Journal of veterinary internal medicine · 2022
Adverse effects of polymyxin B administration to healthy horses.
СтатьяRandomized Controlled Trial, VeterinaryНазвание и аннотация: Перевод в очереди
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van Spijk Julia N, Beckmann Katrin, Wehrli Eser Meret, Boxler Martina, Stirn Martina, Rhyner Thea, Kaelin Dana, Saleh Lanja, Schoster Angelika
Аннотация
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 IU/kg IV, 7 doses q12h, n = 6) and PolyB/gentamicin (PolyB 6000 IU/kg IV, q12h 7 doses; gentamicin 10 mg/kg IV q24h 4 doses n = 4, or q12-24 h 5 doses because of an additional erroneous dose, n = 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 < .01, effect size: .8), number of PolyB doses (P < .001, effect size: .6), and time since last PolyB dose (P < .001, effect size: .5) had a significant effect on ataxia grades, while horse, day, [Genta], [PolyB], and [PolyB]CSF did not. Gentamicin co-administration and [Genta] Cpeak had no effect on median [PolyB] Cpeak (4.67 and 4.89 μg/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.
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 IU/kg IV, 7 doses q12h, n = 6) and PolyB/gentamicin (PolyB 6000 IU/kg IV, q12h 7 doses; gentamicin 10 mg/kg IV q24h 4 doses n = 4, or q12-24 h 5 doses because of an additional erroneous dose, n = 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 < .01, effect size: .8), number of PolyB doses (P < .001, effect size: .6), and time since last PolyB dose (P < .001, effect size: .5) had a significant effect on ataxia grades, while horse, day, [Genta], [PolyB], and [PolyB]CSF did not. Gentamicin co-administration and [Genta] Cpeak had no effect on median [PolyB] Cpeak (4.67 and 4.89 μg/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.