title: Macrolide-induced hyperthermia in foals: Role of impaired sweat responses.
abstract: BACKGROUND
  The mechanism of hyperthermia, a potentially fatal adverse effect of erythromycin treatment of foals, is unknown.
  
  
  OBJECTIVE
  To determine the cause of erythromycin-associated hyperthermia. It was hypothesised that the normal sweat response of foals is impaired by treatment with erythromycin.
  
  
  METHODS
  Blinded, crossover study in 10 healthy pony foals.
  
  
  METHODS
  Foals kept in stalls were given either erythromycin (25 mg/kg bwt orally, 3 times daily) or control for 10 days then turned out for a further 10 days. Quantitative intradermal terbutaline sweat tests were performed on Days 1 (baseline), 3, 10 and 20. The effects on terbutaline-induced sweating of erythromycin, terbutaline concentration and treatment day were analysed by repeated-measures ANOVA with Bonferroni-corrected pairwise post hoc comparisons. Peak temperatures were compared by Wilcoxon's signed rank test and proportions by McNemar's related samples test. Significance was set at P<0.05.
  
  
  RESULTS
  There were significant 2-factor interactions for treatment × terbutaline after baseline, treatment × day at every terbutaline concentration, and day × terbutaline for erythromycin (P<0.001) but not control (P = 0.9) treatment. Sweating was significantly reduced from baseline in erythromycin-treated foals at all subsequent days. Erythromycin-treated foals produced less sweat at all time-points than did control-treated foals (P<0.05). Peak rectal temperatures of erythromycin-treated foals were significantly higher (P = 0.02) than those of controls. During the first 3 days outside more erythromycin-treated than control-treated foals required treatment for hyperthermia (6 vs. 0; P = 0.03).
  
  
  CONCLUSIONS
  We believe drug-induced anhidrosis is the likely cause of hyperthermia in some foals treated with erythromycin.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Stieler
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Sanchez
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Mallicote
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Martabano
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Burrow
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: MacKay
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004917:Erythromycin / Q000009:adverse effects*; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000662:veterinary*; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses; D007271:Injections, Intradermal; D007428:Intradermal Tests; D008297:Male; D013546:Sweating / Q000187:drug effects*; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013566:Sympathomimetics; D004917:Erythromycin; D013726:Terbutaline
keywords: anhidrosis; erythromycin; foal; horse; hyperthermia; sweat