Brain Protection in

Traumatic Brain Injury

Muh.Ramli, A.Husni Tanra

Departement of Anesthesiology, Intensive Care and Pain Management

Faculty of Medicine, Hasanuddin University
Makassar
Brain Protection:

The prevention or amelioration of neuronal damage

evidenced by abnormalities in cerebral metabolism,
histopathology or neurologic function after a hypoxic
or an ischemic event.
Messick & Milde, 1987
 Traumatic Brain Injury

Primary Brain Injury Secondary Brain Injury

Results from what has Physiologic and biochemical
occurred to the brain at the events which follow the
time of the injury. primary injury.
 Traumatic Head
Injury

Primary Injury Secondary Injury

EDH Hipoxia Edema

SDH Hypotension Increase ICP
ICH Hyperglycemia Vasopasme
Contusion Fever Infection
DAI Hypocapnia hydrocephalus
SOME of the SECONDARY EVENTS IN TRAUMATIC BRAIN INJURY

diffuse axonal
BBB inflammation injury
disruption apoptosis

necrosis
edema
formation
Brain trauma ischemia

energy failure
cytokines

Eicosanoids
Acetyl polyamines Calcium
endocannabinoids Choline
ROS

Green pathophysiological processes; Yellow various mediators Shohami, 2000

 Methods of brain protection
Basic methods
Hypothermia - low normothermia
Pharmacology
Intravenous Anesthetic : pentothal
Inhalation anesthetics
Lidocaine
Mannitol
Magnesium
Erythropoietin
Alpha 2 agonists dexmedetomidine
 METHODS OF BRAIN PROTECTION
1. BASIC METHODS
AIRWAY
Good Oxygenation
Hypercapnea ( Normocapnic)
Controll Hypertention ( Normotensive,
Normovolume )
Controll Intracranial Pressure
Controll seizures
METHODS OF BRAIN PROTECTION

2. PHARMACOLOGY
Intravenous Anesthetic : pentothal
Inhalation anesthetics
Lidocaine
Mannitol,
Magnesium
Erythropoietin
Alpha 2 agonists dexmedetomidine

3. HYPOTHERMIA
SITE OF WORK TO PROTECT BRAIN

9 Pre hospital

9 Emergency (Resuscitation) room

9 Operation Theatre

9 Intermediate Care

9 Intensive Care Unit ( ICU)

Pre-hospital management of
head injury

Rescue/
ER
Transport

OR
Diagnosis

ICU
Pre-hospital management of
head injury

Preserve Cerebral
Perfusion Pressure
 Emergency Departement
Airway Patent

Endotraheal Intubation
(GCS < 8)
Avoid Hipoxia
Prevention of obstruction Airway
Maintainance of adequate ventilation
Prevention of neurological deterioration
Rapid Sequense In transport or radiological procedure

Intubation
 Dangerous Intubation
Hypoxic patient or patient with seizure
often with rigid mouth

Forced laryngoscopic without drug

Increase Intracranial pressure

Brain Herniation

Anaesthesiologist give thiopentone and

suxamethonium for anestesia and relaxation
Rapid Sequence Intubation
Premedication
Minimize reflex sympathetic resp:
Lidocain,fentanyl
Defasciculating: NDMB,esmolol
Induction:
Avoid Hipotension: Thiopental or Etomidate
Paralyze : Succinylcoline, Rokuronium

In line position

PaO2 > 100 mmHg

PaCO2 35 40 mmHg
Avoid Hiperventilation
 Preanaesthetic stabilization &
assessment

ABCDEs of resuscitation
Assessment
Injuries
Vital signs
Level of consciousness
 Induction & intubation

Rapid sequence induction + Sellick

manoeuvre + manual in-line traction
~10% severe TBI have C-spine injury
Propofol, Pentotal or etomidate for
induction
Lignocaine, fentanyl and esmolol to blunt
sympathetic response
Succinylcholine or rocuronium for
intubation
 Ventilation
Sedation, analgesia and paralysis
Monitor with ETCO2, pulse oximeter and ABG
analysis
Maintain normocapnoea
Hyperventilation only with deteriorating GCS
 Circulation

. Normotensi,Normovolemi,Isotonic
Resuscitation & identification of
hypotension should be done
simultaneously
Avoid hypotonic and glucose containing
solution
Vasopressors
Hypertonic saline
 Intraoperative management

Induction of anaesthesia
RSI with Sellick manoeuvre and manual
in-line traction of the neck
Neuroprotection properties of
volatile anesthetics
Neuroprotection in term of antinecrotic and
anti-apoptotic effect
Increase CBF in ischemic region.
Reduction of functional CMR
Suppression of convulsions

Werner C. AOSRA Nov 2003

WCA, April 2004. ESA June 2004.
Neuroprotection properties of
volatile anesthetics
Inhibition of lactic acidosis and excitatory
neurotransmitter release
Prevention of pathological Na+, Ca2+ influx.
Inhibition of lipidperoxidation.
Reduction of free radical formation.

Werner C. AOSRA Nov 2003

 Volatile anesthetics
Isoflurane, sevoflurane, desflurane
produce maximum cerebral metabolic
suppression (2 MAC) correct for
imbalance between oxygen supply and
demand.
 Isoflurane
Isoflurane only transient protective against
a severe focal ischemic insult.
Isoflurane did not inhibit postischemic
neuronal apoptosis.
Conclusion: Isoflurane have not brain
protection effect.

Werner C. AOSRA Nov 2003, WCA 2004, ESA 2004.

Cottrell JE: WCA 2004, ESA June 2004
Kawaguchi et al. Anesth Analg 2004
Warner DS.Anesth Analg 2004
 sevoflurane
Sevoflurane improves neurological outcome
following incomplete cerebral ischemia in rat.
Werner C et al.Br J Anesth 1995;83
Isoflurane delay but does not prevent cerebral
infarction in rats subjected to focal ischemia.
Kawaguchi et al. Anesthesiology 2000;92
Sevoflurane provides sustained anti necrotic and
anti apoptotic effect.

Engelhard et al. ASA Annual meeting 2003. Abstract A 740

 Maintenance of Anaesthesia

Narcotic analgesic
Has minimal effect on CBF and CMRO2
Newer narcotics; alfentanil, sufentanil
remifentanil may increase ICP 2 to
systemic hypotension and cerebral
vasodilatation
 Maintenance of anaesthesia

Propofol

Reduces CMRO2, CBF & ICP and

maintain autoregulation
Hypotension
Compare with volatile agents not as easily
titrable and reversed.
 Maintenance of Anaesthesia

Management of intraoperative IC
hypertension
Head elevation
Avoid volatile >1 MAC
Acute hyperventilation
Osmotic diuretics frusemide
Thiopentone or propofol
CSF drainage
Hypertonic saline
Surgical removal of temporal/frontal lobe
 ICU transfer

Maintain ventilation, oxygenation & CPP

Continuous BP monitoring, ETCO2 and
SpO2
ICP monitoring if possible
Adequate O2 supply, fluids and EM drugs
 Intensive care management

Manage CPP and ICP

Classical approach is the staircase or
sequential approach
 Staircase ICP control algorithm

7 Barbiturate coma

6
Surgical decompression
5
Mild hypothermia

4
Mannitol

3 Ventricular drainage

2 Moderate head-up

1 Intubation, normocapneic ventilation

32
 Hypothermia
OR: 34-35o , 36o in ICU.
Moderate hypothermia (33o ) :complication
during rewarming (ICP ) and pneumonia.
CMRO2, EAA release, Glutamate
Membrane stabilization
Ca intracellular
Maintains ATP, Ca influx.
Hyperthermia: Ca influx
 Prophylactic cerebral protection
Outline
Hypothermia
Post cardiac arrest : yes
Post head injury: perhaps, in younger
patient who arrive cool.
Intraoperative : perhaps, but not for
aneurysm surgery
Patients who resisted cooling had a better
outcome

outcome Cooled Resisted cooling

(<33,5oC) (>33,5oC)
Good 62% 77% *)
Not good 38% 33%

*) p < 0.003

Cottrell JE et al. J Neurosurg Anaesth 2004

 Hypothermia Normothermia
n 499 501
Good outcome 65,9% 62,7%
Mortality 28% 32%
Bacteriemia 5% 2,5%

Conclusion: No indication that intraoperative cooling

resulted in any alteration in outcome . Cottrell,
WCA,2004
 Therapeutic moderate hypothermia

Temp 32-35C
Depress CMRO2, & modifies release of
EAA, cytokines, free radicals and
inflammatory mediators
Shivering prevented with sedatives & NMB
Longer hospital stay & more complications
Arrhythmias, myocardial depression,
blood viscosity, coagulopathy
 Decompressive craniectomy

Decrease ICP, decrease midline shift and

increase focal blood flow to traumatised
brain
Reports of exacerbation of oedema &
haemorrhage
Most effective when used early (24-48 h)
after TBI
 Drug of brain protection
PRIMARY INJURY
Secondary Injury

ISCHEMIA HYPOTENSION

CMRO2 THIOPENTAL
O2 availability
HYPOTHERMIA
TISSUE HYPOXIA

LACTIC AVOID HYPERGLYCEMIA

ACIDOSIS (H)+
glutamate NMDA ANTAGONIST Mg
o
HYPOTHERMIA 35 C
Leakage of K+
Ca++ Ca++ CHANNEL BLOCKER

ARACHIDONIC ACID
Prostaglandins INHIBITOR
Fatty acid & thromboxanes Free radical SCAVENGER

CBF INDUCED HYPERTENSION

GANGLIOSIDES
LIPID ANTIOXIDANT
Tirilazad not useful
LIPID
Lam AM.1995 PEROXIDATION
Axonal / Neuronal death
 Pharmacological: Barbiturate
Ca influx
Block Na channel
Free radicals inhibition formation.
Extracellular lactate, glutamate, aspartat
Propofol: glutamate exotoxicity
neuronal damage.
 lidocaine
Blocking Na influx
Reduce post necrotic injury
Truncates ischemic damage in the
penumbra by blocking the apoptotic cell
death pathway that involve cytochrome
lidocaine have brain protection effect.
 Osmodiuretics
Mannitol decreases ICP, increases CPP,
improves CBF in laboratory animals and human.
This effect related to plasma expansion with
reduction of Ht, plasma viscosity, CBV.
Osmolarity must be monitored and should no
exceed 320 mOsm/l.
Rebound effects to be relevant only with a
defective BBB or treatment > 4 days.
Werner C: WCA 2004, AOSRA 2003
 magnesium
Vascular : increased COP, rCBF
Neuronal: NMDA ion channel blockade,
Ca++ channel blockade, enhanced ATP
recovery.
Dose: 2 gm over 15 min and the 8 gm
over 24 hours
 EPO : erythropoietin
Neuroprotective as antiapoptotic agent
Malholtra et al. Curr Atheroscler Rep 2004;6(4)

Stimulate proteins of repair, diminish neuronal

excitotoxicity, anti-oxidant, reduce inflammation,
inhibit neuronal apoptosis, stimulate both
neurogenesis & angiogenesis subsequent to
experimental ischemic, hypoxic and toxic injury
brain protection effect.
Cottrell JE. WCA, April 2004
 Alternative therapy

Hypertonic saline
Alternative to mannitol
Vol expander, perfusion & ICP(>mannitol)
Longer duration
No adverse effects on IV vol and electrolytes as it
is not a diuretic
Lower sepsis related complications
Rebound IC hypertension, hypernatremia, central
pontine myelinosis
 Drugs and mechanism of action

Methionine sulfoximine Delayed glutamate

synthesis
Dizocipine NMDA blocker, AMPA
blocker
Dextromethorphane NMDA antagonist
Nimodipine Ca channel blocker
Vit E Free radical scavenger
Trilazad Lipid membrane protection
Lidocaine Na+ channel blocker
 Experimental modalities
NMDA receptor antagonist: Magnesium
Sodium channel blockers
Tirilazad : ????
Free radical scavengers : mannitol, vit E,vit C,
pentothal.
Modification of arachinodic acid synthesis
Alpha 2 agonist dexmedetomidine :
catecholamine level have correlation with
neuronal damage.
Nimodipine ????
 CONCLUSION
BRAIN PROTECTION can be done by
Basic Method, Pharmacological and Non-
Pharmacological method like Hypothermia
BRAIN PROTECTION have to done in
many site of work from pre-hospital phase
to intensive care
Many new pharmacologic agent has been
trials, but still controversy.
 A close relationship between the
Neurosurgoens & anesthesiologist