Adverse effects of polymyxin B administration to healthy horses.

Abstract

BACKGROUND: Polymyxin B (PolyB) is used to treat endotoxemia in horses; neurologic and nephrogenic adverse effects occur in humans. OBJECTIVES: To describe PolyB adverse effects in horses. ANIMALS: Five healthy horses (ataxia 0/5), 1 horse with cervical osteoarthritis (ataxia 1/5). METHODS: Prospective blinded randomized cross-over trial; 3-weeks wash out. Horses received PolyB (PolyB 6000&#x2009;IU/kg IV, 7 doses q12h, n&#xa0;=&#xa0;6) and PolyB/gentamicin (PolyB 6000&#x2009;IU/kg IV, q12h 7 doses; gentamicin 10&#xa0;mg/kg IV q24h 4 doses n&#xa0;=&#xa0;4, or q12-24&#x2009;h 5 doses because of an additional erroneous dose, n&#xa0;=&#xa0;2). Daily neurological examinations were video recorded, and ataxia graded by 3 observers. Urine status, urinary GGT/creatinine ratio, plasma creatinine, and urea were assessed every other day, EMG daily. Mixed model analysis was used to evaluate factors associated with ataxia grade and [PolyB]. RESULTS: Median ataxia score increased from 0/5 (range 0-2/5) to 2/5 (range 1-3/5) during administration and declined to 0.5/5 (range 0-2/5) after cessation. Gentamicin co-administration (P&#x2009;<&#x2009;.01, effect size: .8), number of PolyB doses (P&#x2009;<&#x2009;.001, effect size: .6), and time since last PolyB dose (P&#x2009;<&#x2009;.001, effect size: .5) had a significant effect on ataxia grades, while horse, day, [Genta], [PolyB], and [PolyB]did not. Gentamicin co-administration and [Genta] Chad no effect on median [PolyB] C(4.67 and 4.89&#xa0;&#x3bc;g/ml for PolyB and PolyB/gentamicin, respectively). Urinary GGT/creatinine ratio was elevated in 3/6 horses receiving PolyB/gentamicin. The EMG remained unchanged. CONCLUSIONS AND CLINICAL IMPORTANCE: PolyB caused transient ataxia, worsening with cumulative PolyB doses and gentamicin co-administration. Nephrotoxicity of PolyB was only evident when gentamicin was co-administered.