Intraventricular Nicardipine in Subarachnoid Hemorrhage

Dose (intraventricular):

  1. nicardipine 4mg q12h until TCDs normalize [NSUH]
  2. nicardipine 2 mg q8h x 10d
  3. nicardipine 4mg q12h x 5-17d [1]
  4. withdraw CSF (same amount as to be  infused); nicardipine 4mg in 2 ml preservative-free saline through EVD q8-12h; clamp drain x 30 minutes then reopen [3]

Intrathecal nicardipine shown to significantly dilate spastic basilar arteries on day 7 in a canine model of vasospasm

In one study, IT nicardipine decreased incidence of symptomatic vasospasm by 26%, angiographic vasospasm by 20% and improved clinical outcome at one month by 15%.

Main side effects:  headache, meningitis

Mechanism of Vasospasm:  unknown, but possibly due to presence of oxyhemoglobin and bilirubin oxidation products in subarachnoid space.  This reduces activity of endogenous vasodilators (s.a. nitric oxide, prostacyclines) and increases the activity of endogenous vasoconstictors (i.e., endothelins).  The net result is an increase in vascular smooth muscle contraction and narrowing of the cerebral vessels.

How nicardipine works:  dihydropiridine CCBs (nimodipine and nicardipine) affect L-type slow-conducting calcium channels on vascular smooth muscle.

Notes:

  1. 1989, FDA approved nimodipine for reduction of cerebral infarction and improvement of outcome following SAH
  2. Cooperative Aneurysm Study – nicardipine gtt (0.15 mg/kg/h) x 14 days; decrease in symptomatic vasospasm vs placebo (32% vs 46%); angiographic vasospasm and elevations of Vm by TCD (>120 cm/s) significantly lower; no difference in outcome at 3 months
  3. significant hypotension reported in nicardipine group (34.5% vs 17.5%) – possibly negated the beneficial effects on outcome
  4. 1980s – attempts to isolate effects of nicardipine to cerebral vasculature –> administer within CSF space
    1. intrathecal administration of nicardipine relieved angiographic vasospasm in canine subarachnoid hemorrhage models
    2. Shibuya et al. – prophylactic intracisternal nicardipine via cisternal drains [2]
      1. 26% decrease in symptomatic vasospasm
      2. 20% decrease in radiographic vasospasm
      3. 15% increase in good clinical outcome at 1 month compared to historical controls
    3. Suzuki et al – 177 patients, 4 mg of nicardipine via cisternal drains; lacked control group
      1. good outcome or only moderate disability in 89.2%
      2. rate of angiographic vasospasm of 11.3%
      3. rate of symptomatic vasospasm of 5.7%
    4. Goodson et al. and Ehtisham et al – successful experience with intraventricular administration of nicardipine in vasospasm refractory to conventional treatments

References

[1] Goodson, Kelly et al. ‘Intraventricular Nicardipine For Refractory Cerebral Vasospasm After Subarachnoid Hemorrhage’. Neurocritical Care 8.2 (2007): 247-252. Web.

[2] Shibuya, M. et al. ‘Effects Of Prophylactic Intrathecal Administrations Of Nicardipine On Vasospasm In Patients With Severe Aneurysmal Subarachnoid Haemorrhage’. Acta neurochir 131.1-2 (1994): 19-25. Web.

[3] Webb, Adam et al. “The Effect Of Intraventricular Administration Of Nicardipine On Mean Cerebral Blood Flow Velocity Measured By Transcranial Doppler In The Treatment Of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage”. Neurocritical Care 12.2 (2009): 159-164. Web. 14 Dec. 2015.

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