Therapeutic hypothermia a physiological analysis of a new potential for post-cardiac arrest care
1 Therapeutic Hypothermia: A Physiological Analysis of a NewPotential for Post-Cardiac Arrest CareByPedram Matthew Rahmanian, NREMT-BResearch Question:Why is the induction of therapeutic hypothermia (TH) positive in increasing survivalrates of out-of-hospital cardiac arrest (OHCA) triggered by ventricular fibrillation (VF)?
2 AbstractThis study aims to answer the Research Question: Why is the induction oftherapeutic hypothermia (TH) positive in increasing survival rates of out-of-hospitalcardiac arrest (OHCA) triggered by ventricular fibrillation (VF)?Annually, nearly 450,000 people in the US and 375,000 people in Europe arevictims of sudden death from cardiac arrest.1Despite numerous treatment options,resuscitation success rates to the time of hospital discharge have remained relativelyunchanged throughout the last 50 years.2While technological advances are increasing thesurvivability of cardiac arrest, patients are still not surviving long enough to bedischarged from the hospital.3The scope of this study focuses on explaining why therapeutic hypothermia isbeneficial for cardiac arrest patients by analyzing the major clinical trials and thephysiology of TH. The scope of this study does not include the use of TH for othermedical conditions except for understanding additional benefits of TH.Therapeutic Hypothermia has many benefits for cardiac arrest patients and hasbeen associated with improving the survival rate of cardiac arrest patients. In addition toincreasing survival rates, TH has also been associated with a decrease in neurologicalimpairment. TH is therefore a beneficial treatment, and has to be implemented as soon aspossible for maximal benefit. 1 Neira, Jorge A., MD, FCCM. “Post-Resuscitation Care Induced Hypothermia to Whom,How, and When?” (Presentation). World Congress of Cardiology, Buenos Aires,Argentina, May 18-21, 2008. slide 3 2 Clumpner, Mike and Jim Mobley. “Raising the Dead: Prehospital Hypothermia forCardiac Arrest Patients May Improve Neurological Outcome and Survival to Discharge.”EMS Sep. 2008: 52-60. pg 52 3 Clumpner, pg 52
3 The earliest stage of the chain of survival in which TH can be successfullyimplemented is in the EMS system. However, if the continuum of care cannot beguaranteed at receiving hospitals, TH should not be started in EMS as an incompletetreatment would cause harm to the patient. Still, EMS agencies can drive theimplementation of TH by pressuring hospitals and thereby creating a sense ofcompetition between them that motivates implementation of TH.Several factors impede the implementation of TH in hospitals. The major factorsinhibiting the implementation of TH are a lack of evidence and concern about thecontinuum of care.4Therefore this article will evaluate the physiology of TH in an effortto promote the inclusion of TH as part of a general protocol.Word Count: 332 4 Neumar, Robert W. et al.“Post Cardiac Arrest Syndrome: Epidemiology,Pathophysiology, Treatment, and Prognostication.” Circulation Cardiovascular Qualityand Outcomes: Journal of the American Heart Association 23 Oct. 2008; 118: 2452-2483pg 2470
4 Table of ContentsAbstract............................................................................................................................... 2Introduction......................................................................................................................... 5The History of Therapeutic Hypothermia........................................................................... 7ILCOR Recommendations ................................................................................................. 9A Review of the Trial Evidence.......................................................................................... 9Reperfusion Injury and the Physiology of Hypothermia .................................................. 12Conclusion ........................................................................................................................ 19References......................................................................................................................... 20Appendix A: Explanation of Terms.................................................................................. 23
5 IntroductionResearch Question: Why is the induction of therapeutic hypothermia (TH) positive inincreasing survival rates of out-of-hospital cardiac arrest (OHCA) triggered byventricular fibrillation (VF)?Annually, ~300,000 adults in the United States experience out-of-hospital cardiacarrest in which the heart stops effectively pumping blood throughout the body.5Nearly450,000 people in the US and 375,000 people in Europe are victims of sudden deathannually from cardiac arrest.6Cardiac Arrest patients today have a variety of treatment regimens available. Withthe pharmacological therapy, intra-aortic balloon pumps, state of the art intensive careunits, and extracorporeal membrane oxygenation treatments7we have today, it seemsapparent that cardiac arrest medical care has progressed tremendously. However, despiteall the treatments available, resuscitation success rates to the time of hospital dischargehas remained relatively unchanged throughout the last 50 years.8According to theNational Registry of CPR, out of the 19,819 adults and 524 children in 2006 whose heartswere re-started, in-hospital mortality rates were 67 and 55 percent respectfully.9Whiletechnological advances increase the survivability of cardiac arrest, patients are not 5 Cooling Therapy for Cardiac Arrest Survivors is as Cost-Effective as AcceptedTreatments for other Conditions. 4 Aug. 2009, American Heart Association. 28Nov. 2009.<http://americanheart.mediaroom.com/index.php?s=43&item=795&printable>.6 Neira, slide 3 7 Clumpner, pg 52 8 Clumpner, pg 52 9 Post-Cardiac Arrest Care Key to Survival. 23 Oct. 2008, American Heart Association.28 Nov. 2009.<http://americanheart.mediaroom.com/index.php?s=43&item=554&printable>.
6 surviving long enough to be discharged from the hospital.10According to University ofPennsylvania’s Dr. Merchant, “TH is the only post-resuscitation therapy shown toimprove both survival and reduce disability after cardiac arrest.”11TH thus deservesfurther analysis into its potential as part of the Advanced Cardiac Life Support (ACLS)standard of care for cardiac arrest.Due to the large proportion of out-of-hospital cardiac arrests, it is in this settingthat the greatest impact could be made by improved treatments. Despite repeatedrecommendations by multiple authoritative bodies (ILCOR and the AHA), therapeutichypothermia has not been implemented as quickly as was expected. This paper aims toanalyze TH on its evidence and physiological impact in post-cardiac arrest care.To approach this topic, it is important to have an understanding of the anatomyand physiology of the heart in its normal state, as well as the hearts reactions duringcardiac arrest.It is also important to define the terms used in this study, these are found inAppendix A. Therapeutic hypothermia can be defined as a condition in which the body’score temperature is below 35°C. There are three levels of hypothermia, mild (35-32°C),moderate (32-30°C), and severe (below 30°C). 10 Clumpner, pg 52 11 Cooling Therapy for Cardiac Arrest Survivors is as Cost-‐Effective as Accepted Treatments for other Conditions.
7 The History of Therapeutic HypothermiaTherapeutic hypothermia (TH) is not a new concept. The use of inducinghypothermia has been used for decades with the belief that cooling the body belownormal physiological temperatures protects the brain from ischemic injury.12Since the1950s, moderate TH (28-32°C) has successfully been used before cardiac arrest (CA) toprovide this kind of cerebral protection from global ischemia during some open-heartsurgeries.13Despite successful description of the use of TH after CA during the late1950s, the practice was abandoned due to uncertainty in the benefits and the difficulty ofits practice.14Within the past decade, TH after CA has witnessed a renewed level of attention asseveral research papers focusing on its use have been published.15There are only fourtrials of mild hypothermia after CA that describe any kind of comparative study; astreatment could not be blinded, only two of these studies were randomized control trials(RCT).16The descriptions of these studies are presented in Table 1. Careful evaluation ofthese two trials guided a recommendation in favor of the use of TH. 12 Collins, Tim J. and Peter J. Samworth. “Therapeutic Hypothermia Following CardiacArrest: A Review of the Evidence.” Nursing in Critical Care: British Associationof Critical Care Nurses 2009; 13:144-151. pg 14413 Nolan, J.P. et al. “Therapeutic Hypothermia After Cardiac Arrest: An AdvisoryStatement by the Advanced Life Support Task Force of the International LiaisonCommittee on Resuscitation.” Circulation Cardiovascular Quality and Outcomes:Journal of the American Heart Association 2003; 108: 118-121. pg 11814 Nolan, pg 118 15 Collins, pg 144 16 Foëx, Bernard A. and John Butler. “Therapeutic Hypothermia After Out of HospitalCardiac Arrest.” Emergency Medicine Journal 2004; 21:590-591. pg 590
8 Table 1: Summary of the TrialsAuthor and Year Sample Research Methodology Findings Study LimitationsBernard et al. (1997) 22 adult patients whoremained unconsciousfollowing an initial VFOHCA. Hypothermicgroup was cooled to33°C for 12 h withsurface cooling and icepacks. Patients werethen actively rewarmedover 6 h.Prospective studyusing a historic controlgroup of 22 patients.Australian Study.Good neurologicaloutcome (GOS 1 or 2)was found in 11/22 inhypothermic groupStudy was not an RCT ormulticenter.Prospective study withsmall sample size of 22historic control. A pilotstudy for Bernard et al(2002) RCT.Yanagawa et al (1998) 28 adult patients in totalwho sustained OHCAand ROSC. 13 selectedfor TH of 33-34°C for48 h. Cooling wasachieved using coolingblankets. Passivelyrewarmed at 1°C/day.Patients treated withstandard practice andnormothermia.Prospective study.Taken from one site inJapan.More survivors andimproved neurologicaloutcome in TH group.Survivors 7/13 vs. 5/15.Patients who fullyrecovered: 3/13 vs 1/15.11/13 in TH vs 6/15control developedpneumonia as acomplication.Not an RCT.Used historic controlsrather thanrandomization. Smallscale, single center.Predominantely malesample: 76% in THcompared with evendistribution in control.The TH group was 6years younger thanhistoric control group.Bernard et al. (2002) 77 patients total, allremained unconsciousfollowing OHCA. 43given TH to 33°C for12 h compared with 34patients givennormothermia. Coolingachieved using icepacks.RCT. Multicenterinvolving 4 hospitalsin Australia.TH group had goodneurological recoverywith 21/43 vs 9/34 fornormorthermic group.TH increased survivalwith 21/43 vsnormothermia 11/34.Odd and even day pre-hospital randomizationthat may be difficult toachieve outside thecontrolled hospitalenvironment. Strictinclusion criteria, onlyinvolved shockable CAs.Excluded women belowage 50.The HACA StudyGroup (2002)275 adult patients intotal who all sustainedOHCA and ROSC. 137received TH to 32-34°Cfor 24 h with anexternal cooling devicethat consists of amattress and cover thatdelivers cold air to theentire body. Following24 h, passivelyremarming commencedover 8 h.Multicenter RCTundertaken in centersacross Europe55% of TH group had agood neurologicaloutcome (CPC 1 or 2)compared with 39% innormothermic group. 6-month mortality was41% in the TH groupand 55% in thenormothermic group.The study endedprematurely because offunds difficulties. Strictinclusion criteria causinga delay in samplerecruitment. However,largest sample sizerelated to TH.GOS, Glasgow Outcome Score; RCT, Randomized Control Trial; ROSC, return of spontaneous circulation; OHCA, out of hospitalcardiac arrest; TH, therapeutic hypothemriaCollins, Tim J. and Peter J. Samworth. “Therapeutic Hypothermia Following Cardiac Arrest: A Review of the Evidence.” Nursing inCritical Care: British Association of Critical Care Nurses 2009; 13:144-151. pg 146
9 The ILCOR RecommendationsIn October of 2002, the Advanced Life Support (ALS) Task Force of the InternationalLiaison Committee on Resuscitation (ILCOR) recommended that:• Comatose adult patients with spontaneous circulation after out-of-hospital cardiacarrest caused by an initial rhythm of Ventricular Fibrillation (VF) should becooled to 32°C to 34°C for 12 to 24 hours.• Such cooling may be beneficial for other rhythms as well, or for in-hospitalcardiac arrest.17A Review of the Trial EvidenceThe earliest of these studies was the preliminary clinical trial by Bernard et al.(1997), which was the pilot for the future Bernard et al. (2002) RCT.18Bernard et al.(1997) performed a study on 22 adult patients who remained comatose after an initial out-of-hospital VF CA. The TH group was cooled to 33°C using ice packs and maintained inTH for 12 hours before being actively re-warmed. Neurological outcomes were assessedusing the Glasgow Outcome Score (GOS).The results of the trial were compared with a historical sample of 22 patients whodid not receive TH after CA.19The study found that 11 of 22 patients had a goodneurological recovery with a GOS of 1 or 2 compared to 3 of 22 patients in thenormothermia historical control group.20This showed that TH improved neurologicaloutcome, however the study was limited due to its use of historic controls, meaning that 17 Christenson, James M., MD, FRCPC. “Hypothermia Recommended After VF CardiacArrest.” Journal Watch Emergency Medicine 13 Aug. 2003.18 Collins, pg 147 19 Collins, pg 147 20 Collins, pg 147
10 the documented notes used in the comparison were not recorded for the purpose of theresearch study.21Yanagawa et al. (1998) followed the preliminary Bernard et al. study of 1997.This study, based in Japan, aimed to compare the effects of hypothermia following out ofhospital cardiac arrest. 28 patients were involved; the hypothermia group were cooled to34°C for 48 hours while the control group was treated per standard practice which did notinclude hypothermia.22The study found that 54% of the hypothermic patients survivedcompared to 33% of the normothermic group. Yet, while only 40% of the normal groupdeveloped pneumonia, pneumonia developed in 85% of the hypothermic patients. Thissuggests that although TH improves outcome after CA, it also increases the incidence ofpneumonia.23However, this study was limited in that it was not a RCT, it was based inone hospital, and it used a historical control group. Furthermore, these factors along withsex and age differences between the two groups led to a potential for either intentional orunintentional research bias towards the sampling methods.24The two randomized controlled trials that served as the basis of the ILCORrecommendations were the Hypothermia after Cardiac Arrest (HACA) trial and theBernard trial.25The HACA trial was conducted in nine centers across five Europeannations while the Bernard Trial was undertaken in four hospitals in Melbourne, 21 Collins, pg 147 22 Collins, pg 147 23 Collins, pg 147 24 Collins, pg 147 25 “Stock Your Emergency Department with Ice Packs: A Practical Guide to TherapeuticHypothermia for Survivors of Cardiac Arrest.” Canadian Medical AssociationJournal 13 March 2009; 176:759-762. pg 759
11 Australia.26The two trials were similar in that they enrolled comatose patientsresuscitated from ventricular fibrillation or pulseless ventricular tachycardia. All patientsreceived advanced cardiac life support with postresusitation care; all were sedated,paralyzed to prevent shivering, and ventilated.27The TH group of both trials were cooledto 32-34°C within six hours of arrest. The hypothermia protocols of the studies differedslightly.In the European study 75 out of the 136 (55%) patients in the hypothermia grouphad a favorable neurological outcome and able to live and work independently sixmonths post arrest compared to 54 of 137 (39%) of the normothermic patients.28After sixmonths, death occurred in 41% of the hypothermic group compared to 55% in thenormothermic group.29The Australian study focused on neurological function at the time of dischargefrom the hospital. Of the 43 patients treated with hypothermia, 21 (49%) had goodneurological function, compared to 9 out of 34 (26%) of patients who did not receiveTH.30A comparison of mortality at discharge presented 51% of TH patients as comparedto 68% of normothermic patients.Mild hypothermia in both studies was associated with fewer deaths and reduceddisability and was statistically significant.31The number-needed-to-treat to reduce 26 Nolan, pg 118 27 “Stock Your Emergency Department with Ice Packs,” pg 759 28 Nolan, pg 119 29 Nolan, pg 119 30 Nolan, pg 119 31 “Stock Your Emergency Department with Ice Packs,” pg 759
12 neurological impairment at six months in the HACA trial was 6. 32The number-needed-to-treat to achieve one additional survivor to discharge in the Bernard trial was 4.33Although well designed, both of these trials were limited by their stringentenrollment criteria. As much as 92% of assessed patients were excluded from the trial.34Why does therapeutic hypothermia lead to this improved outcome in patients? Tounderstand this effect, it is important to understand two concepts, reperfusion injury andthe physiology of hypothermia.Reperfusion Injury and the Physiology of HypothermiaWhen cardiac arrest occurs, there is an immediate cession of blood flow to thebrain. As a result, the cerebral tissue becomes ischemic and oxygen levels are depleted.35Immediately post-resuscitation, there is an excessive increase in cerebral blood flow,however, for the 90 minutes to 12 hours following this, blood flow is decreased to only50% of the baseline value (initial level before CA).36Scientists have known for decadesthat cellular oxygen deprivation causes cell damage and can lead to cellular death,however, due to the work of Dr. Lance Becker of the University of Pennsylvania, we nowhave a better understanding of the physiology behind this occurrence.37When a cellbecomes ischemic, a cycle of three critical reactions occurs within the cell; these cycleslead to further tissue injury and ischemia even after perfusion returns to baseline values, 32 Christenson. 33 Christenson. 34 Nolan, pg 119 35 Koran, Zeb. “Therapeutic Hypothermia in the Postresuscitation Patient: TheDevelopment and Implementation of an Evidence-Based Protocol for theEmergency Department.” Journal of Trauma Nursing Jan-March 2009; 16:48-57.pg 4936 Koran, pg 49 37 Clumpner, pg 53
13 thus earning the term, reperfusion injury.38These reactions include the production ofoxygen free radicals (reactive oxygen species), excitatory amino acid release, andcalcium shifts.39In turn, these lead to mitochondrial damage and apoptosis (programmedcell death).40Within the cell, mitochondria use oxygen to produce energy. Once the oxygen isused, the mitochondrion releases an oxygen free radical. These free radicals are highlyreactive due to an unpaired valence electron.41The reaction of these radicals triggers achemical chain reaction that uses adenosine triphosphate (ATP) and produces lacticacid.42The decreased availability of ATP and increased levels of lactic acid – whichcannot be removed with the decreased perfusion – causes muscle death. Under normalconditions, the body produces antioxidants to counteract the free radicals. However,during major injury or ischemia, the production of these antioxidants is drasticallyreduced and thus the free radicals become a major problem.43Reperfusion injury causes hypotension, vascular and organ dysfunction, cerebraledema and apoptosis.44Hypothermia suppresses many of the chemical reactionsassociated with reperfusion injury and thus counteracts some of the negativephysiological effects that result after resuscitation.45Lowering the core body temperature 38 Clumpner, pg 54 39 Nolan, pg 119 40 Nolan, pg 119 41 Clumpner, pg 54 42 Clumpner, pg 54 43 Clumpner, pg 54 44 Clumpner, pg 54 45 Nolan, pg 119
14 decreases the metabolic rate.46For each 1°C drop in temperature, the cerebral metabolicrate is decreased 6%-7%.47This is advantageous because it decreases oxygen demands inthe same cells that are being deprived of oxygen supplies.48It has been observed that thenegative events (release of free radicals, ion shifts, cell death, etc.) following post-resuscitation ischemia are slowed down by hypothermia.49Mild cardiac hypothermia isthe most potent protector of myocardial function.50Furthermore, approximately 30% of cardiac arrest survivors endure severe braindamage.51Three distinct stages of cerebral damage follow anoxic insult: early,intermediate, and late.52The early stage starts from the moment of insult and lasts an hour after injury.53During this stage, the metabolic demands increase while perfusion decreases. Despite adramatic loss in supplies, the consumption of oxygen, glucose and ATP continue. 54Hypothermia works to significantly reduce the metabolic demands on the brain.55Hypothermia is most beneficial when applied early, within 15 minutes of the onset ofischemia.56 46 Futterman, Laurie G. and Louis Lemberg. “The Significance of Hypothermia inPreserving Ischemic Myocardium.” American Journal of Critical Care 2004;13:79-84. pg 8047 Koran, pg 49 48 Futterman, pg 81 49 Koran, pg 49 50 Futterman, pg 79 51 Koran, pg 49 52 Clumpner, pg 55 53 Clumpner, pg 55 54 Clumpner, pg 55 55 Clumpner, pg 55 56 Futterman, pg 81
15 The intermediate stage spans from 1 to 12 hours post resuscitation.57Excitatoryamino acids and glutamate are released, triggering the ion channels in the brain andcausing a calcium ion rush into the intercellular space.58This activates cytotoxic cascadeswithin the cells causing neuronal cell death.59Increased levels of nitric oxides in the brainafter cardiac arrest can cause vascular dysfunction.60Hypothermia decreases the releaseof excitatory amino acids and glutamate while also decreasing the production of nitricoxide.61The late stage is marked from 12-24 hours post resuscitation.62Markers of thisstage include: cerebral edema, the breakdown of the blood-brain barrier, seizures andirreversible neuronal death.63At this point, hypothermia helps by slowing down thebreakdown and decreasing intracranial pressure and cerebral edema.64In addition to reperfusion injury, patients resuscitated from a ventricularfibrillation cardiac arrest are at a risk of re-fibrillation.65A study led by Dr. KimberleyBoddicker suggests that hypothermia improves defibrillation success and resuscitationoutcomes from VF. In the study, 32 swine were divided into four groups: normothermia(37°C), mild hypothermia (35°C), moderate hypothermia (33°C) and severe hypothermia 57 Clumpner, pg 55 58 Clumpner, pg 55 59Clumpner, pg 55 60Clumpner, pg 55 61 Clumpner, pg 55 62 Clumpner, pg 55 63 Clumpner, pg 55 64 Clumpner, pg 55 65 Boddicker, Kimberly A. et al. “Hypothermia Improves Defibrillation Success andResuscitation Outcomes From Ventricular Fibrillation.” CirculationCardiovascular Quality and Outcomes: Journal of the American Heart Association13 Jun. 2005; 111: 3195-3201. pg 3195
16 (30°C).66After hypothermia had been induced, VF was electrically induced. The VF wasleft unsupported, meaning no CPR or defibrillation, for eight minutes before shockingwith a biphasic defibrillator, providing successive shocks and CPR as needed until returnof spontaneous circulation (ROSC) or no response for greater than 10 minutes.67None of the normothermia group achieved ROSC as compared to 3 out of 8 in themild TH group, 7 of 8 in the moderate TH group, and 5 of 8 in the severe TH group.68This beneficial effect was not due to an alteration of the coronary perfusion pressure, asthat factor was kept constant throughout the groups.69This suggests that a change in themechanical, metabolic, or electrophysical properties of the myocardium was responsiblefor the improved defibrillation and resuscitative outcome with the use of moderate todeep hypothermia.A recent study has shown that for each hour that TH is delayed, the odds ofneurological impairment increase by 30%.70This factor is the reason why it is essential tostart TH in the pre-hospital setting. EMS thus has a crucial role in affecting the futuresurvivability success.As of September 2008, out of the 24,000 EMS agencies in the United States, 100had already implemented a therapeutic hypothermia protocol.71Furthermore, in a surveyled by Benjamin Abella, 265 physicians were questioned regarding their use of TH, theirmethods used, and/or reasons they have not incorporated TH into their practice. Of these 66 Boddicker, pg 3195 67 Boddicker, pg 3195 68 Boddicker, pg 3195 69 Boddicker, pg 3195 70 Clumpner, pg 55 71 Clumpner, pg 55
17 physicians, 87% said they had not used TH.72Of the reasons presented for non-use, 49%felt there were not enough supporting data, 32% cited a lack of incorporation intoadvanced cardiac life support (ACLS) protocols, and 28% mentioned that the methods forcooling were either technically too difficult or too slow.73EMS is a liaison between out-of-hospital patients and medical centers. Anytreatment or care protocol that is to be started in the field of EMS must not possess apotential of harm to the patient. If induced hypothermia is lifted prematurely, the patientmight be harmed, therefore, it is crucial that the medical center continue the treatment.74Hypothermia cannot be implemented in the EMS system if there is no hospital system tocontinue the treatment. It is thus important to analyze the factors inhibiting the inductionof TH protocols in both hospitals and EMS systems.One major setback for the implementation of hypothermia into the standard ofcare for both in-hospital and EMS cardiac arrest care is the lack of evidence. It isimportant to note that although many studies have been conducted examining the effectsof in-hospital therapeutic hypothermia, few studies have researched the effects ofinducing TH within the pre-hospital setting.75The National Association of EMSPhysicians believes that the lack of evidence focused on the induction of TH in the pre-hospital setting precludes the recommendation of the protocol for the standard of care for 72 Abella, Benjamin S. et al. “Induced Hypothermia is Underused After Resuscitationfrom Cardiac Arrest: A Current Practical Survey.” Resuscitation Feb. 2005; 64:181-186.73 Abella et al. 74 “Induced Therapeutic Hypothermia in Resuscitated Cardiac Arrest Patients. PositionStatement Approved by the NAEMSP Board of Directors.” PrehospitalEmergency Care 2008; 12:393-394.75 Clumpner, pg 56
18 all EMS patients resuscitated from CA.76In addition, Dr. G. C. Fisher has argued that alack of thorough detail reports in the two major foundational studies allowed for theclinically skeptic to claim the trials invalid and therefore resist using TH.77To overcomethis factor, either additional research must be conducted, or the current evidence could beaccepted. The European Resuscitation Council serves as an example as it stated that pre-hospital hypothermia is “safe” and effective even if there is a lack of experience.”78Since the induction of TH in a pre-hospital control group is ethically unjustifiable79, EMSfocused trials are difficult, and thus more reliance is placed on the current evidence.Major factors inhibiting the implementation of TH include: the lack of evidence,cost, concern about the continuum of care, the induction methodology, uncertainty ofadverse effects, time, and resources. In addition, personal barriers such as theunawareness and resistance to change of many individuals may be a significant inhibitingfactor.80An in-depth analysis of these factors is presented in the article, “TherapeuticHypothermia: An Analysis of the Factors Inhibiting the Implementation of a GeneralProtocol.” 76 “Induced Therapeutic Hypothermia in Resuscitated Cardiac Arrest Patients.” 77 Fisher, G.C. “Hypothermia After Cardiac Arrest: Feasible but is it Therapeutic?”Anaesthesia: The Association of Anaesthetists of Great Britain and Ireland 2008;63:885-886. pg 88578 Clumpner, pg 56 79 Clumpner, pg 56 80 Neumar, Robert W. et al.“Post Cardiac Arrest Syndrome: Epidemiology,Pathophysiology, Treatment, and Prognostication.” Circulation CardiovascularQuality and Outcomes: Journal of the American Heart Association 23 Oct. 2008;118: 2452-2483 pg 2470
19 ConclusionTherapeutic Hypothermia has many benefits for cardiac arrest patients and hasbeen associated with improving the survival rate of cardiac arrest patients. In addition toincreasing survival rates, TH has also been associated with a decrease in neurologicalimpairment. “TH is the only post-resuscitation therapy shown to improve both survivaland reduce disability after cardiac arrest.”81TH is therefore a beneficial treatment, andshould be implemented as soon as possible, thus within the EMS system. However, if thecontinuum of care cannot be guaranteed at receiving hospitals, TH cannot be started inEMS as an incomplete treatment would cause harm to the patient. Despite severalrecommendations by ILCOR and the AHA, Several factors are inhibiting theimplementation of TH in most medical centers and thus among EMS agencies. An in-depth analysis of these factors is presented in the article, “Therapeutic Hypothermia: AnAnalysis of the Factors Inhibiting the Implementation of a General Protocol.” 81 Cooling Therapy for Cardiac Arrest Survivors is as Cost-Effective as AcceptedTreatments for other Conditions
20 ReferencesAbella, Benjamin S. et al. “Induced Hypothermia is Underused After Resuscitation fromCardiac Arrest: A Current Practical Survey.” Resuscitation Feb. 2005; 64: 181-186.Acute Myocardial Infarction (Heart Attack). Mayo Clinic. Nov. 28, 2009.<http://www.mayoclinic.org/quality/ami.html>.Boddicker, Kimberly A. et al. “Hypothermia Improves Defibrillation Success andResuscitation Outcomes From Ventricular Fibrillation.” CirculationCardiovascular Quality and Outcomes: Journal of the American Heart Association13 Jun. 2005; 111: 3195-3201.Cady, Charles, MD and Steven Andrews MD, EMT-P. “Prehospital Resuscitated CardiacArrest Patients: Role for Induced Hypothermia.” Prehospital Emergency Care2009; 13:402-405.Christenson, James M., MD, FRCPC. “Hypothermia Recommended After VF CardiacArrest.” Journal Watch Emergency Medicine 13 Aug. 2003.Clumpner, Mike and Jim Mobley. “Raising the Dead: Prehospital Hypothermia forCardiac Arrest Patients May Improve Neurological Outcome and Survival toDischarge.” EMS Sep. 2008: 52-60.Cooling Therapy for Cardiac Arrest Survivors is as Cost-Effective as AcceptedTreatments for other Conditions. 4 Aug. 2009, American Heart Association. 28Nov. 2009.<http://americanheart.mediaroom.com/index.php?s=43&item=795&printable>.Collins, Tim J. and Peter J. Samworth. “Therapeutic Hypothermia Following CardiacArrest: A Review of the Evidence.” Nursing in Critical Care: British Associationof Critical Care Nurses 2009; 13:144-151.“Early Defibrillation. Position Statement Approved by the NAEMSP Board of DirectorsSep. 2007.” Prehospital Emergency Care 2008; 12:393-394.Emergency Resuscitation Center: Fighting for Life… At the Edge of Sudden Death.Overview of Science and Mission. The University of Chicago. 28 Nov. 2009.<http://erc.uchicago.edu/html/overviewmission/hypothermiaprotocols.html>Ewy, Gordon A. “Cardiocerebral Resuscitation: The New CardiopulmonaryResuscitation.” Circulation Cardiovascular Quality and Outcomes: Journal of theAmerican Heart Association 2005; 111:2134-2142.Fisher, G.C. “Hypothermia After Cardiac Arrest: Feasible but is it Therapeutic?”Anaesthesia: The Association of Anaesthetists of Great Britain and Ireland 2008;63:885-886.
21 Futterman, Laurie G. and Louis Lemberg. “The Significance of Hypothermia inPreserving Ischemic Myocardium.” American Journal of Critical Care 2004;13:79-84.Foëx, Bernard A. and John Butler. “Therapeutic Hypothermia After Out of HospitalCardiac Arrest.” Emergency Medicine Journal 2004; 21:590-591.Hayes, Jeff, BS, LP. “If I Die… I want to be in Austin, TX.” (Lecture). Texas EMSConference, Ft. Worth, TX, Nov. 23, 2009.“Induced Therapeutic Hypothermia in Resuscitated Cardiac Arrest Patients. PositionStatement Approved by the NAEMSP Board of Directors.” PrehospitalEmergency Care 2008; 12:393-394.Koran, Zeb. “Therapeutic Hypothermia in the Postresuscitation Patient: TheDevelopment and Implementation of an Evidence-Based Protocol for theEmergency Department.” Journal of Trauma Nursing Jan-March 2009; 16:48-57.Martini, Frederic H., Ph.D. et al. Anatomy and Physiology for Emergency Care SecondEdition. New Jersey: Pearson Prentice Hall, 2008.McQuillan, Karen. “Inducing Hypothermia After Cardiac Arrest.” Critical Care Nurse 4Aug. 2009; 29:75-78.Merchant, Raina M. et al. “Cost-Effectiveness of Therapeutic Hypothermia After CardiacArrest.” Circulation Cardiovascular Quality and Outcomes: Journal of theAmerican Heart Association 4 Aug. 2009; 2:421-428.Neira, Jorge A., MD, FCCM. “Post-Resuscitation Care Induced Hypothermia to Whom,How, and When?” (Presentation). World Congress of Cardiology, Buenos Aires,Argentina, May 18-21, 2008.Neumar, Robert W. et al.“Post Cardiac Arrest Syndrome: Epidemiology,Pathophysiology, Treatment, and Prognostication.” Circulation CardiovascularQuality and Outcomes: Journal of the American Heart Association 23 Oct. 2008;118: 2452-2483.Nolan, J.P. et al. “Therapeutic Hypothermia After Cardiac Arrest: An AdvisoryStatement by the Advanced Life Support Task Force of the International LiaisonCommittee on Resuscitation.” Circulation Cardiovascular Quality and Outcomes:Journal of the American Heart Association 2003; 108: 118-121.Post-Cardiac Arrest Care Key to Survival. 23 Oct. 2008, American Heart Association. 28Nov. 2009.<http://americanheart.mediaroom.com/index.php?s=43&item=554&printable>.“Prehospital Management of Acute Myocardial Infarction. Position Statement Approvedby the NAEMSP Board of Directors May 27, 2007.” Prehospital Emergency Care2008; 12:393-394.
22 Rho, Robert W., MD.” Cardiac Arrest: Sudden Cardiac Death.” Conn’s Current Therapy2009. Philadelphia, PA: Saunders Elsevier, 2009.“Stock Your Emergency Department with Ice Packs: A Practical Guide to TherapeuticHypothermia for Survivors of Cardiac Arrest.” Canadian Medical AssociationJournal 13 March 2009; 176:759-762.
23 Appendix AExplanation of Terms• Myocardial Infarction (MI)- heart attack, the term "myocardial infarction" focuseson the myocardium (the heart muscle) and the changes that occur in it due to thesudden deprivation of circulating blood. The main change is necrosis (death) ofmyocardial tissue.• Cardiac Attack- heart attack• Cardiac Arrest- A primary cardiac disorder that results in sudden loss of cardiacoutput and a resultant loss of end-organ perfusion resulting in death unless theprimary cardiac disorder is corrected.• Heart Rhythmso Normal Sinus RhythmNormal beating of the heart.o Ventricular Fibrillation (VF)-
24 Arrhythmia in which uncoordinated contractions of the myocardiumcauses the ventricles to tremble rather than contact properly.o Ventricular Tachycardia (VT)Arrhythmia that consists of rapid ventricular contractions that deter thecirculation ability by decreasing the refill time of the ventricles, thusdecreasing the volume of blood pumped.o Pulseless Electrical Activity (PEA)A clinical condition characterized by unresponsiveness and lack ofpalpable pulse in the presence of organized cardiac electrical activity.o AsystoleCardiac standstill with no cardiac output and no ventricular depolarization;it eventually occurs in all dying patients.• Induced Hypothermia –
25 The lowering of a patient’s core body temperature.• Standard of Care –A diagnostic and treatment process that a clinician should follow for a certaintype of patient, illness, or clinical circumstance• Emergency Medical Services (EMS)-The organized systems with set protocols for responding to, providing definitivecare, and transport of patients in the event of an out-of-hospital medical ortraumatic emergency.• Comatose-A state of unconsciousness.• Return of Spontaneous Circulation (ROSC)-A palpable pulse that is present after clinically documented asystole.