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THERAPEUTIC HYPOTHERMIA BY Dr Dennis Prabhu Dayal TEMPERATURE Two temperatures are important in the human body— Core temperature Skin temperature. Core temperature is the temperature of the brain and inner body, and this temperature extends to about 2 cm beneath the body’s surface. Skin temperature is the temperature at the skin’s surface. In human beings core body temperature is 37 c* or 98.6 F HYPOTHERMIA Definition - a condition in which an organism's core temperature drops below that required for normal metabolism and body functions. Hypothermia is 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) Therapeutic Hypothermia Therapeutic hypothermia(TH) also known as protective hypothermia or targeted temperature management (TTM) is a medical treatment that lowers a patient’s body temperature in order to help reduce the risk of tissue injury from lack of blood flow and reperfusion. RATIONAL OF USING HYPOTHERMIA AS A THERAPY ISCHAEMIC INJURY REPERFUSION INJURY ISCHAEMIC INJURY Cerebral anoxia Cerebral activities are compromised Depletion of glucose and ATP Cells lose structural integrity Mitochondrial damage Calcium hemostasis disturbed Release of excitatory neurotransmitter Cellular necrosis APOPTOSIS – programmed cell death REPERFUSION INJURY Reoxygenation promotes high concentrations of radicals Free oxygen Inflammatory processes activated (tumour necrosis factor,interleukins-1, cytokines), Endothelial dysfunction, Vasomotor dysregulation, Edema, Tissue-level hypoxia Neurological damage. despite adequate arterial oxygenation THEREPEUTIC BENEFIT OF HYPOTHERMIA Experimental studies done on post cardiac arrest animals by inducing hypothermia revealed encouraging results. Hypothermia tempers the post-CA inflammatory cascade aborts activated programmed cell death pathways (APOTOSIS) Hypothermia causes improvement in the oxygen supply-anddemand mismatch by reducing: Excitatory amino acids Free Oxygen radicals Cerebral metabolic rate of oxygen, Cerebral blood volume Intracranial pressure HACA TRIAL HACA TRIAL PUBLISHED IN NEW ENGLAND JOURNAL OF MEDICINE in FEB 2002 HACA (HYPOTHERMIA AFTER CARDIAC ARREST) trial was done on post cardiac arrest patient who attained ROSC (return of spontaneous circulation) to compare mild therapeutic hypothermia vs normothermia AIM The primary objective: · To study the favorable neurologic outcome within six months after cardiac arrest. Secondary objective : To study mortality at six months the incidence of complications during the first seven days. INCLUSION CRITERIA witnessed cardiac arrest, ventricular fibrillation or non perfusing ventricular tachycardia as the initial cardiac rhythm a presumed cardiac origin of the arrest, an age of 18 to 75 years, an estimated interval of 5 to 15 minutes from the patient’s collapse to the first attempt at resuscitation by emergency medical personnel, an interval of no more than 60 minutes from collapse to restoration of spontaneous circulation. EXCLUSIONS CRITERIA a tympanic-membrane temperature below 30°C on admission, a comatose state before the cardiac arrest due to the administration of drugs that depress the central nervous system, pregnancy response to verbal commands after the return of spontaneous circulation evidence of hypotension (mean arterial pressure, less than 60 mm Hg) for more than 30 minutes after the return of spontaneous circulation evidence of hypoxemia (arterial oxygen saturation, less than 85 percent) for more than 15 minutes after the return of spontaneous circulation a terminal illness that preceded the arrest, factors that made participation in follow-up unlikely, enrollment in another study, the occurrence of cardiac arrest after the arrival of emergency medical personnel a known preexisting coagulopathy. HACA TRIAL FEB 2002 The study was carried out between March 1996 and January 2001. 275 patients were enrolled, with 137 patients randomly assigned to the hypothermia group and 138 to the normothermia group (i.e., the group that received standard care after resuscitation). Hypothermia group A total of 75 of the 136 patients (55 percent) in the hypothermia group had a favorable neurologic outcome Normothermia group A total of 54 of the 137 (39 percent) in the normothermia group had a fovorable neurologic outcome. Conclusion of HACA trial 2002 Treatment with hypothermia may be of value in terms of public health. Each year, cardiac arrest occurs in approximately 375,000 people in Europe, about 30,000 of whom would meet our inclusion criteria. “We can be 95 percent confident that treatment with hypothermia would prevent an unfavorable neurologic outcome in 1200 to 7500 of these patients.” (HACA TRIAL 2002) TARGETED TEMPERATURE MANEGEMENT TRAIL IN 2013 This trial studied unconscious survivors of out-of-hospital cardiac arrest . Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Objective of TTM trial was to compare two target temperatures, both intended to prevent fever. AIM: The primary objective for study was all-cause mortality through the end of the trial. Secondary objective was to study a composite of poor neurologic function or death at 180 days. INCLUSION CRITERIA Out of hospital cardiac arrest 18 years+ GCS less than 8 Arrest of presumed cardiac origin Both shockable /non shockable rthyms 20 consecutive minutes of spontaneous circulation EXCLUSION CRITERIA an interval from the return of spontaneous circulation to screening of more than 240 minutes unwitnessed arrest with asystole as the initial rhythm suspected or known acute intracranial hemorrhage or stroke body temperature of less than 30°C. TTM TRIAL 2013 In total, 939 patients were included in the primary analysis. 33°C group 50% of the patients in the 33°C group (235 of 473 patients) had died, 36°C group with 48% of the patients in the 36°C group (225 of 466 patients) had died At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function as compared with 52% of patients in the 36°C group . After analysis the comparable rate was 52% in both groups. CONCLUSION In conclusion, TTM trial does not provide evidence that targeting a body temperature of 33°C confers any benefit for unconscious patients admitted to the hospital after out-of-hospital cardiac arrest, as compared with targeting a body temperature of 36°C. THERAPEUTIC MANAGEMENT AS PER AHA GUIDELINES AHA RECOMMMENDATION CLASS 1 FOR VF/VT RHYTHMS CLASS 2B FOR NONSHOCKABLE RTHYMS EUROPEAN RESUSCITATTIVE COUNCIL RECOMMENDS FOR ALL, BUT ACKNOWLEDGES THAT BENEFIT IS LESS IN NONSHOCKABLE RTHYMS. STAGES OF THERAPEUTIC HYPOTHERMIA INITIATION MAINTENANCE REWARMING NORMOTHERMIA COMPLICATIONS OF THERAPEUTIC HYPOTHERMIA Diuresis Electrolyte imbalance Immunosuppression There is a 20% increase in mortality for every hour of delay in the initiation of therapeutic hypothermia THANK YOU