SlideShare a Scribd company logo
HYPOTHERMIA IN TBI FOR
NEUROPROTECTION
Dr Sumit Sinha
Additional Professor
Deptt of Neurosurgery, AIIMS and
JNATC, New Delhi
Hypothermia in TBI
• TBI- leading cause of death and disabiity
worldwide
• Primary brain injury- shear and neuronal
damage at the time of impact
• Secondary brain injury- ischemia (impaired
autoregulation, ↑ICP, Hypoperfusion) and
reperfusion injury (cascade leading to
apoptosis)
Hypothermia in TBI
• First mentioned in Papyrus 5000 years ago
• Hippocrates- snow packing to stop bleeding
• Sir William Osler- reduction in mortality of
typhoid fever
• Temple Fay- invented cooling blanket- relief in
pain for terminal malignancy
• Rosomoff et al (1950’s)- beneficial effect on ICP in
TBI
• HTh after cardiac arrest trial- better outcomes
with HTh
Hypothermia in TBI
Mechanism
AcutePhase
Reduces the release
of excitatory AA
Down regulates
astrocytic glutamate
trasporter I- which
mediates reverse
transport of
glutamate
Prevents glutamate
induced NO synthesis
Suppresses NMDA rec
phosphorylation
SubacutePhase
Attenuation of
oxidative and
nitrosative stress
markers
Mitigates the
inflammatory response
by reducing astrocytic
and microglial
activation
Decreases expression
of inflammatory
cytokines
Attenuates release of
proapoptotic mediators
Preserves BBB
ChronicPhase
Decrease cerebral
metabolism
Attenuates reperfusion
injury, BBB
permeability, edema
Helps in neuronal
regeneration and
circuit repair
Hypothermia in TBI
CV Effects
Positive inotropic-
arrhytmias
↑ MAP,SVR; ↓HR, CO
↑ VR- ANP,↓ADH- cold
diuresis-
hypotension
Pulmonary Effects
↓PaCO2
↑PaO2/ FiO2
↑Wound infection
No difference in rate
of pneumonia
Hematologic
function
Affects
platelet count,
coagulation
cascade
↑aPTTRenal, Endocrine, GI
effects
Electrolyte disorders-
K,Mg ↓
↓Insulin sensitivity- HG
Ileus, DGE
Liver function/
drug
Metabolism
Affects tubular
secretion and
reabsorption
Reduction in
enzyme activity
↓cP450
Physiological Effects
Hypothermia in TBI
Therapeutic Hypothermia
• hTH started <24 hrs x 3-5 d/
till ↑ICP resolves
• 4/5 trials- ↓mortality/
↑outcome
★ Jiang et al. J Neurosurg 2000
★ Shiozaki et al. J Neurosurg 2003
★ Jiang et al. J Cereb Blood Flow Metab
2006
★ Qui et al. J Crit Care 2007
★ Yan et al. J Clin Neurosci 2010
Prophylactic Hypothermia
• 33-34° <10 hrs x 24-48 hrs
irresp of ICP
• All trials failed to show
improved outcome
✧ Clifton et al. N Engl J Med 2001
✧ Marion et al. N Engl J Med 1997
✧ Shiozaki et al. J Neurosurg 2001
Hypothermia in TBI
No. Target temp/
duration
Mortality Neurol
outcome
Clifton et al. (NABIS:H II Trial) Lancet 2011 97 33/48 No No
Hutchinson et al. (HiTBIC Trial). NEJM 2008. 225 32.5/24 No No
Qui et al. J Crit Care 2007 80 33/96 No Yes
Adelson et al (Cool Kids) HYPO I and II.
Neurosurgery 2005
48/26 32/48 No No
Qui et al.Clin J Traumatology 2005 86 33/103 Yes Yes
Smrcka et al. Acta Neurochirur 2005 72 34/72 No Yes
Zhi et al. Surg neurology 2003 396 34/62.4 Yes Yes
Clifton et al. (NABIS:H Trial) NEJM 2001 392 33/48 No No
Shiozaki et al. J Neurosurg 2001 91 34/48 No No
Jiang et al. J Neurosurg 2000 87 32/>72 Yes Yes
Clifton et al. J Neurotrauma 1993 46 32/48 No No
Marion et al. NEJM 1997 82 32/24 No No
SUMMARY OF DIFFERENT TRIALS ON HYPOTHERMIA
Hypothermia in TBI
NABIS:H trial
• 392 pts- terminated for futility
• 33° x 48 hrs at a mean of 8.4 hrs
• hTH didn’t improve outcome+ more
hypotension
• Weak evidence of better outcome in pts
hypothermic at admission
Clifton GL et al. Lack of effect of induction of hypothermia after
acute brain injury. N Engl J Med 2001;344:556-63
Hypothermia in TBI
NABIS:H trial- Lessons learned!!!
• Pts hypothermic at admission and then
rewarmed- did worse
• >45 yrs- worse with hTH
• <45 yrs presenting with hTH not rewarmed
did well- suggests that there may be a narrow
therapeutic window
Hypothermia in TBI
• 13 Trials- Level II (6) and Level III (7)
• Overall, no difference in mortality, but 46% ↑
chance of good outcome
• hTH >48 hrs has ↓mortality
• level III recommendation for the use of hTH in
TBI
The brain trauma Foundation. Guidelines for the management of
severe traumatic brain injury. J Neurotrauma 2007;24:S21-25
Hypothermia in TBI
• Pts enrolled within 2-2.5 hrs- 33°x 48 hrs
• 232 pts- 119 (hTH)/113 (NT)
• No difference in outcome and mortality
• No utility of hypothermia
Clifton GL et al. Very early hypothermia induction in patients
with severe brain injury (the National Acute Brain Injury Study:
Hypothermia II): a randomised trial. Lancet Neurol 2011;10:131-
39
Hypothermia in TBI
• 77 pts- Terminated for futility
• hTH x 48 hrs- no difference after pediatric
severe traumatic brain injury
Adelson et al. Comparison of hypothermia and normothermia
after severe traumatic brain injury (Cool kids): A phase III
randomised controlled trial. Lancet Neurol 2013;12(6):546-53
Hypothermia in TBI
• 23 RCT- 1614 pts
• Significant benefit- only in low quality trials
• High quality trials- no decrease in death with hTH-
play of chance.
• hTH should not be used except in the context of a
high quality RCT with good allocation concealment
No evidence that
hypothermia is beneficial
Hypothermia in TBI
8 Metanalysis since
2002
Trials No. Mortality Neurological
outcome
Fox et al. CJEM. 2010;12:355-64 12 1327 Y Y
Sydenham et al. The Cochrane databse of systematic reviews
2009
21 1587 Y Y
Peterson et al. J Neurotrauma 2008;25:62-71 13 1339 Y Y
AANS BTF. J Neurotrauma 2007;24:S1-106
Alderson et al. . The Cochrane databse of systematic reviews
2004
Henderson et al. Intens Care Med 2003;29:1637-44 8 748 Y Y
McIntyre et al. JAMA 2003;289:2992-2999
Harris et al. Arch Neurol 2002;59:1077-1083 7 668 Y
Hypothermia in TBI
• 18 RCT (1851 Pts)- GRADE recommendations
• Overall RR of mortality and poor neurologic
outcome with hTH vs controls- 0.84 and 0.81
• High quality trials- RR 1.28
• hTH a/w ↓CPP on rewarming and pneumonia
• No benefit of hTH on mortality or neurologic
outcome
Georgiou et al. Role of Therapeutic hypothemria in improving
outcome after traumatic Brain injury: a systematic review.
Br J Anaesthesia 2013;110(3):357-67
Hypothermia in TBI
Forest Plot of all trials- effect of hTH vs NT on mortality
Hypothermia in TBI
Forest Plot of all trials- effect of hTH vs NT on poor neurological outcome
Hypothermia in TBI
Forest Plot of high quality trials- effect of hTH vs NT on mortality
Forest Plot of high quality trials- effect of hTH vs NT on poor neurological outcome
Hypothermia in TBI
Why lack of evidence so far???
• TBI- heterogenous disease- no study adequately
powered to study effect of hTH
• Peak ICP ↑ occurs >48 hrs- when several trials
have started rewarming
• Peak neuronal death occurs hrs after TBI- target
temp achieved <8 hrs only in some trials
• GOS is a crude assessment measure- subtle
outcome differences missed- GOSE better
Hypothermia in TBI
Future hTH trials should consider !!!!
• Initiation of hTH in prehospital setting
• Maintainence of hTH >48 hrs
• Rewarming acc to physiological rather than
time based criteria
• FU using GOSE
Hypothermia in TBI
Ongoing trials- Results Awaited Eagerly !!!
*Cooper J
*Andrews et al. Trials 2011;12:8
POLAR- RCT
Eurotherm
Hypothermia in TBI
AIIMS JPNATC Experience
PG ± HTh in severe TBI
FINANCIAL DISCLOSURES
Research grant funded by Department
of Biotechnology (DBT) New Delhi,
India
PG ± HTh in severe TBI
Aims and Objectives
• To examine the efficacy of Progesterone drug
and hypothermia, alone or in combination, in
improving neurological outcome in Severe
Traumatic Brain Injury.
• To study the difference in the levels of various
serum biomarkers after treatment and their
correlation with outcome
PG ± HTh in severe TBI
Materials and Methods
• Data Collected-
– Daily- vitals, ICP, CPP, BP, Intake/ Output, GCS score, ABG(pH , K+ , pCO2
,pO2,Hco3)
– Lab Test for 7 days.(Biochemistry,Haematology,Coagulation)
– CT Scan- at admission and Day 6
– Biochemical markers of STBI- (S100,NSE, Progesterone, Estrogen, IL 6, GFAP)-
at admission and 1st Week
INCLUSION CRITERIA EXCLUSION CRITERIA
• 18-65 years. • Any investigational drugs 30 days prior to
enrollment.
• GCS score 4-8 • Severe anoxic intracerebral damage or brain
death.
• <8 hours of injury. • Spinal Cord Injury
• Pregnancy
Type of study: Randomized Placebo controlled study
PG ± HTh in severe TBI
Study groups
Normal
temperature
Progesterone +
Normal
temperature
Hypothermia
Hypothermia
+Progesterone
Follow up at 1 and 6 moths
Primary endpoints:-
i. Glasgow Outcome Score
(GOS)
Secondary endpoints: --
i. Functional Independence
Measure (FIM).
ii. Mortality
PG ± HTh in severe TBI
Materials and Methods (Contd.)
• Injn. Progesterone- 1mg/kg I/M BD X 5 days
• Hypothermia- (surface cooling by blankets-
Blanketrol II, Cincinnati Sub-Zero, Cincinnati)
– 34 degree C X 24 hrs
– Rewarming- 0.5 degree/ 2hrs
• Placebo- 5 ml distilled water I/M BDX 5 days
PG ± HTh in severe TBI
Results
• Total Patients recruited- 107(27 in each A ,C &
D groups and 26 in Group B )
• Mean Age- 32 ± 11.27
• Sex- 90 males and 17 females
• Mean GCS- 6 ± 1.0
• Average time to recruitment- 5.0 ± 1.2 hrs
• Average time to desired temperature (34° C)- 45
± 12 minutes
• Mean ICP-10.21 ± 5.6
Group A
(Control )
Group B
(PG)
Group C
(HTh)
Group D
(HTh+PG)
Mean Age-
(years)
33.96 33.73 31.44 31.25
Sex- M/F 23/4 20/6 24/3 23/4
Mean GCS 6 6 6 6
Mean ICP 7.60 10.75 11.21 10.47
Base-line characteristics of patients with severe TBI
PG ± HTh in severe TBI
Results contd.
PG ± HTh in severe TBI
Results (Contd.)
Primary Endpoints-
GOS at 1 month
(n=90)
GOS at 6 month
(n=81)
PG ± HTh in severe TBI
Results (Contd.)
SECONDARY ENDPOINTS
Overall mortality-20.6%
PG ± HTh in severe TBI
CONCLUSIONS
• Good outcome at 6th month- best in Hypothermia group
(83%), followed by PG group (77%).
• Highest mortality found in Control (26%); Lowest (15%)
in Hypothermia group .
• PRG- shows more (76%) functionally independent pts at
6th month, followed by Hypothermia group (66.5%)
• PG + hTH does not confer any additional advantage
Hypothermia in TBI
TAKE HOME MESSAGE
• hTH should logically be useful in improving
the mortality and neurologic outcome
• Requires well designed large multicentric
RCT’s to prove association
• Presently, no definite Level I or II evidence-
BTF proposes Level III guideline
THANK YOU

More Related Content

What's hot

Cerebral blood flow
Cerebral blood flowCerebral blood flow
Autoregulation of cerebral blood flow part 1/2
Autoregulation of cerebral blood flow part 1/2Autoregulation of cerebral blood flow part 1/2
Autoregulation of cerebral blood flow part 1/2
Sameep Koshti
 
Principles of Neurocritical Care
Principles of Neurocritical CarePrinciples of Neurocritical Care
Principles of Neurocritical Care
NIICS
 
Hemostats in neurosurgery
Hemostats in neurosurgeryHemostats in neurosurgery
Hemostats in neurosurgery
Dr. Shahnawaz Alam
 
Neuromonitoring in anesthesia
Neuromonitoring in anesthesiaNeuromonitoring in anesthesia
Neuromonitoring in anesthesia
Antara Banerji
 
Cerebral Blood Flow and its Regulation
Cerebral Blood Flow and its RegulationCerebral Blood Flow and its Regulation
Cerebral Blood Flow and its Regulation
Dr Kaushal Deep Singh Mathuria
 
Cerebral physiology and effects of anaesthetic agents
Cerebral physiology and effects of anaesthetic agentsCerebral physiology and effects of anaesthetic agents
Cerebral physiology and effects of anaesthetic agents
Richa Kumar
 
IV Fluids in Neurosurgery
IV Fluids in NeurosurgeryIV Fluids in Neurosurgery
IV Fluids in Neurosurgery
RejoyceAnto
 
Third ventricular surgical approaches
Third ventricular surgical approachesThird ventricular surgical approaches
Third ventricular surgical approaches
suresh Bishokarma
 
026 positioning for cranial surgery
026 positioning for cranial surgery026 positioning for cranial surgery
026 positioning for cranial surgery
Neurosurgery Vajira
 
Brain herniation imaging
Brain herniation imagingBrain herniation imaging
Brain herniation imaging
Thorsang Chayovan
 
Intra operative neurophysiological monitoring
Intra operative neurophysiological monitoringIntra operative neurophysiological monitoring
Intra operative neurophysiological monitoring
Kode Sashanka
 
Cerebral blood flow -Varun
Cerebral blood flow -VarunCerebral blood flow -Varun
Cerebral blood flow -Varun
varunbobby
 
Mechanisms of cerebral injury and cerebral protection
Mechanisms of cerebral injury and cerebral protectionMechanisms of cerebral injury and cerebral protection
Mechanisms of cerebral injury and cerebral protection
Dr Kumar
 
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
SHAMEEJ MUHAMED KV
 
Intracranial pressure
Intracranial pressureIntracranial pressure
Intracranial pressure
MUHAMMED ALIF
 
Frontotemporal FTOZ craniotomy
Frontotemporal FTOZ craniotomyFrontotemporal FTOZ craniotomy
Frontotemporal FTOZ craniotomy
Dr. Shahnawaz Alam
 
Meningioma falcine and parasagittal
Meningioma falcine and parasagittalMeningioma falcine and parasagittal
Meningioma falcine and parasagittal
Dr Praveen kumar tripathi
 
Cisterns of brain and its contents along with its classification and approach...
Cisterns of brain and its contents along with its classification and approach...Cisterns of brain and its contents along with its classification and approach...
Cisterns of brain and its contents along with its classification and approach...
Rajeev Bhandari
 
Cns physiology
Cns physiologyCns physiology
Cns physiology
Dr.RMLIMS lucknow
 

What's hot (20)

Cerebral blood flow
Cerebral blood flowCerebral blood flow
Cerebral blood flow
 
Autoregulation of cerebral blood flow part 1/2
Autoregulation of cerebral blood flow part 1/2Autoregulation of cerebral blood flow part 1/2
Autoregulation of cerebral blood flow part 1/2
 
Principles of Neurocritical Care
Principles of Neurocritical CarePrinciples of Neurocritical Care
Principles of Neurocritical Care
 
Hemostats in neurosurgery
Hemostats in neurosurgeryHemostats in neurosurgery
Hemostats in neurosurgery
 
Neuromonitoring in anesthesia
Neuromonitoring in anesthesiaNeuromonitoring in anesthesia
Neuromonitoring in anesthesia
 
Cerebral Blood Flow and its Regulation
Cerebral Blood Flow and its RegulationCerebral Blood Flow and its Regulation
Cerebral Blood Flow and its Regulation
 
Cerebral physiology and effects of anaesthetic agents
Cerebral physiology and effects of anaesthetic agentsCerebral physiology and effects of anaesthetic agents
Cerebral physiology and effects of anaesthetic agents
 
IV Fluids in Neurosurgery
IV Fluids in NeurosurgeryIV Fluids in Neurosurgery
IV Fluids in Neurosurgery
 
Third ventricular surgical approaches
Third ventricular surgical approachesThird ventricular surgical approaches
Third ventricular surgical approaches
 
026 positioning for cranial surgery
026 positioning for cranial surgery026 positioning for cranial surgery
026 positioning for cranial surgery
 
Brain herniation imaging
Brain herniation imagingBrain herniation imaging
Brain herniation imaging
 
Intra operative neurophysiological monitoring
Intra operative neurophysiological monitoringIntra operative neurophysiological monitoring
Intra operative neurophysiological monitoring
 
Cerebral blood flow -Varun
Cerebral blood flow -VarunCerebral blood flow -Varun
Cerebral blood flow -Varun
 
Mechanisms of cerebral injury and cerebral protection
Mechanisms of cerebral injury and cerebral protectionMechanisms of cerebral injury and cerebral protection
Mechanisms of cerebral injury and cerebral protection
 
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
DECOMPRESSIVE CRANIECTOMY - DR SHAMEEJ
 
Intracranial pressure
Intracranial pressureIntracranial pressure
Intracranial pressure
 
Frontotemporal FTOZ craniotomy
Frontotemporal FTOZ craniotomyFrontotemporal FTOZ craniotomy
Frontotemporal FTOZ craniotomy
 
Meningioma falcine and parasagittal
Meningioma falcine and parasagittalMeningioma falcine and parasagittal
Meningioma falcine and parasagittal
 
Cisterns of brain and its contents along with its classification and approach...
Cisterns of brain and its contents along with its classification and approach...Cisterns of brain and its contents along with its classification and approach...
Cisterns of brain and its contents along with its classification and approach...
 
Cns physiology
Cns physiologyCns physiology
Cns physiology
 

Similar to Hypothermia in TbI

Hypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotectionHypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotection
Abhishek Sharma
 
Hypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotectionHypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotection
Sumit2018
 
Dr Gene Ong: Paediatric therapeutic hypothermia
Dr Gene Ong: Paediatric therapeutic hypothermiaDr Gene Ong: Paediatric therapeutic hypothermia
Dr Gene Ong: Paediatric therapeutic hypothermia
Rahul Goswami
 
Hypothermic resuscitation
Hypothermic resuscitationHypothermic resuscitation
Hypothermic resuscitation
taem
 
Hypothermic resuscitation sombat
Hypothermic resuscitation sombatHypothermic resuscitation sombat
Hypothermic resuscitation sombat
Aimmary
 
The TTM trials - why, how and what?
The TTM trials - why, how and what?The TTM trials - why, how and what?
The TTM trials - why, how and what?
scanFOAM
 
Nccu journal club 2.5.13
Nccu journal club 2.5.13Nccu journal club 2.5.13
Nccu journal club 2.5.13
Joshua Kornbluth
 
BTF-Guidelines-for-TBI-Management.pdf
BTF-Guidelines-for-TBI-Management.pdfBTF-Guidelines-for-TBI-Management.pdf
BTF-Guidelines-for-TBI-Management.pdf
TungToManh
 
Hypothermia for TBI FINAL
Hypothermia for TBI FINAL Hypothermia for TBI FINAL
Hypothermia for TBI FINAL
Nancy Kelly
 
Therapeutic hypothermia
Therapeutic hypothermiaTherapeutic hypothermia
Therapeutic hypothermia
Dr fakhir Raza
 
Update on cardiac arrrest and post cardiac arrest management16 1-18
Update on cardiac arrrest and post cardiac arrest management16 1-18Update on cardiac arrrest and post cardiac arrest management16 1-18
Update on cardiac arrrest and post cardiac arrest management16 1-18
Anand Tiwari
 
Major trials in Head Injury.pptx
Major trials in Head Injury.pptxMajor trials in Head Injury.pptx
Major trials in Head Injury.pptx
Soumen Kanjilal
 
Lessons from the TTM trial and planning for the nexst
Lessons from the TTM trial and planning for the nexstLessons from the TTM trial and planning for the nexst
Lessons from the TTM trial and planning for the nexst
scanFOAM
 
Propranolol and Neuro storming.pptx
Propranolol and Neuro storming.pptxPropranolol and Neuro storming.pptx
Propranolol and Neuro storming.pptx
AnnaSandler4
 
Prehospital induced hypothermia post cardiac arrest jun 2010[1]
Prehospital induced hypothermia post cardiac arrest jun 2010[1]Prehospital induced hypothermia post cardiac arrest jun 2010[1]
Prehospital induced hypothermia post cardiac arrest jun 2010[1]
Robert Cole
 
Perioperative Beta Blockers in non-cardiac surgery and POISE
Perioperative Beta Blockers in non-cardiac surgery and POISEPerioperative Beta Blockers in non-cardiac surgery and POISE
Perioperative Beta Blockers in non-cardiac surgery and POISE
MedPeds Hospitalist
 
Therapeutic hypothermia - current evidence
Therapeutic hypothermia - current evidenceTherapeutic hypothermia - current evidence
Therapeutic hypothermia - current evidence
SCGH ED CME
 
Targeted Temperature Management (Therapeutic Hypothermia) in Critical Care: ...
Targeted Temperature Management  (Therapeutic Hypothermia) in Critical Care: ...Targeted Temperature Management  (Therapeutic Hypothermia) in Critical Care: ...
Targeted Temperature Management (Therapeutic Hypothermia) in Critical Care: ...
Bassel Ericsoussi, MD
 
Does ICP monitoring in TBI really help? by Dr Paul Goldrick
Does ICP monitoring in TBI really help? by Dr Paul GoldrickDoes ICP monitoring in TBI really help? by Dr Paul Goldrick
Does ICP monitoring in TBI really help? by Dr Paul Goldrick
CICM 2019 Annual Scientific Meeting
 
Contemporary management of traumatic intracranial
Contemporary management of traumatic intracranialContemporary management of traumatic intracranial
Contemporary management of traumatic intracranial
VictorRolandoZagaCas1
 

Similar to Hypothermia in TbI (20)

Hypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotectionHypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotection
 
Hypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotectionHypothermia in tbi for neuroprotection
Hypothermia in tbi for neuroprotection
 
Dr Gene Ong: Paediatric therapeutic hypothermia
Dr Gene Ong: Paediatric therapeutic hypothermiaDr Gene Ong: Paediatric therapeutic hypothermia
Dr Gene Ong: Paediatric therapeutic hypothermia
 
Hypothermic resuscitation
Hypothermic resuscitationHypothermic resuscitation
Hypothermic resuscitation
 
Hypothermic resuscitation sombat
Hypothermic resuscitation sombatHypothermic resuscitation sombat
Hypothermic resuscitation sombat
 
The TTM trials - why, how and what?
The TTM trials - why, how and what?The TTM trials - why, how and what?
The TTM trials - why, how and what?
 
Nccu journal club 2.5.13
Nccu journal club 2.5.13Nccu journal club 2.5.13
Nccu journal club 2.5.13
 
BTF-Guidelines-for-TBI-Management.pdf
BTF-Guidelines-for-TBI-Management.pdfBTF-Guidelines-for-TBI-Management.pdf
BTF-Guidelines-for-TBI-Management.pdf
 
Hypothermia for TBI FINAL
Hypothermia for TBI FINAL Hypothermia for TBI FINAL
Hypothermia for TBI FINAL
 
Therapeutic hypothermia
Therapeutic hypothermiaTherapeutic hypothermia
Therapeutic hypothermia
 
Update on cardiac arrrest and post cardiac arrest management16 1-18
Update on cardiac arrrest and post cardiac arrest management16 1-18Update on cardiac arrrest and post cardiac arrest management16 1-18
Update on cardiac arrrest and post cardiac arrest management16 1-18
 
Major trials in Head Injury.pptx
Major trials in Head Injury.pptxMajor trials in Head Injury.pptx
Major trials in Head Injury.pptx
 
Lessons from the TTM trial and planning for the nexst
Lessons from the TTM trial and planning for the nexstLessons from the TTM trial and planning for the nexst
Lessons from the TTM trial and planning for the nexst
 
Propranolol and Neuro storming.pptx
Propranolol and Neuro storming.pptxPropranolol and Neuro storming.pptx
Propranolol and Neuro storming.pptx
 
Prehospital induced hypothermia post cardiac arrest jun 2010[1]
Prehospital induced hypothermia post cardiac arrest jun 2010[1]Prehospital induced hypothermia post cardiac arrest jun 2010[1]
Prehospital induced hypothermia post cardiac arrest jun 2010[1]
 
Perioperative Beta Blockers in non-cardiac surgery and POISE
Perioperative Beta Blockers in non-cardiac surgery and POISEPerioperative Beta Blockers in non-cardiac surgery and POISE
Perioperative Beta Blockers in non-cardiac surgery and POISE
 
Therapeutic hypothermia - current evidence
Therapeutic hypothermia - current evidenceTherapeutic hypothermia - current evidence
Therapeutic hypothermia - current evidence
 
Targeted Temperature Management (Therapeutic Hypothermia) in Critical Care: ...
Targeted Temperature Management  (Therapeutic Hypothermia) in Critical Care: ...Targeted Temperature Management  (Therapeutic Hypothermia) in Critical Care: ...
Targeted Temperature Management (Therapeutic Hypothermia) in Critical Care: ...
 
Does ICP monitoring in TBI really help? by Dr Paul Goldrick
Does ICP monitoring in TBI really help? by Dr Paul GoldrickDoes ICP monitoring in TBI really help? by Dr Paul Goldrick
Does ICP monitoring in TBI really help? by Dr Paul Goldrick
 
Contemporary management of traumatic intracranial
Contemporary management of traumatic intracranialContemporary management of traumatic intracranial
Contemporary management of traumatic intracranial
 

More from Sumit2018

Benign primary spinal bony tumors
Benign primary spinal bony tumorsBenign primary spinal bony tumors
Benign primary spinal bony tumors
Sumit2018
 
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
Sumit2018
 
Guidelines in hospital care
Guidelines in hospital careGuidelines in hospital care
Guidelines in hospital care
Sumit2018
 
Hthfinal1 180625071910
Hthfinal1 180625071910Hthfinal1 180625071910
Hthfinal1 180625071910
Sumit2018
 
Subaxial Cervical Spine Injuries
Subaxial Cervical Spine InjuriesSubaxial Cervical Spine Injuries
Subaxial Cervical Spine Injuries
Sumit2018
 
Head trauma traumacon_2011
Head trauma traumacon_2011Head trauma traumacon_2011
Head trauma traumacon_2011
Sumit2018
 
Head injury management lecture.ppt (1)
Head injury management lecture.ppt (1)Head injury management lecture.ppt (1)
Head injury management lecture.ppt (1)
Sumit2018
 
Head injury by Dr. sumit sinha
Head injury by Dr. sumit sinhaHead injury by Dr. sumit sinha
Head injury by Dr. sumit sinha
Sumit2018
 
Head and Spine trauma traumacon 2011.ppt
Head and Spine trauma traumacon 2011.pptHead and Spine trauma traumacon 2011.ppt
Head and Spine trauma traumacon 2011.ppt
Sumit2018
 
Glasgow coma scale.ppt
Glasgow coma scale.pptGlasgow coma scale.ppt
Glasgow coma scale.ppt
Sumit2018
 
Giant pituitary adenomas.ppt
Giant pituitary adenomas.pptGiant pituitary adenomas.ppt
Giant pituitary adenomas.ppt
Sumit2018
 
Guidelines in hospital care
Guidelines in hospital careGuidelines in hospital care
Guidelines in hospital care
Sumit2018
 
Free hand screw
Free hand screwFree hand screw
Free hand screw
Sumit2018
 
Fortis lecture High Grade Spondylolisthesis
Fortis lecture High Grade SpondylolisthesisFortis lecture High Grade Spondylolisthesis
Fortis lecture High Grade Spondylolisthesis
Sumit2018
 
Fortis noida Spinal Bony Tumor
Fortis noida Spinal Bony TumorFortis noida Spinal Bony Tumor
Fortis noida Spinal Bony Tumor
Sumit2018
 
Multidimentional imaging in spinal fractures
Multidimentional imaging in spinal fracturesMultidimentional imaging in spinal fractures
Multidimentional imaging in spinal fractures
Sumit2018
 
Advances tbi.ppt (2)
Advances tbi.ppt (2)Advances tbi.ppt (2)
Advances tbi.ppt (2)
Sumit2018
 
Cns tumors.ppt
Cns tumors.pptCns tumors.ppt
Cns tumors.ppt
Sumit2018
 

More from Sumit2018 (18)

Benign primary spinal bony tumors
Benign primary spinal bony tumorsBenign primary spinal bony tumors
Benign primary spinal bony tumors
 
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
SIMVASTATIN IN ANEURYSMAL SUBARACHNOID HEAMORRHAGE (SASH) TRIAL
 
Guidelines in hospital care
Guidelines in hospital careGuidelines in hospital care
Guidelines in hospital care
 
Hthfinal1 180625071910
Hthfinal1 180625071910Hthfinal1 180625071910
Hthfinal1 180625071910
 
Subaxial Cervical Spine Injuries
Subaxial Cervical Spine InjuriesSubaxial Cervical Spine Injuries
Subaxial Cervical Spine Injuries
 
Head trauma traumacon_2011
Head trauma traumacon_2011Head trauma traumacon_2011
Head trauma traumacon_2011
 
Head injury management lecture.ppt (1)
Head injury management lecture.ppt (1)Head injury management lecture.ppt (1)
Head injury management lecture.ppt (1)
 
Head injury by Dr. sumit sinha
Head injury by Dr. sumit sinhaHead injury by Dr. sumit sinha
Head injury by Dr. sumit sinha
 
Head and Spine trauma traumacon 2011.ppt
Head and Spine trauma traumacon 2011.pptHead and Spine trauma traumacon 2011.ppt
Head and Spine trauma traumacon 2011.ppt
 
Glasgow coma scale.ppt
Glasgow coma scale.pptGlasgow coma scale.ppt
Glasgow coma scale.ppt
 
Giant pituitary adenomas.ppt
Giant pituitary adenomas.pptGiant pituitary adenomas.ppt
Giant pituitary adenomas.ppt
 
Guidelines in hospital care
Guidelines in hospital careGuidelines in hospital care
Guidelines in hospital care
 
Free hand screw
Free hand screwFree hand screw
Free hand screw
 
Fortis lecture High Grade Spondylolisthesis
Fortis lecture High Grade SpondylolisthesisFortis lecture High Grade Spondylolisthesis
Fortis lecture High Grade Spondylolisthesis
 
Fortis noida Spinal Bony Tumor
Fortis noida Spinal Bony TumorFortis noida Spinal Bony Tumor
Fortis noida Spinal Bony Tumor
 
Multidimentional imaging in spinal fractures
Multidimentional imaging in spinal fracturesMultidimentional imaging in spinal fractures
Multidimentional imaging in spinal fractures
 
Advances tbi.ppt (2)
Advances tbi.ppt (2)Advances tbi.ppt (2)
Advances tbi.ppt (2)
 
Cns tumors.ppt
Cns tumors.pptCns tumors.ppt
Cns tumors.ppt
 

Recently uploaded

SMET (Self-Management of Excessive Tension) Cyclic Meditation.pptxv.pptx
SMET (Self-Management of Excessive Tension)  Cyclic Meditation.pptxv.pptxSMET (Self-Management of Excessive Tension)  Cyclic Meditation.pptxv.pptx
SMET (Self-Management of Excessive Tension) Cyclic Meditation.pptxv.pptx
Karuna Yoga Vidya Peetham
 
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
stanslausnzuki569
 
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
bellared2
 
Abdominal trauma, management, liver trauma, splenic trauma,
Abdominal trauma, management, liver trauma, splenic trauma,Abdominal trauma, management, liver trauma, splenic trauma,
Abdominal trauma, management, liver trauma, splenic trauma,
AditiSachdeva12
 
CA stomach.ppt presentation following gastring outlet obstruction
CA stomach.ppt presentation following gastring outlet obstructionCA stomach.ppt presentation following gastring outlet obstruction
CA stomach.ppt presentation following gastring outlet obstruction
Tanveer Khalid
 
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai AvailableGirls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
shamrisumri
 
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
snehamittal#G05
 
How dental support group work...........
How dental support group work...........How dental support group work...........
How dental support group work...........
AvilasDentalGroup
 
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
revolutionary575
 
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptx
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptxYoga, Anatomy & Physiology Certificate Course.pptxv.pptx
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptx
Karuna Yoga Vidya Peetham
 
Therapeutic Diets Applied Nutrition and Dietics in BSc Nursing
Therapeutic Diets Applied Nutrition and Dietics in BSc NursingTherapeutic Diets Applied Nutrition and Dietics in BSc Nursing
Therapeutic Diets Applied Nutrition and Dietics in BSc Nursing
MKSSS BTINE
 
Diagnosis and treatment planning in complete denture.pptx
Diagnosis and treatment planning in complete denture.pptxDiagnosis and treatment planning in complete denture.pptx
Diagnosis and treatment planning in complete denture.pptx
SatvikaPrasad
 
VITAMINS(referred as a Organic compound)
VITAMINS(referred as a Organic compound)VITAMINS(referred as a Organic compound)
VITAMINS(referred as a Organic compound)
saloniswain225
 
MGI DNBSEQ Sequencing Technology short.pptx
MGI DNBSEQ Sequencing Technology short.pptxMGI DNBSEQ Sequencing Technology short.pptx
MGI DNBSEQ Sequencing Technology short.pptx
tnglml2
 
NEET UG 2024: LIVE UPDATES from Supreme Court
NEET UG 2024: LIVE UPDATES from Supreme CourtNEET UG 2024: LIVE UPDATES from Supreme Court
NEET UG 2024: LIVE UPDATES from Supreme Court
kareena rawat
 
heart intro.pptx full introduction about the heart
heart intro.pptx full introduction about the heartheart intro.pptx full introduction about the heart
heart intro.pptx full introduction about the heart
krithikamugunthavel
 
buy oxycodone online at chemworldstore.net
buy oxycodone online at chemworldstore.netbuy oxycodone online at chemworldstore.net
buy oxycodone online at chemworldstore.net
luciatcupups
 
Ethical Principles in Nursing & Healthcare Practice
Ethical Principles in Nursing & Healthcare PracticeEthical Principles in Nursing & Healthcare Practice
Ethical Principles in Nursing & Healthcare Practice
Esraa Mohammed Soltan
 
Yoga for Beginner’s Course- yoga foundation course
Yoga for Beginner’s Course- yoga foundation courseYoga for Beginner’s Course- yoga foundation course
Yoga for Beginner’s Course- yoga foundation course
Karuna Yoga Vidya Peetham
 
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
د حاتم البيطار
 

Recently uploaded (20)

SMET (Self-Management of Excessive Tension) Cyclic Meditation.pptxv.pptx
SMET (Self-Management of Excessive Tension)  Cyclic Meditation.pptxv.pptxSMET (Self-Management of Excessive Tension)  Cyclic Meditation.pptxv.pptx
SMET (Self-Management of Excessive Tension) Cyclic Meditation.pptxv.pptx
 
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
TEST BANK & Solutions Manual For Medical Assisting Administrative & Clinical ...
 
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
 
Abdominal trauma, management, liver trauma, splenic trauma,
Abdominal trauma, management, liver trauma, splenic trauma,Abdominal trauma, management, liver trauma, splenic trauma,
Abdominal trauma, management, liver trauma, splenic trauma,
 
CA stomach.ppt presentation following gastring outlet obstruction
CA stomach.ppt presentation following gastring outlet obstructionCA stomach.ppt presentation following gastring outlet obstruction
CA stomach.ppt presentation following gastring outlet obstruction
 
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai AvailableGirls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
Girls Call ServiCe Chennai X00XXX00XX Tanisha Best High Class Chennai Available
 
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
 
How dental support group work...........
How dental support group work...........How dental support group work...........
How dental support group work...........
 
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
 
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptx
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptxYoga, Anatomy & Physiology Certificate Course.pptxv.pptx
Yoga, Anatomy & Physiology Certificate Course.pptxv.pptx
 
Therapeutic Diets Applied Nutrition and Dietics in BSc Nursing
Therapeutic Diets Applied Nutrition and Dietics in BSc NursingTherapeutic Diets Applied Nutrition and Dietics in BSc Nursing
Therapeutic Diets Applied Nutrition and Dietics in BSc Nursing
 
Diagnosis and treatment planning in complete denture.pptx
Diagnosis and treatment planning in complete denture.pptxDiagnosis and treatment planning in complete denture.pptx
Diagnosis and treatment planning in complete denture.pptx
 
VITAMINS(referred as a Organic compound)
VITAMINS(referred as a Organic compound)VITAMINS(referred as a Organic compound)
VITAMINS(referred as a Organic compound)
 
MGI DNBSEQ Sequencing Technology short.pptx
MGI DNBSEQ Sequencing Technology short.pptxMGI DNBSEQ Sequencing Technology short.pptx
MGI DNBSEQ Sequencing Technology short.pptx
 
NEET UG 2024: LIVE UPDATES from Supreme Court
NEET UG 2024: LIVE UPDATES from Supreme CourtNEET UG 2024: LIVE UPDATES from Supreme Court
NEET UG 2024: LIVE UPDATES from Supreme Court
 
heart intro.pptx full introduction about the heart
heart intro.pptx full introduction about the heartheart intro.pptx full introduction about the heart
heart intro.pptx full introduction about the heart
 
buy oxycodone online at chemworldstore.net
buy oxycodone online at chemworldstore.netbuy oxycodone online at chemworldstore.net
buy oxycodone online at chemworldstore.net
 
Ethical Principles in Nursing & Healthcare Practice
Ethical Principles in Nursing & Healthcare PracticeEthical Principles in Nursing & Healthcare Practice
Ethical Principles in Nursing & Healthcare Practice
 
Yoga for Beginner’s Course- yoga foundation course
Yoga for Beginner’s Course- yoga foundation courseYoga for Beginner’s Course- yoga foundation course
Yoga for Beginner’s Course- yoga foundation course
 
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
 

Hypothermia in TbI

  • 1. HYPOTHERMIA IN TBI FOR NEUROPROTECTION Dr Sumit Sinha Additional Professor Deptt of Neurosurgery, AIIMS and JNATC, New Delhi
  • 2. Hypothermia in TBI • TBI- leading cause of death and disabiity worldwide • Primary brain injury- shear and neuronal damage at the time of impact • Secondary brain injury- ischemia (impaired autoregulation, ↑ICP, Hypoperfusion) and reperfusion injury (cascade leading to apoptosis)
  • 3. Hypothermia in TBI • First mentioned in Papyrus 5000 years ago • Hippocrates- snow packing to stop bleeding • Sir William Osler- reduction in mortality of typhoid fever • Temple Fay- invented cooling blanket- relief in pain for terminal malignancy • Rosomoff et al (1950’s)- beneficial effect on ICP in TBI • HTh after cardiac arrest trial- better outcomes with HTh
  • 4. Hypothermia in TBI Mechanism AcutePhase Reduces the release of excitatory AA Down regulates astrocytic glutamate trasporter I- which mediates reverse transport of glutamate Prevents glutamate induced NO synthesis Suppresses NMDA rec phosphorylation SubacutePhase Attenuation of oxidative and nitrosative stress markers Mitigates the inflammatory response by reducing astrocytic and microglial activation Decreases expression of inflammatory cytokines Attenuates release of proapoptotic mediators Preserves BBB ChronicPhase Decrease cerebral metabolism Attenuates reperfusion injury, BBB permeability, edema Helps in neuronal regeneration and circuit repair
  • 5. Hypothermia in TBI CV Effects Positive inotropic- arrhytmias ↑ MAP,SVR; ↓HR, CO ↑ VR- ANP,↓ADH- cold diuresis- hypotension Pulmonary Effects ↓PaCO2 ↑PaO2/ FiO2 ↑Wound infection No difference in rate of pneumonia Hematologic function Affects platelet count, coagulation cascade ↑aPTTRenal, Endocrine, GI effects Electrolyte disorders- K,Mg ↓ ↓Insulin sensitivity- HG Ileus, DGE Liver function/ drug Metabolism Affects tubular secretion and reabsorption Reduction in enzyme activity ↓cP450 Physiological Effects
  • 6. Hypothermia in TBI Therapeutic Hypothermia • hTH started <24 hrs x 3-5 d/ till ↑ICP resolves • 4/5 trials- ↓mortality/ ↑outcome ★ Jiang et al. J Neurosurg 2000 ★ Shiozaki et al. J Neurosurg 2003 ★ Jiang et al. J Cereb Blood Flow Metab 2006 ★ Qui et al. J Crit Care 2007 ★ Yan et al. J Clin Neurosci 2010 Prophylactic Hypothermia • 33-34° <10 hrs x 24-48 hrs irresp of ICP • All trials failed to show improved outcome ✧ Clifton et al. N Engl J Med 2001 ✧ Marion et al. N Engl J Med 1997 ✧ Shiozaki et al. J Neurosurg 2001
  • 7. Hypothermia in TBI No. Target temp/ duration Mortality Neurol outcome Clifton et al. (NABIS:H II Trial) Lancet 2011 97 33/48 No No Hutchinson et al. (HiTBIC Trial). NEJM 2008. 225 32.5/24 No No Qui et al. J Crit Care 2007 80 33/96 No Yes Adelson et al (Cool Kids) HYPO I and II. Neurosurgery 2005 48/26 32/48 No No Qui et al.Clin J Traumatology 2005 86 33/103 Yes Yes Smrcka et al. Acta Neurochirur 2005 72 34/72 No Yes Zhi et al. Surg neurology 2003 396 34/62.4 Yes Yes Clifton et al. (NABIS:H Trial) NEJM 2001 392 33/48 No No Shiozaki et al. J Neurosurg 2001 91 34/48 No No Jiang et al. J Neurosurg 2000 87 32/>72 Yes Yes Clifton et al. J Neurotrauma 1993 46 32/48 No No Marion et al. NEJM 1997 82 32/24 No No SUMMARY OF DIFFERENT TRIALS ON HYPOTHERMIA
  • 8. Hypothermia in TBI NABIS:H trial • 392 pts- terminated for futility • 33° x 48 hrs at a mean of 8.4 hrs • hTH didn’t improve outcome+ more hypotension • Weak evidence of better outcome in pts hypothermic at admission Clifton GL et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556-63
  • 9. Hypothermia in TBI NABIS:H trial- Lessons learned!!! • Pts hypothermic at admission and then rewarmed- did worse • >45 yrs- worse with hTH • <45 yrs presenting with hTH not rewarmed did well- suggests that there may be a narrow therapeutic window
  • 10. Hypothermia in TBI • 13 Trials- Level II (6) and Level III (7) • Overall, no difference in mortality, but 46% ↑ chance of good outcome • hTH >48 hrs has ↓mortality • level III recommendation for the use of hTH in TBI The brain trauma Foundation. Guidelines for the management of severe traumatic brain injury. J Neurotrauma 2007;24:S21-25
  • 11. Hypothermia in TBI • Pts enrolled within 2-2.5 hrs- 33°x 48 hrs • 232 pts- 119 (hTH)/113 (NT) • No difference in outcome and mortality • No utility of hypothermia Clifton GL et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol 2011;10:131- 39
  • 12. Hypothermia in TBI • 77 pts- Terminated for futility • hTH x 48 hrs- no difference after pediatric severe traumatic brain injury Adelson et al. Comparison of hypothermia and normothermia after severe traumatic brain injury (Cool kids): A phase III randomised controlled trial. Lancet Neurol 2013;12(6):546-53
  • 13. Hypothermia in TBI • 23 RCT- 1614 pts • Significant benefit- only in low quality trials • High quality trials- no decrease in death with hTH- play of chance. • hTH should not be used except in the context of a high quality RCT with good allocation concealment No evidence that hypothermia is beneficial
  • 14. Hypothermia in TBI 8 Metanalysis since 2002 Trials No. Mortality Neurological outcome Fox et al. CJEM. 2010;12:355-64 12 1327 Y Y Sydenham et al. The Cochrane databse of systematic reviews 2009 21 1587 Y Y Peterson et al. J Neurotrauma 2008;25:62-71 13 1339 Y Y AANS BTF. J Neurotrauma 2007;24:S1-106 Alderson et al. . The Cochrane databse of systematic reviews 2004 Henderson et al. Intens Care Med 2003;29:1637-44 8 748 Y Y McIntyre et al. JAMA 2003;289:2992-2999 Harris et al. Arch Neurol 2002;59:1077-1083 7 668 Y
  • 15. Hypothermia in TBI • 18 RCT (1851 Pts)- GRADE recommendations • Overall RR of mortality and poor neurologic outcome with hTH vs controls- 0.84 and 0.81 • High quality trials- RR 1.28 • hTH a/w ↓CPP on rewarming and pneumonia • No benefit of hTH on mortality or neurologic outcome Georgiou et al. Role of Therapeutic hypothemria in improving outcome after traumatic Brain injury: a systematic review. Br J Anaesthesia 2013;110(3):357-67
  • 16. Hypothermia in TBI Forest Plot of all trials- effect of hTH vs NT on mortality
  • 17. Hypothermia in TBI Forest Plot of all trials- effect of hTH vs NT on poor neurological outcome
  • 18. Hypothermia in TBI Forest Plot of high quality trials- effect of hTH vs NT on mortality Forest Plot of high quality trials- effect of hTH vs NT on poor neurological outcome
  • 19. Hypothermia in TBI Why lack of evidence so far??? • TBI- heterogenous disease- no study adequately powered to study effect of hTH • Peak ICP ↑ occurs >48 hrs- when several trials have started rewarming • Peak neuronal death occurs hrs after TBI- target temp achieved <8 hrs only in some trials • GOS is a crude assessment measure- subtle outcome differences missed- GOSE better
  • 20. Hypothermia in TBI Future hTH trials should consider !!!! • Initiation of hTH in prehospital setting • Maintainence of hTH >48 hrs • Rewarming acc to physiological rather than time based criteria • FU using GOSE
  • 21. Hypothermia in TBI Ongoing trials- Results Awaited Eagerly !!! *Cooper J *Andrews et al. Trials 2011;12:8 POLAR- RCT Eurotherm
  • 22. Hypothermia in TBI AIIMS JPNATC Experience
  • 23. PG ± HTh in severe TBI FINANCIAL DISCLOSURES Research grant funded by Department of Biotechnology (DBT) New Delhi, India
  • 24. PG ± HTh in severe TBI Aims and Objectives • To examine the efficacy of Progesterone drug and hypothermia, alone or in combination, in improving neurological outcome in Severe Traumatic Brain Injury. • To study the difference in the levels of various serum biomarkers after treatment and their correlation with outcome
  • 25. PG ± HTh in severe TBI Materials and Methods • Data Collected- – Daily- vitals, ICP, CPP, BP, Intake/ Output, GCS score, ABG(pH , K+ , pCO2 ,pO2,Hco3) – Lab Test for 7 days.(Biochemistry,Haematology,Coagulation) – CT Scan- at admission and Day 6 – Biochemical markers of STBI- (S100,NSE, Progesterone, Estrogen, IL 6, GFAP)- at admission and 1st Week INCLUSION CRITERIA EXCLUSION CRITERIA • 18-65 years. • Any investigational drugs 30 days prior to enrollment. • GCS score 4-8 • Severe anoxic intracerebral damage or brain death. • <8 hours of injury. • Spinal Cord Injury • Pregnancy Type of study: Randomized Placebo controlled study
  • 26. PG ± HTh in severe TBI Study groups Normal temperature Progesterone + Normal temperature Hypothermia Hypothermia +Progesterone Follow up at 1 and 6 moths Primary endpoints:- i. Glasgow Outcome Score (GOS) Secondary endpoints: -- i. Functional Independence Measure (FIM). ii. Mortality
  • 27. PG ± HTh in severe TBI Materials and Methods (Contd.) • Injn. Progesterone- 1mg/kg I/M BD X 5 days • Hypothermia- (surface cooling by blankets- Blanketrol II, Cincinnati Sub-Zero, Cincinnati) – 34 degree C X 24 hrs – Rewarming- 0.5 degree/ 2hrs • Placebo- 5 ml distilled water I/M BDX 5 days
  • 28. PG ± HTh in severe TBI Results • Total Patients recruited- 107(27 in each A ,C & D groups and 26 in Group B ) • Mean Age- 32 ± 11.27 • Sex- 90 males and 17 females • Mean GCS- 6 ± 1.0 • Average time to recruitment- 5.0 ± 1.2 hrs • Average time to desired temperature (34° C)- 45 ± 12 minutes • Mean ICP-10.21 ± 5.6
  • 29. Group A (Control ) Group B (PG) Group C (HTh) Group D (HTh+PG) Mean Age- (years) 33.96 33.73 31.44 31.25 Sex- M/F 23/4 20/6 24/3 23/4 Mean GCS 6 6 6 6 Mean ICP 7.60 10.75 11.21 10.47 Base-line characteristics of patients with severe TBI PG ± HTh in severe TBI Results contd.
  • 30. PG ± HTh in severe TBI Results (Contd.) Primary Endpoints- GOS at 1 month (n=90) GOS at 6 month (n=81)
  • 31. PG ± HTh in severe TBI Results (Contd.) SECONDARY ENDPOINTS Overall mortality-20.6%
  • 32. PG ± HTh in severe TBI CONCLUSIONS • Good outcome at 6th month- best in Hypothermia group (83%), followed by PG group (77%). • Highest mortality found in Control (26%); Lowest (15%) in Hypothermia group . • PRG- shows more (76%) functionally independent pts at 6th month, followed by Hypothermia group (66.5%) • PG + hTH does not confer any additional advantage
  • 33. Hypothermia in TBI TAKE HOME MESSAGE • hTH should logically be useful in improving the mortality and neurologic outcome • Requires well designed large multicentric RCT’s to prove association • Presently, no definite Level I or II evidence- BTF proposes Level III guideline