Neurology International 2010; volume 2:e3

Protective head-cooling during cardiac arrest and cardiopulmonary resuscitation:the original animal studiesEric W. Brader,1 Dietrich Jehle,2Michael Mineo,2 Peter Safar3*1Department of Emergency Medicine,Allegheny General Hospital, Pittsburgh,PA;2State University of New York at Buffalo,Department of Emergency Medicine,Buffalo, NY; 3University of Pittsburgh, Safar Centerfor Resuscitation Research, Pittsburgh,Pennsylvania, USA *deceased

Abstract

Prolonged standard cardiopulmonary resus-citation (CPR) does not reliably sustain brainviability during cardiac arrest. Pre-hospitaladjuncts to standard CPR are needed in orderto improve outcomes. A preliminary dog studydemonstrated that surface cooling of the headduring arrest and CPR can achieve protectivelevels of brain hypothermia (30°C) within 10minutes. We hypothesized that protectivehead-cooling during cardiac arrest and CPRimproves neurological outcomes. Twelve dogsunder light ketamine-halothane-nitrous oxideanesthesia were arrested by transthoracic fib-rillation. The treated group consisted of sixdogs whose shaven heads were moistenedwith saline and packed in ice immediatelyafter confirmation of ventricular fibrillation.Six control dogs remained at room tempera-ture. All 12 dogs were subjected to four min-utes of ventricular fibrillation and 20 minutesof standard CPR. Spontaneous circulation wasrestored with drugs and countershocks.Intensive care was provided for five hours post-arrest and the animals were observed for 24hours. In both groups, five of the six dogs hadspontaneous circulation restored. After threehours, mean neurological deficit was signifi-cantly lower in the treated group (P=0.016,with head-cooled dogs averaging 37% and thenormothermic dogs 62%). Two of the six head-cooled dogs survived 24 hours with neurologi-cal deficits of 9% and 0%, respectively. None ofthe control group dogs survived 24 hours. Weconcluded that head-cooling attenuates braininjury during cardiac arrest with prolongedCPR. We review the literature related to theuse of hypothermia following cardiac arrestand discuss some promising approaches forthe pre-hospital setting.

Introduction

More than 340,000 Americans die each yearof coronary heart disease in the pre-hospitalsetting.1 In addition, there are a large numberof patients who sustain permanent neurologi-cal damage following successful resuscitationfrom cardiac arrest. Adjuncts to cardiopul-monary resuscitation (CPR) are needed toimprove the neurological outcome of thesepatients. Application of protective therapyprior to restoration of circulation, such ashypothermia, may prevent the post-ischemicencephalopathy that follows cardiac arrest.One of the most important mechanisms bywhich therapeutic hypothermia prevents fur-ther damage to the brain is by decreasing theoxygen demand of cerebral tissue.2

Hypothermia, whether intentional or byaccident, has long been known to prevent braindamage during cardiac arrest. Hypothermiahas also been employed after return of spon-tan-eous circulation with some encouragingresults.3,4 Instead of allowing hypothermia to beof value in only these rare patients, it was pro-posed that the application of hypothermia beexamined as a protective tool during “routine”cardiac arrest. This study, completed in 1984,compared cardiac and cerebral resuscitabilityof normothermic versus head-cooled dogs sub-jected to a prolonged CPR insult.5 The authorshypothesized that protective head-cooling dur-ing cardiac arrest and CPR achieves protectivelevels of brain hypothermia and results inimproved neurological outcomes.This study was conducted initially in the early

1980s and published as an abstract in 1985.5

From the 1990s to the present there has been aregained interest in the topic with a flourishingof publications related to the topic. The resulthas been organizations such as the CanadianResuscitation Council and the CanadianAssociation of Emergency Physicians releasingposition statements advocating head-cooling forpatients who present with non-perfusing ven-tricular fibrillation or ventricular tachycardiaand are resuscitated to hemodynamic stabilityyet remain unresponsive.6,7 The optimal methodof achieving cooling is still unclear, with multi-ple methods being applied. The data from thisstudy, conducted over two decades ago, is beingpublished here for both historical value andbecause the data specifically on head-coolingduring cardiac arrest may contribute to thisongoing discussion.

Materials and Methods

A series of pilot experiments was performedto investigate cooling rates of the brain atroom temperature and with head-cooling. The

formal experimental study was set up to inves-tigate the role of head-cooling initiated at theonset of witnessed pre-hospital cardiac arrest.The experimental protocol was designed toreplicate a witnessed cardiac arrest, with fourminutes of ventricular fibrillation (VF), 20minutes of basic life support (BLS), followedby advanced cardiac life support (ACLS). Thisstudy was approved by the institutional reviewboard, and the Animal Care and UseCommittee of the Allegheny-Singer ResearchInstitute.

Pilot studySeveral pilot experiments were preformed

to investigate the feasibility of achieving pro-tective levels of brain hypothermia within tenminutes of cardiac arrest, utilizing head sur-face cooling. Three dogs were prepared in asimilar fashion to the formal study with theexception of having temperature probes, insu-lated and sealed with bone wax, placed in thecardiac portion of the esophagus, below thegalea, in the rectum, and one centimeter intothe right frontoparietal cerebral cortex. Aftertransthoracic electrical induction of VF, Dog #1was allowed to cool undisturbed, with no CPRand no head-cooling, at room temperature,Dog #2 was head-cooled after induction of VFbut had no CPR performed, and Dog #3 washead-cooled while CPR was administered forVF by a Michigan Instruments “thumper.” Afourth undisturbed pilot study was performedwith a prototype cooling device (NH4NO3 – H20;cold pack technology) and with probes in thethalamic, subcortical, and subgaleal regions.

Correspondence: Dietrich Jehle, State Universityof New York at Buffalo, Department of EmergencyMedicine, 462 Grider Street, Buffalo, NY 14215,USA. E-mail: jehle@ecmc.edu

Key words: head-cooling, cerebral hypothermia,cerebral resuscitation, cardiopulmonary resusci-tation.

Acknowledgements: the authors thank Dr. FritzSterz, from the University of Vienna, for hisassistance in providing reference materials forthe preparation of this manuscript. Support wasgenerously granted by Allegheny-SingerResearch Institute and the Safar Center forResuscitation Research.

Received for publication: 9 December 2009.Revision received: 29 January 2010.Accepted for publication: 29 January 2010.

This work is licensed under a Creative CommonsAttribution 3.0 License (by-nc 3.0).

©Copyright E.W. Brader et al., 2010Licensee PAGEPress, ItalyNeurology International 2010; 2:e3doi:10.4081/ni.2010.e3

[page 14] [Neurology International 2010; 2:e3]

Experimental studyTwelve healthy flat-chested mongrel dogs

weighing 12-25 kg were fasted overnight withwater ad lib. All dogs were premedicated withketamine (10 mg/kg IM) and anesthetizedwith halothane (0.75-4.0%), nitrous oxide(50%), and oxygen (50%). Endotracheal intub-ation was performed with a cuffed tube whenanesthesia reached sufficient depth. Pre-insult rectal and cardiac temperatures weremaintained at 37-38°C. Infra-diaphragmaticaortic catheters and Swan-Ganz catheters withtemperature probes were placed by femoralcutdown. All dogs had their heads shaved. Thelevel of anesthesia was allowed to lighten byallowing all dogs to spontaneously breatheroom air for 4-6 min. VF was induced transthor-acically with 100 volts alternating current for 3sec. Upon confirmation of VF, six dogs werecooled by having bags of ice placed aroundtheir heads. All dogs were subjected to 4 minventricular fibrillation and 20 min “controlled”CPR. Sixty chest compressions per minute andone interposed ventilation (TV=25 mL/kg, F101.0) per five compressions were deliveredusing a Michigan Instruments “thumper.”Initial systolic blood pressure during CPR wasmaximized but not allowed to exceed 70mmHg. Initial chest compression was limitedto two inches after 1-2 min manual CPR toloosen the chest. Sandbags were used to stabi-lize the chest laterally. If systolic blood pres-sure was not maintained above 30 mmHg after10 min CPR, the animal was excluded.Restoration of total spontaneous circulation(ROSC) was achieved using the 1984 ACLSprotocol (Figure 1) and the total number ofACLS steps was calculated. Mean arterial pres-sure was maintained above 60 mmHg using acontinuous epinephrine infusion and fluidadministration titrated by pulmonary arterypressure and/or central venous pressure.Following ROSC, the ice bags were removedfrom the head and warming was achieved byheating pads applied to the body but not to thecold, wet head. One hour after ROSC, theweaning process was begun. All dogs received4-5 hr intensive care. Then they were returnedto their cages with supplemental oxygen andmaintenance IVs. Neurological deficit scores(NDS) were obtained at 3, 12, and 24 hr post-resuscitation. A slightly modified version ofthe neurological scoring system of theResuscitation Research Center was employedto assess neurological outcome (Figure 2). AnNDS of 100% represented brain death. No neu-rological scoring was performed when car-diopulmonary decline prevented adequateneurological testing (Figure 3). Data were analyzed using the Student’s two-

tailed t-test for independent means, unlessotherwise referenced.

Results

Pilot studyIn the pilot studies, therapeutic levels of cor-

tical hypothermia were reached within 10 min-utes (<32°C) in head-cooled dogs (ice)whether CPR was applied or not (Figure 4A).Extremely hypothermic subgaleal tempera-tures (26°C) were achieved within 10 minutesin instrumented animals with an ice packtechnology (ammonium nitrate) coolingdevice (Figure 4B).

Experimental studySix preliminary trials of the experimental

study were initially carried out to formalize theprotocol. All of the following 12 animals thatwere fibrillated were able to achieve ROSC andmet inclusion criteria.Head-cooled dogs had significantly better

neurological outcomes than control dogs(P=0.016). Mean NDS for head-cooled dogs atthree hours was 37.2% while mean NDS forcontrol dogs was 61.8%. Two head-cooled dogssurvived 24 hours. One was neurologicallyintact while the other had an NDS of 9%. Nocontrol dogs survived 24 hours. One controldog had life support terminated after braindeath, as defined by NDS (Figure 2), at 18hours. With the exception of the previouslymentioned dog, all dogs who failed to survive24 hours died of cardiopulmonary causes.In spite of statistically significantly lower

core temperatures at the time of defibrillation(P=0.04; one-tailed t-test), head-cooled dogs

had the same ease of cardiac resuscitation. Inaddition, mean ACLS steps required to restorespontaneous circulation was not significantlydifferent between head-cooled and controldogs (P=0.713; 5 vs. 5.7 ACLS steps, respec-tively). In both groups, five of the six dogs hadsuccessful ROSC. Mean arterial pressureobtained during CPR was not significantly dif-ferent (P=0.262) between head-cooled (25.50mmHg) and control (19.85 mmHg) groups. In head-cooled dogs, core temperature

became significantly lower than rectal temper-ature (P<0.001) one minute after ROSC andremained so (P=0.004) at five minutes afterROSC (Figure 5). The nadir of afterdrop, thatis drop in cardiac temperature after ROSC,occurred one minute after ROSC and averaged1.6°C with core temperature falling to 34.5°C.In control dogs, core and rectal temperaturesnever became significantly different (<0.25°Cdifference at 20 min of CPR). Rewarming wasaccomplished in one hour. There was no statis-tical difference in weight (P=0.442), core(P=0.619) and rectal (P=0.941) temperature,conjunctival oxygenation (P=0.945), and arte-rial pressure (P=0.968) between the groups atbaseline.

Discussion

Cardiac arrest results in cerebral hypoperfu-sion with resultant global brain ischemia. Inaddition to the immediate damage caused byhypoxemia, there is a cascade of injuries

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Figure 1. Advanced cardiac life support protocol in use in 1984.

ACLS Step

0 Minutes1. HCO3 -1 mEq/Kg IV #12. Epi 1 mg IV #13. D5 ½ NSS - 10% EBV over 15 minutes IV #14. CPR for 1 minute - then CS with 200J if in VF #25. CS at 200J if still in VF after 1st CS #3

5 Minutes1. Epi 1 mg IV #42. Draw ABG #43. CS at 200J x 2 #5 #6

10 Minutes1. HCO3 - by ABG if available or 0.5 mg/kg #72. Epi 1 mg IV #73. Lidocaine 1 mg/kg IV bolus #74 CS at 200J x 2 #8 #9

15 Minutes1. Epi 1 mg IV #102. CS at 200J x 2 #11 #12

*If no spontaneous circulation - terminate study; **If asystole or EMD - give Epi, HCO3 - CPR as above and atropine 0.5 mg IV for asystole orEMD < 60/min; give no CS or lidocaine.

induced by reperfusion. Reperfusion injuriesare mediated by several mechanisms includingprotein synthesis inhibition, induction of pro-teases, and excitatory amino acid release.8

This study consisted of a dog model thatsimulated pre-hospital cardiac arrest with fourminutes of down time prior to initiation of 20minutes of standard CPR (BLS). Head-coolingwas started at the onset of arrest and was con-tinued during CPR, followed by ACLS. Head-cooled dogs had significantly better neurologi-

cal outcomes than control dogs three hoursafter spontaneous return of circulation. Theseresults have been bolstered further by severalsubsequent studies that reinforce the premisethat there are benefits of induced hypothermiain cardiac arrest.2,9-12 Leonov, et al. also report-ed that mild hypothermia induced after theonset of cardiac arrest improves neurologicalperformance, function, and overall brain mor-phology.9

While several mechanisms may play a role,

head-cooled dogs demonstrated awareness atthree hours post-arrest while no control dogsdid. Although longer, more controlled post-resuscitation studies are needed, it is felt thatthe superior three-hour NDS of head-cooleddogs is a valid indication of cerebral protectionand insult attenuation. It has also been postu-lated that profound subgaleal cooling may redi-rect blood flow from the external to the inter-nal carotid system, thus improving the efficacyof CPR in generating blood flow to the brain.Regional rates of cooling have been exam-

ined in a cold water drowning model in whichcanines were submerged in cold water withclamped endotracheal tubes. Rate of corticalcooling after arrest in this experiment wasfound to be comparable to the rate found in ourfeasibility study. Cortical temperatures werefound to drop faster than cardiac tempera-tures, as would be expected if conduction werethe dominant mechanism of cooling. No divingreflex was noted to occur.13 These findings sug-gest that conductive cooling may be sufficientto account for cerebral protection in cold waterdrowning. As in accidental and intentionalhypothermia, mild afterdrop was found tooccur in head-cooled dog resuscitations.Apparently afterdrop was not of sufficient mag-nitude to trigger rescue arrest as none wasnoted to occur. A limitation of this study is the use of sodi-

um bicarbonate as part of the ACLS protocol.These experiments were conducted originallyin 1984, and at that time sodium bicarbonatewas utilized in the ACLS protocol. However,there is some recent data suggesting sodiumbicarbonate is beneficial in prolonged cardiacarrest.14 Researchers also could not be blindedas to which dogs were in the head-cooledgroup or the control group. Objective NDS scor-ing scales were used in an attempt to mini-mize scoring biases. In addition, the studycould have benefited from longer observationperiods and histological examination of thebrain at autopsy.

Review of the literatureThe therapeutic use of hypothermia was

described as early as the times of theEgyptians, Greeks, and Romans.15 Napoleon’ssurgeon-general reported that wounded sol-diers placed closer to the fire died quicker thansoldiers not warmed.16 In the modern era, ther-apeutic hypothermia was described in a seriesof case reports in 1958 by a surgeon whocooled patients (30-34°C) with signs of severeneurological injury after cardiac arrest. Threeof these patients recovered completely whileone had a moderate neurological deficit afterrecovery.17 Other case reports have describedboth intentional and unintentional hypother-mia enabling patients to remain neurological-ly intact after one hour of total circulatoryarrest in pediatric open heart surgery,18 after

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Figure 2. Canine neurological deficit scoring.

1. Level of Consciousness 0 = Normal30 = Clouded45 = Delirium60 = Stupor100 = Coma

2. Respiration0 = Normal25 = Hyperventilate50 = Severe hyperventilation

100 = Apnea or near apnea

3. Cranial nerve function Pupil size 0 = Normal (4-7mm diameter)2 = Abnormal (8mm diameter)5 = Severe R/L side abnormal

Light reflex 0 = Normal2 = Sluggish or R/L side variable5 = Absent

Eye Position 0 = Normal 2 = Moderately abnormal 5 = Severely Abnormal

4. Lid reflex0 = Normal 2 = Sluggish5 = Absent

5. Corneal Reflex0 = Normal2 = Sluggish R/L side5 = Absent

6. Oculocephalic reflex 0 = Normal (quick return)5 = Abnormal (slow return)10 = Absent

7. Menace reflex 0 = Normal (present)5 = Sluggish10 = Absent

8. Auditory response 0 = Normal5 = Sluggish 10 = No Response

9. Gag Reflex0 = Normal5 = Sluggish10 = Absent

10. Carinal Reflex 0 = Normal5 = Sluggish10 = Absent

11. Position0 = Normal10 = Mildly Abnormal 25 = Severely Abnormal

12. Muscle Tone0 = Normal 10 = Mildly Abnormal 25 = Very Abnormal

13. Paralysis0 = Normal Response/Reflexes10 = Some Movement 25 = Abnormal

14. Pain Stimuli0 = Normal Response10 = Sluggish25 = No Response

15. Feeding/Drinking0 = Normal 15 = Abnormal

16. Chewing0 = Normal 15 = Cannot Chew

17. Sitting0 = Normal 15 = Cannot Sit

18. Standing0 = Can Stand 15 = Cannot Stand

19. Walking0 = Can walk without ataxia15 = Walk with ataxia30 = Cannot walk

20. Cleaning0 = Can clean self10 = Cannot clean self

Maximum score 500 points = 100% neurological deficit = brain death. When testing motor function and behavior, disregard functional impair-ment caused by cutdowns.

forty minutes of submersion in cold water,19

and after three-and-a-half hours of externalCPR.10

The topic of therapeutic hypothermia in thetreatment of cardiac arrest has regained inter-est in the late 1990s. In 1997, Bernard, et al.published a report in which they prospectivelystudied patients who suffered out-of-hospitalcardiac arrest and remained unconscious afterreturn of spontaneous circulation. They sur-face-cooled these patients in the ED and ICUfor twelve hours and compared their neurolog-ical outcome with a control group of similarpatients studied by retrospective chart review.They concluded that neurological outcome wassignificantly improved and mortality decreasedin the mild hypothermic group with noincrease in complications.20 A similar 1998study by Yanagawa, et al. surface-cooledpatients for 48 hours and demonstrated atrend, although not statistically significant,toward increased survivability with mildhypothermia. Their cooled patients had anincreased incidence of pulmonic complica-tions, but they theorized this was because ofextended (five to six days) use of paralytic andsedative agents.21 In 2000, the HypothermiaAfter Cardiac Arrest (HACA) Study Group pub-lished a prospective study on the feasibilityand safety of therapeutic hypothermia aftercardiac arrest.12 They cooled patients in the EDafter out-of-hospital cardiac arrest using head-cooling and external body cooling blankets,maintained these patients in mild hypother-mia for 24 hours, followed by passive re-warm-ing. They concluded that these patients had atwo-fold improvement in outcome as comparedto historical normothermic controls, withoutincreasing the incidence of sepsis, coagulopa-thy, neutropenia, or thrombocytopenia. Yana-gawa, et al. suggested that even patients without-of-hospital cardiac arrest and out-of-hospi-tal ROSC without witnessed arrest, bystanderCPR, or initial rhythm of ventricular asystolemay benefit from induced hypothermia.22

Although there is general agreement thatmild hypothermia is most beneficial whiledeep hypothermia can be detrimental,23,24 dif-ferent studies have used alternative methodsthat achieve hypothermia at different rates.Animal studies have shown that a fifteenminute delay in cooling can negate the benefi-cial effects of mild hypothermia.25 The HACAStudy Group of 2000 took an average of 287minutes to achieve adequate hypothermia,12

and the study by Feldberg, et al. required anaverage of 301 minutes to adequately coolpatients, despite using both cooling blanketsand iced gastric saline lavage.26 Feldberg andcolleagues concluded that externally inducedmild hypothermia is both slow and imprecise.Hachimi-Idrissi, et al. utilized a helmet deviceto achieve mild hypothermia post-ROSC inpatients with cardiac arrest who remained

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Neurological Deficit Scoring (NDS):

ND SCORING SUMMARY:

Points Scores %Best Worst Best Worst

1) Level of Consciousness 0 100 0 202) Respiration 0 100 0 203) Cranial Nerve Function 0 100 0 04) Motor and Sensory Function 0 100 0 205) Behavior 0 100 0 20

TOTAL 0 500 0 100%

Figure 3. Neurological scoring system. Neurological deficit scoring carried out as per pro-tocol, using modifications of the methods of Nemoto, et al. and Grisvold, et al. Clinicalneurological results expressed as neurological deficit (ND) score in percent. ND 100%means brain death and 0% means normal.

Figure 4. (A) Rates of cortical cooling. (B) Rates of cooling by regions of the brain with-out cardiopulmonary resuscitation.

Dog #1 - Room Temp.

Thalamic

Supracortical

Subgaleal

Dog #2 -Head cooledwithout CPRDog #3 -Head cooledwith CPR

Time (minutes)

Time (minutes)

Co

rtic

al te

mp

era

ture

(C

)Te

mp

era

ture

(C

)

0 5 10 15 20

0 2 4 6 8 10 12 14 16 18 20

45

40

35

30

25

20

15

42

40

38

36

34

32

30

28

26

24

22

Figure 5. Core temperature (Swan-Ganz) vs. rectal temperature for head-cooled group.

Te

mp

era

ture

(C

)

Time (minutes)

Core temp

Rectal temp

37.5

37.25

37

36.75

36.5

36.25

36

0 5 10 15 20

A

B

unconscious after return of spontaneous circu-lation. They were able to achieve a tympanictemperature of 34°C in a median of sixty min-utes while it took a median of 180 minutes toachieve mild core hypothermia.27 Nozari, et al.attained tympanic temperatures of 34°C afterapproximately 20 minutes utilizing venoven-ous shunt cooling in an animal model.28 Kim, etal. were able to rapidly reduce core tempera-ture by 1.7°C in chemically paralyzed patientsby rapid infusion of 2 L of 4°C normal saline.29

The plethora of pilot and feasibility studiesin the late 1990s and early 2000s led to tworandomized controlled studies published in theNew England Journal of Medicine in February2002. The study by Bernard et al. comparedmoderate hypothermia to normothermia inpatients who remained unconscious afterresuscitation from out-of-hospital cardiacarrest.11 Patients were randomized to normo-thermia or hypothermia based on day of theweek, and hypothermic patients were cooled inthe field and later in the ED using cold packsapplied to the head and torso. They were main-tained moderately hypothermic for twelvehours, and then were actively re-warmed start-ing at eighteen hours. The researchers con-cluded that moderate hypothermia for twelvehours after resuscitation resulted in a signifi-cant improvement in outcome, but not a signi-ficant improvement in mortality. Therapeutichypothermia was not associated with clinicallysignificant adverse effects.The study by the HACA Study Group ana-

lyzed the use of mild hypothermia in improv-ing neurological recovery after resuscitationfrom out-of-hospital cardiac arrest.12 Patientswho met the inclusion criteria and werebrought to a participating ED were randomizedvia a sealed envelope to either the mildhypothermia or control group. Patients in themild hypothermia group were cooled using anexternal cooling device and maintained mildlyhypothermic for twenty-four hours followed bypassive re-warming. The patients in the mildhypothermic group had both a significantdecreased mortality rate and improved neuro-logical outcome as compared with standard life

support. There was not a significant differencein complication rate between the groups,although there was a non-statistically signifi-cant higher incidence of sepsis in thehypothermic group.

RecommendationsBased on these promising studies, the ALS

Task Force of the International LiaisonCommittee on Resuscitation (ILCOR) recom-mends that unconscious adult patients withspontaneous circulation after out-of-hospitalcardiac arrest should be cooled to 32-34°C for12-24 hours when the initial rhythm is ventric-ular fibrillation.6,30 Although they make no spe-cific recommendation in terms of methodologyto achieve mild hypothermia, a variety of cool-ing methods have been applied in the past.These include cooling blankets, direct applica-tion of ice, iced saline gastric lavage, venouscooling, and cooling during bypass. None ofthese methods has met the ideal criteria ofease of use in the field along with quicklyreaching mildly hypothermic temperatures.There are several very promising cooling tech-niques for use in the pre-hospital setting:including ice packs (Figure 6), cooling hel-mets,27 and cold IV fluid infusion.29,31

Conclusions

Cooling of the head is advantageous oversystemic surface-cooling by limiting the dropin cardiac temperature prior to return of spon-taneous circulation and its ease of application.Head-cooling can be applied clinically with adevice employing cold pack technology that isportable, inexpensive, and applicable by lay-men in the field. This study shows that head-cooling is a promising means of protecting thebrain during CPR that does not have anadverse effect on cardiac resuscitation.

References

1. American Heart Association. HeartDisease and Stroke Statistics, 2006Update. Retrieved March 30, 2006 fromhttp://circ.ahajournals.org/cgi/content/short/113/6/e85

2. Safar P, Xiao F, Radovsky A, et al. Improvedcerebral resuscitation from cardiac arrestin dogs with mild hypothermia plus bloodflow promotion. Stroke 1996;27:105-13.

3. Wolfe KB. Effect of hypothermia on cere-bral damage resulting from cardiac arrest.Am J Card 1960;6:809-12.

4. Rosomoff HL, Shulman K, Raynor R, et al.Experimental brain injury and delayedhypothermia. Surg Gynecol Obstet 1960;

110:27-32.5. Brader E, Jehle D, Safar P. Protective headcooling during cardiac arrest in dogs. AnnEmerg Med 1985:14:510.

6. European Resuscitation Council. ERCGuidelines 2005. Retrieved March 30,2006. http://www.erc.edu/index.php/guide-lines_download_2005/en/?

7. Canadian Association of EmergencyPhysicians. Position statement and guide-lines for the use of hypothermia after car-diac arrest. http://www.caep.ca/002.poli-c ies /002-01.guidel ines /guidel ines-docs/HypothermiaPositionStatement2005-e.pdf

8. Angelos MG, Menegazzi JJ, Callaway, CC.Bench to bedside: resuscitation from pro-longed ventricular fibrillation. Acad EmergMed 2001;8:909-24.

9. Leonov Y, Sterz F, Safar P, et al. Mild cere-bral hypothermia during and after cardiacarrest improves neurologic outcome indogs. J Cerebral Blood Flow Metab 1990;10:57-70.

10. Schissler P, Parker MA, Scott SJ Jr.Profound Hypothermia: value of prolongedcardiopulmonary resuscitation. South MedJ 1981;74:474-7.

11. Bernard SA, Gray TW, Buist MJ, et al.Treatment of comatose survivors of out-of-hospital cardiac arrest with inducedhypothermia. N Engl J Med 2002;346: 557-63.

12. The Hypothermia after Cardiac ArrestStudy Group. Mild therapeutic hypother-mia to improve the neurologic outcomeafter cardiac arrest. N Engl J Med 2002;346:549-56.

13. Tisherman S, Chabal C, Safar P, et al.Resuscitation of dogs from cold-water sub-mersion using cardiopulmonary bypass.Ann Emerg Med 1985;14:389-96.

14. Vukmir RB, Katz L. Sodium BicarbonateStudy Group. Sodium bicarbonateImproves outcome in prolonged prehospi-tal cardiac arrest. Am J Emerg Med 2006;24:156-61.

15. Cool Heart Steering Committee. TheCoolHeart™ Registry Mild Hypothermia inCardiac Arrest. Retrieved April 22, 2004,from http://www.coolheart.com/materi-als/materials.html.

16. Larry IJ. Memoirs of Military Service andcampaigns of the French Army. Vol 2.Baltimore: J Cushing, 1814, 156-64.

17. Williams GR, Spencer FC. The clinical useof hypothermia following cardiac arrest.Ann Surg 1958;148:462-8.

18. Dillard DH, Mohri H, Merendino KA.Correction of heart disease in infancy uti-lizing deep hypothermia and total circula-tory arrest. J Thorac Cardiovasc Surg 1971;61:64-9.

19. Siebke A, Rod T, Breivik H, et al. Survival

Article

[page 18] [Neurology International 2010; 2:e3]

Figure 6. Ice packs to the head.

after 40 minutes submersion without cere-bral sequelae. Lancet 1975;1:1275-77.

20. Bernard SA, Jones BM, Horne MK. Clinicaltrial of induced hypothermia in comatosesurvivors of out-of-hospital cardiac arrest.Ann Emerg Med 1997;30:146-53.

21. Yanagawa Y, Ishihara S, Norio H, et al.Preliminary clinical outcome study of mildresuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resusci1998;39:61-6.

22. Yanagawa Y, Takasu A, Sakamoto T, et al.Indications and limitations of inducedhypothermic therapy for out-of-hospitalcardiopulmonary arrest. Am J Emerg Med2006;24:214-6.

23. Weinrauch V, Safar P, Tisherman S, et al.Beneficial effects of mild hypothermia anddetrimental effect of deep hypothermiaafter cardiac arrest in dogs. Stroke 1992;23:1454-62.

24. Zeiner A, Holzer M, Sterz F, et al. Mild resus-citative hypothermia to improve neurologi-cal outcome after cardiac arrest: a clinicalfeasibility trial. Stroke 2000;31:86-94.

25. Kuboyama K, Safar P, Radovsky A, et al.Delay in cooling negates the beneficialeffect of mild resuscitative cerebralhypothermia after cardiac arrest in dogs: aprospective randomized study. Crit CareMed 1993;21:1348-58.

26. Feldberg RA, Krieger DW, Chuang R, et al.Hypothermia after cardiac arrest: feasibil-ity and safety of an external cooling proto-col. Circulation 2001;104:1799-804.

27. Hachimi-Idrissi A, Corne L, Ebinger G, etal. Mild hypothermia induced by a helmetdevice: a clinical feasibility study. Resu-scitation 2001;51:275-81.

28. Nozari A, Safar P, Stezoski SW, et al. Mildhypothermia during prolonged cardiopul-monary cerebral resuscitation increases

conscious survival in dogs. Crit Care Med2004;32:2110-6.

29. Kim F, Olsufka M, Carlbom D, et al. Pilotstudy of rapid infusion of 2 L of 4˚C normalsaline for induction of mild hypothermiain hospitalized, comatose survivors of out-of-hospital cardiac arrest. Circulation2005;112:715-9.

30. Nolan JP, Morley PT, Hoek TL, et al.Therapeutic hypothermia after cardiacarrest. An advisory statement by theAdvancement Life Support Task Force ofthe International Liaison committee onResuscitation. Resuscitation 2003;57:231-5.

31. Bernard S, Buist M, Monteiro O, et al.Induced hypothermia using large volume,ice-cold intravenous fluid in comatose sur-vivors of out-of-hospital cardiac arrest: apreliminary report. Resuscitation 2003;56:9-13.

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