Transcript ACUTE Head Injury Managament at MMC

BRAIN & SALT
Dr Mohammed Shamsah
MBBS. FRCPC
Chairman of Aneasthesia, Critical Care
and Pain management Council
State Of Kuwait
2011
Osmotherapy among
Neurointensivest
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2011 (Angela et al) neurocrit care reported
survey on Osmotherapy
295 responses
50% were neurologists
Most used osmotherapy as needed either for
ICH (89.9%) or cerebral oedema noted by
imaging (54.9%)
Small minority reported using it prophylactically
(16.8)
Osmotherapy
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HTS 54.9%
Mannitol 45.1%
Reasons for preference include rebound
oedema , duration of benefit , volume expansion
rather than diuresis and lack of side effects
Those who preferred manniltol attributed to
better experience and no need for central
access
More neurosurgeons 61.9% used mannitol as to
neurologists 44.9%
Osmotherapy
28.1% used infusion of HTS others used
either boluses or both
 65.9% prefare 3% saline
 Some use Na acetate to Rx
hyperchloraemic acidosis (more
pronounced in fellows)
 67% reported target Na 150 – 160
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Outline
Introduction
 Physiology
 Best evidence available
 Complications
 Conclusion
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WHY TO WORRY ABOUT
TBI???
Outcome
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For severe Injury (GCS<8)
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36% mortality
Quality of life (GCS<8)
Vegetative - 5%
 Severe disability - 16%
 Moderate disability - 16%
 Good - 27%
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PHYSIOLOGY OF THE
BRAIN
VOLUME REGULATION OF
THE BARIN
ICP 8-12 mmHg
 ICP > CVP and atmospheric pressure
 To maintain ICP at normal level only small
variations are accepted since the brain
has a limited space for expansion
 This control is largely achieved by the
blood brain barrier (BBB)
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Cerebral Blood Flow
Regulation of Cerebral Vascular
Resistance
CBF
Normal
50 - 100
ml / min
MAP
PaCo2
(mmHg)
(mmHg)
Normal 60 - 150 mmHg
Normal 30 - 50 mmHg
BBB
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Impermeable for solutes including small
solutes Cl and Na and only water can
pass
BBB Capillary Membrane
Protects the brain from transient changes
in the blood biochemistry
 Control interstitial milieu of the brain
 Facilitates transfer of many substances by
active transport
 Permeability to water 30 times lower than
in other organs but water passes freely
 Na has a relatively high reflection
coefficient
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Forces are equal for fluid shift in all
compartments (IF,ICF,Capillary)
5500mmHg = osmotic pressure created by small solutes similar to
the size in plasma
K
Na
Cl
2-
ICF
PO4
IF 5500mmHg
5500 mmHg
Only H2O
Pc = 20 - 30 mmHg
P onc = 20 - 30 mmHg
∆ Pc or Ponc --> filtered water
In either direction according to
The imbalance -->  osmotic
pressure in the opposite side -->
Halting further fluid shift
Capillary
5500 mmHg
Injured BBB
 Pc or  P onc -->  solutes and water filtered --> opposing
osmotic pressure forces weaker . Always will be close to
plasma/interstitium --> filtration is halted by increase in ICP
K
Na
Cl
2-
PO4
IF 5500mmHg
ICF
5500 mmHg
Hypoxia causes intracellular
oedema with no disturbance
Of BBB --> no increase in
Water content but redistribution
Small Solutes and H2O
Capillary
Pc = 20 - 30 mmHg
5500 mmHg
P onc = 20 - 30 mmHg
Haemodynamic effects of the rigid cranium
Venous pressure outside dura 1 - 5 mmHg < tissue pressure inside dura (ICP) 10 - 12 mmHg
Venous vessels collapse subdurally
Degree of collapse depends on the pressure between ICP and Pout (RESISTOR)
out upstream just before collapse = ICP
RESISTOR protects the brain from variation in venous pressure
out has to be greater than ICP to be transmitted to the brain
Consequently head elevation should not affect ICP neither moderate increase in PEEP
Head elevation reduces ICP by reducing CPP
Venular resistance
Arterial resistance
Haemodynamic effects of the rigid cranium
Filtration -->  ICP -->  venous collapse -->  Pout upstream --> retrograde transmission of only 80 - 90% of the pressure
Because of Rv --> increase filtration further
New steady state will be reached when ICP 8 - 9 times initial change in hydrostatic / oncotic pressure
This phenomena explains why small change in hydrostatic / oncotic pressure result in large change in ICP
Disturbed BB in Cats showed that change in arterial pressure will change ICP to the same extent as the initial change in
Arterial pressure (p < 0.05 and < 0.01)
Venular resistance
Arterial resistance
TYPES OF OEDEMA
BRAIN: CEREBRAL EDEMA-CYTOTOXIC
(Caused mainly by activation of cytokines, ROS and other
pro-inflammatory mediators)
BRAIN: CEREBRAL EDEMA-VASOGENIC
( Caused by Break down of BBB Caused mainly by activation of
NMDA receptors by glutamate)
Oedema
Vasogenic :- caused by the break down of
BBB
 Cytotoxic :- cellular swelling of necrotic an
apoptotic cells
 Trauma has mixture of both
 Initial mechanical injury and then
secondary hypoxic injury
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Effect of arterial and oncotic
pressure variation on ICP
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Auto regulation is important for the preservation
of constant CBF
Disturbed BBB with loss of auto regulation will
affect the hydrostatic pressure greatly thereby
causing and increase in cerebral oedema that
will only be stopped by increased ICP
Low oncotic pressure independent of auto
regulation will increase filtration fraction that will
only stop by an opposing increase in ICP
Cerebral Spinal Fluid
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Produced by the choroid plexus
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Average volume 90 - 150 ml
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(0.35 ml / minute or 500 ml / day)
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Reabsorbed through the arachnoid villi
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Drainage may be blocked by inflammation of the
arachnoid villi, diffuse cerebral edema, mass effect of
hemorrhage or intraventricular hemorrhage
Patterns of Injury
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Primary Injury
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Occur at the moment of impact
 Skin/Bones/Meninges/Brain/Blood
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Secondary Injury
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Occur after impact
 Expanding
hematomas
 Brain edema/swelling
 Hypoxemia/Ischemia/Shock
 Fever/infection
 Electrolyte imbalance
vessels
MECHANISMS OF 2nd INJURY
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Global
Hypoxia and ischemia of brain
 Decreased cerebral blood flow due to
increased intracranial pressure
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Local
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impairment of cerebral blood flow or extra
cellular milieu due to the presence of injured
brain
PATHOPHYSIOLOGY
Primary damage – the only treatment is by
prevention.
 Secondary damage – multifactorial and
time dependent.
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SOME of the SECONDARY EVENTS IN TRAUMATIC BRAIN INJURY
BBB
disruption
diffuse axonal
injury
inflammation
apoptosis
necrosis
edema
formation
ischemia
Brain trauma
energy failure
cytokines
Eicosanoids
endocannabinoids
Acetyl
Choline
ROS
polyamines
Calcium
Shohami, 2000
Blue – pathophysiological processes; Yellow – various mediators
Dynamic Changes Following Stroke/Trauma
Hours
2
8 hrs
Days
7
Weeks / Months
14
Ca , Na+
Glut, ROS
I
N
J
U
R
Y
Necrosis
Apoptosis
Inflammation
Repair
Remodeling
Plasticity
Functional
Recovery
Barone &Feuerstein JCBF, 1999
Herniation
Surgery
Surgery
Decompression
 Removing hematoma
 Removing injured brain
 Removing Bone/Foreign Bodies
Fracture Repair
Repair of Spinal Fluid Leak
Non-surgical Management
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Secondary Injury
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Expanding hematomas
Brain edema/swelling
Hypoxemia/Ischemia/Shock
Fever/infection
Electrolyte imbalance
Seizures
Coagulopathy
Other non-neurologic (DVT,
pneumonia…)
Let’s talk…
Guidelines of TBI
 Mechanism of action of HS
 Evidence available
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The Guidelines for the Management of
Severe Closed Head Injury
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Strengths
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Excellent concept
Strong effort
Big step towards
standardizing care
Blah blah…
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Challenges & Limitations
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Summary statements
Poor data
Conservative
Not always useful
Can limit treatment
HTS Mechanism Of Action
Osmotic
 Haemodynamic
 Vasoregulatory
 Neurochemical
 Immunologic
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Osmotic
Increases osmotic gradient resulting in
shift of fluid from interstitium to
intravascular (more pronounced with intact
BBB)
 Counteract the effect of the accumulated
extracellular osmolytes by increasing
intravacular osmolarity to draw fluid from
the interstitial space and thereby reducing
ICP
 Reduces CSF production
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Haemodynamic
Increases CO
 increases MAP
 Smaller volumes therefore less overload
and haemodilution
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Vasoregulatory
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Studies have shown that ischaemia causes
secondary injury
Oedema , vasospasm and hyperperfusion (1st 2
weeks after injury) are causes of ischaemia
HTS dehydrates endothelium and RBCs leading
to increase diameter of vessels and movement
of RBC. It also increases plasma volume 
counteract vasospasm and hypoperfusion by
increasing CBF
Vasoregulatory
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Stimulates autonomic nervous system to reduce central
vascular resistance
Doyle et al 2001 : reported peripheral skin and muscle
vasoconstriction secondary to vagal stimulation
(mediated through lung osmo receptors) resulted in
shunting of flow to the cerebral circulation
Reduces leukocytes adherence to endothelium
Releases endothelium relaxing factor and endothelin
leading to vasodilatation
Releases prostocycline causing vasodilatation and
inhibition of platelets aggregation (Seen human umbilical
vein endothelial cells in vitro)
Vasoregulatory
Vagal stimulation causes release of atrial
naturitic peptide causing moderate
diuresis / naturesis .
 Studies have shown that intraventricular
administration of atrial naturitic peptide
reduces ICP in rats with with global
ischaemia/reperfusion model (Neurol res
1997)
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Neurochemical
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Increase Glutamate concentration extracellulary
causes massive cell death
HTS prevents pathologic Glutamate release,
since increased extracellular Na returns
glutamate/Na pump to its normal glutamate
reuptake function
Reduces intracellular Ca leading to less
neuronal excitation
Restores Na, Cl , and resting membrane
potential
Immunologic
Suppressive inflammatory effect
 Reduces rate of infectious complications
 Supresses CD4 suppression and
normalizes natural killer cell activity in rat
model
 Limits amount of bacterial translocation
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Clinical Evidence
HTS for Resuscitation
Vasser Et al reported on 166 trauma
patients undergoing helicopter transport in
which SBP maintained > 110 mmHg with
7.5% HTS/4.2% dextran versus RL.
 HTS group had less volume requirements
for haemodynamic stabilization and higher
SBP
 Subgroup analysis showed better survival
in the TBI subgroup Rx with HTS
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HTS for Resuscitation
Vasser et al also reported in a different
study that the addition of dextran to HTS
did not improve outcome
 In a meta-analysis (8 trials) performed by
Wade et al comparing HTS/Dextran vs
isotonic fluid resuscitation in hypotensive
patients. There was an increased survival
in the HTS/Dextran group P = 0.04 at
24hrs and to discharge
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HTS for Resuscitation
Cooper et al in an RCT compared 7.5%
HTS vs LR in the field (pre-hospital
resuscitation bolus therapy of 250 ml plus
additional fluids by paramedics)
 229 patients
 No difference in total fluid requirements,
SBP , ICP, CPP, inotropic support , and
survival
 This could be due to advanced pre
hospital protocol that emphasized
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HTS and Intracranial
Hypertension
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Tseng et al in a case series of Poor Grade SAH
23.5% HTS (2ml/kg/20 min)
 ICP for 2 hrs
 Cerebrovascular resisistance for 20 min
Increased CBF 20-50% in ischaemic area
Improved rheology indices
Increased Na level by 11 meq/L and osmalality
rose by 27 mOsm/L
HTS and Intracranial
Hypertension
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Vialet et al randomised 20 TBI patients to
either 7.5% (2ml/kg) HTS or 20% mannitol
HTS Reduced number of episodes and duration
of intracranial hypertension two times more
effectively than mannitol , had a better osmotic
load with a greater rise in osmalility .
No serious SE
90 days outcome including mortality showed no
difference
Confirms that increasing Na osmolar load could
be more effective in treating high ICP
HTS and Intracranial
Hypertension
200 ml of 3% / 20 min HTS in an
observational study of 18 patients with TBI
 Decreased ICP that lasted one hour
 Increased CPP
 3% has comparable osmolality to mannitol
 This study confirms that 3% HTS can be
used effectively and safely instead of
mannitol when applied at similar osmolality
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HTS and Intracranial
Hypertension
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Lescot et al performed 1 – 5 days after severe
TBI in an observational study of 14 patients
receiving 40 ml of 20% hypertonic saline as
continuous infusion over 20 min
Opposite effect on contusioned and non
contusioned brain areas
Decreased volume of non contused hemisphere
with concomitant rise in specific gravity
Increased volume in contused hemisphere
without change in density
HTS and Intracranial
Hypertension : Lescolt et al
Decreased ICP
 Wide variability of specific gravity change
in the non contused hemisphere
 This wide variability implies that BBB is
unequally affected among patients with
TBI
 In the contused region BBB disruption
occurred over several days
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HTS and Intracranial Hypertension :
Fulminant hepatic failure
Murphy et al in a prospective trial of 30 patients
with intracranial hypertension secondary to liver
failure randomized to 30% HTS infusion at a rate
of 5 – 20 ml to maintain Na level 145 - 155 vs
standard of care
 Less incidence of intracranial hypertension with
HTS
 ICP decreased relatively to its value at the
beginning of the infusion
All patient received haemifiltration to buffer the
sudden harmful serum load
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HTS and Intracranial
Hypertension
Qureshi et al reported 27 patients with
multiple causes of increased ICP treated
with continuous infusion of 3% hypertonic
saline to a target Na of 145 – 155 meq/L
 Inverse relationship between serum Na
and ICP in the 12 hrs
 Reduced oedema and lateral
displacement in serial CT
 Effect lasted 72 hrs
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Hyperosmolar Na lactate versus
Manitol inTBI (Intensive Care medicine 2009)
34 patients with GCS <8 with IntraCranial
Hypertension
 Receive equallyhyperosmolar and
isovolumic therapy consisting of either
manitol or sodium lactate
 Lactated sodium had more pronounced
effect on ICP and more frequently
successful
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Stroke
Survival Outcome
Wade et al in 1997 performed a
metanalysis of TBI shocked subgroups
received HTS/dextran (n=223) 
improved survival odds ration 2.12
(P=0.048).
 Cooper et al in 2004 RCT HTS /NS with
an out of hospital GCS <8 & SBP
<100mmhg (n=229)  mortality higher
than 50% in the treatment group and no
difference in GOSE at 6 months
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ICP was monitored in only 27.5% of patients
Some patients died before receiving ICP monitor
Maybe a longer course of hypertonic osmotherapy is
required to show an effect
Dilutional effect of crystaloid
ICP was placed according to physician after
randomization. Thus the initial resuscitation could have
improved the patient and hence hindered its insertion
ICP inserted after admission to ICU hence the effect on
ICP was not detected
Trend towards greater nosocomial infection in the
treatment group !!
Complications : Neurological
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Osmotic demyelination syndrome due to a rapid
rise of Na affecting deep white matter , with pons
being most susceptible
Human trials did not report rapid increase in Na
When Na reached 187 in certain cases no
osmotic demyelination was seen in MRI
Subdural and intracerebral haemorrhage in
children and cats have been reported with rapid
rise in Na
Complications : Renal
Insuffeciency
Burn patients had more renal failure when
resuscitated with HTS compared to RL
 May not apply to TBI
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Complications
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Dilutional coagulopathy . However smaller
volumes should over come this effect
No fluid overload have been reported in SAH
when received HTS
Hypokalaemia
Hyperchloraemic metabolic acidosis that can be
easily treated with solutions with 50/50
Cl/acetate
Rebound increased in ICP after 24 hrs : this
could be due to intrinsic half life of HTS
Conclusion
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A number of level 2 evidence confirm its
equivalent effect to mannitol in reducing ICP ,
and improving CPP
No clear cut evidence regarding mortality with
prolonged consitent osmotherapy
More studies are required to identify clNo Strong
Solid level one evidence available except for the
prehospital administration with great limitations
early which type of BBB disruption in TBI would
benefit from HTS
THAN KYOU