1

MANAGEMENT OF BRAIN

EDEMA AND ICP IN

STROKE PATIENTS

Stephan A. Mayer, MDStephan A. Mayer, MDDirector, Neuro-ICU

Columbia University

New York, NY

Disclosures�� NOVO NORDISKNOVO NORDISK

�� Research funding Research funding �� Speaking honorariaSpeaking honoraria�� Consulting feesConsulting fees

�� RADIANT MEDICALRADIANT MEDICAL

�� Stock optionsStock options�� MEDIVANCE, INC.MEDIVANCE, INC.

�� Research grantResearch grant�� Speaking honorariaSpeaking honoraria�� Consulting feesConsulting fees�� Stock OptionsStock Options

�� ESP PHARMAESP PHARMA

�� Speaking honorariaSpeaking honoraria�� YAMANOUCHI PHARMACEUTICALSYAMANOUCHI PHARMACEUTICALS

�� Speaking honorariaSpeaking honoraria

0

10

20

30

40

50

60

70

80

INF ICH

Intubated

Not intubated

Overall

INFARCTION ICH

30-DAY PERCENT FATALITY

57 %

6 % 9 %

74%

18 %

31%

Mayer SA, et al: Cost and outcome of mechanical ventilation for life-

threatening stroke. Stroke 2000;31:2346-2353.

2

What we WANT….

What we Usually GET:

�� 39 year39 year--old manold man

�� CVA day 3CVA day 3

�� R R hemiplegia hemiplegia

and neglectand neglect

�� L arm L arm extendsextends

briefly to medial briefly to medial

arm pincharm pinch

Mass Effect & Tissue Shifts are the Problem!

�� Frank JI. Frank JI. NeurologyNeurology 1995 Jul;45(7):12861995 Jul;45(7):1286--9090

�� 19 patients deteriorating to Stupor 19 patients deteriorating to Stupor from large ischemic MCA/ICA infarctsfrom large ischemic MCA/ICA infarcts

�� ICP > 15 mmHg present in only 5 ICP > 15 mmHg present in only 5 patients!patients!

�� Schwab S, et al. Schwab S, et al. NeurologyNeurology 1996 Aug; 7(2):393081996 Aug; 7(2):39308

�� 48 patients with Malignant MCA 48 patients with Malignant MCA infarctioninfarction

�� ALL patients had signs of ALL patients had signs of herniation herniation PRIOR to an increase in ICP > 20 PRIOR to an increase in ICP > 20 mmHgmmHg

�� Routine ICP Monitoring is NOT helpfulRoutine ICP Monitoring is NOT helpful

3

Neurologic Deterioration in

Noncomatose Patients with ICH(Mayer et al, Neurology 1994)

�� Deterioration occurred in Deterioration occurred in 33%33%

�� Predicted primarily by Predicted primarily by large large hematoma hematoma volumevolume on initial CT scan (mean 13 h after on initial CT scan (mean 13 h after onset)onset)

�� Worsening was associated with substantial Worsening was associated with substantial mortality (47 % mortality (47 % vsvs. 3%). 3%)

�� Conclusion: Conclusion: Edema associated with Edema associated with large established hemorrhageslarge established hemorrhages is the is the most important cause of late (>12 hours) most important cause of late (>12 hours) clinical deterioration after ICHclinical deterioration after ICH

The Columbia UniversitySubarachnoidHemorrhageOutcomesProject

SAH Day 0 SAH Day 18

Global Cerebral Edema in

Acute SAH

Claassen, et al, Stroke 2002

Kreiter, et al, Stroke 2002

Develops in 20% of SAH patients

Predicted by LOC at onset

Associated with increased mortality,

disability, and cognitive impairment

Delayed edema associated with

Triple- H Therapy!-

4

Optimization of BP in states of

elevated ICP

5

ICP/CPP Management

1501251007550250

0

25

50

75

Cerebral Perfusion Pressure (mmHg)

Ce

reb

ral B

loo

d F

low

(m

l/1

00

g/m

in) Zone of Normal

Autoregulation

Maximum

Constriction

Maximum

Dilatation

Passive

Collapse

0

25

50

ICP

(m

m H

g)

Extremes of CPP can aggravate ICP when

intracranial compliance is reduced

1501251007550250

0

25

50

75

Cerebral Perfusion Pressure (mmHg)

Ce

reb

ral B

loo

d F

low

(m

l/1

00

g/m

in)

0

25

50

ICP

(m

m H

g)

Vasodilatory Cascade Zone

Autoregulation Breakthrough

Zone

Extremes of CPP can aggravate ICP when

intracranial compliance is reduced

1501251007550250

0

25

50

75

Cerebral Perfusion Pressure (mmHg)

Ce

reb

ral B

loo

d F

low

(m

l/1

00

g/m

in)

0

25

50

ICP

(m

m H

g)

Vasodilatory Cascade Zone

Autoregulation Breakthrough

Zone

TARGET RANGE

6

Brain Oxygen Tension Monitoring:

LICOX

�� Adjustment of Cerebral Adjustment of Cerebral

Perfusion Pressure Perfusion Pressure

levels based on the levels based on the

needs of each patientneeds of each patient

�� Early warning of Early warning of

differences between differences between

brain tissue oxygen brain tissue oxygen

supply and demand supply and demand

�� Independent, sensitive Independent, sensitive

outcome predictionoutcome prediction

PbrO2

ICP

CPP

60

Target CPP:

100-120

Antihypertensives in the Neuro-ICU

++++0000Chronotropy reducChronotropy reduc

++++0000Inotropy Inotropy reductionreduction

++++++++++++++++++++++Afterload Afterload reductionreduction

Preload reductionPreload reduction

Sinus Sinus bradycardiabradycardia

Heart block Heart block

CHFCHF

Cardiogenic Cardiogenic shockshock

BronchospasmBronchospasm

HypovolemiaHypovolemia

Low CPP Low CPP

Infusion >3 daysInfusion >3 days

00Common Common

ContraindicationsContraindications

00++++++00Increased CBV + Increased CBV +

ICPICP

Slower, t Slower, t 1/2 1/2 66--8 h 8 h Rapid, t Rapid, t 1/2 1/2 10 min 10 min Rapid, t Rapid, t 1/21/2 22--4 h4 hOnset/OffsetOnset/Offset

11--2 mg/min2 mg/min

Bolus 20Bolus 20--80 mg80 mg

0.5 0.5 -- 10 10 µµg/kg/ming/kg/min55--15 mg/hr15 mg/hrDosageDosage

LabetalolLabetalolNitroprussideNitroprussideNicardipineNicardipineDrugDrug

0 +++ 0

7

Treatment Options for

Cytotoxic Brain Edema

�� OsmotherapyOsmotherapy

�� HypothermiaHypothermia

�� HemicraniectomyHemicraniectomy

Osmotherapy

Fluid Management and Brain

Edema: Principles

�� Severe acute brain injury results in Severe acute brain injury results in

physiologic changes favoring SIADH physiologic changes favoring SIADH

and free water retentionand free water retention

�� Brain swelling and ICP correlates Brain swelling and ICP correlates

withwith serum serum osmolalityosmolality, , not volume not volume

statusstatus

��Free water administration Free water administration

exacerbates brain edemaexacerbates brain edema

8

NICU Fluid Management Principles

�� Give only isotonic crystalloidsGive only isotonic crystalloids�� Normal salineNormal saline

�� RingerRinger’’s Lactate solutions Lactate solution

�� Avoid all sources of free waterAvoid all sources of free water�� NO D5W or halfNO D5W or half--normal salinenormal saline

�� NO halfNO half--concentrated feedsconcentrated feeds

�� Maintain Maintain euvolemiaeuvolemia�� Positive fluid balancePositive fluid balance

�� CVP >5 mm hgCVP >5 mm hg

Hyper-Osmolar Therapy

�� Two SolutionsTwo Solutions�� 20% 20% MannitolMannitol

�� Hypertonic salineHypertonic saline

�� Two treatment paradigmsTwo treatment paradigms

��Bolus therapyBolus therapy�� Reduce acutely elevated ICPReduce acutely elevated ICP

�� Reverse brain tissue shiftingReverse brain tissue shifting

��Standing therapyStanding therapy�� Establish a hyperEstablish a hyper--osmolar osmolar statestate

�� ““Prune outPrune out”” waterwater--logged cerebral tissues logged cerebral tissues

ICP: General Care Issues

�� Elevate head of bed 30Elevate head of bed 30°°

�� Use only isotonic fluids (0.9% saline)Use only isotonic fluids (0.9% saline)

�� Control fevers aggressivelyControl fevers aggressively

�� Seizure prophylaxisSeizure prophylaxis

�� No routine steroids useNo routine steroids use

Option: 3% saline or mannitol for target osmolality of 300-320 mOsms/L

9

STANDING OSMOTHERAPY

1.1. CODE YELLOWCODE YELLOW

•• Osms Osms 300300--320, Na320, Na++ 150150

2.2. CODE ORANGECODE ORANGE

•• Osms Osms 320320--340, Na340, Na++ 155155

3.3. CODE REDCODE RED

•• Osms Osms 340340--360, Na 360, Na ++ 160160

Standing Hyper-Osmolar Therapy

�� Two optionsTwo options

�� 20%20% MannitolMannitol�� 1 g/kg IV every 6 hours1 g/kg IV every 6 hours

�� NS 1 ml/kg/hr, adjusted to keep NS 1 ml/kg/hr, adjusted to keep CVP CVP ≥≥55 and fluid and fluid input = outputinput = output

�� 3% Hypertonic Saline3% Hypertonic Saline�� 1 ml/kg/hr1 ml/kg/hr

�� Reduce rate and Reduce rate and diurese diurese as needed to keep as needed to keep CVP CVP ≤≤1010 and output = input and output = input

�� 0.25 to 1.5 g/kg IV wide open0.25 to 1.5 g/kg IV wide open

�� Dose up to Q1H on an asDose up to Q1H on an as--needed basisneeded basis

�� Mechanisms:Mechanisms:

•• Acute dehydrating effect (osmotic gradient Acute dehydrating effect (osmotic gradient across BBB)across BBB)

•• Secondary Secondary hyperosmolality hyperosmolality (diuretic effect)(diuretic effect)

•• Reflex vasoconstriction (viscosity effect)Reflex vasoconstriction (viscosity effect)

�� MythologyMythology

•• Rebound effect?Rebound effect?

•• Loss of efficacy when Loss of efficacy when osms osms exceed 320 exceed 320 mOsmmOsm/L/L

Mannitol

10

Hypertonic Saline: Hypertonic Saline:

Mechanism of ActionMechanism of Action

�� Osmotic dehydrating effectOsmotic dehydrating effect

�� Depends on intact BBBDepends on intact BBB

�� Reflection coefficient of Reflection coefficient of NaCl NaCl is 1.0, compared to is 1.0, compared to

0.9 for 0.9 for mannitolmannitol

�� HS drives water from interstitial and HS drives water from interstitial and

intracellular spaces of the brain into the intracellular spaces of the brain into the

intravascular compartmentintravascular compartment

�� Water removed from cerebral tissues is then Water removed from cerebral tissues is then

redistributed throughout the entire intravascular redistributed throughout the entire intravascular

volumevolume

Intracranial 4 Compartment Model

CSF150 ml Blood

150 ml

Brain

ECF

400 ml

Brain ICF800 ml

= SODIUM

Na+ = 140 mEq/L

Intracranial 4 Compartment Model

CSF150 ml Blood

150 ml

Brain

ECF

450 ml450 ml

Brain ICF

900 ml900 ml

= SODIUM

Na+ = 140 mEq/L

11

Intracranial 4 Compartment Model

CSF150 ml Blood

300 ml

Brain

ECF

450 ml

Brain ICF900 ml

= SODIUM

Na+ = 155 mEq/L

WATER

HS

Intracranial 4 Compartment Model

CSF150 ml Blood

300 ml

Brain

ECF

400 ml

Brain ICF900 ml

= SODIUM

TOTAL

BLOOD VOLUME

Na+ = 155 mEq/L

Intracranial 4 Compartment Model

CSF150 ml Blood

150 ml

Brain

ECF

400 ml

Brain ICF800 ml

= SODIUM

Na+ = 155 mEq/L

12

SURGICAL DECOMPRESSIONSURGICAL DECOMPRESSION

SEDATIONSEDATION

CPP OPTIMIZATIONCPP OPTIMIZATION

OSMOTHERAPYOSMOTHERAPY

HYPERVENTILATIONHYPERVENTILATION

PENTOBARBITALPENTOBARBITAL

HYPOTHERMIAHYPOTHERMIA77

66

55

44

33

22

11

Columbia

Stepwise ICP

Protocol

Evidence: 3% Saline Infusion

�� Qureshi Qureshi AI, et al, AI, et al, Crit Crit Care Med 2000;28:3001Care Med 2000;28:3001

�� 3% saline reduces ICP and CT 3% saline reduces ICP and CT

midline shift in patients with TBI or midline shift in patients with TBI or

neoplasmneoplasm

�� Effect not seen with ICH or infarctionEffect not seen with ICH or infarction

�� Fisher, et al, J Fisher, et al, J Neurosurg Anesth Neurosurg Anesth 1992;4:41992;4:4--1010

�� 3% saline infusion reduces ICP in 3% saline infusion reduces ICP in

pediatric TBI patientspediatric TBI patients

�� Effect modest : 4 mm Hg over 2 Effect modest : 4 mm Hg over 2

hourshours

Changes in

Sodium

concentration &

ICP in NICU

patients treated

with 3% saline

solution

TBI

Post-

op

Quereshi, et al,

13

Bolus Hyper-Osmolar Therapy

�� Goal: Goal: �� Acutely reduce ICPAcutely reduce ICP

�� Acutely reduce symptomatic brain tissue Acutely reduce symptomatic brain tissue

shiftsshifts

�� Two optionsTwo options

�� 20% 20% MannitolMannitol�� 0.50.5--1.5 g/kg IV as needed1.5 g/kg IV as needed

�� 23.4% Hypertonic Saline23.4% Hypertonic Saline�� 0.50.5--2.0 ml/kg2.0 ml/kg

Evidence: 10% Saline Infusion�� Schwarz, et al, Stroke Schwarz, et al, Stroke

2002;33:1362002;33:136

�� 8 MCA stroke 8 MCA stroke

patients patients

�� 22 episodes of ICP 22 episodes of ICP

crisis (>20 mm Hg) crisis (>20 mm Hg)

after after mannitolmannitol

�� 75 75 mL mL of 10% HSof 10% HS

�� Effective in all casesEffective in all cases

�� 10 mm Hg drop in 10 mm Hg drop in

ICP at 35 minutesICP at 35 minutes

�� CPP increased 15 CPP increased 15

mm Hgmm Hg

�� Effect lasted up to Effect lasted up to

4 hours4 hours

Effect of Hypertonic Saline in CBF in SAH

patients

Tseng M-Y, Stroke 2003;34:1389.)

�� 10 poor grade 10 poor grade

SAH patientsSAH patients

�� 2 2 mLmL/kg of /kg of

23.5% saline23.5% saline

�� ICP fell 74%ICP fell 74%

�� CPP rose 27%CPP rose 27%

�� CBF rose 23%CBF rose 23%

�� Peak effect @ Peak effect @

2020--60 minutes60 minutes

CPP

CVR

TCD

mFV

MAP ICP

14

Hypertonic Saline: Other Benefits? Hypertonic Saline: Other Benefits?

�� Can improve CBF, CPP, and brain O2 Can improve CBF, CPP, and brain O2

deliverydelivery

�� Presumably results from endothelial dehydrationPresumably results from endothelial dehydration

�� Effect is not seen in all experimental modelsEffect is not seen in all experimental models

�� Membrane stabilizing effectMembrane stabilizing effect

�� Stabilizes membrane resting potentialsStabilizes membrane resting potentials

�� Modulation of inflammatory responseModulation of inflammatory response

�� Reduced PMN inflammatory responseReduced PMN inflammatory response

Hypertonic Saline: Complications Hypertonic Saline: Complications

�� Congestive heart failureCongestive heart failure

�� HypokalemiaHypokalemia

�� Hyperchloremic Hyperchloremic metabolic acidosismetabolic acidosis

�� Use 50/50 chloride/acetate solutionUse 50/50 chloride/acetate solution

�� CoagulopathyCoagulopathy

�� Rebound edema with correction of NaRebound edema with correction of Na++

�� Central Central pontine myelinolsispontine myelinolsis

2% 3% 2% NS 3% NS

15

Vasopressin Antagonists

in the Neuro-ICU

�� Causes a pure Causes a pure ““aquauresisaquauresis””

�� Minimal effect onMinimal effect on intravscular intravscular volume volume

�� Potential indicationsPotential indications

�� Correction of Correction of hyponatremiahyponatremia

�� ““Fine tuningFine tuning”” of sodium level while weaning of sodium level while weaning hypertonic saline hypertonic saline

�� Adjuvant to 20% mannitol or 23.4% Adjuvant to 20% mannitol or 23.4% hypertonic saline for rapid induction of hypertonic saline for rapid induction of hyperosmolar hyperosmolar state to combat ICP or state to combat ICP or herniation herniation syndromes syndromes

Hypothermia

Hypothermia: Rationale

�� Experimental focal ischemiaExperimental focal ischemia

�� Hypothermia reduces infarct volume Hypothermia reduces infarct volume andand

postischemic postischemic edemaedema

�� Reduces cerebral metabolismReduces cerebral metabolism

�� Decreases ischemic Decreases ischemic depolarizations depolarizations and and

excitatory neurotransmitter releaseexcitatory neurotransmitter release

�� Stabilizes cell membranes & BBBStabilizes cell membranes & BBB

�� Reduces heat shock protein expressionReduces heat shock protein expression

�� Reduces Reduces proteolytic proteolytic enzyme activityenzyme activity

�� Attenuates reperfusion injury & Attenuates reperfusion injury &

inflammatory responseinflammatory response

16

Hypothermia: Rationale

��ClinicalClinical�� Lower body temperature is Lower body temperature is

associated with improved outcome associated with improved outcome after strokeafter stroke

��Stroke patients with reduced body Stroke patients with reduced body temperature (<36.5temperature (<36.5°° C) on C) on admission have reduced mortality & admission have reduced mortality & better outcomes better outcomes (Reith et al)(Reith et al)

��Fever in the first 24 hours is Fever in the first 24 hours is associated with worse outcome associated with worse outcome (Castillo et al)(Castillo et al)

�� Systemic coolingSystemic cooling

�� SURFACE BLANKET COOLINGSURFACE BLANKET COOLING

�� SubZeroSubZero, , Aquamatic Aquamatic (conventional water(conventional water--

circulating)circulating)

�� Polar Air (forced air convection cooling)Polar Air (forced air convection cooling)

�� Artcic Artcic Sun (Sun (““adhesiveadhesive”” water circulating)water circulating)

�� ENDOVASCULAR CATHETER COOLINGENDOVASCULAR CATHETER COOLING

�� RadiantRadiant

�� AlsiusAlsius

�� Innercool Innercool (metallic)(metallic)

Hypothermia Methods :

How to Cool the Brain?

MEDIVANCE ARCTIC SUN

17

Heat

exchange

InflowOutflow

3 infusion

lumens

Intravascular heat exchange catheter

designed for insertion in the jugular

vein and combined central

venous capabilities

(multiple infusion

ports)

For Investigational Use Only; Not Available For Sale in the U.S.

�� Hyperacute Hyperacute (begin <6 hours)(begin <6 hours)

�� GOAL is to reduce infarct volume with a brief, GOAL is to reduce infarct volume with a brief,

early early blast of moderateblast of moderate hypothermia (12hypothermia (12--24 24

hours)hours)

�� Seems feasible only with endovascular cathetersSeems feasible only with endovascular catheters

�� Subacute Subacute (begin 6(begin 6--24 hours)24 hours)

�� GOAL is to prevent critical swelling and GOAL is to prevent critical swelling and

secondary injury with secondary injury with sustained mildsustained mild hypothermiahypothermia

�� Feasible with catheter or blanketsFeasible with catheter or blankets

�� Late Late ““rescuerescue”” hypothermia (>24 hours)hypothermia (>24 hours)

�� GOAL is to prevent GOAL is to prevent herniation herniation from from cytotoxic cytotoxic

edema with moderate hypothermiaedema with moderate hypothermia

�� Essentially an alternative to Essentially an alternative to hemicraniectomyhemicraniectomy

Timing of hypothermia?

Moderate Hypothermia Experience

Schwab et al Krieger et alStroke 2001;32:2033-2035. Stroke 2001;32:1847

N 50 10

Patients 57 yrs; NIHSS 25 71 yrs; NIHSS 20

Rx Interval 22 hrs (range 4-75) 6 hrs (range 1-8)

Time to cool 6.5 hrs (range 3.5-11) 3.5 hrs (range 2.5-6)

Duration 55 hrs (range 24-72) 47 hrs (range 20-96)

Survival 56% 70%

3 mo Rankin 2.6 (range 2-4) 1.9 (range 0-4)

Complics Hypotension (94%) Arrhythmia/brady (70%) Pneumonia (70%) Infection (40%) Arrythmia/brady (62%) Hypotension (30%)

18

+55h/ -4h/ 38.3ºC +144h/ +95h/ 36.8ºC

THEREAFTERMaintain normothermia until

ICU discharge

6 HOURS to 3-7 DAYSMaintain mild hypothermia until patient is no

longer at risk for infarct swelling

0-6 HOURSBegin moderate hypothermia for 12-24 hours

followed by controlled rewarming

ICU Temperature Management Protocol for MCA Infarction?

19

Hemicraniectomy

DAY 0

DAY 2

20

DAY 3

DAY 5

DAY 8

21

Surgical Decompression�� RationaleRationale

�� Reverse tissue shifts by allowing Reverse tissue shifts by allowing expansion of edematous brain tissue away expansion of edematous brain tissue away from the from the diencephalon diencephalon and and mesencephalon mesencephalon

�� Reduce ICP and increase CPPReduce ICP and increase CPP

�� Preserve CBF and minimize secondary Preserve CBF and minimize secondary ischemic injuryischemic injury

�� Similar concept as decompression of Similar concept as decompression of large large cerebellar cerebellar hemorrhage or infarctionhemorrhage or infarction

�� Technique used in head traumaTechnique used in head trauma

Animal Model50 Wistar rats- Permanent MCA Occlusion

- Group A: No Hemicraniectomy

- Group B: Hemicraniectomy 1 hour after occlusion

- Group C: Hemicraniectomy 24 hours after occlusion

Forsting M. Stroke 1995 Feb; 26(2): 259-64

1.8 +/1.8 +/-- 0.20.259 mm59 mm330%0%1515CC

1.3 +/1.3 +/-- 0.20.226 mm26 mm330%0%1515BB

3.1 +/3.1 +/-- 0.20.2160 mm160 mm3335%35%2020AA

NeuroNeuro ScoreScoreMean Infarct Mean Infarct

SizeSizeMortalityMortalityNumberNumberGroupGroup

Hemicraniectomy Procedure

Steiner T, et al. Neurology 2001;57:S61-8

> 14 -15 cm

22

Clinical Studies

66666 (33%)6 (33%)181820022002WalzWalz

N/AN/AN/AN/A2 (12%)2 (12%)

9 (47%)9 (47%)

17 HC17 HC

19 19 hypothermhypotherm

20022002GeorgiadisGeorgiadis

33

00

1313

55

3 (16%)3 (16%)

10 (67%)10 (67%)

19 19

15 no HC15 no HC

20012001MoriMori

00

00

88

22

4 (33%)4 (33%)

10 (83%)10 (83%)

12 12

12 no HC12 no HC

20012001HoltkampHoltkamp

1717995 (16%)5 (16%)313119981998SchwabSchwab

88333 (21%)3 (21%)141419971997CarterCarter

1616

00

55

55

11 (34%)11 (34%)

16 (76%)16 (76%)

32 32

21 no HC21 no HC

19951995RiekeRieke

Not Severely Not Severely

DisabledDisabled

Severely Severely

DisabledDisabled

DeadDead# of Pts# of PtsYearYearAuthorAuthor

Heidelberg Experience

3 month Outcome

�� Overall Mortality 27%Overall Mortality 27%

�� 34 % for 34 % for ““late HClate HC””

�� 16 % for 16 % for ““early HCearly HC””

�� All survivors could All survivors could ambulate (with ambulate (with assistance)assistance)

�� Of 11 dominant Of 11 dominant hemispherehemisphere

�� No global aphasiasNo global aphasias

�� 3 returned to work3 returned to work

0

2

4

6

8

10

12

14

16

Dead 60-70 70-80 80-90

Barthel Index ("Early" group)

More Long-term Outcomes-- 18 patients examined 718 patients examined 7--26 26

months after months after hemicraniectomyhemicraniectomy

-- Mortality 33%Mortality 33%

-- Mean age survivors 40.7 Mean age survivors 40.7 vs vs nonnon--survivors 64.5 survivors 64.5 (p=0.006)(p=0.006)

-- Mean Mean Barthel Barthel Index of Index of Survivors = 61Survivors = 61

-- Better functional outcomes Better functional outcomes in younger patientsin younger patients

0

1

2

3

4

5

6

0-30 35-55 60-100

Barthel Index

Walz B, et al. J Neurol 2002 Sep;

249(9): 1183–1190

23

Hemicraniectomy for MCA Infarction: the

HeADDFIRST Trial

• NIH-funded pilot clinical trial

• 4908 screened

• 66 patients with complete MCA infarction

were eligible (1.3%)

• 40 patients enrolled

• 26 patients met the randomization criteria

� Randomized to surgery or standardized

medical therapy for >7.5 septal or >4

mm pineal midline shift

Frank JI, et al

HEADFIRST: Main Results

4 (26.7%)4 (26.7%)5 (45.5%)5 (45.5%)Dead at 21 days*Dead at 21 days*

52.352.353.553.5Age (years)Age (years)

6/96/96/56/5Hemisphere (L/R)Hemisphere (L/R)

151511 11 NN

HemicraniectomyHemicraniectomyMedicalMedical

Benefit from Surgery No Benefit

95% CI

90% CI

80% CI

Hemicraniectomy Metaanalysis

�� 138 patients with MCA infarction138 patients with MCA infarction

�� Minimum F/U of 4 monthsMinimum F/U of 4 months

�� Age was only significant predictor of survival Age was only significant predictor of survival with good recoverywith good recovery

�� Side, extra territories, timing, Side, extra territories, timing, herniation herniation signs did not matter!signs did not matter!

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

All Age <50 Age >50

Dead

Severe Dis

Mild-Mod Dis

Independent

Gupta R, Connolly ES, Mayer SA, Elkind MSV:

Hemicraniectomy for massive middle cerebral

artery territory infarction: a systematic review.

Stroke 2004;35:539-543.

24

Hemicraniectomy

�� Likely reduces mortality from Likely reduces mortality from malignant MCA infarctionmalignant MCA infarction

�� Appears superior to hypothermia for Appears superior to hypothermia for treatment of spacetreatment of space--occupying cerebral occupying cerebral infarctioninfarction

�� Early Early hemicraniectomy hemicraniectomy (before signs (before signs of of herniationherniation) more effective than late ) more effective than late hemicraniectomyhemicraniectomy

�� Survival with good functional outcome Survival with good functional outcome most likely in younger patientsmost likely in younger patients