• vasospasms (VSPs) in subarachnoid hemorrhage (SAH) are provoked by blood in the subarachnoid space. The breakdown products lead to changes in the arterial wall involving cytokines, inflammatory response, free radical production, and others ⇒ arterial contraction or structural changes with thickening of the vessel wall [Dorsch, 1995].
  • VSPs typically appear on days 3-4, peaking on days 5-9, and may persist for up to 3-4 weeks
    • when detected < 3 days after SAH, a prior episode of bleeding should be assumed
  • VSPs occur in up to 70% of SAH patients (usually in the artery with the ruptured aneurysm);  about 1/3-1/2 are symptomatic, leading to Delayed Ischemic Deficit (DID). DID is the leading cause of neurological impairment (focal deficits, encephalopathy) and mortality in SAH patients [Dorsch, 2002]
  • patients at increased risk for developing spasms are characterized by:
    • younger age
    • greater volume of blood in the subarachnoid space (see Fisher grade)
    • poor baseline clinical status (higher Hunt-Hess score)
    • delayed initiation of treatment
  • early detection and appropriate treatment of VSP can prevent or minimize the development of DID
Vasospasms in subarachnoid hemorrhage
  • a clinical syndrome manifested by cognitive changes and/or focal neurological impairment lasting ≥ 1 hour and/or cerebral infarction
  • present in approximately 30% of patients with SAH  (Yamaki, 2019)
  • multifactorial etiology
    • vasospasms (VSP)
    • intracranial hypertension, cerebral edema, and impaired vascular autoregulation
    • presence of cortical spreading depression leading to microvascular dysfunction
    • microthrombosis due to activation of the coagulation cascade and inhibition of the fibrinolysis (microemboli are detectable by TCD/TCCD)
  • other causes of clinical deterioration should be excluded (rebleeding, hydrocephalus, intracranial hemorrhage, NCSE, etc.)

Vasospasms Classification

  • clinical symptomatology
    • asymptomatic
    • symptomatic
  • extent
    • diffuse
    • segmental
      • isolated
      • multifocal
  • localization
    • proximal
    • distal
  • time from the SAH onset
    • early
    • delayed

Clinical presentation

  • worsening of headache and neck stiffness
  • confusion, disorientation, decreased consciousness
  • late onset of neurological impairment (hemiparesis, dysarthria/aphasia, visual disturbances)
  • seizures
  • fever

Vasospasms detection


  • TCD/TCCD allows repeated bedside monitoring  ( → TCCD diagnosis of vasospasms)
    • in vasospasms (VSP), a typical velocity increase > 50 cm/s or 25%/24h can be detected
  • progression of intracranial hypertension can also be monitored → see here


  • non-contrast computed tomography (NCCT) excludes recurrent bleeding, obstructive hydrocephalus, or progression of cerebral edema
  • CT angiography (CTA) shows the extent and severity of vasospasm  Diffuse vasospasms in both MCAs and ACAs
  • CT perfusion (CTP) allows assessment of the risk of DID
    • a prolonged transit time (TTP, MTT) is observed in the territory of the affected artery
    • in severe cases, there is a decrease in regional perfusion (CBF) or blood volume (CBV) → a pattern of ischemic injury  Vasospasm on CTA with hypoperfusion demonstrated by CT perfusion    [Binaghi, 2007]
  • MRI outperforms CT in the evaluation of vasospasm-induced ischemia (DWI sequence) and small hemorrhage detection (GRE/SWI sequence)
  • MR angiography (MRA) and MR perfusion (MRP) detect VSPs and help assess their hemodynamic significance  MCA vasospasm on MRA


  • considered the “gold standard”
  • the typical finding on DSA is segmental arterial narrowing
  • detection of vasospasms in peripheral, less easily visualized vessels remains a limiting factor
Vasospasm on DSA


  • an individualized approach is required
  • consider these factors:
    • severity of the vasospasm
    • presence of significant hypoperfusion in the distal circulation
    • dynamics
    • number and location of VSPs (focal or diffuse, single or multiple)
    • signs of hyperperfusion
    • signs of intracranial hypertension
    • clinical status

Maintaining Cerebral Perfusion

  • effect of 3H therapy (Hypertension, Hypervolemia, and Hemodilution) is not proven
    • a review of controlled trials showed no beneficial  effect of 3H therapy or its components on increasing cerebral blood flow (CBF) [Dankbaar, 2010]
  • maintain normovolemia with central venous pressure (CVP) at 10-12 cm H2O (mm Hg) or pulmonary artery wedge pressure (PAWP) at 14-20 mmHg
  • maintain hematocrit at 30-35% to optimize blood viscosity
  • systolic blood pressure (SBP) should be maintained at ≤ 130-140 mmHg preoperatively and 150-175 mmHg postoperatively
  • administer inotropes and vasopressors if mean arterial pressure (MAP) is < 90 mm Hg

Drug therapy

  • nimodipine and cilostazol are likely the most effective treatments for preventing morbidity and mortality  (Dayyani, 2022)
  • clazosentan, nicardipine, and magnesium have beneficial effects on delayed cerebral ischemia and vasospasm, but they were not found to reduce mortality/disability (Dayyani, 2022)
Ca2+ blockers


(Dilceren / Nimotop) vial 10mg/50mL (1mg /5mL); or 30 mg/ tablet

  • calcium channel blocker recommended by AHA/ASA guidelines
  • nimodipine reduces the incidence of ischemic neurological deficits and improves overall outcomes; however, the protective effect in vasospasm is not proven
  • PO nimodipine – 6 x 60 mg (2 tablets) for ~ 21 days –  there is no evidence of greater efficacy of parental administration
    • if the capsule cannot be swallowed, pierce both ends of the capsule with a needle and aspirate the contents into a syringe. Empty the contents into the patient’s nasogastric tube and flush with 30 mL of normal saline (0.9%)
  • IV nimodipine
    • start IV infusion at a rate of 1 mg(5mL)/hour  for the first 2 hours (watch for hypotension and tachycardia); if well tolerated, increase the rate to 2 mg (10mL)/hour
    • when administered into a peripheral vein, concurrently administer normal saline
    • protect infusion set from direct sunlight; in diffused daylight/artificial light, nimodipine may be used for up to 10 hours without special protection
    • combine with vasopressors if hypotension persists
    • use parenteral administration only for a few days, then switch to oral for another 7-21 days
Phosphodiesterase inhibitors

(Milrinone / Primacor / Asicord) usually 1 mg/1mL


  • PDE-III inhibitor with inotropic, lusitropic, and vasodilatory properties
  • 200 μg/mL in 5% Dextrose – 100 or 200 mL Flexible Containers
  • continuous intravenous infusion
  • initially start at 0.5 μg/kg/min, incrementally increase to 1.5 μg/kg/min [Fraticelli, 2008]
    • the dose is doubled compared to doses used in heart failure patients (max 0.75 μg/kg/min)
    • stop dose increase if the heart rate exceeds 100 /min or BP drops by > 20%
  • administer for 14 days
  • renal impairment requires dose reduction:
    • CrCl <50 mL/min: 0.43 μg/kg/min
    • CrCl <40 mL/min: 0.38 μg/kg/min
    • CrCl <30 mL/min:  0.33 μg/kg/min
    • CrCl <20 mL/min:  0.28 μg/kg/min
    • CrCl <10 mL/min:  0.23 mμg/kg/min


(Cilostazol / Pletal)  50 or 100 mg/tablet


  • selective inhibitor of phosphodiesterase 3 may attenuate cerebral vasospasm due to its antiplatelet and vasodilator effects
  • dose: 100 mg twice daily
  • effective in preventing cerebral VSP with a low risk of severe adverse events  (Senbokuya, 2013)
  • significant reduction of VSPs (50 vs. 77%) and reduction of symptomatic VSPs (13 vs. 40% !) was reported



  • dilute before IV administration
  • 1-2 g (2-4 mL) + 100 ml of D5W, infusion rate ≤ 3 mL/min (⇒ 30 min infusion)
    • should not be administered parenterally to patients with AV block or myocardial damage
  • magnesium is a neuroprotective agent that acts as an N-methyl-D-aspartate (NMDA) receptor antagonist and a calcium channel blocker
    • hypomagnesemia is associated with a higher incidence of VSP and a worse prognosis  [Van den Bergh, 2005]
    • some authors report better results with IV administration of Mg2+ 500 mg daily compared to milrinone [Soliman, 2019]
    • a larger multicenter phase III trial found no significant difference at six months between patients treated with magnesium or placebo  [Wong, 2010]
  • monitor magnesium levels and maintain normal or slightly elevated serum Mg2+ levels   [Westermaier, 2010]  [Ma, 2010]
  • statins or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors may reduce the incidence of VSP and DID by reducing inflammation and improving endothelial function
  • clinical trials and meta-analyses provide mixed results
  • continue statin therapy if the patient is already taking them
  • prophylactic use of statins for aneurysmal SAH (aSAH) is not recommended
    • STASH trial showed no benefit of using  40 mg of simvastatin for long-term or short-term outcomes in patients with aSAH
  • further randomized controlled trials are needed to evaluate the safety and efficacy of statins in this context
Endothelin receptor antagonists (ET1)


  • experimental therapy; may reduce the risk of vasospasm, but no clinical benefit has been demonstrated
    • CONSCIOUS 1 and CONSCIOUS 2 trials – clazosentan reduced the risk for vasospasm after aSAH but did not improve functional outcomes
    • REACT trial (phase 3) – clazosentan failed to meet the primary endpoint of preventing clinical deterioration due to delayed cerebral ischemia in patients with aSAH

Percutaneous angioplasty (PTA), local application of vasodilators

  • PTA should only be considered for symptomatic vasospasms after failure of conventional therapy
  • PTA results in mechanical disruption of the spasm; the effect is long-lasting
    • alteration of myocyte structure
    • disruption of collagen in the vessel wall
  • can be performed in proximal VSPs (siphon, M1, A1, V4, AB, and P1); the procedure is associated with frequent complications (vessel rupture, dissection, or occlusion)
  • the best clinical effect can be expected in patients with an initial Hunt-Hess score of 1-3 who are treated within 2 hours after the onset of clinical symptoms of vasospasm (improvement in up to 80%) [Zubkov, 1994]
    • CT perfusion may be used for appropriate patient selection
    • procedure should be performed in patients with large penumbra and a small core
    • in the presence of a large core, the effect cannot be expected, and the risk of hemorrhagic transformation is high
  • PTA in the presence of an untreated aneurysm increases the risk of rebleeding; it is advisable to treat the aneurysm first
    • if the aneurysm cannot be treated because of spasms, local vasodilators should be used instead of PTA
  • angioplasty may be combined with local application of vasodilators; dosing is not standardized and mostly based on case reports and small cohorts
    • appropriate for diffuse or distal involvement
    • short-term effect compared with angioplasty
    • papaverine is no longer used (as it induces systemic hypotension and precipitates with heparin (may cause microembolization)

(Dilceren / Nimotop) usually 1 mL/0.2 mg


  • IV:  1-2 mg/h (5-10mL/h) by continuous infusion + 10 ml/h NS concomitantly
    • AEs: hypotension, tachycardia
    • combine with vasopressors in case of hypotension
    • parenteral administration is not more effective than oral administration in preventing vasospasm
    • infusion pumps with polyethylene tubing and needles with polyethylene handles (or all-metal) must be used, infusion solution is light sensitive, must not be used in direct sunlight
  • IA:  50 mL (10mg) + 50mL NS (to get 10% solution; 10mL containing 1mg)  … IA infusion 1mL/min (0.1mg /min)
    • 0.5-2 mg into a single artery, total max dose 5 mg   [Kim,2009]

(Verapamil / Isoptin / Lekoptin)  usually 1mL/2.5 mg


  • IA:   bolus 1-3 mg (or 44 μg/kg) locally  [Feng,2002] 
  • AEs: hypotension, bradycardia



  • IA:  0.5-2 mg as a slow bolus

(Asicord / Primacor)


  • IA: 1mg/ml  –  0.25 mg/min – infused for 30 minutes
  • regression of vasospasm with combined IA and subsequent IV administration has been reported  [Arakawa, 2001]  [Fraticelli, 2008]
  • IV administration alone seems to be effective  [Crespy, 2019]

(Magnesium sulfate)  usually 1mL/40 mg or 1mL/80mg


  • IA: 10mL (1g) + 28 mL NS …. 0.25-1 g per artery  [Shah, 2009]
    • may be used in combination with nicardipine (2.5-20.0 mg/h for 30-60 min)
    • magnesium is believed to inhibit cerebral vasospasm by causing smooth muscle relaxation and vasodilation by mechanisms similar to the calcium channel antagonists
  • IV: a large phase III study showed no significant benefit in cerebral vasospasm prevention or improved favorable outcomes when administered via IV infusion (Wong, 2010)

(Papaverine hydrochloride)  1mL/30mg


  • IA:  300mg (10 mL) + 100mL of NS (solution concentration is < 3mg/mL)  …. IA infusion 3mL/min for 30 minutes or 1.3 mL/min for 60 minutes [Kassel, 1992][Clouston, 1995] 
  • usually not used due to AEs
Angioplasty for proximal MCA vasospasm

Thrombolytic therapy

  • meta-analysis suggests a clinically relevant beneficial effect of subarachnoid clot lysis achieved by intracisternal tPA injections  (Amin-Hanjani, 2004]
    • ARR of 14.4% for delayed ischemic neurological deficit
  • therapy is associated with an increased risk of intracranial bleeding
  • clinical trials are needed to determine the safety and efficacy of this approach

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Vasospasms after subarachnoid hemorrhage
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