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Review course 2014
Dr.Anand.M.Tiwari
IDCC,F.N.B Critical care medicine
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 377 deaths daily.
 1356 –injury
 Yr 2012—1,38,245 death
 Yr 2013----1,37, 597
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Prevention Emergency
Care
Critical
Care
Brain
specific
therapy
 MOI-
anand tiwari reveiw course 2014
1.Auto strikes
tree.
2.Head strikes
windshield.
3.Brain strikes
inside of frontal
skull.
4.Brain
rebounds and
hits inside of
occiput.
(Contracou
p Injury)
 Diffuse axonal injury
24% mortality
 Focal lesion
39% mortality
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 Hypoxia
 Hypotension
 Hypocapnia Remember H Effect
 Hypercapnia
 Hyperthermia
 Hypoglycemia
 Hyperglycemia
 Hypernatremia
 Hyponatremia
 Hyperosmolarity
 infections
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Review of 25 studies
HEMS showed survival benefit in some
Which component??
Methodology?
 Assessment.
 Intervention * suboptimal interventions.
 50% patient extracrainal injuries.
 Cervical clearance.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 GCS
 RTS
 APACHE
 Pupillary diameter and reactivity
 Age
 Hypotension
 CT scan features
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 GCS 13– mild
 GCS 9-13- Moderate.
 GCS < 8 - Severe
anand tiwari reveiw course 2014
Correction of reversible
causes,Hypoxia,hypotension,c2h5oh intoxication
E V M*
Sedation
intubation
anand tiwari reveiw course 2014
Field cervical spine clearance is
not possible with altered LOC
1
2 3
4
1
2
3
4
anand tiwari reveiw course 2014
 (a) a lateral view
 the base of the occiput to upper border of
first thoracic vertebrae,
 (b) an anterior-posterior view
 C2 to T1 spinous processes.
 (c) an open-mouth odontoid view
 C1 lateral masses as well as the whole
odontoid process
anand tiwari reveiw course 2014
2
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Normal CT scan
 Diffuse Axonal Injury
anand tiwari reveiw course 2014
Patient continues to remain
unconscious .
Mild DAI Moderate DAI Severe DAI
coma between 6
and 24 hours
coma for more
than 24 hours
without
presence of
decerebrate
posturing
coma for more
than 24 hours
and with
presence of
decerebrate
posturing as a
motor response
on nociceptive
stimulation.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 Definite role in defining shear injuries and
for prediction of prognosis
anand tiwari reveiw course 2014
 F
 A
 S
 T
 H
 U
 G
anand tiwari reveiw course 2014
Give your patient a fast hug (at least) once a day.
Vincent JL.
 Crystalloids NS,RL
 Colloids
 Blood transfusion Trigger
 Use of vasopressor- Dopamine/noradrenaline
anand tiwari reveiw course 2014
 Feeding ASAP ,<24 HRS
 Hyper catabolic
 NG feed ? Orogastric tube Enteral route
 Can consider prokinetic
 PEG long term
anand tiwari reveiw course 2014
Perel P, Yanagawa T, Bunn F, Roberts IG, Wentz R. Nutritional support for head-injur
patients. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.:
CD001530. DOI: 10.1002/14651858.CD001530.pub2.
Early nutritional therapy in trauma: after A, B, C, D, E, the
importance of the F (FEED)
Alberto Bicudo-Salomão, ACBC-MTI
; Renata Rodrigues de MouraII
;
José Eduardo de Aguilar-Nascimento, TCBC-MTIII
Rev. Col. Bras. Cir. vol.40 no.4 Rio de Janeiro July/Aug. 2013
anand tiwari reveiw course 2014
Neuroassesment
Sedation vacation
 Risk group- prolong sedation/extracranial
injuries
 Anticoagulant/LMWH___-????
 Look for –illeo femoral
 Graduated TED stockings/pneumatic calf
compressor unproven reasonable alternative
anand tiwari reveiw course 2014
 Head in neutral position
 Venous drainage
 No compression of neck veins by tube tie
anand tiwari reveiw course 2014
 GCS charting frequently
 Daily fast hug
 Hemodynamic monitoring
 Fluid balance
 BBB care
 Brain specific monitoring
 Neurosurgical consultation as needed
anand tiwari reveiw course 2014
BATTLE’S SIGN RACCOON EYES
anand tiwari reveiw course 2014
CSF Fistule : Rhinorrhoea / Otorrhoea
Risk of meningitis
** Early Rx -- Carbapenem .
**Topical (intrathecal or intraventricular)
therapy colistin (off label ) for A.baumanii
meningitis.
Craniofacial
trauma
CSF leak
new onset
fever
Median time
presentation 12 days.
suspicion of gram
negative meningitis
124 Case Report- A.baumanii meningitis
 Know your ICU/organism prevalent and
resistant pattern
 Preemptive antibiotics ????
 Stratify risk factors
 Site specific ,bbb penetration
 Other factors
anand tiwari reveiw course 2014
 Which mode?
 No permissive hypercapnia
 Peep ???
 Weaning—
 Off ventilator does not mean extubation
anand tiwari reveiw course 2014
Hyperventilation
 Euglycemia =<150mg% favarouable
 Na Disturbances- SIADH
CSW syndrome
Diabetes insipidus
Core temp-- Normal
anand tiwari reveiw course 2014
 CPP= MAP-ICP
 70……BTF initial adoption*aggressive
fluid/vasopressor..pulmonary complications
 …60
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
ICP MONITORING
Ocular ultrasound
Jugular bulb oximetry
Transcranial Doppler
Cerebral micro dialysis
 Intracranial pressure monitoring
 1.comatose patients with-
 Glasgow Coma Scale (GCS) 3-8 with abnormal computed
tomography (CT) scans
 2.Normal CT scans with two or more of the following
features at admission:
 Age over 40,
 Unilateral or bilateral motor posturing, or
 A systolic blood pressure of less than 90 mm Hg.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
] The optic nerve sheath diameter
measurement was found to be well-
correlated with the values of
ICP and its value significantly increased to
7.0 ± 0.58 mm, when ICP rose in value to
>20 mm Hg
 EEG-SEP monitoring reflects to remaining
metabolic activity of brain parenchyma.
 EEG recordings usually get suppressed and
difficult to interpret during deep sedation.
anand tiwari reveiw course 2014
 Surgical decompression
 CSF drainage
 Decompressive craniectomy
 Osmotherapy
 Hyperventilation
 Hypotheramia
 Barbiturate coma
 Steroids
 Cerebral vasospasm-nimodipine
 Seizure prophylaxis
anand tiwari reveiw course 2014
Fig. 7. The Columbia
stepwise protocol for ICP
anand tiwari reveiw course 2014
MANNITOL
 Single bolus & prolonged
 Improves rheological value
of RBCs & CPP
 Rebound phenomenon.
 Currently preferred
HYPERTONIC SALINE
 Studies with single bolus &
infusion …but limitations
 Osmotic mobility
decreases leukocyte
adhesion.
 Central pontine myelinosis
(if hypoNa+)
 ??
anand tiwari reveiw course 2014
?? Mannitol Vs H.S.
?? Optimal conc. Of H.S.
?? Outcomes of prolonged H.S. in
raised ICP
MANNITOL 20%
 .25-1 gm/kg @ prn
 Rheological effects
 Adverse effects
HTS 1.7%--29.2%
 5% 2ml/kg 4-6 hrly.
 Serum osmolarity*-320
 Na*..155 meq/l
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
 In this prospective evaluation of early PTS
prophylaxis,
 LEV did not outperform PHE.
 Cost and need for serum monitoring should
be considered in guiding the choice of
prophylactic agent.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Discuss BTF guideline for surgery
 An epidural hematoma (EDH) greater than 30
cm3
should be surgically evacuated regardless of
the patient's Glasgow Coma Scale (GCS) score.
 An EDH less than 30 cm3
and with less than a 15-
mm thickness and with less than a 5-mm midline
shift (MLS) in patients with a GCS score greater
than 8 without focal deficit can be managed
nonoperatively with serial computed
tomographic (CT) scanning
 close neurological observation in a neurosurgical
center.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Discuss BTF guideline for evacuation??
 An acute subdural hematoma (SDH) with a thickness greater
than 10 mm or a MLS greater than 5 mm on CT scan should
be surgically evacuated, regardless of the patient's GCS
score.
 All patients with acute SDH in coma (GCS score less than 9)
should undergo intracranial pressure (ICP) monitoring.
 A comatose patient (GCS score less than 9) with an SDH less
than 10-mm thick and MLS less than 5 mm should undergo
surgical evacuation of the lesion if the GCS score decreased
between the time of injury and hospital admission by 2 or
more points on the GCS and/or the patient presents with
asymmetric or fixed and dilated pupils and/or the ICP
exceeds 20 mm Hg
anand tiwari reveiw course 2014
 Barbiturate coma BIS-5-20 EEG-Burst
suppression.
 Decompression craniotomy.
 Hypothermia 35*
 CSF drainage
 Reconsider treatment.
anand tiwari reveiw course 2014
 Refractory cases
 Decrease CMRO2/
 Problem hypotension
 remember pearl harbor incident
 Aim till burst suppression on EEG
 Gradual taper –delayed awakening
,predispose patient to nosocomial infection
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
Awaits
RESCUEicp
results
 reduces all cause mortality***
 May be beneficial in improving neurological
outcomes
if cooling maintained for 48 hrs.
anand tiwari reveiw course 2014
anand tiwari reveiw course 2014
EUROTHERM3235
Recruitment
321 patients have now been recruited to
the trial. Thank you for continuing to enrol!
 HBOT
Stem cell transplant
anand tiwari reveiw course 2014
 Thank you
anand tiwari reveiw course 2014

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Management of traumatic brain injury

  • 1. Review course 2014 Dr.Anand.M.Tiwari IDCC,F.N.B Critical care medicine anand tiwari reveiw course 2014
  • 2. anand tiwari reveiw course 2014
  • 3.  377 deaths daily.  1356 –injury  Yr 2012—1,38,245 death  Yr 2013----1,37, 597 anand tiwari reveiw course 2014
  • 4. anand tiwari reveiw course 2014 Prevention Emergency Care Critical Care Brain specific therapy
  • 5.  MOI- anand tiwari reveiw course 2014 1.Auto strikes tree. 2.Head strikes windshield. 3.Brain strikes inside of frontal skull. 4.Brain rebounds and hits inside of occiput. (Contracou p Injury)
  • 6.  Diffuse axonal injury 24% mortality  Focal lesion 39% mortality anand tiwari reveiw course 2014
  • 7. anand tiwari reveiw course 2014
  • 8.  Hypoxia  Hypotension  Hypocapnia Remember H Effect  Hypercapnia  Hyperthermia  Hypoglycemia  Hyperglycemia  Hypernatremia  Hyponatremia  Hyperosmolarity  infections anand tiwari reveiw course 2014
  • 9. anand tiwari reveiw course 2014 Review of 25 studies HEMS showed survival benefit in some Which component?? Methodology?
  • 10.  Assessment.  Intervention * suboptimal interventions.  50% patient extracrainal injuries.  Cervical clearance. anand tiwari reveiw course 2014
  • 11. anand tiwari reveiw course 2014
  • 12.  GCS  RTS  APACHE  Pupillary diameter and reactivity  Age  Hypotension  CT scan features anand tiwari reveiw course 2014
  • 13. anand tiwari reveiw course 2014
  • 14.  GCS 13– mild  GCS 9-13- Moderate.  GCS < 8 - Severe anand tiwari reveiw course 2014 Correction of reversible causes,Hypoxia,hypotension,c2h5oh intoxication E V M* Sedation intubation
  • 15. anand tiwari reveiw course 2014 Field cervical spine clearance is not possible with altered LOC
  • 16. 1 2 3 4 1 2 3 4 anand tiwari reveiw course 2014
  • 17.  (a) a lateral view  the base of the occiput to upper border of first thoracic vertebrae,  (b) an anterior-posterior view  C2 to T1 spinous processes.  (c) an open-mouth odontoid view  C1 lateral masses as well as the whole odontoid process anand tiwari reveiw course 2014
  • 18. 2 anand tiwari reveiw course 2014
  • 19. anand tiwari reveiw course 2014 Normal CT scan
  • 20.  Diffuse Axonal Injury anand tiwari reveiw course 2014 Patient continues to remain unconscious .
  • 21. Mild DAI Moderate DAI Severe DAI coma between 6 and 24 hours coma for more than 24 hours without presence of decerebrate posturing coma for more than 24 hours and with presence of decerebrate posturing as a motor response on nociceptive stimulation. anand tiwari reveiw course 2014
  • 22. anand tiwari reveiw course 2014
  • 23.  Definite role in defining shear injuries and for prediction of prognosis anand tiwari reveiw course 2014
  • 24.  F  A  S  T  H  U  G anand tiwari reveiw course 2014 Give your patient a fast hug (at least) once a day. Vincent JL.
  • 25.  Crystalloids NS,RL  Colloids  Blood transfusion Trigger  Use of vasopressor- Dopamine/noradrenaline anand tiwari reveiw course 2014
  • 26.  Feeding ASAP ,<24 HRS  Hyper catabolic  NG feed ? Orogastric tube Enteral route  Can consider prokinetic  PEG long term anand tiwari reveiw course 2014 Perel P, Yanagawa T, Bunn F, Roberts IG, Wentz R. Nutritional support for head-injur patients. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD001530. DOI: 10.1002/14651858.CD001530.pub2. Early nutritional therapy in trauma: after A, B, C, D, E, the importance of the F (FEED) Alberto Bicudo-Salomão, ACBC-MTI ; Renata Rodrigues de MouraII ; José Eduardo de Aguilar-Nascimento, TCBC-MTIII Rev. Col. Bras. Cir. vol.40 no.4 Rio de Janeiro July/Aug. 2013
  • 27. anand tiwari reveiw course 2014 Neuroassesment Sedation vacation
  • 28.  Risk group- prolong sedation/extracranial injuries  Anticoagulant/LMWH___-????  Look for –illeo femoral  Graduated TED stockings/pneumatic calf compressor unproven reasonable alternative anand tiwari reveiw course 2014
  • 29.  Head in neutral position  Venous drainage  No compression of neck veins by tube tie anand tiwari reveiw course 2014
  • 30.  GCS charting frequently  Daily fast hug  Hemodynamic monitoring  Fluid balance  BBB care  Brain specific monitoring  Neurosurgical consultation as needed anand tiwari reveiw course 2014
  • 31. BATTLE’S SIGN RACCOON EYES anand tiwari reveiw course 2014 CSF Fistule : Rhinorrhoea / Otorrhoea Risk of meningitis
  • 32. ** Early Rx -- Carbapenem . **Topical (intrathecal or intraventricular) therapy colistin (off label ) for A.baumanii meningitis. Craniofacial trauma CSF leak new onset fever Median time presentation 12 days. suspicion of gram negative meningitis 124 Case Report- A.baumanii meningitis
  • 33.  Know your ICU/organism prevalent and resistant pattern  Preemptive antibiotics ????  Stratify risk factors  Site specific ,bbb penetration  Other factors anand tiwari reveiw course 2014
  • 34.  Which mode?  No permissive hypercapnia  Peep ???  Weaning—  Off ventilator does not mean extubation anand tiwari reveiw course 2014 Hyperventilation
  • 35.  Euglycemia =<150mg% favarouable  Na Disturbances- SIADH CSW syndrome Diabetes insipidus Core temp-- Normal anand tiwari reveiw course 2014
  • 36.  CPP= MAP-ICP  70……BTF initial adoption*aggressive fluid/vasopressor..pulmonary complications  …60 anand tiwari reveiw course 2014
  • 37. anand tiwari reveiw course 2014 ICP MONITORING Ocular ultrasound Jugular bulb oximetry Transcranial Doppler Cerebral micro dialysis
  • 38.  Intracranial pressure monitoring  1.comatose patients with-  Glasgow Coma Scale (GCS) 3-8 with abnormal computed tomography (CT) scans  2.Normal CT scans with two or more of the following features at admission:  Age over 40,  Unilateral or bilateral motor posturing, or  A systolic blood pressure of less than 90 mm Hg. anand tiwari reveiw course 2014
  • 39. anand tiwari reveiw course 2014 ] The optic nerve sheath diameter measurement was found to be well- correlated with the values of ICP and its value significantly increased to 7.0 ± 0.58 mm, when ICP rose in value to >20 mm Hg
  • 40.  EEG-SEP monitoring reflects to remaining metabolic activity of brain parenchyma.  EEG recordings usually get suppressed and difficult to interpret during deep sedation. anand tiwari reveiw course 2014
  • 41.  Surgical decompression  CSF drainage  Decompressive craniectomy  Osmotherapy  Hyperventilation  Hypotheramia  Barbiturate coma  Steroids  Cerebral vasospasm-nimodipine  Seizure prophylaxis anand tiwari reveiw course 2014 Fig. 7. The Columbia stepwise protocol for ICP
  • 42. anand tiwari reveiw course 2014
  • 43. MANNITOL  Single bolus & prolonged  Improves rheological value of RBCs & CPP  Rebound phenomenon.  Currently preferred HYPERTONIC SALINE  Studies with single bolus & infusion …but limitations  Osmotic mobility decreases leukocyte adhesion.  Central pontine myelinosis (if hypoNa+)  ?? anand tiwari reveiw course 2014 ?? Mannitol Vs H.S. ?? Optimal conc. Of H.S. ?? Outcomes of prolonged H.S. in raised ICP
  • 44. MANNITOL 20%  .25-1 gm/kg @ prn  Rheological effects  Adverse effects HTS 1.7%--29.2%  5% 2ml/kg 4-6 hrly.  Serum osmolarity*-320  Na*..155 meq/l anand tiwari reveiw course 2014
  • 45. anand tiwari reveiw course 2014
  • 46.  In this prospective evaluation of early PTS prophylaxis,  LEV did not outperform PHE.  Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent. anand tiwari reveiw course 2014
  • 47. anand tiwari reveiw course 2014 Discuss BTF guideline for surgery
  • 48.  An epidural hematoma (EDH) greater than 30 cm3 should be surgically evacuated regardless of the patient's Glasgow Coma Scale (GCS) score.  An EDH less than 30 cm3 and with less than a 15- mm thickness and with less than a 5-mm midline shift (MLS) in patients with a GCS score greater than 8 without focal deficit can be managed nonoperatively with serial computed tomographic (CT) scanning  close neurological observation in a neurosurgical center. anand tiwari reveiw course 2014
  • 49. anand tiwari reveiw course 2014 Discuss BTF guideline for evacuation??
  • 50.  An acute subdural hematoma (SDH) with a thickness greater than 10 mm or a MLS greater than 5 mm on CT scan should be surgically evacuated, regardless of the patient's GCS score.  All patients with acute SDH in coma (GCS score less than 9) should undergo intracranial pressure (ICP) monitoring.  A comatose patient (GCS score less than 9) with an SDH less than 10-mm thick and MLS less than 5 mm should undergo surgical evacuation of the lesion if the GCS score decreased between the time of injury and hospital admission by 2 or more points on the GCS and/or the patient presents with asymmetric or fixed and dilated pupils and/or the ICP exceeds 20 mm Hg anand tiwari reveiw course 2014
  • 51.  Barbiturate coma BIS-5-20 EEG-Burst suppression.  Decompression craniotomy.  Hypothermia 35*  CSF drainage  Reconsider treatment. anand tiwari reveiw course 2014
  • 52.  Refractory cases  Decrease CMRO2/  Problem hypotension  remember pearl harbor incident  Aim till burst suppression on EEG  Gradual taper –delayed awakening ,predispose patient to nosocomial infection anand tiwari reveiw course 2014
  • 53. anand tiwari reveiw course 2014 Awaits RESCUEicp results
  • 54.  reduces all cause mortality***  May be beneficial in improving neurological outcomes if cooling maintained for 48 hrs. anand tiwari reveiw course 2014
  • 55. anand tiwari reveiw course 2014 EUROTHERM3235 Recruitment 321 patients have now been recruited to the trial. Thank you for continuing to enrol!
  • 56.  HBOT Stem cell transplant anand tiwari reveiw course 2014
  • 57.  Thank you anand tiwari reveiw course 2014

Editor's Notes

  1. Basilar skull fracture indicated by any of following: Bleeding from ear or nose Clear or serosanguineous fluid running from nose or ear Swelling and/or discoloration behind ear (Battle’s sign) Swelling and discoloration around both eyes (raccoon eyes) Battle’s sign can occur from immediately following injury to within 1–2 hours postinjury. Raccoon eyes are a sign of anterior basilar skull fracture. Through thin cribriform plate in upper nasal cavity and allow spinal fluid and/or blood to leak out. Raccoon eyes with or without drainage from nose are an absolute contraindication to inserting a nasogastric tube or nasotracheal intubation.
  2. The optic nerve sheath diameter measurement was found to be well-correlated with the values of ICP and its value significantly increased to 7.0 ± 0.58 mm, when ICP rose in value to &amp;gt;20 mm Hg On the other hand, TCD also measures rise in ICP indirectly. Pulsatility index (difference between systolic and diastolic flow velocity, divided by the mean flow velocity), is found to be correlated with the increase in ICP.[11] It can signify either rise in the ICP or decrease in the cerebral perfusion pressure (CPP).[11] These non-invasive tools may be used when use of invasive monitoring cannot be used or rather contraindicated.[9,10,11] However, both tools need to be validated in randomized controlled trials before they can be recommended for routine use in patients with severe TBI. If the brain is hypoperfused, oxygen extraction will be increased and SjvO2 will be reduced.[12,13] On the other hand, if CBF is adequate for the brain&amp;apos;s metabolic need, then SjvO2 will remain normal. This monitoring should be used in conjunction with moderate to severe hyperventilation therapy for patients with intracranial hypertension.
  3. Temperature management TBI initiates several metabolic processes that can exacerbate the injury.[36] Hyperthermia is one of the potential factors exaggerating the secondary injury. Hyperthermia may develop due to infections or some neurogenic mechanisms. Recent observational study of 7145 patients has shown that both degree and duration of early post head injury fever are strongly correlated with outcome.[37] It is prudent to keep the patients normothermic and antipyretics as well as surface cooling can be used to attain this.[36,37,38] On the other hand, there is evidence that hypothermia may limit some of these deleterious metabolic responses and improve the outcome.[39,40] However, the literature suggests that therapeutic hypothermia should be instituted as soon as practical (in the emergency room) and beneficial effect usually seen when it has been continued for at least 72 h.[40] In a RCT (n = 82), role of moderate hypothermia (32-33°C) in closed head injury (GCS 5-7) patients was found to hasten the neurologic recovery and improved the outcome.[41] A Cochrane review in 2009 analyzed 23 trials with a total of 1614 patients and found no evidence supporting the use of hypothermia during the treatment of TBI, but did find a statistically significant increased risk of pneumonia and other potentially harmful side-effects.[42] The important multicenter randomized controlled trial (The Eurotherm 3235 trial) on therapeutic hypothermia (32-35°C) in ICP reduction following TBI has recently been completed; however, its results is still awaiting and could be important to give better insight about this therapy.[4
  4. n HBOT, 100% oxygen at environmental pressures greater than 1 atmosphere absolute is administered for respiration in an airtight vessel. Therefore, there is a substantial increase in partial pressure of oxygen to the tissues that can help to improve the oxygen delivery to the injured brain tissue and also reduces brain edema. This therapy has shown some promising results to decrease the overall mortality in patients with severe TBI; however, there were no substantial improvement found related to neurological outcome of these patients.[50] In addition, the potential side-effects of oxygen toxicity are also concern. Thus, large well-defined controlled trials are needed to prove its effectiveness in patients with TBI. BI generates many pro-inflammatory mediators and leads to secondary brain injury. The main goal of developing future neuroprotective treatments for TBI is to minimize the detrimental and neurotoxic effects of these inflammatory mediators and help in the regeneration and repair after injury.[51,52,53,54] Many agents such as selfotel, pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol, statins were investigated; however found to be ineffective in clinical trials. The beneficial role of other agents such as progesterone, thyrotropin-releasing hormone and cyclosporine has yet to be tested in large trials. The other potential area of the target is apoptotic pathways. Many agents are being investigated to block the intermediate pathways related to apoptosis. However, the apoptotic changes are also essential for normal functioning of cells; therefore, blocking the pathways by these agents would lead to possible potential complications.[