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Targeted temperature management in traumatic brain injury
1. Targeted Temperature
Management in Severe
Traumatic Brain Injury
Dhaval Shukla
Professor of Neurosurgery,
NIMHANS, Bangalore.
Targeted Temperature Management in TBI
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2. Bramlett HM, et al. J Cereb Blood Flow Metab, 2004.
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July 2018 Sayeed I, et al. Progress in Brain Research, 2009.
Targeted Temperature Management in TBI
4. TTM
Hypothermia
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July 2018 Sayeed I, et al. Progress in Brain Research, 2009.
Targeted Temperature Management in TBI
5. Therapeutic Hypothermia –
Clinical Effects
• Reduces brain metabolism (~ 6-8% per 1°C) and
demand, restores a favourable balance with
cerebral blood flow in injured brain
• Lowers the intracranial pressure
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July 2018 Cariou A, et al. Anaesth Crit Care Pain Med 2017.
Targeted Temperature Management in TBI
6. Cooling Methods
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Targeted Temperature Management in TBI
7. Badjatia N, et al. NNSCNA 2013.
Targeted Temperature Management in TBI
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Low K, Mg, PO4; Insulin resistance;
Hypotension; Bradycardia; Coagulopathy.
8. Targeted Temperature Management in TBI
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July 2018 Badjatia N, et al. NNSCNA 2013.
9. TTM – Established Indications
American Heart Association (AHA) – Class 1
• Induce hypothermia for unconscious adult patients with return of
spontaneous circulation after out-of-hospital cardiac arrest
• The temperature should be maintained between 32°C and 36°C
• Routine prehospital cooling of with IV rapid infusion is not advised
Contraindications:
• Recent major surgery within 14 days - Hypothermia may increase the
risk of infection and bleeding.
• Systemic infection/sepsis - Hypothermia may inhibit immune function
and is associated with an increase in risk of infection.
• Coma from other causes (drug intoxication, preexisting coma prior to
arrest)
• Known bleeding diathesis or with active ongoing bleeding
Targeted Temperature Management in TBI
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10. TTM for TBI
Peterson K, et al. J Neurotrauma, 2008.
The small benefit with hypothermia is
negated by the side effects
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Targeted Temperature Management in TBI
11. BTF [3rd Edition]
Recommendations on TTM
• BTF – Level III (Optional)
• Cautious use of hypothermia for adults
• Not recommended for children
• Local cooling of the brain and combination of
hypothermia with drugs should be evaluated
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Targeted Temperature Management in TBI
12. Recent Trial of TTM in TBI
• NABIS:H II - 2011
• Very early hypothermia induction in patients with severe
brain injury (theNational Acute Brain Injury Study:
Hypothermia II): a randomised trial
• Eurotherm 3235 – 2015
• European society of intensive care medicine study of
therapeutic hypothermia (32-35°C) for intracranial pressure
reduction after traumatic brain injury
• Brain-Hypothermia (B-HYPO) - 2015
• Prolonged Mild Therapeutic Hypothermia versus Fever
Control with Tight Hemodynamic Monitoring and Slow
Rewarming in Patients with Severe Traumatic Brain Injury: A
Randomized Controlled Trial
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Targeted Temperature Management in TBI
13. NABIS:H II – 2011
• Planned sample size 240 from 2005 onwards
• Terminated for futility in 2009
• 97 patients within 2.5 hours of injury were enrolled
at the University of Texas
• Hypothermia Induction: 2 L of cold crystalloid and
application of wet sheets or gel packs
• Maintained at 33°C for 48 h by surface cooling
• Rewarmed by 0·5°C every 2 h
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Targeted Temperature Management in TBI
Clifton G, et al. Lancet Neurol 2011.
14. NABIS:H II
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Targeted Temperature Management in TBI
Clifton G, et al. Lancet Neurol 2011.
15. NABIS:H II
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Targeted Temperature Management in TBI
Clifton G, et al. Lancet Neurol 2011.
The only complication that was increased in frequency in the hypothermia group compared with the
normothermia group was episodes of increased ICP (p=0.003), which resulted in a significant
increase in the total rate of complications in patients in the hypothermia group (p=0.01).
16. Eurotherm3235 Trial - 2015
• Aimed to recruit 600 patients from18 countries
from 2009 onwards
• Recruitment was suspended in 2014 owing to
safety
• 387 patients at 47 centers
• Hypothermia induction: bolus of IV refrigerated
0.9% NaCl (20 to 30 ml/ kg)
• Maintained with the usual cooling technique for at
least 48 hrs.
• Rewarmed at 0.25°C per hour
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Targeted Temperature Management in TBI
Andrews PJD, et al. N Engl J Med 2015.
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Targeted Temperature Management in TBI
18. Eurotherm3235 Trial
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Targeted Temperature Management in TBI
Andrews PJD, et al. N Engl J Med 2015.
19. Eurotherm3235 Trial
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Targeted Temperature Management in TBI
Andrews PJD, et al. N Engl J Med 2015.
20. Brain-Hypothermia (B-HYPO) -2015
• Within 6 h after the onset of TBI
• TH (32–34°C) and fever control (35.5–37°C)
• Hypothermia induction: Cooling blankets, rapid cold
fluid infusion, and/or cold gastric lavage
• Maintained for ≥72 h, using surface cooling blankets
• Rewarmed at <1°C/day
• Temperature was maintained at <38°C for 7 days
after the onset of TBI
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Targeted Temperature Management in TBI
Maekawa,T, et al. Journal of Neurotrauma 2015.
21. Brain-Hypothermia (B-HYPO) -2015
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Targeted Temperature Management in TBI
Maekawa,T, et al. Journal of Neurotrauma 2015.
22. BTF [4th Edition]
Recommendations on TTM
• Level I and II A
• There was insufficient evidence to support a Level I
or II A recommendation for this topic.
• Level II B
• Early (within 2.5 hours), short-term (48 hours post-
injury) prophylactic hypothermia is not
recommended to improve outcomes in patients
with diffuse injury
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Targeted Temperature Management in TBI
BTF. 2016.
23. Hypothermia in Children with TBI
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July 2018 Zhang B, et al. World Neurosurg 2015.
24. Hypothermia in Children with TBI
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July 2018 Zhang B, et al. World Neurosurg 2015.
25. Fever
• Cerebral metabolism increased by 5-7% for each oC
rise in temperature
• Increased glucose & O2 consumption
• Fever early after TBI associated with
• Poor GCS on presentation
• Presence of DAI and edema on the initial CT
• Systolic hypotension
• Hyperglycemia
• Leukocytosis
Badjatia N. Crit Care Med 2009
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26. Fever
• Fever in 1st week is associated with
• Increased ICP
• Neurologic impairment
• Prolonged ICU stay
• Intermediate decline
• Long-term poor outcome
Badjatia N. Crit Care Med 2009
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27. Ongoing Trials
• LTH-1
• Randomized Controlled Trial of Long-term Mild
Hypothermia for Severe Traumatic Brain Injury
• Longer hyperthermia (34–35 °C) for 5
• HOPES
• HypOthermia for Patients requiring Evacuation of
Subdural Hematoma: A Multicenter, Randomized Clinical
Trial
• SDH preoperative induction for 48 h
• POLAR
• Prehospital hypothermia
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Targeted Temperature Management in TBI
28. Summary
• Evidence from animal models indicates that lowering
temperature by few degrees can substantially produce
neuroprotection.
• Maintenance of normothermia and fever prevention
after brain injury is generally considered a standard
therapy in the ICU.
• Ongoing clinical trials will inform us about the potential
role of maintaining normothermia or inducing
hypothermia in critically ill patients with a brain injury.
• Future research should refine patient selection on the
basis of biomarkers, and may use novel methods such
as ultraselective brain cooling and pharmacologic
thermomodulation.
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July 2018 JS, et al. NEJM 2008.