title: Oral and intravenous thyroxine (T4) achieve comparable serum levels for hormonal resuscitation protocol in organ donors: a randomized double-blinded study.
abstract: BACKGROUND
  Thyroxine (T4) administration is advocated in the management of organ donors; however, the bioavailability of oral thyroxine is unknown in this patient population.
  
  
  OBJECTIVE
  The primary objective of this study was to compare the percentage of the study time (from study drug administration to organ procurement) that patients in the oral vs the intravenous group required inotropic support. Secondary objectives included plasma levels of T3 and T4 and number of organs donated following oral vs intravenous T4 administration.
  
  
  METHODS
  Randomized double-blinded study.
  
  
  METHODS
  Adult medical-surgical intensive care unit.
  
  
  METHODS
  Thirty-two adult solid organ donors.
  
  
  METHODS
  Patients were randomized to receive either an oral or intravenous dose of T4 (2 μg·kg⁻¹). All patients received an oral and intravenous study drug preparation, one of which was a placebo. The study was double-blinded, and randomization occurred in blocks of four and six.
  
  
  METHODS
  The number and duration of inotropic/vasopressor therapies and free serum levels of T3 and T4 were determined hourly until procurement.
  
  
  RESULTS
  Following T4 administration, all patients remained on inotropic/vasopressor therapy for the same mean (SD) duration [93 (3)%] of the study period. There was a similar and gradual decrease in the number and dosages of inotropes/vasopressors required in both groups. There was no difference in T3 or T4 levels between groups. Oral bioavailability of T4 was 93% of the intravenous group at six hours and 91% overall. At six hours, the mean area under the curve for T4 was similar between the intravenous group [92.2 (33); 95% confidence interval (CI) 76 to 108.4] and the oral group [86.1 (14); 95% CI 79.4 to 92.8].
  
  
  CONCLUSIONS
  Orally administered T4 is well absorbed and achieves a bioavailability of approximately 91-93% of intravenous T4 in organ donors. Inotropic/vasopressor requirements and hemodynamic responses following oral or intravenous thyroxine administration were comparable. Oral T4 is suitable for hormonal therapy for organ donors. This trial was registered at www.clinicaltrials.gov : NCT00238030.
authors.affiliation: Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre - University Hospital, Schulich School of Medicine and Dentistry, Western University, 339 Windermere Road, London, ON, N6A 5A5, Canada, michael.sharpe@lhsc.on.ca.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sharpe
authors.forename: Barbara
authors.initials: B
authors.lastname: van Rassel
authors.forename: Wael
authors.initials: W
authors.lastname: Haddara
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013974:Thyroxine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors; D014019:Tissue Donors; D014284:Triiodothyronine / Q000097:blood*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D014284:Triiodothyronine; D013974:Thyroxine