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Therapeutic Hypothermia. Joseph Foley 12-17-2009. Therapeutic Hypothermia. Background. Sudden Cardiac Death Estimated number of out-of-hospital SCD cases is 300,000 per yr in US Incidence anywhere from 35-125/100,000 people with 25% less than 65y/o Cobb JAMA 2002

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therapeutic hypothermia

TherapeuticHypothermia

Joseph Foley

12-17-2009

therapeutic hypothermia2
Therapeutic Hypothermia

Background

  • Sudden Cardiac Death
    • Estimated number of out-of-hospital SCD cases is 300,000 per yr in US
    • Incidence anywhere from 35-125/100,000 people with 25% less than 65y/o
      • Cobb JAMA 2002
      • de Vreede-Swagemakers JACC 1997
    • If ROSC and admitted, median survival to discharge in US is 7.9%
      • Lloyd-Jones Circulation 2009
    • Favorable outcomes of those admitted to hospital is 11-48% indicating large number of pts who either die or have permanent severe neurological damage
      • Becker Ann Emer Med 1993

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

therapeutic hypothermia3
Therapeutic Hypothermia

Background

  • Hypothermia
    • Definition- a condition in which an organism's temperature drops below that required for normal metabolism and body functions.
    • Subdivided into four different degrees:
      • Mild (32 - 35ºC or 90 - 95ºF)
      • Moderate (28 - 32ºC or 82.4 - 90ºF )
      • Severe (20 - 28ºC or 68 - 82.4ºF)
      • Profound ( < 20ºC or < 68ºF)

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in history
Hypothermia in History
  • History
    • The Greek physician Hippocrates advocated the packing of wounded soldiers in snow and ice
    • Hypothermia has played a major role in the success or failure of many military campaigns
      • Hannibal's loss of nearly half his men in 218 BC while crossing the Alps
      • Near decimation of Napoleon's armies during Russian Invasion of 1812.
    • Losses of lives to hypothermia continued in one degree or another through the first and second world wars.
    • During the second world war Nazi Germany conducted numerous cold experiments on human prisoners.
    • Civilian examples of deaths caused by hypothermia are found during the sinking RMS Titanic, RMS Lusitania and RMS Empress of Ireland.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in history5
Hypothermia in History

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in nature
Hypothermia in Nature

Background

  • Hibernation
    • A state of inactivity and metabolic depression in animals, characterized by lower body temperature, slower breathing, and lower metabolic rate.
    • Hibernating animals conserve energy, especially during winter by utilizing body fat as an energy reserves, at a slow metabolic rate and get their energy via gluconeogenesis.
      • Carey et al. Physiological Reviews 2003.
    • This slowed metabolic rate is what leads to a reduction in body temperature and not the other way around.
    • Before entering hibernation most species eat a large amount of food and store energy in fat deposits in order to survive the winter.
    • Hibernation isn’t continuous and is typically interrupted by sporadic arousals wherein body temperature is restored to normal levels.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in nature7
Hypothermia in Nature
  • Hibernation
    • Animals that hibernate:
      • Bats,
      • Ground squirrels and other rodents,
      • Mouse lemurs,
      • The West European Hedgehog,
      • Monotremes (Echnidas & Platypus)
      • Marsupials (pygmy-possum).

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in nature8
Hypothermia in Nature

Background

  • Hibernation
    • Hibernating ground squirrels may have abdominal temperatures as low as −2.9 °C (27 °F) for more than three weeks at a time, although the temperatures at the head and neck remain at 0 °C or above.
    • One animal that some famously consider a hibernator is the bear, which actually goes through "denning“ rather than "true hibernation".
    • During a bear's winter sleep state, the degree of metabolic depression is much less than that observed in smaller mammals and it can be easily aroused.
    • Body temperature remains relatively stable (depressed from 37 °C (99 °F) to ~ 31 °C (88 °F))

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in pop culture
Hypothermia in Pop Culture

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in medicine
Hypothermia in Medicine

Background

  • Cryotherapy
  • Cryonics
    • Low-temperature preservation of humans and animals that can no longer be sustained by contemporary medicine until resuscitation may be possible in the future.
    • Currently, human cryopreservation is not reversible.
    • The most famous known cryopreserved patient is baseball player Ted Williams
    • There is a popular urban legend that Walt Disney was cryopreserved but is false because he was actually cremated.

1 on 1 anytime Shaq…bring it!

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in medicine11
Hypothermia in Medicine
  • Spinal Cord Injuries

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in medicine12
Hypothermia in Medicine
  • Hypothermia is protective when it is induced before or during an anoxic result
    • Young RSK, Neurologic outcome in cold water drowning. JAMA 1980.
  • Hypothermia may act as an anticonvulsant.
    • Orlowski JP, Hypothermia and barbiturate coma for refractory status epilepticus. Crit Care Med 1984.
  • Hypothermia decreases cerebral edema after traumatic brain injury
    • Shiozaki TS, Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 1993.
    • Jagid J, Head cooling decreases brain temperature after traumatic brain injury, Departments of Neurosurgery and Pediatrics*, Miller School of Medicine, University of Miami, 2004.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia in medicine13
Hypothermia in Medicine
  • Hypothermia is used for cerebral protection during operations involving cardiopulmonary bypass.
    • Swain JA, Cardiac surgery and the brain. N Engl J Med 1993.
  • Cardiac Transplantation
    • Normally a donor's heart is injected with KCl prior to being removed from the donor's body and packed in ice in order to preserve it.
    • The ice can usually keep the heart fresh for a maximum of 4-6 hours with proper preservation
    • Cooling an organ from 37 º C to approximately 0 º C slows metabolism by a factor of 12-13

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

summary
Summary
  • Hypothermia has been used for centuries to treat wounds & preserve organs in a variety of different settings.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia
Physiologic Effects of Hypothermia

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia16
Physiologic Effects of Hypothermia
  • Decreased oxygenation
    • Shifts oxyhemoglobin-dissociationcurve to left
    • Vasoconstriction
    • VQ mismatch
    • Increased blood viscosity
  • Metabolicacidosis
    • Lactate generation due to shiveringand decreased tissue perfusion
    • Impaired hepaticmetabolism and impaired acid excretion.
      • Danzl, Accidental hypothermia, N Engl J Med 1994.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia17
Physiologic Effects of Hypothermia
  • Dehydration, ileusand fluid shifts with body temperatures below 32 º C.
  • Electrolyte imbalances.
    • Hypothermia masks potassium-induced changes in the electrocardiogram.
  • Cold-induced renalglycosuria
  • Hematocritincreases 2% per 1 degree º C decline intemperature.
    • Danzl, Accidental hypothermia, N Engl J Med 1994.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia18
Physiologic Effects of Hypothermia
  • Coagulopathies despitenormal clotting factor levels because cold directly inhibits the enzymatic reactions of the coagulationcascade.
    • Not reflected normal PT or PTT, sincethese tests are routinely performed only at 37 °C.
  • Platelet activity declines because thromboxaneB2production is temperature-dependent.
  • Cold-inducedthrombocytopenia from direct BM suppression and hepatosplenic sequestration.
  • Hypercoagulabilityoccurs with possible thromboembolism.
    • Danzl, Accidental hypothermia, N Engl J Med 1994.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia19
Physiologic Effects of Hypothermia
  • Metabolism is reduced by 5% to 8% per degree Celsius reduction of core temperature.
  • Decreased neurologic electrical activity and therefore O2 demand and CO production.
  • Ca++ buffering capacity of cells fails leading to cell death.
    • Ca++ sequestration is ATP and/or oxygen dependent
  • Cellular depolarization causes release of glutamate, which further promotes Ca++ influx.
  • Above processes attenuated by hypothermia.
    • Siesjo, Ann NY AcadSci 1989
    • Busto, Stroke 1989
    • Illievich, AnesthAnalg1994

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia20
Physiologic Effects of Hypothermia
  • Reperfusion after cardiac arrest with normothermic, oxygenated blood leads to the formation of reactive oxygen species.
    • Causes cellular damage by lipid peroxidation, DNA toxicity, and induction of apoptosis.
  • Several studies have shown that hypothermia attenuates oxidative stress and lipid peroxidation.
    • Globus MY, J Neurochem 1995
    • Horiguchi T, J Neurotrauma 2003
    • Lei B, Stroke 1994

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia21
Physiologic Effects of Hypothermia
  • Functions as immune modulator by inhibiting neutrophil infiltration and function, reducing lipid peroxidation and leukotriene production.
    • Wang GJ, Neuroscience 2002
    • Akriotis V, J Leukoc 1985
    • Dempsey RJ, Neurosurgery 1987
  • Activation of microglia, which contributes to neuronal injury by production of NO, TNF-α, and glutamate, is mitigated.
    • Kumar K, Neuroreport 1997

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

physiologic effects of hypothermia22
Physiologic Effects of Hypothermia
  • Hypothermia attenuates cytochrome p450 transit, thus the initiation of apoptosis, and subsequent caspaseactivation.
    • Xu L, J Cereb Blood Flow Metab 2002
    • Zhao H, J Cereb Blood Flow Metab 2005
    • Fukuda H, Brain Res 2001
  • Hypothermia suppresses apoptosis
    • Antiapoptoticprotein Bcl-2, a potent cell-death suppressor, is enhanced.
    • Proapoptoticfactor BAX is suppressed.
      • EberspacherE, ActaAnaesthesiol Scand 2005
      • Zhang Z, Brain Res Mol BrainRes 2001

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

summary23
Summary
  • Metabolism is reduced by 5% to 8% for each 1° C decrease in core temperature.
  • Hypothermia minimizes reperfusion injuries, functions as an immune modulator and prevents apoptosis on a cellular level

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

board review
Board Review

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

osborn waves
Osborn Waves

Background

  • In 1953, Dr. John Osborn described the J wave as an “injury current” resulting in ventricular fibrillation during experimental hypothermia.
    • Osborn JJ. Experimental hypothermia: Respiratory and blood pH changes in relation to cardiac function. Am J Physiol 1953.
  • Hypothermia increases the epicardial to endocardial K+ current during repolarization.
  • Transmural voltage gradient reflected on ECG as a prominent J, or Osborn, wave.
  • Differential dx = early Repolarization, Hypercalcemia, and the Brugada syndrome.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

osborn waves26
Osborn Waves

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data
Clinical Data
  • Williams & Spencer from John Hopkins University
  • 1958 Annals of Surgery
  • Case Report
    • 4 patients, both traumatic and nontraumatic cardiac arrest victims, 2 children, and 2 adults
    • No-flow times of ~ 5 minutes were resuscitated to favorable neurological outcome with open heart cardiac massage and hypothermia induced with surface cooling after ROSC for 24-72 hours.
  • The authors stated,
    • “Patients who show evidence of CNS damage following cardiac resuscitation should be promptly cooled to 32°C to 34°C”

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data28
Clinical Data
  • Similar case series described again by same group in 1959.
    • 19 patients with anoxic neurologic injury after in-hospital cardiac arrest and ROSC after open cardiac massage.
    • 12 patients received hypothermia (30 - 33 ° C) between 1 and 6 hours after cardiac arrest, and 6 survived;
    • 7 patients did not undergo hypothermia, and 1 survived.
      • Williams GR Jr, Spencer FC: Clinical use of hypothermia following cardiac arrest. Ann Surg 1959.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data29
Clinical Data
  • Peter Safar championed hypothermia for years but it generally laid dormant (or hibernated) until the 1990s.
    • ClinAnesth 1965 – Management of comatose patient
    • Crit Care Med 1978 - Resuscitation after global brain ischemia-anoxia
    • IntAnesthesiolClin 1979 - Pathophysiology and resuscitation after global brain ischemia
    • Ann Emer Med 1985 - Resuscitation of dogs from cold-water submersion using cardiopulmonary bypass

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data30
Clinical Data
  • In 1991, dog model of cardiac arrest
  • 10 minutes of VF followed by 5 minutes of CPR before defibrillation and ROSC
  • Significant benefit at 72 hours when mild hypothermia was induced within 15 minutes of ROSC and maintained for 60 minutes.
    • Stertz F, P Safar, et al. Crit Care Med 1991.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data31
Clinical Data
  • In a study by Kuboyama, using a dog model, the benefit of hypothermia diminished if induction was delayed by 15 minutes after ROSC.
  • Histology showed decrease in the neurologic injury despite this delay.
    • Kuboyama, P Safar, et al.Crit Care Med 1993

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

clinical data32
Clinical Data
  • Benefits limited with moderate hypothermia <30°C owing to arrhythmias, infections, and coagulation problems.
    • Danzl, Accidental hypothermia, N Engl J Med 1994.
  • Animal experiments demonstrated that mild hypothermia (32°C-34°C), was safer than moderate hypothermia and had protective and resuscitative effects on the brain after cardiac arrest.
    • Sertz, Safar, et al. J Cereb Blood Flow Metab 1990

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

therapeutic hypothermia pilot study
Therapeutic Hypothermia Pilot Study
  • “Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardia Arrest”
  • Bernard Ann Emer Med 1997
  • Australia, single center

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard ann emer med 1997
Bernard Ann Emer Med 1997

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard ann emer med 199735
Bernard Ann Emer Med 1997

Background

  • Methods
    • Ice packs used to decrease tympanic temperature to 33 °C.
    • Intubated, sedated, paralyzed.
    • Maintained at 33 °C for 12 hours and then rewarmed over 6 hours to 36 °C with heated oxygen and surface heating.
    • GCS score used to determine neurologic outcomes, no formal neuropsych eval.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard ann emer med 199736
Bernard Ann Emer Med 1997

Background

  • Results
    • ROSC in Hypothermia 23.1min vs. Normothermia 25.2min
    • A core temperature < 34 °C reached at mean of 74 minutes after ROSC.
    • No significant complications from hypothermia.
      • Sepsis, coagulopathy, neutropenia, thrombocytopenia
    • At 72hrs, if fully conscious were transferred to the CCU unless still intubated or critically ill.
    • Pts hemodynamically stable but still comatose at 72hrs underwent trach/PEG.
    • Pts deeply comatose, with unreactive pupils and multisystem organ dysfunction, were considered to have a hopeless prognosis, and active therapy was withdrawn.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard ann emer med 199737
Bernard Ann Emer Med 1997

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

randomized clinical trials
Randomized Clinical Trials

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard nejm 2002
Bernard NEJM 2002
  • Australian, multicenter
  • Randomized on odd and even days & not blinded***

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard nejm 200240
Bernard NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard nejm 200241
Bernard NEJM 2002
  • Methods
    • Cooling began pre-hospital with ice packs.
    • Maintained at 33 °C for 12 hours and then rewarmed over 6 hours to 36 °C.
    • ASA for all, Heparin/Thrombolytics & if angioplasty indicated
    • All received Lidocainegtt x 24hrs
    • Pts formally assessed by rehab

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard nejm 200242
Bernard NEJM 2002

Background

Home

Physiology

Rehab

Clinical Data

Long-Term Facility

PublishedReviews

Long-Term Facility

UK Protocol

Conclusions

bernard nejm 200243
Bernard NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

bernard nejm 200244
Bernard NEJM 2002

Background

Physiology

Clinical Data

49%

26%

p=0.046

ARR = 23%

NNT = 4.3

PublishedReviews

UK Protocol

Conclusions

bernard nejm 200245
Bernard NEJM 2002
  • Results
    • ROSC
      • Hypothermia 26.5min vs. Normothermia 25.0min
    • Core temperature reached goal at 120min
    • Nonsignificant mortality rates
      • Hypothermia group 22/43 (51 %) vs. normothermiagroup 23/34 (68 %) (P=0.145)
    • The primary cause of death was cardiac
      • 5/22 in hypothermia group
      • 4/23 in normothermiagroup
      • Remaining deaths in both groups primarily from severe neurologic injury and withdrawal of care.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

randomized clinical trials46
Randomized Clinical Trials

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 2002
HACA NEJM 2002
  • Austria, Randomized
  • Physicians responsible for assessing neurologic outcome within the first six months after the arrest were unaware of the treatment assignments.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200248
HACA NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200249
HACA NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200250
HACA NEJM 2002
  • Methods
    • Hypothermia group cooled to target temp 32 - 34°C within 4 hrs of ROSC using an external cooling mattress, ice packs if unsuccessful.
    • Temperature maintained at 32 - 34°C for 24 hours, followed by passive rewarming over 8 hrs.
    • Tympanic then bladder temperature

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200251
HACA NEJM 2002
  • Results
    • ROSC in Hypothermia 22min vs. Normothermia21min
    • Median interval between ROSC and the initiation of cooling was 105 minutes
    • Median interval between ROSC and goal temperature between 32-34°C was 8 hrs
      • In 19 patients, target temperature could not be reached.
    • Ice packs required for 70% of patients
    • Hypothermia discontinued early in 14 pts

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200252
HACA NEJM 2002

Background

Physiology

Clinical Data

  • ARR Favorable Neurologic Outcome = 16%
    • NNT = 6
  • ARR Death = 14%
    • NNT = 7

PublishedReviews

UK Protocol

Conclusions

haca nejm 200253
HACA NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

haca nejm 200254
HACA NEJM 2002

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

other studies
Other Studies
  • Hachimi-IdrissiResuscitation2001
    • Belgium
    • 30 comatose survivors after cardiac arrest with asystole/PEA as primary rhythms.
    • Hypothermia was induced to 34 °C with only a helmet device (Frigicap®) containing a solution of aqueous glycerol and maintained for 4 hours.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

other studies56
Other Studies
  • Hachimi-IdrissiResuscitation2001
    • ROSC in Hypothermia 34 min vsNormothermia 33 min
    • Tympanic temperature reached goal in median of 60 min and bladder temperature in median time of 180 min
    • Maintained at goal temp for 4 hrs
    • Survival to favorable neurological recovery:
      • Hypothermia group 2/16 (13%)
      • Normothermia group 0/14 (0%)
      • Not statistically significant.

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

other studies57
Other Studies
  • LaurantJACC 2005
    • France, Randomized
    • 61 comatose survivors of out-of-hospital VF/Asystolic arrest
    • Cooled with high-flow hemofiltration ± hypothermia to 32 °C for 24hrs.
    • Primary outcome – survival at 6 months
      • 7/22 (32%) in HF-HT group
      • 9/20 (45%) in HF group
      • 4/19 (21%) in Control group

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

welcome to prime time
Welcome to Prime Time

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

welcome to prime time59
Welcome to Prime Time

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials
Further Trials

Background

  • “Efficacy and Safety of Endovascular Cooling After Cardiac Arrest: Cohort Study and Bayesian Approach”
  • Holzer Stroke 2006
  • Hypothesis
    • Efficacy and safety of endovascular cooling in unselected survivors of cardiac arrest.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials61
Further Trials

Background

  • Holzer Stroke 2006
      • Austria
      • 97 consecutive comatose survivors after witnessed cardiac arrest with any presenting rhythm treated with mild hypothermia induced by an endovascular device to 941 historical controls.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials62
Further Trials

Background

  • Holzer Stroke 2006
    • Cooling with femoral CoolGard 3000 to 33°C for 24hrs then rewarmed at a rate of 0.5°C/hr to 36°C.
    • Bladder temperatures

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials63
Further Trials

Background

  • HolzerStroke 2006
    • 29% in hypothermia group did not have VF as presenting rhythm.
    • 30 day survival with a favorable neurological outcome
      • Hypothermia group 51/79 (53%)
      • Normothermia group 320/941 (34%)
      • p = .0003, ARR 19%, NNT 5
      • No significant adverse events

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials64
Further Trials

Background

  • “From evidence to clinical practice: Effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest”
  • OddoCrit Care Med 2006
  • Hypothesis
    • Therapeutic Hypothermia can be safely implemented regardless of presence of shock, non VT/VF rhythm.
    • There is a limit to TH duration, beyond which it would lack benefit.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials65
Further Trials

Background

  • Oddo Crit Care Med 2006
    • Switzerland
    • Retrospective cohort study, single center
    • Cooled with external blanket in ED then cooling mattress in ICU
    • Primary Outcome
      • Good neurologic recovery with CPC 1-2 at 30 days

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials66
Further Trials

Background

  • Oddo Crit Care Med 2006
    • 55 consecutive patients treated with hypothermia and 54 historic control patients from the period before implementation of hypothermia.
      • Initial rhythm was VF in 86 of them (43 pts in each group)
      • Initial rhythm was asystole or PEA in the remaining 23 (12 in hypothermia group, 11 in control group).

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials67
Further Trials

Background

  • Oddo Crit Care Med 2006

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials68
Further Trials

Background

  • OddoCrit Care Med 2006
  • Results
    • Primary Outcome - CPC 1-2 at 30 days
      • VT/VF group
        • 24/43 (56%) in patients receiving hypothermia
        • 11/43 (26%) in control group (P = .004).
        • ARR 30% NNT = 3
      • Asystole or PEA group
        • 2/12 in patients receiving hypothermia
        • 0/11 in control group
        • Not statistically significant, but trend toward good outcome

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials69
Further Trials

Background

  • Oddo Crit Care Med 2006

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials70
Further Trials

Background

  • Oddo Crit Care Med 2006

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials71
Further Trials

Background

  • “Clinical application of mild therapeutic hypothermia after cardiac arrest”
  • ArrichCrit Care Med 2007
  • Goals
    • Monitor implementation of therapeutic hypothermia,
    • Observe feasibility of adherence to the guidelines,
    • Document complications & outcomes of hypothermic treatment

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials72
Further Trials

Background

  • ArrichCrit Care Med 2007
    • Observational study from European Resuscitation Council Hypothermia After Cardiac Arrest Registry (ERC HACA-R)
    • 587 patients with ROSC after cardiac arrest and 462 (79%) treated with therapeutic hypothermia irrespective of the presenting rhythm.
    • 347 (59%) were cooled with an endovascular device, and 114 (19%) received other cooling methods such as ice packs, cooling blankets, and cold fluids.
    • Interval between ROSC to initiation of cooling was 159 mins in HACA-R, which was longer than the median 105 mins reported by the HACA trial study group

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

further trials73
Further Trials

Background

  • ArrichCrit Care Med 2007
    • Demonstrates a benefit in terms of neurological outcome at 6 months – CPC 1-2
      • 45% in hypothermia group vs. 32% in normothermia group
      • ARR 13%; NNT = 7.6; P = 0.02
    • Nonsignificant increase of favorable outcome in hypothermic patients in Asystole/PEA groups
      • 35/124 [28%] in the hypothermic group vs
      • 14/73 [19%] in the normothermic group
      • ARR 9%; NNT = 11.1; P = 0.18

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi
Hypothermia and STEMI

Background

  • “COOLing as an Adjunctive Therapy to Percutaneous Intervention in Patients With Acute Myocardial Infarction (COOL-MI)”
  • O’Neill TCT 2003
  • Hypothesis
    • Treatment with endovascular cooling will be safe and will be associated with a reduction in infarct size in patients with AMI.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi75
Hypothermia and STEMI

Background

  • O’Neill TCT 2003
    • Multicenter
    • 177 pts cooled to target temperature 33°C with endovascular cooling vs 180 controls
    • Primary endpoint was final infarct size at 30 days measured using 99mTc-sestamibi SPECT imaging.
    • Primary safety endpoint was MACE

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi76
Hypothermia and STEMI

Background

  • O’Neill TCT 2003
    • Median time from onset of cooling to the first balloon inflation was only 17 minutes
    • 30 day primary composite safety endpoint
      • 3.9% in control group and 6.2% in hypothermia group (p=0.45).
    • 30 day median final infarct size
      • 10.0% of LV in control group and 10.0% of LV in hypothermia group (p=0.47).
      • Anterior MI with temp <35°C at reperfusion had a smaller median infarct size, compared with temp >35°C (5.0% vs 16.5%, p=0.007)

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi77
Hypothermia and STEMI

Background

  • “Primary PCI and mild induced hypothermia in comatose survivors of ventricular fibrillation with STEMI”
  • Knafelj Resuscitation 2007
  • Slovenia, 2003-2005, single center, non-randomized, sequential design

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi78
Hypothermia and STEMI

Background

  • Knafelj Resuscitation 2007
    • Primary outcome:
      • Feasibility and safety of combining primary PCI and Mild Hypothermia in comatose survivors of cardiac arrest with STEMI after ROSC
    • STEMIs managed with only bare metal stents, no thrombus aspiration or distal protection were used, otherwise followed ACC guidelines

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi79
Hypothermia and STEMI

Background

  • Knafelj Resuscitation 2007
    • Hypothermia induced with IV NS 30 ml/kg at 4◦C infused over 30 min and ice packs.
    • Target body temperature of between 32 and 34 ◦C, maintained for 24 h and then passively re-warming.
    • Started immediately after primary PCI following admission to the ICU (26/40 patients).

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi80
Hypothermia and STEMI

Background

  • KnafeljResuscitation 2007
    • Median time delay from collapse to start of IH was 125 min
    • Collapse to balloon time 115 min in Hypothermia vs 143 min in Normothermia
    • Median time to target temperature <34 ◦C was 240 min
    • Median delay from collapse to the target temperature was 367 min
    • ICU length of stay
      • 9.3 days in Hypothermia vs. 7.4 days in Normothermia

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi81
Hypothermia and STEMI

Background

  • Knafelj Resuscitation 2007

Physiology

Clinical Data

In-hospital

ARR 31%

NNT = 3.2

ARR 39%

NNT = 2.6

6 months

ARR 30%

NNT = 3.3

ARR 34%

NNT = 2.9

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi82
Hypothermia and STEMI

Background

  • “Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute STEMI undergoing immediate PCI”
  • WolfrumCrit Care Med 2008
  • Goals
    • Determine if MTH could be started before primary PCI and not interfere with rapid reperfusion therapy in patients comatose after cardiac arrest due to STEMI

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi83
Hypothermia and STEMI

Background

  • Wolfrum Crit Care Med 2008
    • Germany
    • Single center
    • Induced hypothermia in 16 consecutive patients with STEMI after successful resuscitation before PCI and compared them to 17 historic consecutive patients without cooling.
    • Primary Outcomes
      • 6 month mortality
      • 6 month favorable neurologic status

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi84
Hypothermia and STEMI

Background

  • Wolfrum Crit Care Med 2008
    • Cooled to a target temperature of 32°C -34°C with cold packs, cooling mattresses - Blanketrol II and IV ice-cold saline.
    • Goal was to reach the target temperature within 4 hrs after initiation of MTH, maintained for 24 hrs.
    • Initiated in the ED or ICU, before transfer to the cath lab for primary PCI.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

hypothermia and stemi85
Hypothermia and STEMI

Background

  • Wolfrum Crit Care Med 2008
    • ROSC – 24 min in hypothermia and 18 min in normothermia
    • Median of 3L of cold saline (4°C) infused during the initial 4 hrs; no pulmonary edema observed.
    • Target temperature was reached within 175 mins
    • Door-to-ballon times 82 min in hypothermia vs 85 min in normothermia

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

summary86
Summary

Background

  • Mild Therapeutic Hypothermia to 32-34°C for 24hrs improves neurologic outcome and mortality at 30 days and 6 months
    • Benefit seen in shock, non-VT/VF, STEMI
    • No significant side effects, ?higher incidence of sepsis/pneumonia
  • Recommended by ILCOR since 2003 and AHA since 2005

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews
Published Reviews

Background

  • Cheung CJEM 2006
    • Systemic Review
    • 4 trials analyzed
      • Bernard 2002
      • HACA 2002
      • Hachimi-Idrissi 2001
      • Mori 2002 (abstract, unpublished)
    • 436 patients, with 232 cooled to a core temperature of 32°C–34°C met inclusion criteria.
    • Pooled data demonstrated that mild hypothermia decreased in-hospital mortality (RR 0.75); and reduced the incidence of poor neurologic outcome (RR 0.74).
    • NNT were 7 patients to save 1 life, and 5 patients to improve neurologic outcome.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews88
Published Reviews

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews89
Published Reviews

Background

  • SBU 2006
    • Sweden
    • 2 trials analyzed
      • Bernard 2002 (judged poor quality)
      • HACA 2002 (judged high quality)
    • “The scientific evidence is insufficient… to show that treatment with induced hypothermia after resuscitation from cardiac arrest improves survival or lowers the risk for permanent functional impairment. Although the scientific evidence is too weak to support reliable conclusions, the method appears to be promising and potentially may be of clinical importance. However, it is essential to continue testing this method in Sweden under scientifically acceptable conditions so that its benefits, risks, and cost effectiveness can be assessed.”

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews90
Published Reviews

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews91
Published Reviews

Background

  • Flynn VA Report 2008
    • Assessed 3 trials
      • Holzer 2005, HACA 2002, Bernard 2002
    • Assessed available RCTs/MAs
      • Cheung 2006, SBU 2006
      • ANZHSN 2005 – insufficient evidence for CoolGard endovascular cooling
      • CEDIT 2004 – cannot recommend CoolGard endovascular cooling
      • Mullner Cochrane Review 2003

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews92
Published Reviews

Background

  • Flynn VA Report 2008
    • Assessed policy recommendations
      • ILCOR 2003
      • AHA 2005 - relied on consensus, supporting literature review characterized as quasi-systematic.
    • Conclusion – “TAP retrieved no recent rigorous evidence to materially change SBU’s conclusions in 2006”
    • More evidence needed in RCTs

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews93
Published Reviews

Background

  • “Hypothermia after Cardiac Arrest”
  • Janata Progress in CV Dz 2009
  • Literature Review
  • 37 Non-randomized trials
  • 15 studies with control patients
    • Pooled ARR ~25%
    • NNT ~4

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews94
Published Reviews

Background

  • Janata Progress in CV Dz 2009

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews95
Published Reviews

Background

  • “Hypothermia for Neuroprotection in adults after cardiopulmonary resuscitation”
  • Arrich Cochrane Review 2009

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews96
Published Reviews

Background

  • Arrich Cochrane Review 2009

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews97
Published Reviews

Background

  • Arrich Cochrane Review 2009
    • 5 trials included through 2007
      • Bernard 2002
      • HACA 2002
      • Hachimi-Idrissi 2001
      • Laurent 2005 (not included in meta-analysis d/t heterogeneity as hemofiltration used for TH)
      • Mori 2000 (abstract & unpublished)

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews98
Published Reviews

Background

  • Arrich Cochrane Review 2009

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

published reviews99
Published Reviews

Background

  • Arrich Cochrane Review 2009

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

summary100
Summary

Background

  • Difficult data set to analyze
    • Rare event
    • Impossible to randomize
    • Low sample size
    • Heterogeneity
  • Available data favor therapeutic hypothermia for good neurologic outcome and/or mortality

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Execution

Feasibility

Background

Theory

Possible Adverse Side Effects

Physiology

Improved Neurologic Outcome & Mortality

Cost/Benefit Analysis

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol102
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Identification of eligible patients
  • Identification of ineligible patients
  • Cooling induction
  • Maintenance
  • Rewarming
  • Disposition

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol103
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Identification of eligible patients
    • Comatose survivors after out-of-hospital cardiac arrest with a primary rhythm of VT/VF regardless of presence of shock.
    • Hypothermia should be considered for non-VF rhythms and in-hospital cardiac arrest
    • ≤ 60 min CPR prior to ROSC
    • Pre-arrest GCS = 15 or independent ADLs

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol104
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Identification of ineligible patients
    • Written DNR/DNI
    • Cognitive status severely impaired before arrest
    • Underlying coagulopathy or bleeding disorder
    • Other known reason for coma/arrest (e.g. septic shock, severe acidosis, trauma, etc.)
    • Questionable head injury or head CT with mass or hemorrhage
    • Unstable cardiac rhythms not terminated during initial management

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol105
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Cooling induction
    • If eligible, page UKMDS to activate “CHILL” team
      • Similar to STEMI team
    • Prior to cooling
      • Intubate patient
      • Insert arterial pressure monitoring line
      • Insert CVC (preferably Edwards SVO2) catheter
      • Insert temperature sensing Foley catheter
      • Sedate with IV Midazolam and Fentanyl
      • Paralyze with Vecuronium to prevent shivering

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol106
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Cooling induction
    • Target temperature and duration?
      • 32°C-34°C for 24 h after reaching the target.
      • Goal 6 hrs to target temperature.
    • Methods of induction?
      • Ice-cold LR or NS 30 mL/kg with pressure bags via large bore cannulas,
        • Avoid in patients with pulmonary edema or severely reduced LV systolic function.
      • Combine with cooling device.
        • Our institution has Blanketrol II readily available.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol107
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Cooling induction
    • Blanketrol II
      • Both manual & automatic controls
      • Capability to cool at a rate of 4 o C/min and warm at a rate of 3 o C/min.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol108
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Cooling induction
    • Hypothermia and STEMI?
      • Proceed to Cath lab for PCI with continuation/induction of cooling and continuous temperature measurement must be provided.
      • Follow ACC/AHA Guidelines

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol109
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Cooling induction
    • Early Goal Directed Therapy
      • See handout

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol110
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Maintenance
    • Maintain temperature 32°C-34°C for 24 h after reaching the target.
    • Check water level in Blanketrol II – refill with distilled water if needed.
    • Nursing to monitor Temp, MAP, CVP, SVO2, hourly & record on specific TH flowsheet
      • If Swan-Gantz Catheter in place also monitor SVR, CI
    • Labs q6h – Lactate, BMP, CBC, Trop/CK/CK-MB, ABG (corrected for temperature)

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol111
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Maintenance
    • Side Effect Monitoring
      • Bradycardia higher risk if Temp < 30°C.
      • Lidocaine if recurrent VT/VF
      • Closely monitor for infection, no evidence for prophylactic antibiotics despite higher rates of sepsis & pneumonia
      • Closely monitor for electrolyte imbalance.
      • Potentially higher bleeding complications after PCI.
        • Platelet function unaltered by hypothermia.
      • Altered drug action and metabolism.
        • Reduces systemic clearance of cytochrome P450 metabolized drugs between 7%-22% per °C.
      • Paralyze to prevent shivering

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol112
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Rewarming
    • Goal is to rewarm over 6-8 hours
    • Using Blanketrol II increase warming blanket setting by 0.5°C every 1-2 hours
    • Discontinue when patient reaches 36°C.
    • Maintain normothermia (36.5°C-37.5°C) up to 72 hrs after cardiac arrest.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol113
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Disposition
    • Daily Neurologic Evaluation
      • Most useful prognostic indicators of poor neurologic outcome
      • At coma onset:
        • Absent pain withdrawal +LR 1.7
      • At 24hrs:
        • Absent pain withdrawal +LR 4.7
        • Absent pupil response +LR 10.2
        • Absent motor response +LR 4.9
        • Absent corneal reflex +LR 12.9
      • At 72hrs:
        • Absent pupil response +LR 3.4
        • Absent motor response +LR 9.2
        • Seizure or myoclonus +LR 1.4

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol114
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Disposition
    • Neurology
      • “Although decisions to proceed with care or withdraw care may take place at later times for a variety of reasons, the most useful signs occur at least 24 hours and in the case of motor response at 72 hours post–cardiac arrest.”
        • Booth, JAMA 2004

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol115
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Disposition

Physiology

Home

Rehab

Clinical Data

Long-Term Facility

PublishedReviews

UK Protocol

Long-Term Facility

Conclusions

proposed uk post cardiac arrest therapeutic hypothermia protocol116
Proposed UK Post-Cardiac Arrest Therapeutic Hypothermia Protocol

Background

  • Disposition
    • Utilize consultants
      • Daily Neurology evaluation
      • PT/OT for Rehab assessment
      • Pulmonary for vent management
      • Surgery for Tracheostomy/PEG if poor outcome or ventilator dependence
      • Palliative Care

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

potential impact
Potential Impact

Background

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

potential impact118
Potential Impact

Background

  • Every year about 785,000 Americans have a first heart attack.
  • Another 470,000 who have already had one or more heart attacks have another attack.
  • 10,337 deaths from Heart Disease in KY in 2005
  • Estimated number of out-of-hospital cardiac arrest cases is 300,000 per yr in US
    • CDC website

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

potential impact119
Potential Impact

Background

  • Data from UK ED
    • 125 hospitalizations for survivors of out-of-hospital cardiac arrest since 12/2006
  • ARR in most studies ~20%, NNT ~ 5
  • Institution of therapeutic hypothermia protocol at UK and treatment for 24hrs would prevent an unfavorable neurologic outcome and/or mortality in ~25 of these patients.
  • Only 13-25 % of cardiac-arrest patients receive therapeutic hypothermia in the USA
    • Main reasons cited: insufficient data, treatment not mentioned in ALCS protocols and technical difficulties related to cooling.
    • Already in place at St. Joseph’s Hospital and with local EMS groups.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

conclusions
Conclusions

Background

  • Therapeutic Hypothermia to 32°C-34°C for 24 h in patients with ROSC after cardiac arrest
    • Improved in-hospital mortality and 6 month neurologic outcome
    • ARR ~20% from all available studies, NNT ~5
  • Neurologic outcome assessed by Pittsburgh Cerebral Performance Categories
    • Good outcome = CPC 1 or 2
      • CPC 1 - Normal or minimal disability (able to care for self, discharged directly to home)
      • CPC 2 - Moderate disability (discharged to a rehabilitation facility)
  • Minimal side effects
  • Advocated by ILCOR since 2003 and AHA since 2005 despite recommendation being based on only 3-4 randomized clinical trials in 2001-2002.

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions

areas for future research
Areas for Future Research

Background

  • Practical methods for out-of-hospital cooling.
  • Methodologically sound studies to further investigate the effect of cooling on patients with non-VF/VT rhythm, or in-hospital cardiac arrest.
  • Widen inclusion criteria
  • Comparisons of earlier cooling (pre-hospital) vs late cooling (in-hospital),
  • Different levels of hypothermia (e.g. 32°C vs 34°C),
  • Different durations of cooling (e.g. 12 hours vs 24 hours vs 48 hours)
  • Safety reporting for any unexpected adverse events.
  • Cost benefit analyses

Physiology

Clinical Data

PublishedReviews

UK Protocol

Conclusions