - all in Australia; the Clinical Research Centre at St. Vincent's Hospital, University College Dublin, Dublin (A.D.N., K.A., S.M., C.F.); the Cardiothoracic and Vascular Intensive Care Unit (R.L.P., S.M.) and the Department of Critical Care Medicine (Y.W.C.), Auckland City Hospital, and the School of Nursing, University of Auckland (R.L.P.), Auckland, Intensive Care Research (A.H.), Medical Research Institute of New Zealand (R.L.P., S.M.), and the Intensive Care Unit, Wellington Regional Hospital (E.L.), Wellington, and the Department of Intensive Care, Christchurch Hospital, Canterbury (D.K.) - all in New Zealand; the Sections of Anesthesiology and Intensive Care (N.N., J.D.), Cardiology (J.D.), and Neurology (G. Lilja, T.C.), Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Helsingborg Hospital, Helsingborg (N.N.), and the Department of Anesthesia and Intensive Care Medicine, Skåne University Hospital, Malmo (J.P.D.) - all in Sweden; the Departments of Emergency Care and Services (M.B.S.) and Intensive Care (M.B.), Helsinki University Hospital and University of Helsinki, and the Department of Neurology, Helsinki University Hospital (M. Tiainen) - all in Helsinki; the Department of Intensive Care, Hôpital Universitaire de Bruxelles-Université Libre de Bruxelles (F.S.T.), and the Department of Intensive Care, Erasme University Hospital (F.A.) - both in Brussels; the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada (D.K.); the Emergency Department and Department of Clinical Medicine, Aarhus University Hospital and Aarhus University (H.K.), the Departments of Intensive Care Medicine (A.M.G., S.C., H.M.-A.) and Anesthesiology and Intensive Care (A.G.), Aarhus University Hospital, and the Department of Clinical Medicine, Aarhus University (A.M.G.) - all in Aarhus, Denmark; Reanimation Medicale, Centre Hospitalier Universitaire, Franche-Comte, Unité de Formation et de Recherche Santé, University of Franche-Comte, Besançon, France (G.C.); the Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, and the School of Medicine, Vita-Salute San Raffaele University, Milan (G. Landoni); the Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam (J.H.); the Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Medicine, University of Oslo (T.O.), and the Department of Cardiology, Oslo University Hospital-Ullevål (G.Ø.A., E.Q., A.F.) - both in Oslo; the Intensive Care Department, Ministry of National Guard Health Affairs, the College of Medicine, King Saud bin Abdulaziz University Hospital for Health Sciences, and King Abdullah International Medical Research Center - all in Riyadh, Saudi Arabia (Y.A., H.T.); the Cardiology Department, Tan Tock Seng Hospital, the School of Medicine, National University of Singapore Yong Loo Lin School of Medicine, and the Department of Medicine, Nanyang Technological University Lee Kong Chian School of Medicine - all in Singapore (Y.W.C.); the Department of Internal Intensive Medicine, University Medical Center Maribor, Maribor, Slovenia (A.M., F.S.); the Department of Intensive Care Medicine, Bern University Hospital (M.H.), and the Departments of Intensive Care Medicine (M.I.) and Anesthesiology and Pain Medicine (A.L.), Inselspital, Bern University Hospital, University of Bern, Bern, and the Institute of Intensive Care Medicine, University Hospital of Zurich, Zurich (M.P.H.) - all in Switzerland; and the Department of Adult Critical Care, University Hospital of Wales, Cardiff (M.P.W., J.C.), the Intensive Care Unit, Bristol Royal Infirmary, Bristol (M. Thomas, K.S., J.B.), the Regional Intensive Care Unit, Royal Victoria Hospital (P.J.M.), and the Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast (P.J.M.), Belfast, and the Academic Department of Critical Care, Queen Alexandra Hospital, Portsmouth (D.P.) - all in the United Kingdom.
Background:
Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes.
Methods:
We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months.
Results:
A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups.
Conclusions:
In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).
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