ICU Management of Subarachnoid...

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ICU Management of ICU Management of ICU Management of ICU Management of Subarachnoid Hemorrhage Subarachnoid Hemorrhage Subarachnoid Hemorrhage Subarachnoid Hemorrhage

Amedeo Merenda, MDAmedeo Merenda, MDAssistant Professor Assistant Professor Clinical Neurology and NeurosurgeryClinical Neurology and NeurosurgeryNeurocritical Care DivisionNeurocritical Care DivisionUniversity of MiamiUniversity of MiamiMiller School of MedicineMiller School of Medicine

DisclosuresDisclosuresDisclosuresDisclosures

• I have no relevant commercial relationship to disclose.

Objectives Objectives Objectives Objectives

• Review the most updated evidence and the clinical applications of therapies for patients with aneurysmal SAH

• Provide recommendations for management of aneurysmal SAH

http://www.mdguidelines.com/images/Illus

trations/subh_non.jpg

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Saccular: - Prevalence 1-4% of the adult population (Komotar et al)- Annual risk of rupture:

0.15-0.4% (< 7 mm), ≈1% (7-10 mm), ≥4% (> 10 mm)

• Traumatic SAH: most common form (240,000 cases/year in US)

ICH-relatedAVMs

Subarachnoid Hemorrhage (SAH) EpidemiologySubarachnoid Hemorrhage (SAH) EpidemiologySubarachnoid Hemorrhage (SAH) EpidemiologySubarachnoid Hemorrhage (SAH) Epidemiology

Other

�Intracranial CA/VA dissections

�Cervical AVM

�Tentorial AV-fistula

�Vasculitis

�Reversible Vasoconstrictive

Syndrome

�Cocaine use

�Coagulation disorders

�Pretruncal SA

10%

10%

75%

5%

Aneurysms

Spontaneous SAH:•

Neuroepidemiology. 2006;26:147-50 Neurosurgery. 2007; 61:1131-7 Neurosurgery. 2008;62:183-93

- aSAH in US: 10-15 cases/100,000 pop./year- 30,000 cases/year in US; F:M 3: 2- Mean age at onset: 55 years

Aneurysmal SAH (aSAH)Aneurysmal SAH (aSAH)Aneurysmal SAH (aSAH)Aneurysmal SAH (aSAH)

Presentation

- Thunderclap HA

- Worst headache of life

- Initial LOC (45%)

- Coma/Stupor (10%)

- Meningismus

- Cranial nerve deficits (10%)

• 3rd CN palsy (PCOM a.)

• 6th CN palsy

- Seizures (8%)

Diagnosis

- CT scan sensitive:

• 99% within 12h

• 92% within 24h

• 58% day 5

-Lumbar puncture if high clinical

suspicion but negative CT:

• Xantochromia (6h- 2wks)

• Spectrophotometry for bilirubin

- CTA* or catheter angiography

ASAP to identify aneurysm and

define its seize and shape

Future Neurology. 2013;8(2):205-224

*98% sensitivity; may miss aneurysms <3 mm

http://emedicine.medscape.com/article/1198462-overview

Neurosurg Focus. 2003;15(1)

aSAH: Neurosurgical Disease & Systemic IllnessaSAH: Neurosurgical Disease & Systemic IllnessaSAH: Neurosurgical Disease & Systemic IllnessaSAH: Neurosurgical Disease & Systemic Illness

Macdonald, R. L. (2013) Delayed neurological deterioration after subarachnoid haemorrhage

Nat. Rev. Neurol. doi:10.1038/nrneurol.2013.246

ICTUS�� ICP�� Transient Global Ischemia�� Sympathetic nervous system activationICTUS�� ICP�� Transient Global Ischemia�� Sympathetic nervous system activation

Medical complications

strongly influence outcome!

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aSAH: A Devastating EventaSAH: A Devastating EventaSAH: A Devastating EventaSAH: A Devastating Event

• High overall mortality: historically ~ 50% ( ~1 in 8 patients

die prior to reaching the hospital. In-hospital > 25%).

• 18% in-hospital mortality in modern neurocritical care era

Stroke. 1994;25:1342

Stroke. 2009;40(3):994Ann Neurol. 2006;60:518

Neurosurgery.1997; 41: 140-147

Neurosurg. 2013;73:217–22

Neurology. 1998;50:1413–8Crit Care. 2015;19(309)

• 30% of deaths within 48 h of admission

• 56 % by SAH day 7

• 76 % by SAH day 14

Contemporary single-center study of 1200 cases of SAH: 12.5 yr study period

18 % (216/1200) died during hospitalization

Survival analysis

Stroke. 1994;25:1342


Neurosurgery.1997; 41: 140-147

Neurosurg. 2013;73:217–22

Neurology. 1998;50:1413–8

• High overall mortality (historically ~ 50%)

• 18% in-hospital mortality in modern neurocritical care

• Survivors:o Significant long-term disability (> 50%)

o Neurocognitive impairment: 20% at 3 months

aSAH: A Devastating EventaSAH: A Devastating EventaSAH: A Devastating EventaSAH: A Devastating Event

Grade Neurologic status Mortality GOS

1 Mild headache,

slight nuchal rigidity

1% 4

2 Severe headache,

stiff neck, cranial

nerve palsy

5% 4

3 Drowsy or

confused, mild focal

neurologic deficit

10-19% 3

4 Stuporous,

moderate or severe

hemiparesis

30-40%

(10%)

2

5 Coma, decerebrate

posturing

85%

(70%)

2

Grade GCS Major

focal

deficit

Mortality GOS

1 15 - 5% 4

2 13-14 - 9% 4

3 13-14 + 20% 3

4 7-12±

33% 2

5 3-6±

77% 2

WFNSWFNS Grading ScaleGrading Scale

Hunt and Hess Hunt and Hess Grading ScaleGrading Scale

Poor Outcome Predicted by Initial Clinical Severity

GOOD GRADE SAH

POOR GRADE SAH

Stroke. 1994;25:1342


Neurosurgery.1997; 41: 140-147 Neurology. 1998;50:1413–8

Neurosurg. 2013;73:217–22

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Hospital mortality according to admission Hunt-Hess grade over a 12.5-year

study period. Each time epoch represents 300 consecutive admissions.

Improved In-Hospital Mortality in High-Volume

Centers in Modern Neurocritical Care Era

More aggressive

aneurysm Rx

protocols and

advanced critical

care strategies

directed at

minimizing

secondary injury

85 %

≈70 %

30 %

10 %

Contemporary

single-center

study of 1200

cases of aSAH

Crit Care. 2015;19(309)

Who Dies and Why?Who Dies and Why?Who Dies and Why?Who Dies and Why?

Crit Care. 2015;19(309)

Cardiac!

Delayed Cerebral Ischemia!

Prolonged coma after RSE, ICA rupture due to balloon

angioplasty, hemorrhagic conversion of infarct

Neurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAHNeurocritical Care Focus in aSAH

• Limit acute brain injury from ↑ICP

o Hydrocephalus

o Global cerebral edema

• Prevent rebleeding

• Prevent/Treat seizures

Immediate

care

• Prevent/Treat delayed cerebral ischemia

• Manage other medical complications:o Fever

o Hyponatremia

o Neurogenic stunned myocardium/pulmonary edema

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• Subarachnoid blood impedes CSF flow and/or resorption

Hydrocephalus Hydrocephalus Hydrocephalus Hydrocephalus

Surg. Neurol. 1998; 49:563–565 Stroke. 2009;40(3):994.Neurosurgery 1999; 45:1120–1127

• 15% of patients (40% of whom symptomatic)

Future Neurology. 2013;8(2):205-224

• EVD insertion if symptomatic HCP,

or in any patient with poor gradeo Outcome relates better to post-EVD

insertion HH grade

• 18-26% of patients require VP

shunt for persistent HCP

Rebleeding of Unsecured Aneurysm:Rebleeding of Unsecured Aneurysm:Rebleeding of Unsecured Aneurysm:Rebleeding of Unsecured Aneurysm:

• 4-17% rebleed on day 0 (most of rebleeding within first 2-6 h)

oCumulative risk 20% at 14 days

• RFs: Poor grade, longer time to Rx, size >10 mm, SBP> 160

•

Neurocrit Care. 2011; 15:241-6

Stroke. 2009;40(3):994Stroke. 2012 43:1711-37Arch Neurol. 2005; 62:410-6

World Neurosurg. 2013; 79:307-12

• Early clipping or coiling (within first 24-72hrs)

• BP control prior to securing aneurysm:

o IV Labetalol, nicardipine, enalapril

oAnalgesia

• Antifibrinolytic Rx (if aneurysm treatment delayed)

> 70% mortality, �� odd of survival w/o severe disability

Arch Neurol. 2005; 62: 410-6.

J Neurol Sci. 2007 15; 258:11-6

• Microsurgical Clipping:

o Preservation of parent vessels and perforators

o Permanent obliteration in about 90% of patients

o Highest complication rate with large and BA aneurysms

Future Neurology. 2013;8:205-224.J. Neurosurg. 1999; 90:868–874

Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Early Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm RepairEarly Aneurysm Repair

Stroke. 2013;44:1897-902Stroke. 1999; 30: 470–476 J Neurol Neurosurg Psychiatry. 2002; 73: 591–593

• Endovascular Coiling:oObliteration of small-necked aneurysms in 90% of cases

oWide neck: coils may migrate and be a source of emboli

oRate of thromboembolic events 12.5% (RF size > 10 mm)

oRisk of coil compaction after several yrs. �� rebleeding

http://www.nvca.be/en/treatments/endo_aneurysm_coiling

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• Skills of treating interventionalist/neurosurgeon have a

great impact on outcome – High Volume Centers!

• Cannot treat all patients with one modality regardless of

anatomical, clinical and other factors.

• Coiling can be considered if:

J Neurosurg. 2010; 112: 551–556

• Neck width < 4 mm

• Dome to neck ratio ≥ 2:1

• Aspect ratio > 1.6

AJNR 2009 30: 1513-1517

Favorable geometry

Coiling or Clipping?Coiling or Clipping?Coiling or Clipping?Coiling or Clipping?

Criteria for coiling of aneurysms

without need for adjunctive

techniques (e.g. stent placement

and balloon remodeling)


• Posterior circulation Location

oMCA aneurysms better off with clipping

oDistal arterial segments aneurysms better off with surgery

• Poor clinical status, comorbidities, age > 70 years (favor coiling)

• No large intracerebral hematoma (> 50 ml) with mass effect

Neurosurg Psychiatry. 2002; 73: 591–593J Neurosurg. 1984; 61: 17–23 AJNR 1994;15:815

High risk cases

• Skills of treating interventionalist/neurosurgeon have a

great impact on outcome – High Volume Centers!

• Cannot treat all patients with one modality regardless of

anatomical, clinical and other factors.

• Coiling can be considered if:

Lancet 2002; 360: 1267-74


P= 0.0019

Death or Dependency:

23.5% coil vs % 30.9% clip

ARR 7.4%

• 42 centers (mainly UK, and EU)

• Patients for whom either Rx

appropriate

• 2143 patients (out of 9559

assessed) randomized:

o 88% of patients

o 90% of aneurysms

o 97% of aneurysms in

o MCAant. circ.

< 15%

< 10 mm

good grade

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Stroke. 2010; 41: 1743-1747 Lancet Neurol. 2009; 8: 427.Lancet. 2005;366:809.

2005

2009

2010

• ��Death/Dependency at 5-year follow-up

• ��prevalence of epilepsy & cognitive decline at 1 yr.

• Slightly ��rate of late rebleeding (risks (risks small with either Rxsmall with either Rx!)!)

o At the end of 1st year: 2.6% - coiling vs. 1% - surgery

o Long-term follow-up (mean of 9 yrs): risk still low after >1 yr.

Coiling associated with

ARR 3%

Criticisms: • Small percentage randomized (only 22% of eligible

patients): can results be generalized?

• Clipping by nonsubspecialized neurosurgeons, but

minimum case experience required for coiling by

interventionalist

• Delay of treatment in clip group (> 14hrs longer than in

coil group): pretreatment deaths confounded difference!


• All eligible SAH (472 out of 725 screened) randomized

• 358 patients actually treated

• Crossover allowed (38% of those assigned to coiling

crossed over to clipping)

• Median size of aneurysm 6 mm; 83% anterior circ.


J Neurosurg 2013 Jul;119(1):146-57

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No significant difference in poor outcome between groups for

anterior circulation aneurysms (n = 339) at any time point

post hoc analysis


J Neurosurg 2013 Jul;119(1):146-57.

But significant benefit in clinical outcomes from coiling for

posterior circulation aneurysms (n= 69)

post hoc analysis


J Neurosurg 2013 Jul;119(1):146-57.

But clipping resulted in significantly better:• Degree of aneurysm obliteration (87% vs 52% - p<0.0001)

• Rate of aneurysm retreatment (5% vs 13% p = 0.01)

BRAT authors: Clipping appears the preferable management strategy for anterior circulationaneurysms 50 centers, began in 2012 , currently recruiting

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• No BP target defined in SAH with unsecured aneurysm

Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Blood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure Control

Stroke. 2012; 43: 1711-37

Prospective – 273 pts:

SBP > 160 mm Hg possible RF for prehospitalization rebleeding

Stroke. 2001;32:1176-1180

• SBP <160 mm Hg is reasonable

• Many physicians more comfortable with a SBP < 120-140 mmHg

Stroke. 2011;42(5):1351-1356.

• But in poor grade SAH excessive ↓BP offset by ↑risk of infarcKon

CPP <70 associated with

metabolic crisis and

brain tissue hypoxia!

Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Blood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure ControlBlood Pressure Control

Impaired cerebral

autoteregulation

in aSAH

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Stroke. 2012 Jun;43(6):1711-37J Neurosurg. 2002;97(4):771. Cochrane Database Syst Rev. 2013, 8

Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Rebleeding prevention: Antifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapyAntifibrinolytic therapy

Cumulative rebleeding-free survival

according to antifibrinolytic group

Starke et al. Stroke. 2008;39:2617-2621

73 patients (EACA for ≤ 72h)

• Rebleeding 2.7%

175 patients (no EACA)

• Rebleeding 11.4%

• DVT: 8 fold � EACA group

• No difference in outcome

Cochrane Database Syst Rev. 2003 (9 trials) and 2013 (10 trials):

�risk of DVT but not pulmonary embolism

��risk of re-bleeding by 35%

��risk of delayed cerebral ischemia if Rx > 72h

2012 ASA guidelines: short term therapy < 72 hrs

reasonable when definitive treatment of the aneurysm

is unavoidably delayed and there are no other

contraindications (Class IIa, Level of Evidence B)

4 g IVx1, 1g/h

• New [focal neurological signs and/or � in LOC] > 1h

• Appearance of new infarctions on CT or MRI

Delayed Cerebral Ischemia (DCI): Delayed Cerebral Ischemia (DCI): Delayed Cerebral Ischemia (DCI): Delayed Cerebral Ischemia (DCI): DefinitionDefinitionDefinitionDefinition

Stroke. 2006;37:409-413

• Risk: starts day 3 post-SAH, peaks day 5-14, ends day 14-21

Stroke 2009; 40: 1963–1968 Stroke 2010; 41: 2391–2395 Future Neurology. 2013; 8:205-224.

DCI �� INFARCTON

Prevent Detect/Treat

and/or

DCI: DCI: DCI: DCI: A more clinically relevant definition than A more clinically relevant definition than A more clinically relevant definition than A more clinically relevant definition than symptomatic vasospasm symptomatic vasospasm symptomatic vasospasm symptomatic vasospasm

o Many with angiographic

vasospasm have no DCI:

• Vasospasm: 40-60% SAH

• Leads to DCI in 20-30%

o Some with DCI have no

angiographic vasospasm.

o Correlation w outcome strong

for DCI, weak for angiographic

vasospasm

Future Neurology. 2013;8:205-224 Stroke. 2009;40:2362

o Likely mechanisms independent

of large vessel vasospasm cause

ischemic brain injury, as well as

genetic susceptibility to

ischemia Nature Reviews Neurology 2014; 10, 44–58

Nature Reviews Neurology 2014; 10, 44–58

• Microthrombi formation

• Cortical spreading ischemia

• Microcirculatory spasm

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IVH & thickness of blood on CT most consistent predictors

DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: Prediction Prediction Prediction Prediction –––– Radiologic ScalesRadiologic ScalesRadiologic ScalesRadiologic Scales

Fisher

Grade

Blood Pattern on CT #of patients w

clinical VSP

1 No blood detected 0/11

2 Diffuse or vertical layers <1 mm thick* 0/7

3 Localized SA clot or vertical layers ≥ 1 mm thick* 23/24

4 ICH or IVH with minimal or no SAH 0 / 5

“Vertical” cisterns: interhemispheric, insular, and ambient.

Surg Neurol.2005; 63: 229-234Neurosurgery 1980; 61: 1-9

Clearly

observed

vasospasm

even in these

patients

1980

Claassen et al’s Group, Columbia University

DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: DetectionDetectionDetectionDetection

• Neurological examinationsoGCS Hourly , NIH stroke scale 6 hourly

Neurocrit. Care 2011; 15:211–240Neurosurgery 2009; 65:316–323.Neurology 2004; 62:1468–1481

Stroke. 2013 ;44:1260-6.

• Limb weakness?

• Aphasia/Neglect?

• Mutism, LOC?

• Daily Transcranial Doppler Ultrasoundo Neither sufficiently sensitive nor specific:

o Data are best for MCA (80% sensitive and specific)

o MCA MFV < 120 cm/s absence

o MCA MFV> 200 cm/s = presence

o Lindegaard index (MCA/EC-ICA) > 6 = presence

o Dynamic MFV changes (twofold increase) = high risk

o Requires confirmatory studies

International Journal of Vascular Medicine

Volume 2013 (2013), Article ID 629378

MFV ��:

• Stenosis

• Vasospasm

• Hyperdynamic

flow

Cerebrovasc. Dis.2008; 27:144–150

CT perfusion:• Prolonged mean transit time (MTT) >6.4 more

sensitive for vasospasm (92%)

• Reduced CBF more specific for vasospasm (95%)Cerebrovasc Dis 2008;26:163–170

DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: DCI/Vasospasm: Confirmatory StudiesConfirmatory StudiesConfirmatory StudiesConfirmatory Studies

Conventional 4-vessel cerebral angiography

• Gold standard, allows Rx, but invasive

• Noninvasive

• Good correlation with angiography

• Contrast load, radiation exposure!CTA

• High negative predictive value of 95-100%

• May overestimate the degree of arterial narrowing

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Decreased CBF in the

posterior circulation

Prolonged mean transit time

(=slow blood flow) through

the posterior territories

DSA confirms severe

vasospasm (arrows) in

the basilar artery

Barrow Quarterly - Volume 17, No. 3, 2001

CPT is able to quantify cerebral perfusion parameters: CBF, CBV, MTT.

Quantitative cerebral perfusion maps are constructed.

DCI: Detection in DCI: Detection in DCI: Detection in DCI: Detection in PoorPoorPoorPoor----Grade SAH patients Grade SAH patients Grade SAH patients Grade SAH patients

http://www.priniotakis.gr/ catalog3/ images/salesheet%20licox%20eng %20(3). jpgActa Neurochir. Suppl. 2002; 81: 307–309

Partial Brain tissue PO2 monitoring

Correlates with infarction

• CTA/CTP � screening for Neurocrit. Care 2011; 15,211–240

Clin. Neurophysiol. 2004; 115:2699–2710

α/δ ratio from baseline:• Quantitative continuous EEG: � > 10% in 6 cons. recordings (sensitivity 100%, specificity 76%)

� > 50% in single recording (sensitivity 89%, specificity 84%)

J. Neurosurg. 2004; 100:400–406http://openi.nlm.nih.gov/detailedresult.php?img=2660341_1751-0147-51-10-1&req=4

Microdialysis (markers of ischemia/injury)

Correlates with �CBF on PET

Hypoxic ptiO2 < 10 mmHg

in glycerol, glutamate, LPR

perfusion deficits

• Need to place probe in area at greatest risk for vasospasm. This is difficult!

• Vasospasm generally predicted by CT scan.

•

• But development of ischemia more variable (both in terms of whether it develops and where)

The The Importance of Probe Importance of Probe Placement for Placement for Focal Focal NeuromonitoringNeuromonitoring TecniquesTecniques

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Multiple Cortical/Deep Infarcts

• 28/57 patients (49%)

• Did not correlate with

vasospasm by TCD/angiogram

Rabinstein et al. Stroke 2005;36:992-997

StrokeJOURNAL OF THE AMERICAN HEART ASSOCIATION

Patterns of Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage

Rabinstein AA, Weigand S, Atkinson JLD, Wijdicks EFM

DCI: DCI: DCI: DCI: PreventionPreventionPreventionPrevention

• Volume repletion: EUVOLEMIA!oHypovolemia is bad:

oMust account for insensible losses (~800 cc/d, higher if fever)

oMost patients need at list 3 liter/d of IV NS (125 ml/h)

oCannot use fluid restriction to treat hyponatremia!

Stroke. 2009; 40:2575

Stroke. 1989;20: 1511-5. .

Cochrane Database Syst Rev. 2004 Oct 18; (4): CD000483

(N. Engl. J. Med. 1983; 308: 619–624) o Allen et al Multicenter RCT

o No effect on angiographic vasospasm

o But improves outcome (relative risk of DCI reduced by 0.69)

•Oral Nimodipine

• Action on harmful calcium-dependent mechanisms

Class I, level A

Class I, level B

Meticulous attention to input/output

60 mg q4hrs x 21 days

Randomized trial: 82 patients

•Hypervolemia(albumin for CVP < 8)

VS•Normovolemia

(albumin for CVP < 5)

StrokeStrokeStrokeStroke. 2000;31:383. 2000;31:383. 2000;31:383. 2000;31:383----391391391391

Prophylactic Hypervolemia: Prophylactic Hypervolemia: Prophylactic Hypervolemia: Prophylactic Hypervolemia: Not useful Not useful Not useful Not useful

Over the 14-day study period.

Higher CVP target led to:

o� fluid intake

o Similar fluid balance

o Similar CBF on Xenon CT

o No difference in outcomes

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• Clazosentan: CONSCIOUS-2 (Multicenter phase III RCT)• Endothelin receptor antagonist

• Endothelin 1 is a potent vasoconstrictor

• 1147 patients randomized to drug vs placebo

• Effect on angiographic vasospasm

• But no benefit on outcome

• IV Magnesium (Ca antagonist and NMDAr antagonist)• Hypomagnesaemia associated with poor outcome and DCI

• Phase II study: Mg infusion decreased DCI and poor outcome

• 2010-Phase III (N=327) IMASH: 14 d of Mg: no benefit on OC

• 2012-Phase III (N= 1204) MASH- II: no benefit on OC

• 2013-Meta-analysis of 13 trials: no benefit on OC

DCI DCI DCI DCI PreventionPreventionPreventionPrevention: What did not work: What did not work: What did not work: What did not work

J Crit Care. 2013 28: 173-81Lancet. 2012; 380:44-9

Lancet Neurol. 2011; 10: 618-625Stroke 2010; 41,921–926

The current evidence does not support routine

induction of hypermagnesemia. However,

hypomagnesemia should be avoided!

• Statins • Improve vasomotor reactivity via upregulation of

endothelial NO synthetasis ??• 6 small single center RCTs: safe in SAH

• Mixed results in VSP ppx and outcome improvementStroke. 2010;41:e47 Cochrane Database Syst Rev. 2013;4:CD008184.

DCI DCI DCI DCI PreventionPreventionPreventionPrevention: What did not work: What did not work: What did not work: What did not work

Lancet Neurol. 2014; 13 :667-675

o803 pts: Simvastatin 40 mg/d x 21 days VS placebo

Lancet Neurol. 2014; 13 :667-675

Safe but No benefit: Statins NOT recommended for DCI ppx

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Neurocrit Care. 2011; 14: 489-99

Intrathecal

Thrombolysis

Acta Neurochirurg Suppl. 2015; 120: 281-6

Intrathecal

Nimodipine

NEWTON trial:

• Completed enrollment in NA

• Positive results

• Unpublished yet

• Phase III trial planned

DCI DCI DCI DCI PreventionPreventionPreventionPrevention: Approaches : Approaches : Approaches : Approaches Under InvestigationUnder InvestigationUnder InvestigationUnder Investigation

Intraventricular administration

of Nimodipine slow-release

microparticle system EG-1962

To achieve high CSF levels of

nimodipine w plasma levels that

do not exceed those associated

w hypotension (>30 ng/ml)

Thickness of subarachnoid blood

correlates with VSP

Accelerating subarachnoid blood

clearance may prevent VSP?

Rationale

rTPa: at time of clipping or

microcather infusion in lumbar

cistern/cisterna magna

Methods

Meta-analysis of 5 RCTs:

� ↓in poor OC and VSP

w/o �in hemorrhage

� Methodological flaws!

� Definitive trial required!

Evidence

Published online February 13, 2015

Phase 1/2a multicenter,

controlled, randomized,

open-label dose-

escalation, safety,

tolerability, and

pharmacokinetic study

Intraventricular EG-1962 vs

oral nimodipine within 60 h of aSAH.

http://www.sec.gov/Archives/edgar/data/1472091/000156761915001095/s000911x3_s1.htm

Safe, tolerated.

Met exploratory endpoints:

- �GOSE (6-8) 90-day �risk of DCI/VSP

EG-1962 reduced the risk of angiographic vasospasm/DCI by ≈ 50%

72 patients (WFNS 2-4) randomized:

54 to EG-1962 and 18 to nimodipine

5 of 18

27 of 45

26 of 151

DCI Management (DCI Management (DCI Management (DCI Management (SecuredSecuredSecuredSecured Aneurysm!)Aneurysm!)Aneurysm!)Aneurysm!)

• Hyperdynamic therapy (not “triple H”) • Induced Hypertension (+ Euvolemia)

• CO augmentation (dobutamine, milrinone)

• In the presence of cardiac dysfunction/NSM

• Endovascular therapy • IA vasodilator (e.g. verapamil, nicardipine)

• Rapid onset, short action, may require multiple Rx

• Transluminal balloon cerebral angioplasty

• Focal vasospasm of larger vessels

• Durable, but up to 10% risk of vessel rupture or dissection

Class IIa, level B

Neurocrit Care. 2011 15:211-40Curr Treat Options Neurol. 2005;7:99

Class IIb, level B

Neurosurgery 2001: 48,723–728

Stroke. 2012; 43: 1711-37

Stroke. 2012; 43: 1711-37

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DCI: DCI: DCI: DCI: Induced HypertensionInduced HypertensionInduced HypertensionInduced Hypertension

• Phenylephrine, norepinephrine

• No evidence-based standards regarding BP endpoints

• If nimodipine causes hypotension:

o �dose /interval (e.g. 30 mg q2h, or 30 mg q4h)

o or discontinue

Neurocrit Care. 2011; 15: 211-40. Stroke 2012; 43:1711–1737

Periodic neurological

assessments to define BP target

Max: SBP < 200-220/ MAP < 150

Initial MAP ��by 20-35%

No improvement within 1h? � Endovascular Rx

Nature Reviews Neurology 2014; 10, 44–58

SeizuresSeizuresSeizuresSeizures• 1-8% at onset, 5% during hospitalization

• 7% of patients: epilepsy during first yr. after discharge

• Nonconvulsive seizures potential contributor to coma

• 7-19% of SAH patients

• cEEG recommended in poor-grade SAH patients

Neurocrit. Care 2011; 15: 211–240

Neurology 2003; 60: 208–214 J. Neurosurg. 2007; 107: 253–260

Neurocrit Care. 2012; 17:367-73

J. Clin. Neurophysiol.2005; 22:92–98J. Neurosurg. 2007; 106: 805–811

Stroke. 2012; 43: 1711-37

• May result in rebleeding of unsecured aneurysm

• Prophylaxis (Levetiracetam) commonly given, for 3–

7 days2012 ASA guidelines: Class IIb; Level of Evidence B

• If acute seizure, AED continued for 6 months

• Phenytoin worsens functional outcome: no longer

recommended

• 20-57% of SAH patients

• Late onset correlates with DCI in poor grade patients

Future Neurology. 2013;8:205-224.

Other medical complications: Other medical complications: Other medical complications: Other medical complications: HyponatremiaHyponatremiaHyponatremiaHyponatremia

Negative

fluid balance

Positive/Even

fluid balance

Urine Na >40 meq/L

Urine osm high

Serum uric acid low U.O. > Input

o Never restrict isotonic IVFs! (free water restrict, but give NS!)

o NS + salt tablets (2-3 g q6-8h), 3% saline infusion

o Fludrocortisone acetate (0.1 to 0.2 mg PO/IV BID) to promote Na/water retention if excessive diuresis (CSWS)

o Monitor Na q6-12hrs

(BNP?)

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• 41-72% of SAH patients; associated with:

o↑risk of DCI, poor outcome (mRS 4-6), length of stay

Neurosurgery 2008; 63: 212–217 Neurocrit. Care 2009; 10: 11–19 Neurosurgery 2009; 64: 897–908

Other medical complications: Other medical complications: Other medical complications: Other medical complications: FeverFeverFeverFever

Keep T at 37 C for 2

wks from SAH:

Antipyretics (1st line),

surface/intravascular

cooling (2nd line)

Neurosurgery 2010; 66: 696–700

mRS 4–6 in 21% p= 0.04 mRS 4–6 in 46%

T 37 C surface or

endovascular cooling

for first 14 days

Conventional

Fever Control

40 cons. patients 80 patients 2003 -2005 1996-2004

(Columbia University

SAH Outcomes Project)

Neurogenic Stunned Myocardium (NSM)Neurogenic Stunned Myocardium (NSM)Neurogenic Stunned Myocardium (NSM)Neurogenic Stunned Myocardium (NSM)

Neurocrit. Care 2006; 5:243–249 Circulation 2005; 112:3314–3319 Neurology 2009; 72:635–642

• �CO and

Hypotension

• Transient ECG

abnormalities

• STE, ��Troponin:

May mimic AMI!

• Reversible RWMA

on echo

• Sometimes apical

ballooning on echo

(Takotsubo

cardiomyopathy)

SAH� ICP �� Transient Global Ischemia � Cathecolamine Surge �� LV dysfunctionSAH� ICP �� Transient Global Ischemia � Cathecolamine Surge �� LV dysfunction

Apical akinesis of LV

http://emedicine.medscape.com/ar

ticle/1513631-overview

LV dysfunction

Vasospasm/DCI

Vasopressors

Elevated troponin

Problematic in

the face of VSP

2009 meta-analysis: link to DCI, poor outcome and mortality2009 meta-analysis: link to DCI, poor outcome and mortality

oNeeds inotropes (1st line)

o Endovascular Rx preferred over induced hypertension

o Intra-aortic balloon pump option (secured aneurysm)

Bybee K A , Prasad A Circulation 2008;118:397-409

Those with an LV EF <40% and

troponin T of <2.8 likely have NSCand not acute MI

J Neurosurg. 2003; 98: 524–528.

NSM vs AMI

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ConclusionsConclusionsConclusionsConclusions

• EVD/ICP monitoring in symptomatic HCP/ poor grade• CPP > 70 mmHg , ICP < 20 mmHg

• Early repair. SBP < 140-160 with unsecured aneurysm

• Permissive hypertension after securing aneurysm • Tolerate spontaneous SBP up to 180-200 mmHg

• To prevent DCI:• Nimodipine (60 mg q 4hrs x 21 days; dose & interval if drop in BP)

• Normovolemia (meticulous maintenance of fluid balance; do not fluid restrict in hyponatremia)

• Normothermia (target T 37 °C for first 2 weeks!)

• To treat DCI:• Stepwise induced hypertension (and maintain normovolemia!)

• Inotropes if cardiac dysfunction/NSM

• Early use of endovascular Rx for refractory cases/NSM

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