Neurosurgery notes/Vascular/Haemorrhagic diseases/SAH/SAH complication/Cerebral vasospasm

Cerebral vasospasm

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SAH complication

General

  • Aka Cerebral Vasospasm (CVS)/Delayed ischaemic neurological deficit (DIND)/delayed cerebral ischaemia (DCI)
  • CBFlow is reduce in SAH, the reduction is greater, higher the fisher grade
  • Takes 10-14 days for it to return to normal and longer the higher the grade

Also seen in

  • Other intracranial hemorrhages (e.g. intraventricular hemorrhage from AVM, and SAH of unknown etiology),
  • Head trauma (with or without SAH)
  • Brain surgery
  • Lumbar puncture
  • Hypothalamic injury
  • Infection
  • May be associated with preeclampsia

Numbers

  • Incidence
    • Radiographic cerebral vasospasm (CVS)
      • Present in 20–100% of arteriograms at 7th day following SAH
    • Clinical vasospasm + Radiographic cerebral vasospasm
      • Present in 30% of patients with SAH
    • Radiographic CVS may occur in the absence of clinical deficit, and vice-versa
  • Cause of mortality in 7% of SAH
  • Cause of stroke in 26% of SAH
  • 1/3 of survivors suffer of spasm have moderate to severe disability

Diagnosis criteria

  • Delay onset or persisting Neuro deficit
    • Onset between 4-20 days
  • Deficit to appropriate arteries
  • R/o
    • Rebleed: CT
    • HCP: CT
    • Cerebral edema: CT
    • Seizure: does not recover
    • Metabolic disturbance: Hyponatremia: Blds
    • Hypoxia: ABG
    • Sepsis: blds
  • Ancillary tests
    • Transcranial Doppler
    • CBF studies

Definition

DCI: (delayed cerebral ischaemia)

  • Delayed development of a neurological deficit,
  • Decline in Glasgow coma scale of at least 2 points, and/or cerebral infarction unrelated to aneurysm treatment or other causes.
  • DCI is an umbrella term that encompasses a number of clinical entities including
    • Symptomatic/clinical vasospasm
    • Delayed ischemic neurological deficit (DIND)
    • Asymptomatic delayed cerebral infarction

EBI: early brain injury

  • Direct mechanical damage from the SAH
  • Transient increase in ICP
  • Reduction of CBF
  • Apoptosis and Oedema formation.

Clinical vasospasm: symptomatic vasospasm: Delayed ischaemic neurological deficit

  • The occurrence of focal neurological impairment (hemiparesis/aphasia/apraxia/hemianopia/neglect) or a decrease of at least 2 points on the GCS that
  • Last for >1hr
  • Cannot be attributed to other causes
    • HCP
    • Seizures
    • Fever
    • Infections
    • Respiratory failure
    • Electrolyte abnormalities
  • The diagnosis is one of exclusion, and sometimes cannot be made with certainty

Radiographical vasospasm: angiographic vasospasm

  • Arterial narrowing on angiography with slowing of contrast filing
  • Previous or future angiography showing the same vessel with normal caliber.
  • Visible in 50% of patient with SAH on day 7
  • Angiographic vasopsams: present in 70% of patients with SAH
  • Only 30% of patients with SAH has DIND (vs 50% that has vasospasm)

Clinical features

Findings usually develop gradually, and may progress or fluctuate.

  • Confusion/Dec. level of consciousness with/without focal neurological deficit (speech/motor)

Non-localising

  • New/Inc. h/a
  • Alteration of level of consciousness
  • Disorientation
  • Meningismus

Localising:

  • Cranial nerve palsies and focal motor deficits.
  • Syndromic (ACA > MCA):
    • ACA syndrome
      • Frontal lobe findings: abulia (disorder of lack of motivation), grasp/suck reflex, urinary incontinence, drowsiness, slowness, delayed responses, confusion, whispering
      • Bilateral anterior cerebral artery distribution infarcts are usually due to vasospasm following an AComm aneurysm rupture
    • MCA syndrome
      • Hemiparesis,
      • Monoparesis
      • Aphasia or apractagnosia of non dominant hemisphere (inability to use objects or performed skilled motor activities due to lesion @ lower occipital or parietal lobe),
      • Ideomotor apraxia and sensory apraxia

Diagnosis of exclusion:

  • Hence must do MRI to r/o rebleed and bld to r/o Hyponatremia

Risk factor

Clinical Presentation factors

  • Higher SAH grade (hunt and hess)
    • Correlation of DIND with Hunt and Hess grade
        • Hunt and Hess grade
        % DIND (clinical vasospasm)
        1
        22%
        2
        33%
        3
        52%
        4
        53%
        5
        74%
  • Hypovolemia

Patient factors

  • Older
  • Active smoking
  • Hx of HTN

Radiological factors

  • More blood on CT
    • Modified¹⁰⁴ grading system of Fisher⁹⁸ (correlation between the amount of blood on CT and the risk of vasospasm)
        • Modified Fisher scale group
        Blood on CTᵃ
        Symptomatic vasospasm
        0
        No SAH or IVH
        ㅤ
        1
        Focal or diffuse thin SAH, no IVH
        24%
        2
        Focal or diffuse thin SAH, with IVH
        33%
        3
        Focal or diffuse thick SAH, no IVH
        33%
        4
        Focal or diffuse thick SAH, with IVH
        40%
        ᵃmeasurements made in the greatest longitudinal & transverse dimension on a printed EMI CT scan (no scaling to actual thickness) performed within 5 d of SAH in 47 patients; falx never contributed more than 1 mm thickness to interhemispheric blood
    • Blood clots are spasmogenic when in contact with proximal 9cm of ACA and MCA
      • Higher risk when high pressure arterial blood in contact with vessel at the base of the brain
  • Pial enhancement on CT ≈ Day 3 post-SAH (with IV contrast administration) correlate with higher risk of CVS (indicates increased permeability of BBB)-(controversial)

Intervention factors

  • If patient had early surgery, post op CT is has little SAH → lower risk of vasospasm
  • Antifibrinolytic (tranexamic acid) therapy reduces rebleed but inc. hydrocephalus and vasospasm
  • Angiographic dye can exacerbate vasospasm

Severity

  • CVS Top 3 cause of morbidity and mortality surviving SAH pts
    • Exceeded by
      • Aneurysmal rupture
      • Re-bleeding
  • CVS ranges in severity
    • From mild reversible dysfunction ↔ to severe permanent deficits secondary to ischaemic infarction
    • Extensive enough to be fatal in 7% of SAHs
  • Earlier onset of CVS is associated with greater deficit

Time course

  • Onset: mainly insidious but 10% are sudden and have severe deterioration
  • Never before 3 days
  • Peak at 7 days
  • Rarely starts after 17 days
  • Main risk between 3 and 14 days
  • DIND resolves by day 12 post SAH
  • Vasospasm resolves over 4 weeks

Pathogenesis: poorly understood

  • Appears to occur in intracerebral arteries that have been encased in blood clot, usually within the subarachnoid space
Vasospasm is caused by smooth muscle contraction, due to
  • Impaired vasodilatory mediators AND
  • Overactive vasoconstrictive mediators
Biphasic vasospasm: early vs chronic
  • Blood exits artery → Hb in contact with vessel wall → influx and release of Ca in smooth muscle wall → vasospasm (early vasospasm)
  • Inflammation → remodelling and narrowing of vessel wall (chronic vasospam)
    • Pathological changes in vasospasm
        • Time
        Vessel layer
        Pathologic change
        Day 1–8
        Adventitia
        ↑ inflammatory cells (lymphocytes, plasma cells, mast cells) and connective tissue
        ㅤ
        Media
        Muscle necrosis and corrugation of elastica
        ㅤ
        Intima
        Thickening with endothelial swelling and vacuolization, opening of interendothelial tight junctions
        Day 9–60
        Intima
        Proliferation of smooth muscle cells → progressive intimal thickening
    • In humans, CVS is a chronic condition with definite long-term changes in the morphology of the involved vessels.
Pathophysiology of Delayed Cerebral Ischemia Vasospasm (Large Vessel) Mass Effect Hydrocephalus CPP CBF ICP Adrenergic Surge Vasoconstriction (Small Vessel) Microthrombosis Perfusion Mismatch (Small Vessel) CSD BBB Breakdown Cerebral Edema Inflammatory Response Oxidative Stress Apotosis/Necrosis SIRS Cardiac Injury Lung Injury Microemboli Perfusion Mismatch (Small Vessel) CSD Loss of Autoregulation Inflammatory Response Oxidative Stress Seizures SIRS Hypermetabolism SIADH/Cerebral Salt Wasting o c o
Direct mediators
  • The formed components of blood have each been shown to contribute to vasospasm
    • Auto-oxidation of Hb into MetHb and superoxide sp. → damage endothelium and initiates inflammation → imbalance between Endothelin 1 overproduction vs NO underproduction
    • Oxyhemoglobin in pure form can cause contraction of cerebral arteries when contacting the extra-luminal surface of the vessel
    • Hemoglobin scavenges Nitric Oxide, a powerful vasorelaxant
    • Platelet-derived growth factor induces vascular proliferation → vascular stiffening and impaired ability to dilate
  • Endothelial dysfunction:
    • Theories include
      • Decreased production of Nitrous Oxide and prostacyclins
      • Overproduction of Endothelin-1
    • Vacuolization of endothelial cells, and loss of their tight junctions
  • Vessel innervation by the sympathetic nervous system.
    • Interruption of sympathetic innervation prevents vasospasm in rats
Proposed mechanisms of vasospasm include
  • Contraction of the smooth muscle in the media of the vessel wall, as a result of:
    • Vasoconstrictors within the haemorrhagic arterial blood
    • Vasoactive substances released into the CSF
    • Neuronal mechanisms via nervi vasorum (nerves in the vessel wall)
      • Increased vasoconstrictor tone (possibly due to denervation supersensitivity)
      • Loss of vasodilator tone
      • Time dependent relative imbalance favouring vasoconstrictor over vasodilator innervation
      • Sympathetic hyperactivity: e.g. due to hypothalamic injury from elevated ICP
    • Impairment of endothelial derived relaxant factor (EDRF):
      • Vascular endothelium plays an obligatory role in vasodilatation caused by several pharmacologic agents by releasing a relaxant substance called EDRF
  • Proliferative vasculopathy
  • Immunoreactive process
  • Inflammatory process
  • Mechanical phenomenon
    • Stretching of arachnoid fibers
    • Direct compression by blood clot
    • Platelet aggregation

Investigation

Transcranial Doppler: (see radiology)

  • Narrow lumen → inc. velocity of blood flow → detect by doppler effect
  • To monitor MCA, ACA, ICA, VA, and BA velocities
    • Best correlated for MCA
      • In regions of thinner bone – insonation windows
  • Able to detect Spasm 24-48hrs before clinical symptoms
  • Lindegaard ratio: velocity ratios between MCA vs ICA
  • Once values are elevated it takes weeks for it to come down
  • Interpretation of transcranial Doppler for vasospasm
      • Mean MCA velocity (cm/sec)
      MCA:ICA (Lindegaard) ratio
      Interpretation
      <120
      <3
      Normal
      120–200ᵃ
      3-6
      Mild vasospasmᵃ
      >200
      >6
      Severe vasospasm
      ᵃvelocities in this range are specific for vasospasm but are only ≈ 60% sensitive
      • High velocity could be due to hyperemia only, to differentiate hyperemia vs vasospasm need Lindegaard ratio
       
      Transcranial Doppler. Indicative waveform from insonation of the middle cerebral artery using transcranial Doppler. The systolic and diastolic flow velocities (FV) are marked. The FVs is used to gauge the progression of vascular spasm or to quantify the Lindegaard ratio
      Transcranial Doppler. Indicative waveform from insonation of the middle cerebral artery using transcranial Doppler. The systolic and diastolic flow velocities (FV) are marked. The FVs is used to gauge the progression of vascular spasm or to quantify the Lindegaard ratio
       
  • Disadvantage
    • Operator dependent
    • Only detect spasm in large anterior circulation

Alteration in intracranial pulse wave

CTA

  • Specific for vasospasm, but may overestimate the degree of stenosis

DSA

  • Disadvantage
    • Invasive
    • Labour intensive
    • Procedural risk.
  • Advantage
    • Most sensitive modality for detecting both small and large vessel spasm,
    • Allows for interventions such as intra- arterial vasodilator therapies or balloon angioplasty
  • Some units routinely perform day 4– 7 catheter angiogram for comatose patient to check for vasospasm

MRA

  • Useful management of vasospasm but cannot replace angiography

Continuous quantitatively analysed EEG

  • Dec. of % of alpha activity (from 0.45 --> 0.17) ("relative alpha") predicts vasospasm faster than TCD or angiography
    • Alpha waves are seen in the electroencephalogram (EEG) during a normal wakeful state where the subject is quietly resting.
  • Dec. of total EEG wave amplitude is 91% sensitive for vasospasm

Alteration in CBF

  • MRI: DWI and PWI can detect early ischaemia
  • CT perfusion study
  • Xenon CT:
    • May detect large global changes in CBF,
      • But too insensitive to detect focal blood flow changes
    • Does not correlate with increased TCD velocities positron emission tomography (PET) or SPECT scans (nonquantitative, and takes longer than xenon studies)

PPV & NPV of various tests for cerebral vasospasm

Test
ㅤ
PPV (%)
NPV (%)
TCD
MCA
83-100
29-98
ㅤ
ACA
41-100
37-80
ㅤ
ICA
73
56
ㅤ
PCA
37
78
ㅤ
BA
63
88
ㅤ
VA
54
82
CTA
ㅤ
43-100
37-100
CTP
ㅤ
71-100
27-99

Changes that triggers intervention

  • Increase in either
    • TCD mean now velocity in the MCA (FVMCA) > 50cm/sec over 24hrs OR
    • Mean FVMCA of at least 200cm/sec or Lindegaard ratio of more than 6 or both
  • CT perfusion - CBF < 25ml/100g/min or mean transit time (MTT) >6.5sec or both
  • Severe angiographic vasospasm (narrowing of at least 70% from baseline) detected by DSA or CTA
  • EEG reduced alpha variability
  • Abnormal levels of brain oxygen (Pti02 < 20mmHg) or CMD (i.e. lactate/pyruvate ratio LPR >40) and glucose < 0.5mM and second line for glutamate >40 mM or both

Management

Prevention

General

  • No effective prophylactic intervention for CVS
  • Early treatment of aneurysm can actually inc risk of vasospasm
    • Manipulation of the vessel
  • Removal of clot can reduce the blood load → reduce spasm risk

Nimodipine

  • British aneurysm Nimodipine trial Pickard et al 1989
    • Class 1 evidence
    • Neuroprotective action by decreasing influx of Ca after cerebral ischaemia due to DCI
    • Decreases the incidence of microthrombi and antagonises Cortical Spread Ischaemia
    • Improves long term outcome of poor grade SAH cases
    • Can cause drop in MAP and CCP
    • Nimodipine does not counteract vasospasm
  • Cisternal nimodipine
    • NEWTON-2 Cisternal
      • Study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint
      • Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of microparticle formulation of nimodipine (EG-1962).

Statins: No use

  • Mech
    • Reduce inflammation,
    • Increase production of nitric oxide through upregulation of nitric oxide synthase
    • Prevent thrombogenesis
  • Meta analysis
    • Shen et al 2017
      • Statins significantly decreased the occurrence of vasospasm (on TCDoppler) after aneurysmal SAH.
      • The incidence of DIND, delayed cerebral infarction, and mortality were not affected by statin treatment.

Other drugs being investigated

  • Clazosentan – Endothelin A receptor antagonist
  • Fasudil – Rho kinase inhibitor
  • Statins
  • Magnesium – Ca channel antagonist
  • Dantrolene – inhibits ryanodine receptors
  • Intrathecal thrombolytics
  • Antiplatelet drugs
  • Albumin
  • Erythropoietin
  • Cilostazol – inhibits phosphodiesterase 3

DO NOT DO TRIPLE H THERAPY

  • Hypertense patients
    • HIMALAIA trial: very high MAP 130mmHg/SBP 230mmHg does not translate to better outcome and can cause more cardiac complications
    • Oppong 2002 et al:
      • MAP<95 mmHg, standard MAP [SMAP]) and over (MAP ≥ 95 mmHg, increased MAP [IMAP]) the maximal therapeutic target
      • IMAP beyond the therapeutic target independently correlated with unfavourable clinical and radiographic outcome of aSAH in individuals with cerebral vasospasm.
        • Not sure if it is confounded as when pt develop vasospasm you drive the MAP up
      • Blood pressure values did not show impact on the study endpoints in patients that did not develop vasospasm.
        • Showed no evidence of any benefit in driving BP above 90mmHg for patient who has no clinical vasospasm

DO NOT DO PROPHYLACTIC cerebral angioplasty

Treatment

  • If not treatment will progress to cerebral infarction

Changes that triggers intervention

  • Increase in either
    • TCD mean now velocity in the MCA (FVMCA) > 50cm/sec over 24hrs OR
    • Mean FVMCA of at least 200cm/sec or Lindegaard ratio of more than 6 or both
  • CT perfusion - CBF < 25ml/100g/min or mean transit time (MTT) >6.5sec or both
  • Severe angiographic vasospasm (narrowing of at least 70% from baseline) detected by DSA or CTA
  • EEG reduced alpha variability
  • Abnormal levels of brain oxygen (Pti02 < 20mmHg) or CMD (i.e. lactate/pyruvate ratio LPR >40) and glucose < 0.5mM and second line for glutamate >40 mM or both

Treatment decision tree

Vasospasm state
Description
Management
No vasospasm
Clinically intact
Normal TCD
Normotension: SBP>120/30% above baseline
NS 200ml/hr
Subclinical vasospasm
Clinically intact
High TCD (>200cm/s) or radiographic evidence of vasospasm
Arterial line
Pulmonary artery catheter
Check LVF: ECG/Echo/TropT for pt's with heart disease or old pt
Monitor complications of Triple H
Aim SBP>160mmHg
AIM PCWP12-14mmHg
NS 200-250ml/hr: if Na low give 0.45%NS
Start DDAVP if UO>200ml/hr 4hrsly
AIM Hct <35%
Clinical vasospasm
DIND
High TCD/radio evidence of spasm
Inc. SBP to max of 220mmHg for secured and 160mmHg for unsecured
Inc. PCWP to 18-21mmHg: monitor for pulmonary oedema
If not working: Consider cerebral angiography +/- angioplasty =/- intraarterial Verapamil
After all this let BP fall to a level without neurology then maintain BP there
  • DO NOT TX ANGIOGRAPHIC VASOSPASMs only
  • DO NOT USE Triple H THERAPY use hemodynamic augmentation instead
  • GOAL: maintain euvolaemia and normal circulating blood volume

Direct pharmacological dilation

  • Indication: Hypertension is not managing to control neurological deficit
Endothelin receptor antagonist
  • Clazosentan (Clazosentan to Overcome Neurological iSChemia and Infarct Occurring after Subarachnoid hemorrhage [CONSCIOUS-1/2/3])
    • Smooth-muscle 𝐸𝑇𝐴 receptor induces vasoconstriction
    • Endothelium 𝐸𝑇𝐵 receptor releases nitric oxide, resulting in vasodilation
    • Clazosentan is a selective 𝐸𝑇𝐴 receptor antagonist, for which an approximately 1000-fold higher affinity to the 𝐸𝑇𝐴 receptor than to the 𝐸𝑇𝐵 receptor
    • Increased rates of pulmonary complications, hypotension, and anemia.
    • Conscious 1
      • (1, 5, and 15 mg/h doses) produced a dose-dependent reduction in moderate or severe angiographic vasospasm, with a 65% relative risk reduction with the highest dose. this suggests that endothelin-1 plays an important role in the pathogenesis of angiographic vasospasm
    • Conscious 2
      • Randomised, double-blind, placebo-controlled, phase 3 study,
        • aSAH secured by surgical clipping to clazosentan (5 mg/h, n=768) or placebo (n=389) for up to 14 days
      • Lung complications, anaemia, and hypotension were more common with clazosentan.
      • Clazosentan at this 5mg (other doses had too many complications) had reduce vasospastic arterial narrowing, did not also reduce the incidence of poor outcome.
    • Conscious 3
      • Double-blind, placebo-controlled, phase III trial randomized patients with aSAH secured by endovascular coiling to ≤14 days intravenous clazosentan (5 or 15 mg/h) or placebo
      • Stopped prematurely
        • Recruitment was halted prematurely (October 2010) after completion of CONSCIOUS-2, in part because the 5 mg/h dose did not achieve its primary end point in clipped patients;
        • Also, this dose had a similar relative risk reduction in angiographic vasospasm in CONSCIOUS-1 as did the highest dose (15 mg/h) being tested in CONSCIOUS-3 in coiled patients.
          • Not ethical to continue using high dose in Consious 3 trial patients
      • 15 mg/h significantly reduced postaSAH vasospasm-related morbidity/all-cause mortality; however, neither dose improved outcome (extended Glasgow Outcome Scale).
Calcium channel blocker
  • Has more neuroprotective effect than vasospasm prevention by
    • Inc. RBC deformability —> improves viscosity
    • Prevention of calcium entry into ischemic cells which may mediate the injury from cerebral infarction
    • Has anti-platelet aggregating effect
    • Dilatation of collateral leptomeningeal arteries —> improves blood flow
  • Oral/IV:
    • Nimodipine:
      • Has preferential CNS action
      • Blocks L type Ca channel
      • Does not alter vasospasm
      • No statistical significant difference in mortality
      • But improved outcomes
      • No difference oral or IV route
    • Nicardipine
      • No improvements in outcome
  • Intra-arterial:
    • Can be done by angiographers who are not interventional radiologist
    • Effects are more short lived--> require repeated infusion
    • Nimodipine
      • Is used in the UK
    • Verapamil
      • 8mg over 2mins
    • Nicardipine
      • 10-40mg
      • Vascular smooth muscle > cardiac smooth muscle
      • Restores vessels to at least 60% of normal diameter.
      • 70% of those treated had no stroke on CT.
      • May cause a drop in SBP, but not > 30%
      • ℞ intra-arterial therapy: 10–40mg per procedure. Three retrospective case series have reported vessel dilation and transient improvement in neuro deficits.
  • Intrathecal
    • Nicardipine surgical implants (placed during clipping not for coiling):
      • Reduced the incidence of vasospasm and delayed ischemic
      • Improving clinical outcome after severe SAH
      • Studying being done to look at EVD infusion of nicardipine gel
  • Side effects
    • Systemic hypotension: tx with volume expansion
    • Renal failure
    • Pulmonary oedema
Ryanodine receptor blocker:
  • Dantrolene.
    • Mediates intracellular calcium release from the sarcoplasmic reticulum.
    • One of the few drugs shown to both prevent and reverse vasospasm
Magnesium
  • MASH-2 Mees et al 2012
    • Phase 3 randomised, placebo-controlled trial n 1204
    • Magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage
Sympatholytic
  • Noradrenaline
  • Phenylephrine
Intra-arterial papaverine
  • Inhibition Phosphodiesterase à dec. breakdown of cAMP and cGMP à inc. of cAMP and cGMP à inc. cGMP prot kinases à inhibit Ca entry into cell or inc. Ca uptake by reticulum à dec. intracellular Ca à vasodilation
  • Not used as can exacerbate vasospasm, cause thrombocytopenia and elevate ICP if not closely titrated
  • Short-lived
αICAM-1 inhibition
  • Antibody to intracellular adhesion molecule

Indirect pharmacological dilatation

  • Hemodynamic augmentation
    • Consisting of
      • Maintenance of euvolemia AND
        • Use fluids to maintain euvolemia
      • Induced arterial hypertension
        • Inducing HTN may be risky with an unclipped ruptured aneurysm
        • Administer pressors to increase SBP in 15% increments until neurologically improved or SBP of 220mm Hg is reached.
        • Agents include:
          • Beta agonist (1 st line)
            • Dopamine
              • Start at 2.5 mcg/kg/min (renal dose)
              • Titrate up to 15–20 mcg/kg/min
            • Dobutamine:
              • Positive inotrope
              • Start at 5 mcg/kg/min
              • Increase dose by 2.5 mcg/kg/min up to a maximum of 20 mcg/kg/min
          • Alpha agonist: Mainly used and when beta agonist don’t work
            • Neosynephrine (phenylephrine):
              • Does not exacerbate tachycardia
              • Start at 5 mcg/min
              • Titrate every 2–5minutes: double the rate up to 64 mcg/min, then increase by 10 mcg/min up to a max of 10 mcg/kg
            • Levophed (norepinephrine bitartrate)
              • Start at 1–2 mcg/min
              • Titrate every 2–5minutes: double the rate up to 64 mcg/min, then increase by 10 mcg/min
          • Prevent reflex bradycardia: atropine 1mg IM q3-4 hrs
      • Complications of hemodynamic augmentation:
        • Intracranial complications
          • May exacerbate cerebral edema and increase ICP
          • May produce hemorrhagic infarction in an area of previous ischemia
        • Extracranial complications
          • Pulmonary edema in 17%
          • 3 rebleeds (1 fatal)
          • MI in 2%
          • Complications of Pulmonary artery catheter:
            • Catheter related sepsis: 13%
            • Subclavian vein thrombosis: 1.3%
            • Pneumothorax: 1%
            • Hemothorax: may be promoted by coagulopathy from dextran
      • HTN failed if ischemic signs persist at systolic>220 mmHg or CPP > 120 mmHg
      • Monitoring
        • Urinary catheter
        • Arterial line
        • Pulmonary artery catheter
          • Monitor cardiac output
          • Monitor PCWP
        • Transcranial Doppler
        • Perfusion CT scan
  • ✖Triple H therapy: Hypertension, Hypervolemia, Hemodilution
    • Hypervolemia
      • Over filling the patient has no benefit
      • Normal saline/plasmolyte: 200-250 ml/hr
      • Aim
        • Central venous pressure between 8 and 10 mm Hg or a pulmonary capillary wedge pressure in the range of 14 to 16 mm Hg
      • Aggressive monitoring with transpulmonary thermodilution monitoring system is beneficial for poor grade patients
      • Do not perform hypervolemia in patients with massive edema or a large cerebral infarction
    • Hypertension
    • Haemodilution
      • Aim haematocrit =30%: transfuse if < 25%
      • Aim Hb >9
    • Outcome of triple H
      • 74% permanent neurological improvement occurred in
      • 16% No change. (7% had temporary improvement)
      • 10% deteriorated.
  • Cervical sympathectomy
    • To promote Dilation
    • Technique not generally used or no longer accepted

Endovascular mechanical dilation: transluminal balloon angioplasty (TBA)

  • Only feasible in large vessels
  • Clinical improvements in 70%
  • Indication
    • Failure of Hypertension to tx deficit
    • Ruptured aneurysm is secured
    • Optimal results when done within 12 hrs of onset of symptoms
    • May be done immediately post-clipping for vasospasm that was observed pre-op
    • Controversial use in:
      • Asymptomatic vasospasm seen on the contralateral side during angioplasty for ipsilateral vasospasm. Some would balloon the asymptomatic side, but others cite the complication rate and would observe
  • When to use TBA vs IAD
    • TBA: Generally reserved for grade III (51%-75%) or grade IV (>75%) proximal vessel vasospasm
  • CI: CVA
    • ✖ recent cerebral infarction (stroke): a contraindication to TBA. Prior to TBA, perform CT or MRI to rule out
  • Complication
    • Arterial occlusion
      • PTA in the proximal anterior and proximal posterior cerebral arteries must be performed cautiously because these vessels are relatively deficient in tunica media and elastic tissue, which theoretically makes them more prone to rupture.
    • Arterial rupture
    • Displacement of aneurysmal clip
    • Arterial dissection
  • Technique
    • Advance the guide catheter into the ICA or VA
    • Deliver 10 to 20 mg of verapamil over the course of 2 minutes, while monitoring for hypotension.
    • Move to the next vessel in the diagnostic study.
    • After examining all vessels, we assess the effect of verapamil on the treated vessels and decide whether angioplasty is also needed
    • When diagnostic findings show that vasospasm is severe enough to warrant PTA, we first anticoagulate the patient with heparin and then proceed to position the balloon microcatheter within the affected vessel.
    • When severe vasospasm makes PTA technically difficult because of inadequate luminal diameter, we administer verapamil and wait 15 to 20 minutes to achieve enough vasodilation to attempt the angioplasty.
  • Outcome:
    • No RTC
    • Repeat angioplasty was required in only 3% to 4% of patients.

Endovascular pharmacological dilation by intra-arterial drug (IAD) injection

  • Pros
    • Vasodilatory effects
      • Shorter-lived
      • Less profound at their peak than with angioplasty.
    • Can be repeated, this requires multiple arterial catheterizations.
    • Help open up vessels to allow placement of the angioplasty balloon, and for vessels inaccessible to angioplasty balloons.
    • Can target smaller vessel as angioplasty only can direct proximal vessels only
  • Cons:
    • Short acting only
  • Agents currently used for chemical spasmolysis:
    • Nimodipine
    • Verapamil: the primary drug employed
    • Nicardipine
    • Papaverine:
      • ✖multivessel infusions of papaverine à inc. of cerebral blood volume à Inc. ICP
    • Nitroglycerine

Removal of potential vasospasmogenic agents

  • Blood clot removal
    • Does not completely prevent vasospasm
    • Methods
      • While clipping
      • Subarachnoid irrigation
        • With
          • Thrombolytic agents at the time of surgery OR
          • Post-op through cisternal catheters (must be initiated within ≈ 48 hrs of clipping) or intrathecally.
        • Hazardous with incompletely clipped aneurysm
        • SAH different from ICH but CLEAR-2 study which showed no difference between tPA vs Normal saline
  • CSF drainage:
    • Tomita et al 1986
      • Un controlled cohort study (Level 4) N=38
      • Via serial lumbar punctures, continuous ventricular drainage, or postoperative cisternal drainage
      • More you drain the CSF the lesser symptomatic Vasospasm (not defined)

Protection of the CNS from ischemic injury

  • Calcium channel blockers
  • NMDA (N-methyl-D-aspartate) receptor antagonists eg ketamine: causes more death
  • Free radical scavengers:
    • Tirilazad mesylate: did not show benefit in most except poor grade pt (post-hoc)

Balancing blood viscosity to prevent spasm and also allow good O2 supply

  • Hct: 35%
    • A good compromise between lowered viscosity without overly reducing O2 carrying capacity (hemodilution is used to lower Hct; phlebotomy is not used)
  • By
    • Fluid dilution
    • Others
      • Plasma
      • Albumin,
      • Low molecular weight dextran (technique not generally used or no longer accepted)
      • Perfluorocarbons (experimental or research technique with potential for future application)
      • Mannitol