Clinical paper| Volume 126, P185-190, May 2018

Effect of target temperature management at 32–34 °C in cardiac arrest patients considering assessment by regional cerebral oxygen saturation: A multicenter retrospective cohort study



      Target temperature management (TTM) is used in comatose post-cardiac arrest patients, but the recommended temperature range is wide. This study aimed to assess the effectiveness of TTM at 32–34 °C while considering the degree of cerebral injury and cerebral circulation, as assessed by regional cerebral oxygen saturation (rSO2).


      This is a secondary analysis of prospectively collected registry data from comatose patients who were transferred to 15 hospitals in Japan after out-of-hospital cardiac arrest (OHCA) from 2011 to 2013. The primary outcome was all-cause mortality at 90 days after OHCA, and the secondary outcome was favorable neurological outcomes as evaluated according to the Cerebral Performance Category. We monitored rSO2 noninvasively with near-infrared spectroscopy, which could assess cerebral perfusion and the balance of oxygen delivery and uptake.


      We stratified 431 study patients into three groups according to rSO2 on hospital arrival: rSO2 ≤40% (n = 296), rSO2 41–60% (n = 67), and rSO2 ≥61% (n = 68). Propensity score analysis revealed that TTM at 32–34 °C decreased all-cause mortality in patients with rSO2 41–60% (average treatment effect on treated [ATT] by propensity score matching [PSM] −0.51, 95%CI −0.70 to −0.33; ATT by inverse probability of treatment weighting [IPW] −0.52, 95%CI −0.71 to −0.34), and increased favorable neurological outcomes in patients with rSO2 41–60% (ATT by PSM 0.50, 95%CI 0.32–0.68; ATT by IPW 0.52, 95%CI 0.35–0.69).


      TTM at 32–34 °C effectively decreased all-cause mortality in comatose OHCA patients with rSO2 41–60% on hospital arrival in Japan.


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        • Hypothermia after Cardiac Arrest Study Group
        Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.
        N Engl J Med. 2002; 346: 549-556
        • Bernard S.A.
        • Gray T.W.
        • Buist M.D.
        • Jones B.M.
        • Silvester W.
        • Gutteridge G.
        • et al.
        Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.
        N Engl J Med. 2002; 346: 557-563
        • Morrison L.J.
        • Deakin C.D.
        • Morley P.T.
        • Callaway C.W.
        • Kerber R.E.
        • Kronick S.L.
        • et al.
        Part 8: advanced life support: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
        Circulation. 2010; 122: S345-421
        • Peberdy M.A.
        • Callaway C.W.
        • Neumar R.W.
        • Geocadin R.G.
        • Zimmerman J.L.
        • Donnino M.
        • et al.
        Part 9: post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2010; 122: S768-86
        • Nielsen N.
        • Wetterslev J.
        • Cronberg T.
        • Erlinge D.
        • Gasche Y.
        • Hassager C.
        • et al.
        Targeted temperature management at 33 °C versus 36 °C after cardiac arrest.
        N Engl J Med. 2013; 369: 2197-2206
        • Taccone F.S.
        • Dell’Anna A.
        Comment in: targeted temperature management after cardiac arrest.
        N Engl J Med. 2014; 370: 1357-1358
        • Rittenberger J.C.
        • Callaway C.W.
        Temperature management and modern post-cardiac arrest care.
        N Engl J Med. 2013; 369: 2262-2263
        • Callaway C.W.
        • Donnino M.W.
        • Fink E.L.
        • Geocadin R.G.
        • Golan E.
        • Kern K.B.
        • et al.
        Part 8: post-Cardiac arrest care: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
        Circulation. 2015; 132: S465-S482
        • Knaus W.A.
        • Draper E.A.
        • Wagner D.P.
        • Zimmerman J.E.
        APACHE II: a severity of disease classification system.
        Crit Care Med. 1985; 13: 818-829
        • Vincent J.L.
        • Moreno R.
        • Takala J.
        • Willatts S.
        • De Mendonça A.
        • Bruining H.
        • et al.
        The SOFA (Sepsis-related organ failure assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European society of intensive care medicine.
        Intensive Care Med. 1996; 22: 707-710
        • Storm C.
        • Leithner C.
        • Krannich A.
        • Wutzler A.
        • Ploner C.J.
        • Trenkmann L.
        • et al.
        Regional cerebral oxygen saturation after cardiac arrest in 60 patients–a prospective outcome study.
        Resuscitation. 2014; 85: 1037-1041
        • Ito N.
        • Nishiyama K.
        • Callaway C.W.
        • Orita T.
        • Hayashida K.
        • Arimoto H.
        • et al.
        Noninvasive regional cerebral oxygen saturation for neurological prognostication of patients with out-of-hospital cardiac arrest: a prospective multicenter observational study.
        Resuscitation. 2014; 85: 778-784
        • Nishiyama K.
        • Ito N.
        • Orita T.
        • Hayashida K.
        • Arimoto H.
        • Beppu S.
        • et al.
        Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: a prospective, observational, multicentre study.
        Resuscitation. 2015; 96: 135-141
        • Hegnauer A.H.
        • D’Amato H.E.
        Oxygen consumption and cardiac output in the hypothermic dog.
        Am J Physiol. 1954; 178: 138-142
        • Mezrow C.K.
        • Sadeghi A.M.
        • Gandsas A.
        • Shiang H.H.
        • Levy D.
        • Green R.
        • et al.
        Cerebral blood flow and metabolism in hypothermic circulatory arrest.
        Ann Thorac Surg. 1992; 54: 609-615
        • Busto R.
        • Globus M.Y.
        • Dietrich W.D.
        • Martinez E.
        • Valdés I.
        • Ginsberg M.D.
        • et al.
        Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain.
        Stroke. 1989; 20: 904-910
        • Chopp M.
        • Knight R.
        • Tidwell C.D.
        • Helpern A.
        • Brown E.
        • Welch K.M.
        • et al.
        The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia.
        J Cereb Blood Flow Metab. 1989; 9: 141-148
        • Jacobs I.
        • Nadkarni V.
        • Bahr J.
        • Berg R.A.
        • Billi J.E.
        • Bossaert L.
        • et al.
        Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).
        Resuscitation. 2004; 63: 233-249
      1. Emergency Life-saving Technicians Act.
        Ministry of Health, Labour and Welfare, JAPAN2017 ( [Accessed August 6, 2017])
        • Ebell M.H.
        Practical guidelines for do-not-resuscitate orders.
        Am Fam Physician. 1994; 50 (1303-4): 1293-1299
        • Tobias J.D.
        Cerebral oxygenation monitoring: near-infrared spectroscopy.
        Expert Rev Med Devices. 2006; 3: 235-243
        • Yao F.S.
        • Tseng C.C.
        • Ho C.Y.
        • Levin S.K.
        • Illner P.
        Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery.
        J Cardiothorac Vasc Anesth. 2004; 18: 552-558
        • Casati A.
        • Fanelli G.
        • Pietropaoli P.
        • Proietti R.
        • Tufano R.
        • Danelli G.
        • et al.
        Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia.
        Anesth Analg. 2005; 101: 740-747
        • Jennett B.
        • Bond M.
        Assessment of outcome after severe brain damage.
        Lancet. 1975; 1: 480-484
        • Perkins G.D.
        • Jacobs I.G.
        • Nadkarni V.M.
        • Berg R.A.
        • Bhanji F.
        • Biarent D.
        • et al.
        Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein Resuscitation registry templates for out-of-hospital cardiac arrest: a statement for healthcare professionals from a task force of the International Liaison Committee on resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, heart and stroke foundation of Canada, InterAmerican Heart Foundation, resuscitation council of southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical care, Perioperative and Resuscitation.
        Circulation. 2015; 132: 1286-1300
        • Austin P.C.
        An introduction to propensity score methods for reducing the effects of confounding in observational studies.
        Multivariate Behav Res. 2011; 46: 399-424
        • Guo S.
        • Fraser M.W.
        Propensity score analysis: statistical methods and applications.
        second edition. SAGE, California2015
        • StataCorp
        Stata Treatment effects reference manual: potential outcomes/counterfactual outcomes, release 14.
        StataCorp LP, Texas2015
        • Rubin D.B.
        Estimating causal effects from large data sets using propensity scores.
        Ann Intern Med. 1997; 127: 757-763
        • Hirose T.
        • Shiozaki T.
        • Nomura J.
        • Hamada Y.
        • Sato K.
        • Katsura K.
        • et al.
        Pre-hospital portable monitoring of cerebral regional oxygen saturation (rSO2) in seven patients with out-of-hospital cardiac arrest.
        BMC Res Notes. 2016; 9: 428
        • Kurth C.D.
        • Steven J.L.
        • Montenegro L.M.
        • Watzman H.M.
        • Gaynor J.W.
        • Spray T.L.
        • et al.
        Cerebral oxygen saturation before congenital heart surgery.
        Ann Thorac Surg. 2001; 72: 187-192
        • Bosson N.E.
        • Kaji A.H.
        • Koenig W.J.
        • Niemann J.T.
        • et al.
        Effect of therapeutic hypothermia on survival and neurologic outcome in the elderly.
        Ther Hypothermia Temp Manage. 2016; 6: 71-75
        • Ro Y.S.
        • Shin S.D.
        • Song K.J.
        • Lee E.J.
        • Lee Y.J.
        • Kim J.Y.
        • et al.
        Interaction effects between hypothermia and diabetes mellitus on survival outcomes after out-of-hospital cardiac arrest.
        Resuscitation. 2015; 90: 35-41
        • Natsukawa T.
        • Sawano H.
        • Natsukawa M.
        • Yoshinaga Y.
        • Sato S.
        • Ito Y.
        • et al.
        At what level of unconsciousness is mild therapeutic hypothermia indicated for out-of-hospital cardiac arrest: a retrospective, historical cohort study.
        J Intensive Care. 2015; 3: 38
        • Hifumi T.
        • Kuroda Y.
        • Kawakita K.
        • Yamashita S.
        • Oda Y.
        • Dohi K.
        • et al.
        Fever control management is preferable to mild therapeutic hypothermia in traumatic brain injury patients with abbreviated injury scale 3–4: a multi-center, randomized controlled trial.
        J Neurotrauma. 2016; 33: 1047-1053
        • Madden L.K.
        • DeVon H.A.
        A systematic review of the effects of body temperature on outcome after adult traumatic brain injury.
        J Neurosci Nurs. 2015; 47: 190-203
        • Chan P.S.
        • Berg R.A.
        • Tang Y.
        • Curtis L.H.
        • Spertus J.A.
        • American Heart Association’s Get With the Guidelines-Resuscitation Investigators
        Association between therapeutic hypothermia and survival after in-hospital cardiac arrest.
        JAMA. 2016; 316: 1375-1382
        • Engsig M.
        • Soholm H.
        • Folke F.
        • Gadegaard P.J.
        • Wiis J.T.
        • Molin R.
        • et al.
        Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac arrest patients treated with targeted temperature management.
        Clin Epidemiol. 2016; 8: 761-768
        • Choi S.W.
        • Shin S.D.
        • Ro Y.S.
        • Song K.J.
        • Lee E.J.
        • Ahn K.O.
        • et al.
        Effect of therapeutic hypothermia on the outcomes after out-of-hospital cardiac arrest according to initial ECG rhythm and witnessed status: a nationwide observational interaction analysis.
        Resuscitation. 2016; 100: 51-59
        • Frydland M.
        • Kjaergaard J.
        • Erlinge D.
        • Wanscher M.
        • Nielsen N.
        • Pellis T.
        • et al.
        Target temperature management of 33 °C and 36 °C in patients with out-of-hospital cardiac arrest with initial non-shockable rhythm–a TTM sub-study.
        Resuscitation. 2015; 89: 142-148