slide1 l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Prevention of Vasospasm in Subarachnoid Hemorrhage PowerPoint Presentation
Download Presentation
Prevention of Vasospasm in Subarachnoid Hemorrhage

Loading in 2 Seconds...

play fullscreen
1 / 45

Prevention of Vasospasm in Subarachnoid Hemorrhage - PowerPoint PPT Presentation


  • 1037 Views
  • Uploaded on

Roy T. Hendley, MS, PharmD PGY-1 Pharmacy Resident The Methodist Hospital Houston, Texas January 21, 2008. Prevention of Vasospasm in Subarachnoid Hemorrhage. Learning Objectives. Assess grading scales and risk for vasospasm Describe Triple H therapy

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Prevention of Vasospasm in Subarachnoid Hemorrhage' - elina


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1
Roy T. Hendley, MS, PharmD

PGY-1 Pharmacy Resident

The Methodist Hospital

Houston, Texas

January 21, 2008

Prevention of Vasospasm in Subarachnoid Hemorrhage

learning objectives
Learning Objectives
  • Assess grading scales and risk for vasospasm
  • Describe Triple H therapy
  • Describe the use of calcium channel blockers in vasospasm prevention
  • Describe the evolving role of HMG-CoA Reductase Inhibitors in the management of vasospasm
  • Identify novel therapeutic approaches for management of vasospasm in SAH
cerebrovascular accident classification

Cerebrovascular

Accident

Cerebrovascular Accident Classification

Stroke

Trauma

Epidural Hemorrhage

Subdural Hemorrhage

70-85%

15-30%

Vasospasm

Ischemic

Hemorrhagic

Hypertension

AVM

Spontaneous Intracerebral Hemorrhage

Embolus

Thrombus

Subarachnoid Hemorrhage

Hypoperfusion

TIA

Aneurysm

Cerebellum

Pontine

Basal Ganglia

stroke characteristics 1 12
Stroke Characteristics1-12

SICH = Spontaneous Intracerebral

ISC = Ischemic

sah grading scales
SAH Grading Scales
  • Hunt and Hess (neurological status)
  • WFNS* (Glasgow Coma Scale + motor deficit)
  • Fisher (vasospasm risk)
  • Claassen (ischemia risk 2° to vasospasm)
  • Ogilvy and Carter (predict outcome of therapy)
    • H/H + Fisher + aneurysm size

* World Federation of Neurological Surgeons

fisher grading scale
Fisher Grading Scale

Fisher. Neurosurgery. 1980 Jan;6(1):1-9.

sah management issues
SAH Management Issues
  • Hemorrhage
    • expansion, evacuation, hemostasis
  • Intracranial Pressure (ICP) management
  • Fever reduction
  • Seizure prophylaxis
  • Hyponatremia
    • SIADH vs. Cerebral Salt Wasting
  • Vasospasm prevention
vasospasm theory
Vasospasm Theory
  • Lysed erythrocytes
    • oxyhemoglobin
      • influx of calcium into VSMC causing contraction
      • free radicals forming vasoactive substances
  • Inflammatory response
    • TXA2, leukotrienes and histamine in CSF
  • Sloughing of endothelial cells
    • vasoactive substances reach VSMC
  • Failure of nitric oxide mechanism

Oyama. Crit Care Nurse. 2004 Oct;24(5):58-67.

slide10

Development of Delayed Vasospasm

DINDs

Suhardja. Nat Clin Pract Cardiovasc Med. 2004 Dec;1(2):110-6.

the fisher grading scale is based upon

:10

The Fisher grading scale is based upon:
  • Glasgow Coma Scale
  • CT-defined hemorrhage pattern
  • intraventricular hemorrhage
  • aneurysm size
the vasospasm theory consists of

:10

The vasospasm theory consists of:
  • lysed erythrocytes
  • inflammatory mediators
  • sloughing of endothelial cells
  • failure of nitric oxide mechanism
  • all of the above
the highest incidence of vasospasm occurs after onset of sah

:10

The highest incidence of vasospasm occurs ______ after onset of SAH.
  • 1 - 2 days
  • 1 - 21 days
  • 3 - 14 days
  • 14 - 21 days
vasospasm prevention
Vasospasm Prevention
  • Intracranial pressure (ICP) management
    • Triple H therapy
      • albumin
  • Calcium Channel Blockers
  • HMG-CoA Reductase Inhibitors
  • Milrinone
  • Magnesium sulfate
icp management
ICP Management
  • Fluids
  • Vasopressors to maintain MAP* > 90 mmHg
    • norepinephrine
    • vasopressin
    • phenylephrine
  • Goal: maintain cerebral perfusion
    • CPP** = MAP – ICP
    • normal CPP range: 70 – 100 mmHg

*MAP = mean arterial pressure

**CPP = cerebral perfusion pressure

triple h therapy18
Triple H Therapy
  • Hypertension
  • Hemodilution
  • Hypervolemia
  • Fluids used most often
    • 0.9% NaCl
    • 3% NaCl
    • Albumin 5%
slide19

Albumin

  • Neuroprotective in ischemic stroke
    • hemodiluent
    • antioxidant
    • endothelial cell apoptosis inhibitor
    • maintenance of neuronal metabolism
  • Neuroprotective in SAH
    • modulates calcium, glutathione, TNF-α, nitric oxide and arachidonic acid
    • inhibits apoptosis
    • inhibits adhesion molecules

Suarez. J Neursurg 2004;100:585.

which of the following therapies is not a component of triple h therapy

:10

Which of the following therapies is NOT a component of Triple H therapy:
  • epinephrine 1 mg/min
  • NS 1 liter at 100 ml/hr
  • albumin 5% at 2 ml/min
  • hydralazine 10 mg PO every 8 hours
calcium channel blockers22
Calcium Channel Blockers
  • Dihydropyridine
    • amlodipine (Norvasc®)
    • nicardipine (Cardene®)
    • nimodipine (Nimotop®)
  • Non-dihydropyridine
    • verapamil (Isoptin®)
    • diltiazem (Cardizem®)
nicardipine versus nimodipine
Nicardipine versus Nimodipine
  • Nicardipine
    • significant ability to reduce vasospasms
    • no mortality benefit
  • Nimodipine:
    • greater mortality benefit
    • less ability to reduce vasospasms

Feigin. Neurology 1998; 50:876-883.

nimodipine
Nimodipine
  • MOA:
    • dihydropyridine blocks calcium influx through L-type calcium channels
  • Dose: 60 mg orally every 4 hours for 21 days
    • if NPO, extract liquid and flush through NGT
  • Adverse effects:
    • hypotension  cardiovascular collapse
appropriate route s of administration for nimodipine used to prevent vasospasm include

:10

Appropriate route(s) of administration fornimodipine used to prevent vasospasm include:
  • oral
  • intravenous
  • both oral & intravenous
  • intraventricular
nimodipine has demonstrated greater benefit than nicardipine for which of the following

:10

Nimodipine has demonstrated greater benefit than nicardipine for which of the following:
  • prevention of vasospasms
  • mortality
  • both
  • neither. Agents have similar outcomes.
hmg coa reductase inhibitor trials
HMG-CoA Reductase Inhibitor Trials

↑ Nitric Oxide (NO)

Attenuated vasospasm and DINDs after induced SAH

Dose dependent increase in NO independent of LDL

Restored endothelial function independent of LDL and NO

effects of pravastatin after sah
Effects of Pravastatin after SAH

Primary Endpoints

  • vasospasm
    • incidence
    • severity
    • duration

Secondary Endpoints

  • DINDs
  • mortality

Tseng Stroke. 2005;36:1627-32.

pravastatin results
Pravastatin Results

Tseng Stroke. 2005;36:1627-32.

slide31

Pravastatin results (cont’d.)

**Data extended to Tseng et al. Stroke. 2007;38:1545-50.

simvastatin reduces vasospasm after sah
Simvastatin Reduces Vasospasm after SAH
  • Primary Endpoints
    • Vasospasm
  • Secondary Endpoints
    • Markers
      • von Willebrand factor (vWF)
      • astrocyte protein S100β

Lynch Stroke. 2005;36:2024-26.

simvastatin results
Simvastatin Results

Lynch Stroke. 2005;36:2024-26.

simvastatin results34
S100β

mean concentrations

218 pg/ml  69 pg/ml

vWF

mean concentrations

24ng/ml  14ng/ml

Simvastatin Results

p < 0.05

p < 0.01

summary of hmg coa reductase inhibitors for vasospasm prevention
Cholesterol-dependent

↓ LDL (oxLDL)

Cholesterol-independent

Nitric Oxide restoration

Summary of HMG-CoA Reductase Inhibitors for Vasospasm Prevention
  • ↓ Incidence vasospasm 42-58%
  • ↓ DINDs 14 days – 6 months
  • ↓ Mortality 75%
  • ↓ VMCA (EC function) 30%
  • ↓ need for rescue therapy 37%
slide36

Pleiotropic effects of HMG-CoA Reductase Inhibitors

Endothelial function

Anti-thrombotic

Plaque stability

Angiogenesis

STATINS

Anti-inflammatory

Immunomodulatory

Vascular cytoprotection

Anti-oxidant

Mason.Clin Sci (Lond). 2003 Sep;105(3):251-66.

slide37

:10

JG, a 55-year-old Caucasian female, presented to the emergency department (ED) reporting a sudden onset of "the worst headache of my life." A CT scan revealed a SAH due to a ruptured aneurysm which was then repaired. Medication orders at admission included nimodipine, norepinephrine and albumin. The physician consults pharmacy to dose the HMG-CoA Reductase Inhibitor for vasospasm prevention. Based on current literature, your recommendation is:

  • Somatostatin 10 mg PO daily
  • Sandostatin 30 mg PO daily
  • Simvastatin 80 mg PO daily
  • Pravastatin 10 mg PO daily
milrinone
Milrinone
  • MOA: PDE III inhibitor
    • vasodilating and inotropic properties
  • Dosing:
    • load: 8 mg over 30 minutes
    • infusion: 0.5 – 1.5 mcg/kg/min for 14 days
  • Administration: Intra-arterial then intravenous
  • Contraindications:
    • HR > 100 bpm
    • 20% decrease in blood pressure

Fraticelli. Stroke. 2008 Mar;39(3):893-8.

magnesium sulfate
Magnesium Sulfate
  • MOA:
    • neuroprotective and vasodilatory effects
    • impedes formation of reactive O2 species
    • inhibits platelet aggregation
  • Dose:
    • 12 g in 500 mL of 0.9% NaCl
    • infused intravenously at rate of 21 mL/hour
  • Goal:
    • serum magnesium: 3 - 4 mg/dL

Muroi. Surg Neuro 2008;69:33-9.

slide41

:10

JG’s condition began to worsen post-aneurysm repair. JG was intubated and an extraventricular drain was immediately placed to manage hydrocephalus. CPP 50 mmHg (nl: 70-100 mmHg) MAP 75 mmHg (nl: 90-110 mmHg) ICP 25 mmHg (nl: 0-10 mmHg)Which of the following medications would NOT be used to INCREASE the CPP?

  • nimodipine IV
  • lisinopril
  • norepinephrine
  • albumin
  • A & B
summary of vasospasm prevention
Summary of Vasospasm Prevention
  • Triple H therapy
  • Nimodipine
  • HMG-CoA Reductase Inhibitors
acknowledgements
Acknowledgements
  • David Romerill, Pharm.D., BCPS
  • TMH Continuing Pharmacy Education Board
references
References

1. Rosamond W, Flegal K, Friday G, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171..

2. Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology 1989 Sep;39(9):1246-50.

3. Rosamond WD, Folsom AR, Chambless LE, et al. Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerotic Risk in Communities (ARIC) Cohort. Stroke. 1999;30:736 –743.

4. Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003 Jan;2(1):43-53.

5. Taylor TN, Davis PH, Torner JC, Holmes J, Meyer JW, Jacobson MF. Lifetime cost of stroke in the United States. Stroke. 1996 Sep;27(9):1459-66.

6. Roos YB, Dijkgraaf MG, Albrecht KW, et al. Direct costs of modern treatment of aneurysmal subarachnoid hemorrhage in the first year after diagnosis. Stroke. 2002 Jun;33(6):1595-9.

7. Furlan AJ, Eyding D, Albers GW, et al. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006 May;37(5):1227-31.

8. Schütz H, Bödeker RH, Damian M, et al. Age-related spontaneous intracerebral hematoma in a German community. Stroke. 1990 Oct;21(10):1412-8.

9. Ingall TJ, Whisnant JP, Wiebers DO, et al. Has there been a decline in subarachnoid hemorrhage mortality? Stroke. 1989 Jun;20(6):718-24.

10. Lanzino G, Kassell NF, Germanson TP, et al. Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg. 1996 Sep;85(3):410-8.

11. Mayberg MR, Batjer HH, Dacey R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Circulation. 1994 Nov;90(5):2592-605.

12. Johnston SC, Selvin S, Gress DR. The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology. 1998 May;50(5):1413-8.