Phenytoin Drug Monitoring

After loading dose

  • First concentration: draw within 2-3 days
    • if rapid therapeutic levels needed, draw 2 hours after IV loading dose or 24 hours after oral loading dose to determine maintenance dose or need to reload
  • Second concentration: draw within 5-8 days of therapy initiation with subsequent doses of phenytoin adjusted accordingly
  • if levels unchanged over 3-5 days, monitor once a week (acute clinical setting).
  • stable / long-term therapy, monitor every 3-12 months

 

Corrected for Low Albumin:

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Corrected for Renal Failure (CrCl <10):

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REFERENCE:

Uptodate: Phenytoin: Drug information.  Accessed 04/25/2020.

Risk Score to Predict QTc Prolongation in Hospitalized Patients

For patients with COVID-19, we are using drugs that prolong QT-interval.  The risk of life-threatening arrhythmias from QT prolongation may be higher.  This article reports a scoring system to identify patients that are at risk for QT prolongation.

The study found that the following factors predicted QTc prolongation:  female, sepsi, LV dysfunction, administration of QT-prolong drug, >= 2 QT prolonging drugs, loop-diuretic, age >68, serum K <3.5, admitting ATc >450ms.

A risk score was developed.  Risk was classified as low (score of 0-6), moderate (7-10) and high (11-21).

 

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A high risk score >11 was associated with 74% Sn and 77% Sp (PPV 79% NPV 76) for predicting QTc prolongation.  Incidence of QTc prolongation 15% in low risk, 37% in moderate risk and 73% in high risk.

 

 

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Reference:

Tisdale, J., Jaynes, H., Kingery, J., Mourad, N., Trujillo, T., Overholser, B., & Kovacs, R. (2013). Development and Validation of a Risk Score to Predict QT Interval Prolongation in Hospitalized Patients. Circulation: Cardiovascular Quality And Outcomes, 6(4), 479-487. doi: 10.1161/circoutcomes.113.000152

COVID-19 Acute Necrotizing Encephalopathy

Case report: COVID-19 associated acute necrotizine hemorrhagic encephalopathy – ANE – associated iwth other viral infections.  Female, late 50s, 3-day cough, fever, altered mental status.

Work-up NEG for influenza, nasopharyngeal swab (+) coronavirus, CSF limited – traumatic LP, CSF bacterial culture NG, HSV HSV 1 and 2, varicella, WNV NEG; unable to test CSF for SARSCoV-2.

CT head:   symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram

MRI: hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions

Acute necrotizing encephalopathy

  • rare complication of influenza / viral infections
  • related to intracranial cytokine storms –> BBB breakdown
  • no direct viral invasion or parainfecitous demyelination
  • reported mostly in pediatric population but occurs in adults as well

Imaging Features

  • symmetric, multifocal lesions with invariable thalamic involvement
  • Other commonly involved locations include the brain stem, cerebral white matter, and cerebellum
  • hypoattenuating on CT
  • MRI shows T2 FLAIR hyperintense signal with internal hemorrhage
  • Postcontrast images may demonstrate a ring of contrast enhancement

 

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Image from noncontrast head CT demonstrates symmetric hypoattenuation within the bilateral medial thalami (arrows). B, Axial CT venogram demonstrates patency of the cerebral venous vasculature, including the internal cerebral veins (arrows). C, Coronal reformat of aCT angiogram demonstrates normal appearance of the basilar artery and proximal posterior cerebral arteries.

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MRI images demonstrate T2 FLAIR hyperintensity within the bilateral medial
temporal lobes and thalami (A, B, E, F) with evidence of hemorrhage indicated by hypointense signal intensity on susceptibility-weighted images (C, G) and rim enhancement on postcontrast
images (D, H).

 

Reference:

Poyiadji, N., Shahin, G., Noujaim, D., Stone, M., Patel, S., & Griffith, B. (2020). COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology, 201187. doi: 10.1148/radiol.2020201187