Effect of phenylbutazone and repeated endotoxin administration on hemostasis in neonatal calves

Twenty newborn Holstein calves were allotted at random to 4 groups: group A received 0.9% sterile saline solution; group B received phenylbutazone (5 mg/kg of body weight, IV) and 0.9% sterile saline solution; group C received progressively increasing doses of endotoxin (0.1 to 15 micrograms/kg); and group D received phenylbutazone and endotoxin similarly as did calves of groups B and C, respectively. Phenylbutazone was given once daily and saline solution or endotoxin were given every 8 hours for 5 days. Clinical variables--PCV, plasma total protein and fibrinogen concentrations, platelet count, prothrombin time, activated partial thromboplastin time, and fibrin degradation products concentration were measured at 24-hour intervals. Necropsy was performed on each calf. Phenylbutazone suppressed the clinical response to endotoxin challenge until large doses (7.5 to 15 micrograms/kg) were administered. Calves of groups C and D remained stable until they abruptly developed severe dyspnea necessitating euthanasia. Thrombocytopenia and leukopenia developed after the initial endotoxin dose. Prothrombin time was prolonged and PCV suddenly decreased at 96 hours. Necropsy revealed consistent lesions in the vascular endothelium and lungs. Phenylbutazone administration did not enhance or ameliorate endotoxin-induced hemostatic alterations or pathologic lesions.