Sudden cardiac arrest constitutes a major public health burden in both developed and developing countries. In those successfully resuscitated from cardiac arrest, subsequent mortality is still high (∼75%) and is due to a combination of ischaemia and reperfusion injury. The purpose of this review is to describe the experimental and clinical evidence supporting therapeutic hypothermia in survivors of sudden cardiac arrest. We also discuss controversies and unresolved issues in therapeutic hypothermia, including the optimum target temperature for therapeutic hypothermia, and the role of pre-hospital induction of hypothermia. We conclude with a perspective on therapeutic hypothermia as it applies to the Singapore context.
NicholGThomasECallawayCWHedgesJPowellJLAufderheideTP. Regional variation in out-of-hospital cardiac arrest incidence and outcomes. JAMA2008;300(12):1423–31 doi: 10.1001/jama.300.12.1423.
2.
ChughSSJuiJGunsonKSteckerECJohnBTThompsonBIliasN. Current burden of sudden cardiac death: Multiple source surveillance versus retrospective death certificate-based review in a large US community. J Am Coll Cardiol2004;44(6):1268–75 doi: 10.1016/j.jacc.2004.06.029.
3.
de Vreede-WagemakersJJMGorgelsAPMDubois-ArbouwWIvan ReeJWDaemenMJAPHoubenLGE. Out-of-hospital cardiac arrest in the 1990s: A population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol1997;30(6):1500–5 doi: 10.1016/S0735-1097(97)00355-0.
4.
ByrneRConstantOSmythYCallagyGNashPDalyK. Multiple source surveillance and aetiology of out-of-hospital sudden cardiac death in a rural population in the west of Scotland. Eur Heart J2008;29(11):1418–23 doi: 10.1093/eurheartj/ehn155.
5.
HuaWZhangLFWuYFLiuXQGuoDSZhouHL. Incidence of sudden cardiac death in China: Analysis of 4 regional populations. J Am Coll Cardiol2009;54(12):1110–8 doi: 10.1016/j.jacc.2009.06.016.
6.
DeoRAlbertCM. Epidemiology and genetics of sudden cardiac death. Circulation2012;125(4):620–37 doi: 10.1161/CIRCULATIONAHA.111.023838.
7.
GoASMozaffarianDRogerVLBenjaminEJBerryJD. Heart disease and stroke statistics – 2013 update: A report from the American Heart Association. Circulation2013:127(1):e6–245 doi: 10.1161/CIR.0b013e31828124ad.
NeumarRWNolanJ PAdrieCAibikiMBergRABottigerBW. Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication. A Consensus Statement from the International Liaison Committee on Resuscitation. Circulation2008;118(23): 2452–83 doi: 10.1161/CIRCULATIONAHA.108.190652.
10.
PoldermanKHVaronJ. Cool hemodynamics — the intricate interplay between therapeutic hypothermia and the post-cardiac arrest syndrome. Resuscitation2014;85(8):975–6 doi: 10.1016/j.resuscitation.2014.06.002.
11.
DraganceaIRundgrenMEnglundEFribergHCronbergT. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation2013;84(3):337–42 doi: 10.1016/j.resuscitation.2012.09.015.
12.
LaverSFarrowCTurnerDNolanJ. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med2004;30(11):216–8 doi: 10.1007/s00134-004-2425-z.
13.
PoldermanKH. Application of therapeutic hypothermia in the ICU: Opportunities and pitfalls of a promising treatment modality. Part 1: Indications and evidence. Intensive Care Med2004;30(4):556–75 doi: 10.1007/s00134-003-2152-x.
14.
FayT. Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc1943;24:611–9.
15.
XiaoFSafarPRadovskyA. Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats. Am J Emerg Med1998;16(1):17–25 doi: 10.1016/S0735-6757(98)90059-6.
16.
HicksSDDeFrancoDBCallawayCW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression. J Cereb Blood Flow Metab2000;20(3):520–30 doi: 10.1097/00004647-200003000-00011.
17.
HolzerMBernardSAHachimi-IdrissiSRoineROSterzFMullnerM. Hypothermia for neuroprotection after cardiac arrest: Systematic review and individual patient data meta-analysis. Crit Care Med2005;33(2):414–8 doi: 10.1097/01.CCM.0000153410.87750.53.
18.
SterzFSafarPTishermanSRadovskyAKuboyamaKOkuK. Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med1991;19(3):379–89.
19.
BernardSAJonesBMHorneMK. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med1997;30(2):146–53 doi: 10.1016/S0196-0644(97)70133-1.
20.
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med2002;346(8):549–56 doi: 10.1056/NEJMoa012689.
21.
BernardSAGrayTWBuistMDJonesBMSilvesterWGutteridgeGSmithK. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med2002;346(8):557–63 doi: 10.1056/NEJMoa003289.
22.
HarukuniIBhardwajA. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin2006;24(1):1–21 doi: 10.1016/j.ncl.2005.10.004.
23.
EltzschigHKEckleT. Ischemia and reperfusion — from mechanism to translation. Nat Med2011;17(11):1391–401 doi: 10.1038/nm.2507.
24.
EltzschigHKCollardCD. Vascular ischaemia and reperfusion injury. Br Med Bull2004;70(1):71–86 doi: 10.1093/bmb/ldh025.
25.
SattlerRRothsteinJD. Regulation and dysregulation of glutamate transporters. Handb Exp Pharmacol2006;175:277–303 doi: 10.1007/3-540-29784-7_14.
26.
LiptonSARosenbergPA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med1994;330(9):613–22 doi: 10.1056/NEJM199403033300907.
27.
BaiJLydenPD. Revisiting cerebral post-ischaemic reperfusion injury: New insights in understanding reperfusion failure, hemorrhage and oedema. Int J Stroke2015;10(2):143–52 doi: 10.1111/ijs.12434.
28.
PanJKonstasABatemanBOrtolanoGPile-SpellmanJ. Reperfusion injury following cerebral ischaemia: Pathophysiology, MR imaging and potential therapies. Neuroradiology2007;49(2):93–102 doi: 10.1007/s00234-006-0183-z.
29.
LemastersJ. The mitochondrial permeability transition and the calcium, oxygen and pH paradoxes: One paradox after another. Cardiovasc Res1999;44(3);470–3 doi: 10.1016/S0008-6363(99)00368-5.
30.
BednarMMRaymondSMcAuliffeTLodgePAGrossCE. The role of neutrophils and platelets in a rabbit model of thromboembolic stroke. Stroke1991;22(1):44–50 doi: 10.1161/01.STR.22.1.44.
31.
RosomoffHLHoladayDA. Cerebral blood flow and cerebral oxygen consumption during hypothermia. Am J Physiol1954;179(1):85–8.
32.
AronowskiJStrongRGrottaJC. Reperfusion injury: Demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab1997;17(10):1048–56 doi: 10.1097/00004647-199710000-00006.
33.
ColbourneFCorbettD. Delayed postischemic hypothermia: A six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci1995;15(11):7250–60.
34.
NolanJ PMorleyPTVanden HoekTLHickeyRWKloeckWGBilliJ. Therapeutic hypothermia after cardiac arrest: An advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation2003;108(1):118–21 doi: 10.1161/01.CIR.0000079019.02601.90.
35.
NolanJPMorleyPTVanden HoekTLHickeyRW, Advancement Life Support Task Force of the International Liaison committee on Resuscitation. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation2003;57(3):231–5 doi: 10.1016/S0300-9572(03)00184-9.
36.
KimYMYimHWJeongSHKlemMLCallawayCW. Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies. Resuscitation2012;83(2):188–96 doi: 10.1016/j.resuscitation.2011.07.031.
37.
NielsenNWetterslevJCronbergTErlingeDGascheYHassagerC. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med2013;369(23):2197–206 doi: 10.1056/NEJMoa1310519.
38.
KimFNicholGMaynardCHallstromAKudenchukPJReaT. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: A randomized clinical trial. JAMA2014;311(1):45–52 doi: 10.1001/jama.2013.282173.
39.
LearyMGrossestreuerAVIannaconeSGonzalezMShoferFSPoveyC. Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest. Resuscitation2013;84(8):1056–61 doi: 10.1016/j.resuscitation.2012.11.003.
40.
SendelbachSHearstMOJohnsonPJUngerBTMooneyMR. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation2012;83(7):829–34 doi: 10.1016/j.resuscitation.2011.12.026.
41.
Italian Cooling Experience (ICE) Study Group. Early- versus late-initiation of therapeutic hypothermia after cardiac arrest: Preliminary observations from the experience of 17 Italian intensive care units. Resuscitation2012;83(7):823–8 doi: 10.1016/j.resuscitation.2011.12.002.
42.
NielsenNHovdenesJNilssonFRubertssonSStammetPSundeK. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand2009;53(7):926–34 doi: 10.1111/j.1399–6576.2009.02021.x.
43.
YannopoulosDZvimanMCastroVKolandaiveluARanjanRWilsonRF. Intra-cardiopulmonary resuscitation hypothermia with and without volume loading in an ischemic model of cardiac arrest. Circulation2009;120(14):1426–35 doi: 10.1161/CIRCULATIONAHA.109.848424.
44.
NgMWongASLChewHCShahidahNPekP PPohJ. Pilot prospective study of therapeutic hypothermia for treatment of post-cardiac. Int J Cardiol2014;173(3):612–3 doi: 10.1016/j.ijcard.2014.03.132.
45.
OngMEHChanYHAnatharamanVLauSTLimSHSeldrupJ. Cardiac arrest and resuscitation epidemiology in Singapore (CARE I study). Prehosp Emerg Care2003;7(4):427–33 doi: 10.1080/312703002120.
46.
BerdowskiJBergRATijssenJGKosterRW. Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies. Resuscitation2010;81(11):1479–87 doi: 10.1016/j.resuscitation.2010.08.006.
AgarwalDAHessE PAtkinsonEJWhiteRD. Ventricular fibrillation in Rochester, Minnesota: Experience over 18 years. Resuscitation2009;80(11):1253–8 doi: 10.1016/j.resuscitation.2009.07.019.
