title: Correlation of Free and Total Phenytoin Serum Concentrations in Critically Ill Patients.
abstract: BACKGROUND
  Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). The clinical utility of the Sheiner-Tozer equation for adjusting total phenytoin levels for hypoalbuminemia remains controversial.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the correlation of this formula in predicting phenytoin serum concentrations.
  
  
  METHODS
  A retrospective cohort study was conducted in the adult ICU between January 1, 2010, and June 21, 2013. Patients meeting the following study criteria were included: age ≥18 years, admission to the ICU, simultaneously drawn total and free serum phenytoin concentrations with albumin ≤48 hours of phenytoin draws. Study end points were the correlation as well as the level of agreement in the interpretation of the free and adjusted phenytoin concentrations using the Sheiner-Tozer formula in critically ill patients with hypoalbuminemia.
  
  
  RESULTS
  A total of 238 patients were analyzed. Mean adjusted total phenytoin and free levels were 16.1 ± 8.1 and 1.5 ± 0.8 µg/mL, respectively (r = 0.817; P < 0.001). Absolute agreement with level interpretation between adjusted total phenytoin and free levels was 77% (κ = 0.633; P < 0.001). Adjusted phenytoin serum concentrations more frequently overestimated the free level.
  
  
  CONCLUSIONS
  There is a significant correlation between free and adjusted total phenytoin levels using the Sheiner-Tozer equation in critically ill patients. However, disagreement was noted with interpretation, primarily because of the adjusted concentration overestimating the free level. This imprecision may lead to inaccurate decision making regarding the management of phenytoin in this patient population. Thus, free phenytoin levels should be utilized.
authors.affiliation: Banner-University Medical Center Phoenix, AZ, USA Mitchell.buckley@bannerhealth.com.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Buckley
authors.affiliation: Banner-University Medical Center Phoenix, AZ, USA.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Reeves
authors.affiliation: Midwestern University, Glendale, AZ, USA.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Barletta
authors.affiliation: Banner-University Medical Center Phoenix, AZ, USA.
authors.forename: Dale S
authors.initials: DS
authors.lastname: Bikin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D016638:Critical Illness; D003657:Decision Making; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000097:blood* / Q000627:therapeutic use; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin
keywords: critical care; drug monitoring; neurology; seizures; therapeutic monitoring