BrainChill.info : An Educational Web Site on Mild Therapeutic Hypothermia for Cerebral Protection after Cardiac Arrest  

BrainChill.info : An Educational Web Site on Mild Therapeutic Hypothermia for Cerebral Protection after Cardiac Arrest

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GOAL: Preserving Brain Function after Cardiac Arrest



- Therapeutic Hypothermia for Cerebral Protection at Erie County Medical Center: Video Presentation -
Global Brain Ischemia after Cardiac Arrest : Preserving Brain Function with Hypothermia
Mild Therapeutic Hypothermia can protect the brain if started early and maintained for 24 hours at the range of 32 to 33 degrees Celcius
- PennVideo - - OHCA - - Apoptosis - - Apop.Micro. - - List of protocols - - PennCRS - - References - - Network - - AHA - - Europe -

APOPTOSIS - Extrinsic Pathway:

TNF, FAS, TRAIL
Death Receptor Binding
Caspase 8
IAP Inhibition
SMAC/DIABLO
->Caspase 3 Activation
->Substrate Cleavage
->Apoptosis Completed

TNF-alpha is elevated after cardiac arrest

Intrinsic Pathway leading to Apoptosis:

DNA injury/O2 radiacals/Radiation
BIM/PUMA/BH3
BLC-XL - BCL2
BAX - BAK
Cytochrome release from mitochondria
->APAF1 and apoptosome
->Caspase 9 Activation
->Caspase 3 activation
In general, Therapeutic Hypothermia should be initiated within the first six hours after the hypoxic/anoxic event

The exact mechanism by which hypothermia protects the brain remains unknown: possibilities include inhibition of apoptosis.

AHA Guidelines state : "...In summary, providers should not actively rewarm hemodynamically stable patients who spontaneously develop a mild degree of hypothermia (>33 C or 91.5 F) after resuscitation from cardiac arrest. Mild hypothermia may be beneficial to neurologic outcome and is likely to be well tolerated without significant risk of complications. In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. Thus, unconscious adult patients with ROSC after out-of-hospital cardiac arrest should be cooled to 32C to 34C (89.6F to 93.2F) for 12 to 24 hours when the initial rhythm was VF (Class IIa). Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for in-hospital arrest (Class IIb).

NEJM : Volume 346:549-556 Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. Background : Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation. Methods: In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32 C to 34 C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days. Results: Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral-performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups. Conclusions: In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.
AHA Guidelines state : "...In summary, providers should not actively rewarm hemodynamically stable patients who spontaneously develop a mild degree of hypothermia (>33 C [91.5 F]) after resuscitation from cardiac arrest. Mild hypothermia may be beneficial to neurologic outcome and is likely to be well tolerated without significant risk of complications. In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. Thus, unconscious adult patients with ROSC after out-of-hospital cardiac arrest should be cooled to 32 C to 34 C (89.6 F to 93.2°F) for 12 to 24 hours when the initial rhythm was VF (Class IIa). Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for in-hospital arrest (Class IIb)"
Therapeutic Hypothermia is relatively easy to perform in most ICU settings (see protocol links, above)

As stated in AHA Guidelines, 2005 : Both permissive hypothermia (allowing a mild degree of hypothermia >33 C [91.5 F] that often develops spontaneously after arrest) and active induction of hypothermia may play a role in postresuscitation care. In 2 randomized clinical trials, induced hypothermia (cooling within minutes to hours after ROSC) resulted in improved outcome in adults who remained comatose after initial resuscitation from out-of-hospital ventricular fibrillation (VF) cardiac arrest. Patients in the study were cooled to 33 C (91.5 F) or to the range of 32C to 34C (89.6 F to 93.2 F) for 12 to 24 hours. The Hypothermia After Cardiac Arrest (HACA) study included a small subset of patients with in-hospital cardiac arrest. A third study documented improvement in metabolic end points (lactate and O2 extraction) when comatose adult patients were cooled after ROSC from out-of-hospital cardiac arrest in which the initial rhythm was pulseless electrical activity (PEA)/asystole. In the HACA and Bernard studies, only about 8% of patients with cardiac arrest were selected for induced hypothermia (ie, patients were hemodynamically stable but comatose after a witnessed arrest of presumed cardiac etiology). This highlights the importance of identifying the subset of patients who may most benefit. Although the number of patients who may benefit from hypothermia induction is limited at present, it is possible that with more rapid and controlled cooling and better insights into optimal target temperature, timing, duration, and mechanism of action, such cooling may prove more widely beneficial in the future.11 A recent multicenter study in asphyxiated neonates showed that hypothermia can be beneficial in another select population. Complications associated with cooling can include coagulopathy and arrhythmias, particularly with an unintentional drop below target temperature. Although not significantly higher, cases of pneumonia and sepsis increased in the hypothermia-induction group. Cooling may also increase hyperglycemia. Most clinical studies of cooling have used external cooling techniques (eg, cooling blankets and frequent applications of ice bags) that may require a number of hours to attain target temperature. More recent studies suggest that internal cooling techniques (eg, cold saline, endovascular cooling catheter) can also be used to induce hypothermia. Providers should continuously monitor the patient's temperature during cooling.












Dr. Dietrich Jehle has been instrumental in developing and implementing hypothermia protocols at ECMC in Buffalo, NY and has led a NYS DOH approved effort to institute pre-hospital cooling for OHCA patients. Dr. Jehle had also performed early original basic science research on cerebral protective effects of hypothermia in the 1980s; please see link:
Dr. Jehle
For more information, please contact : Dr. Mike Meyer,University at Buffalo Professor of Clinical Neurology and Nuclear Medicine, Erie County Medical Center Chief of Neurology and Stroke Services, Attending Neurologist for SUNY Dept Neurology and Jacobs Neurological Institute, SUNY Buffalo (Contact information: ECMC Dept. Neurology, 462 Grider Street, Buffalo, NY tel 716-898-3638)
Dr. Meyer & ECMC Stroke Center Dr. Meyer : STROKE

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