Equations for Phenytoin Dosing and Monitoring

#1.  loading dose for subtherapeutic phenytoin concentration:



#2. adjust for renal disease



#3. adjust for hypoalbuminemia



#4. adjust in elderly and critically ill with hypoalbuminemia




**Vd = volume of distribution (0.5-1 L/kg)



Tesoro, E. P. and G. M. Brophy. “Pharmacological Management Of Seizures And Status Epilepticus In Critically Ill Patients”. Journal of Pharmacy Practice 23.5 (2010): 441-454.

**Thanks to Benjamin Wee (Clinical Pharmacist @ Lenox Hill Hospital) for giving me this resource.

Minocycline in Moyamoya Bypass Surgery

Dosage used in the study:

  • intraoperative and postoperative IV minocycline hydrochloride (200 mg/d) until 4 days after surgery



  • semisynthetic tetracycline
  • clinically used as an antibiotic and anti-inflammatory drug
  • Neuroprotection:
    • neuroprotective potential reported in animal models of cerebral ischemia
    • reduces infarction size in rats due to the prevention of inflammatory reactions by suppressing microglial activation, down-regulating proinflammatory cytokines, and blocking MMP expression
    • prevents reperfusion-related ICH by blocking MMP-9 in mice
    • neuroprotective role as an antiapoptotic agent and antioxidant
  • Mechanism in ischemia-reperfusion injury
    • maintains BBB? –> reducing risk of vasogenic edema and hemorrhagic convesrion?
    • Moyamoya patients have higher expression of MMP-9 –> can perioperative minocycline prevent surgical complications (cerebral hyperperfusion or ischemia)




Proposed mechanisms:

  1. Minocycline blocks MMP-9, prevents neurological deterioration due to cerebral hyperperfusion.
  2. Minocycline compensated for deleterious effect of BP lowering by protecting contralateral and/or remote brain


Higher risk of reperfusion injury in Moyamoya due to

  1. poor network formation of pial arteries –> poorer hemodyamic distribution after revascularization
  2. fragile peripheral pial artery (thin media and internal elastic lamina) in Moyamoya disease
  3. increased expression of VEGF and MMP-9


Study conclusion:

The administration of minocycline in combination with strict blood pressure control could represent secure and effective postoperative management for the prevention of symptomatic CHP after STA-MCA anastomosis for MMD.



  1. small number of patients who developed focal deficits
  2. heterogenous group
  3. no data on preoperative hemodynamic status – no SPECT stress testing
  4. CBF studies performed under different institutions
  5. did not measure MMP-9 levels




Fujimura, Miki et al. “Minocycline Prevents Focal Neurological Deterioration Due To Cerebral Hyperperfusion After Extracranial-Intracranial Bypass For Moyamoya Disease”. Neurosurgery74.2 (2014): 163-170.



Tranexamic Acid in SAH


TXA Dose: tranexamic acid 1 g IV every 6 h not exceeding 48–72 h


Neither aminocaproic acid nor tranexamic acid is approved by the US Food and Drug Administration for prevention of aneurysm rebleeding.

AHA/ASA (2012)

For patients with an unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications, shortterm (<72 hours) therapy with tranexamic acid or aminocaproic acid is reasonable to reduce the risk of early aneurysm rebleeding (Class IIa; Level of Evidence B). (Revised recommendation from previous guidelines)

NCS (2011)

An early, short course of antifibrinolytic therapy prior to early aneurysm repair (begun at diagnosis; continued up to the point at which the aneurysm is secured or at 72 h post-ictus, whichever is shorter) should be considered (Low Quality Evidence; Weak Recommendation). •

Delayed (>48 h after the ictus) or prolonged (>3 days) antifibrinolytic therapy exposes patients to side effects of therapy when the risk of rebleeding is sharply reduced and should be avoided (High Quality Evidence; Strong Recommendation). •

Antifibrinolytic therapy is relatively contraindicated in patients with risk factors for thromboembolic complications (Moderate Quality Evidence; Strong Recommendation). •

Patients treated with antifibrinolytic therapy should have close screening for deep venous thrombosis (Moderate Quality Evidence; Strong Recommendation). •

Antifibrinolytic therapy should be discontinued 2 h before planned endovascular ablation of an aneurysm (Very Low Quality Evidence; Weak Recommendation). •




Connolly, E. S. et al. “Guidelines For The Management Of Aneurysmal Subarachnoid Hemorrhage: A Guideline For Healthcare Professionals From The American Heart Association/American Stroke Association”. Stroke 43.6 (2012): 1711-1737.

Diringer, Michael N. et al. “Critical Care Management Of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations From The Neurocritical Care Society’S Multidisciplinary Consensus Conference”. Neurocritical Care 15.2 (2011): 211-240.

Sakusic, Amra and Alejandro A. Rabinstein. “Case Studies In Neurocritical Care”. Neurologic Clinics34.3 (2016): 683-697.



TCD Acoustic Windows

Two Scanning Planes: 

  1. Axial scan
    1. Mesencephalic view
      1. Probe parallel to zygomatic arch
      2. Identify midbrain (“butterfly”) at about half of the scanning plane
      3. Can identify Pcomm in 75%
    2. Diencephalic view
      1. Tilt transducer 10degrees up
      2. Identify III ventricle, then posteriorly the pineal gland (hyperechogenic) and anteriorly the thalamus and internal capsule
      3. Identify lateral ventricles
  2. Coronal scan
    1. Rotate probe 90degrees from axial position
    2. Identify III ventricle, lateral ventricles, thalamus, internal capsule
    3. Useful for assessment of midline shift


Four TCD Acoustic Windows:b9781437714173000127_f12-01-9781437714173

  1. Temporal window
    1. Above zygomatic arch, anterior to tragus
    2. Axial plane, mesencephalic view
    3. Divided into anterior, middle and posterior zones
    4. Identify MCA (M1, M2), A1, P2, P2, C1 of carotid siphon, Acomm and Pcomm, distal end of BAni_2014_62_5_510_144443_f4
  2. Occipital window
    1. Probe on median sub-occipital line
    2. Patient sitting or lying down with head turned to opposite direction, chin lowered toward shoulder
    3. US beam passes through foramen magnum
    4. Visualize intracranial segment of vertebral arteries and basilar trunk
    5. Y shape, with flow moving away from probe
    6. Slight lateral movements to display both AICA, PICA
  3. Orbital window
    1. Transducer perpendicular to eyelid, patient’s eyes closed, looking opposite probe
    2. Insonate ophthalmic artery, C2, C3, C4 carotid siphon
    3. Potential retinal injuries – reduce power by 10-15%
  4. Submandibular window
    1. Transducer underneath angle of mandible in front of masseter muscle, probe toward skull
    2. Allows terminal segment (C5, C6) of ICA and C1 segment of carotid siphon


MCA: depth of 4.5-6.0cm, blood flow toward probe

Identify sphenoid bone (butterfly wing sign)



D’Andrea, Antonello et al. “Transcranial Doppler Ultrasonography: From Methodology To Major Clinical Applications”. World Journal of Cardiology 8.7 (2016): 383.


FASTHUG is a checklist developed by intensivists to ensure that key aspects of care are addressed during rounds.  The mnemonic FASTHUG stands for:

  • F = Feeding
  • A = Analgesia
  • S = Sedation
  • T = Thromboembolic prophylaxis
  • H = HOB elevation
  • U = Stress ulcer prophylaxis
  • G = Glucose control

This checklist however, does not address pharmacotherapy issues, and has been modified by clinical pharmacists to FASTHUG-MAIDENS.  FASTHUG as above, except for H which was changed to mean Hyperactive or hypoactive Delirium.  MAIDENS stands for:

  • Medication reconciliation
  • Antibiotics 
  • Indications for meds
  • Drug dosing
  • Electrolytes, Hematology and other lab tests
  • No drug interactions, allergies, duplication or side effects
  • Stop dates



Masson, Sarah C et al. “Validity Evidence For FASTHUG-MAIDENS, A Mnemonic For Identifying Drug-Related Problems In The Intensive Care Unit”. The Canadian Journal of Hospital Pharmacy 66.3 (2013).

Hyponatremia Protocol

Na <133 mEq/L or a decrease of 6 mEq/L in 24 to 48 hours:

  1. NaCl tabs 3 g PO/NGT q6h
  2. Start 3%NaCl at 20 mL/h
  3. BMP q6h

Na <130:
Increase rate by 20 mL/h (max rate = 80 mL/h)
If on hold at present, initiate 3 percent NaCl infusion at 20 mL/h IV

Na = 130-135:
Increase rate by 10 mL/h (max rate = 80 mL/h)
If on hold at present, initiate 3 percent NaCl infusion at 10 mL/h IV

Na = 136-140:
No change

Na ≥140:
Hold infusion



Woo, Carolyn H. et al. “Performance Characteristics Of A Sliding-Scale Hypertonic Saline Infusion Protocol For The Treatment Of Acute Neurologic Hyponatremia”. Neurocritical Care 11.2 (2009): 228-234. Web.

Lindegaard Index

V MCA : VICA ratio

Lindegaard Index: differentiates vasospasm vs hyperemia

  1. MCA
    1. ratio between intracranial velocity and external carotid artery flow velocity
    2. >3 = vasospasm, ❤ hyperemia
  2. Vertebrobasilar artery
    1. ratio between basilar artery and extracranial vertebral artery
    2. >2 with elevated velocity in basilar = vasospasm

Indications of severe narrowing in TCDs:

  1.  BFV >200 cm/s
  2. rapid rise in flow velicities (>50cm/sec/day)
  3. Lindegaard ratio (VMCA:VICA) >6 (severe)

Best Doppler parameter = peak systolic velocity – threshold of 182 cm/s corresponds to maximal diagnostic accuracy

Lindegaard: differentiate high intracranial flow velocities associated with hyperemia from those with BFV increase from VSP

overall accuracy better than velocity measurements alone

3.6 appears to be threshold to diagnose mild spasm (<25% narrowing) in M1 segment whereas 4.4 indicates moderate to severe spasm (>25% narrowing)



Sn 42% Sp 76% for ACA when 120 cm/sec used as threshold for ACA spasm

TCCS threshold of 75cm/s mean BFV associated with Sn 71% and Sp 85%

V ACA : V ICA ratio can be helpful to differentiate spasm from the normal artery; the ratio VACA : V ICA varies between 0.54 and 2.55


Other Vessels:

few published data on TCD diagnosis of ICA, PCA, VA, BA spasm

sensitivity = 25%, 48%, 44%, and 77%

specificity = 91%, 69%, 88%, and 79%

Sn / Sp greater for BA spasm when ratio  of mean BFV in BA vs extracranial VA is used, with threshold at >2; Sn 100% Sp 95%

Normal reference ranges V PCA : V VA (0.76-2.90)

TCD is not useful to detect VSP in more distal branches. Data lacking.



Le Roux, Peter D, Joshua M Levine, and W. Andrew Kofke. Monitoring In Neurocritical Care. 1st ed. Philadelphia, PA: Elsevier/Saunders, 2013. Print.

Miller, Ronald D. Miller’s Anesthesia. 8th ed. 2015. Print.

EVD Weaning Protocols

10cm H20 prior to weaning

Initiation of weaning left to discretion of attending neurosurgeon.


  1. raise drain height by 5 cm q24h to final level of 25 cm H20
  2. on Day 4, close the drain
  3. reopen if:
    1. ICP>20mm H20 x >5 minutes
    2. neurologic deterioration
    3. CT next day shows hydrocephalus

RAPID WEANING (within 24 hours)

  1. close drain immediately
  2. reopen if:
    1. ICP>20mm H20 x >5 minutes
    2. neurologic deterioration
    3. CT next day shows hydrocephalus

Failure of weaning = VP shunt insertion

**No differnece in incidence of HCP / need for VP shunting (62.5 vs 63.4% p=0.932)

**gradual weaning group spent 2.8 more days in the ICU (p=0.0002)

Neurocritical Care Society Guideline:

EVD weaning should be accomplished as quickly as is clinically feasible so as to minimize the total duration of EVD monitoring and VRI risk.

Two main methods to select those who will need permanent CSF diversion: clamping trial vs progressive wean.1. Clamping Trial: clamp EVD and monitor ICP, clinical status, ventricle size – determine whether VPS is required2. Progressive wean – progressively increase level of ventricular drainage (usually 5mm Hg/d) while monitoring ICP, clinical status, ventricular size, drainage volume Only 1 RCT (Klopfenstein, see reference listed) comparing the two methods. Clamping trial associated with shorter duration of EVD and ICU and hospital LOS with similar clinical outcomes.Currently decision to shunt is based on clinical deterioration. There is little information about the effects of subclinical hydrocephalus on cognitive function, chronic headache and fatigue. Studies have shown decrease in CBF in NPH, correlating with cognitive dysfunction.


Fried, Herbert I. et al. “The Insertion And Management Of External Ventricular Drains: An Evidence-Based Consensus Statement”. Neurocritical Care 24.1 (2016): 61-81. Web.

Klopfenstein, Jeffrey D. et al. “Comparison Of Rapid And Gradual Weaning From External Ventricular Drainage In Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Randomized Trial”. Journal of Neurosurgery 100.2 (2004): 225-229. Web.

Rabinstein, A. and Lanzino, G. (2018). Aneurysmal Subarachnoid Hemorrhage. Neurosurgery Clinics of North America, 29(2), pp.255-262.