Therapeutic Hypothermia
Fakhir Raza Haidri
Induced Hypothermia Post Cardiac Arrest
With ROSC
• In 2002, the New England Journal published two well designed
studies 1...
What does “improved outcomes” mean?
• Both studies showed improved neurologic outcomes, not just
improved mortality.
A Meta analysis
• Meta-analysis including these two trials and another for patients
resuscitated from PEA or asystole and ...
ILCOR Advisory Statement
• “ Unconscious adult patients with spontaneous circulation after outof-hospital cardiac arrest s...
Theoretical Basis for Hypothermia
• Slow cerebral metabolism
• Reduce apoptosis (programmed cell death)
• Blunt excitatory...
Why does it work? Theoretical Basis:
• Slowed cerebral metabolism decreased 5 to 7% for each degree
Centigrade reduction i...
Why does it work? Theoretical Basis:
• Apoptosis:
• Apoptosis involves mitochondrial dysfunction and release of destructiv...
Why does it work? Theoretical Basis:
• Excitatory neurotoxicity
• As neurons become ischemic, they cannot maintain membran...
Why does it work? Theoretical Basis:
• Modulation of immune response and edema
•
•
•
•

Hypothermia suppresses release of ...
Inclusion Criteria

Exclusion Criteria

• Non-Traumatic cardiac
arrest with return of
circulation
• TH initiated within 6 ...
Internal Method
External Method
Complications of Cooling
• hypovolemia (hypothermia induced dieresis)
• coagulopathy (impaired coagulation cascade and
thr...
Complications of Rewarming
• worsening cerebral edema
• further changes in electrolyte abnormalities (especially
hyperkale...
Goal
• CPC 1 and CPC 2
Clinical Performance Category
• CPC 5. Brain death: apnea, areflexia, EEG silence, etc.
• CPC 4 . Coma or vegetative state...
Hypothermia in Comatose Survivors From
Out-of-Hospital Cardiac Arrest: Pilot Trial
Comparing 2 Levels of Target Temperatur...
Methods and Results
• Patients were eligible if they had a witnessed out-of-hospital cardiac
arrest from March 2008 to Aug...
Conclusions
• The findings of this pilot trial suggest that a lower cooling level may
be associated with a better outcome ...
Original Article

Targeted Temperature Management at
33°C versus 36°C after Cardiac Arrest
• N Engl J Med 2013; 369:2197-2...
Background
• Unconscious survivors of out-of-hospital cardiac arrest have a high
risk of death or poor neurologic function...
Methods
• International trial
• randomly assigned 950 unconscious adults after out-of-hospital
cardiac arrest of presumed ...
Results
• 50% of the patients in the 33°C group (235 of 473 patients) had
died, as compared with 48% of the patients in th...
Conclusions
• In unconscious survivors of out-of-hospital cardiac arrest of presumed
cardiac cause, hypothermia at a targe...
Any

Questions
Therapeutic hypothermia
Upcoming SlideShare
Loading in …5
×

Therapeutic hypothermia

2,556 views

Published on

Therapeutic hypothermia latest recommendations
post cardiac arrest
Asystole
defibrillation

Published in: Health & Medicine
  • Be the first to comment

Therapeutic hypothermia

  1. 1. Therapeutic Hypothermia Fakhir Raza Haidri
  2. 2. Induced Hypothermia Post Cardiac Arrest With ROSC • In 2002, the New England Journal published two well designed studies 1,2 showing dramatically improved outcomes when patients are actively cooled after resuscitation from V. Fib or Pulseless V. Tach. This led to an advisory statement by the ILCOR (International Liaison Committee on Resuscitation) that such patients should be cooled. • 1. Bernard S. et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. NEJM 2002, Feb 21; 346(8): 557-563. • 2. The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. NEJM 2002, Feb 21; 346(8): 549-556.
  3. 3. What does “improved outcomes” mean? • Both studies showed improved neurologic outcomes, not just improved mortality.
  4. 4. A Meta analysis • Meta-analysis including these two trials and another for patients resuscitated from PEA or asystole and cooled for 4 hours 2 . Neurologic recovery was improved and independent of method of cooling. Number needed to treat 4 – 13. 1. • Holzer M, et al. Hypothermia for neuroprotection after cardiac arrest: Systemic review and individual patient data meta-analysis. Crit Care Med, 2005; 33(2): 414418.
  5. 5. ILCOR Advisory Statement • “ Unconscious adult patients with spontaneous circulation after outof-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours when the initial rhythm was ventricular fibrillation.” “ Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest.” • International Liaison Committee on Resuscitation. Therapeutic hypothermia after cardiac arrest – An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 2003; 108: 118-121.
  6. 6. Theoretical Basis for Hypothermia • Slow cerebral metabolism • Reduce apoptosis (programmed cell death) • Blunt excitatory neurotoxicity • Modulate immune response
  7. 7. Why does it work? Theoretical Basis: • Slowed cerebral metabolism decreased 5 to 7% for each degree Centigrade reduction in body temperature. Decrease core temperature 4°C = 20-28% reduction in cerebral metabolism. Protective effects appear to be much greater than explained by this mechanism alone 1,2 . 1. Milde LN. Clinical use of mild hypothermia for brain protection: a dream revisited. J. Neurosurg Anesth 1992; 4: 211-215. 2. Small DL, et al. Biology of ischemic cerebral cell death. Prog Cardiovasc Dis, 1999; 42: 185-207.
  8. 8. Why does it work? Theoretical Basis: • Apoptosis: • Apoptosis involves mitochondrial dysfunction and release of destructive intracellular enzymes. Hypothermia can prevent these two processes leading to apoptosis
  9. 9. Why does it work? Theoretical Basis: • Excitatory neurotoxicity • As neurons become ischemic, they cannot maintain membrane potential, depolarize and release glutamate. • Energy-requiring mechanisms of re-uptake are impaired. • Surrounding neurons are stimulated longer than normal in an ischemic state, causing more damage. Hypothermia is believed to stabilize cell membranes and has been shown in animals to slow excitatory neurotoxicity • Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem, 1995; 65: 1704-1711. 4. Busto R, et al
  10. 10. Why does it work? Theoretical Basis: • Modulation of immune response and edema • • • • Hypothermia suppresses release of inflammatory cytokines (TNF- α and IL-1) It also slows production of free radicals Reduces disruptions of the blood-brain barrier, decreasing edema. Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells. • Crit Care Med, 2002; 30: 1499-1502. 2. Globus M, et al.
  11. 11. Inclusion Criteria Exclusion Criteria • Non-Traumatic cardiac arrest with return of circulation • TH initiated within 6 hours of arrest • Systolic BP > 90 or MAP > 60 after fluid resuscitation with or without pressors • > 12 years old • GCS > 8 • Greater than 6 hours since arrest • DNR • Non-mechanically ventilated patient • Pregnancy • Active bleeding • Arrest secondary to sepsis
  12. 12. Internal Method
  13. 13. External Method
  14. 14. Complications of Cooling • hypovolemia (hypothermia induced dieresis) • coagulopathy (impaired coagulation cascade and thrombocytopenia • electrolyte disorders (hypothermia induced dieresis, K+, Mg++, Ca++) • insulin resistance • changes in drugs effects and metabolism (altered clearance of fentanyl, midazolam, and atracurium)
  15. 15. Complications of Rewarming • worsening cerebral edema • further changes in electrolyte abnormalities (especially hyperkalemia) • hyperthermia (induced fever)
  16. 16. Goal • CPC 1 and CPC 2
  17. 17. Clinical Performance Category • CPC 5. Brain death: apnea, areflexia, EEG silence, etc. • CPC 4 . Coma or vegetative state: any degree of coma without the presence of all brain death criteria. Unawareness, even if appears awake (vegetative state) without interaction with environment; may have spontaneous eye opening and sleep/awake cycles. Cerebral unresponsiveness. • CPC 3. Severe cerebral disability: conscious, dependent on others for daily support because of impaired brain function. Ranges from ambulatory state to severe dementia or paralysis • CPC 2. Moderate cerebral disability: conscious, sufficient cerebral function for independent activities of daily life. Able to work in sheltered environment • CPC 1. Good cerebral performance: conscious, alert, able to work, might have mild neurologic or psychologic deficit • Lancet 1975. 1(7905):480-4
  18. 18. Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest: Pilot Trial Comparing 2 Levels of Target Temperature • Circulation. published online November 6, 2012;
  19. 19. Methods and Results • Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. • Target temperature was randomly assigned to 32°C or 34°C. • The primary outcome was survival free from severe dependence (Barthel Index score 60 points) at 6 months. • Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. • Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P0.12).
  20. 20. Conclusions • The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-ofhospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms.
  21. 21. Original Article Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest • N Engl J Med 2013; 369:2197-2206, December 5, 2013
  22. 22. Background • Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. • Our objective was to compare two target temperatures, both intended to prevent fever.
  23. 23. Methods • International trial • randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. • The primary outcome was all-cause mortality through the end of the trial. • Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.
  24. 24. Results • 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (P=0.51). • At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C (P=0.78). • In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (P=0.87). • The results of analyses adjusted for known prognostic factors were similar.
  25. 25. Conclusions • In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.
  26. 26. Any Questions

×