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.


  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


Multiple dosing regimens and preparations have been used in the administration of intrathecal nicardipine. Initial studies used 4 mg nicardipine diluted in 10 mL of 0.9% normal saline delivered through a cisternal drain. More recent studies have used the same dosage in a smaller dilution volume of 2 mL of 0.9% normal saline to minimize the volume injected intrathecally. Because the more recent series involved intraventricular administration via the external ventricular drain (EVD), one can speculate that a smaller dilution volume was used to decrease chemical irritation to the ependymal surface of the ventricles and maximize delivery. Goodson et al. proposed a more concentrated preparation in which premixed nicardipine hydrochloride 4 mg/1.6 mL solution was mixed with preservative-free 0.4 mL sodium chloride to yield a total volume of 2 mL. Other reported dosages and frequencies have ranged from 2 to 4  mg every 6–12  h, the most commonly reported regimen being 4 mg every 12 h. Reported duration varies from as little as one to two injections during maximal cerebral vasospasm up to 10 days of treatment when administered in a prophylactic manner. [4]

The cumulative ventriculostomy-associated infection risk was 6%. Intrathecal nicardipine injections for aSAH-related cerebral vasospasm appears efcacious and safe. Administration of 4 mg of nicardipine every 12 hours was the most commonly reported dosing regimen. Intrathecal nicardipine decreases mean flow velocities on transcranial Doppler and reduces angiographic and clinical vasospasm. [4]


[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.

[4] Hafeez, S., et al. Systematic Review of Intrathecal Nicardipine for the Treatment of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage

The Alpha Delta Ratio in Subarachnoid Hemorrhage

cEEG protocol from one of the studies on Alpha Delta Ratio in SAH:

  1. start CEEG monitoring after aneurysm secured and within 5 days of onset
  2. use 8 electrodes: international 10–20 system: F4, T4, P4, O2, F3, T3, P3, O1 + 1 ground electrode (Fz) and 1 reference electrode (Cz)
  3. continue EEG while in ICU, or stop when patient develops scalp irritations, or did not tolerate electrodes
  4. for sedated patients, use first EEG epoch at least 2 h off sedation
  5. take regular short (30 min) EEG recordings after ICU discharge
  6. restart cEEG recording if patient readmitted to ICU

Example of changes that occurred as a result of DCI


EEG analysis:

  1.  EEG data filtered between 0.5Hz and 35 Hz, fragmented into epochs of 1h each
  2. of each epoch, 5 consecutive minutes containing least amount of artifacts selected
  3. power spectral densities estimated using Welch’s method from which 12 qEEG features were calculated
  4. Total power calculated for all individual EEG channels represents the power of the isgnal between 1-30 Hz, frequency bands were calculated as a ratio of total power
  5. alpha/delta ratio and alpha-beta/delta-theta ratio (ABDTR) calculated from the frequency bands
  6. spectral edge frequency x – frequency below which x percent of total power of given signal located; SEF75 and SEF90 used as qEEG features
  7. asymmetry of EEG calculated by comparing power of channels on L to the R
  8. Bispectral index (BSI) calculated in the frequency range 1-7Hz (BSI slow) and 7-25 Hz (BSI fast)

Article suggests further studies:

Live qEEG feedback can be compared to clinical performance and more detailed information regarding the gain in therapeutic window can be obtained. Furthermore, if qEEG monitoring and automatic analyses provide a reliable indication of DCI development, a study in which therapeutic interventions are guided by qEEG parameters would be of great interest.


Rots, M. L. et al. ‘Continuous EEG Monitoring For Early Detection Of Delayed Cerebral Ischemia In Subarachnoid Hemorrhage: A Pilot Study’. Neurocritical Care (2015): n. pag. Web. 11 Nov. 2015.

Neuromuscular Blocking Agents

Cisatracurium (Nimbex)

  • nondepolarizing neuromuscular blocker
  • metabolized by plasma ester hydrolysis and Hofmann elimination
  • best choice in both hepatic and renal dysfunction


  • long acting
  • contraindicated in CAD (vagolytic effect, tachycardia)


  • intermediate acting (30 minutes)
  • cleared by the kidney and liver


  • rapid onset and intermediate duration
  • better choice for short procedures

Neuromuscular Blocking Agents Pediatric Emergency Medicine Practice en_a09t03


ENLS 2017 Pharmacotherapy. Neurocritical Care Journal.