Evaluation of Diphenhydramine as an Antihistamine in Dogs Anesthetized for Surgical Excision of Mast Cell Tumours

This thesis determined in phase 1 the pharmacokinetics and cardio-respiratory effects of diphenhydramine (DHP) in conscious research dogs administered 1 mg/kg, IV, or 2 mg/kg, IM. Phase 2 consisted of a blinded clinical trial to investigate the effectiveness of DPH in anesthetized dogs to prevent the negative cardiovascular effects associated with potential histamine release during surgical excision of mast cell tumours (MCT). Dogs were anesthetized with a balanced anesthetic and analgesic technique and then allocated to receive DPH (1 mg/kg, IV) or saline. Plasma DPH and histamine concentrations were measured and correlated with cardio-respiratory parameters. Phase 1 results provided descriptive pharmacokinetics of DPH administered IV or IM in healthy dogs. Cardio-respiratory parameters remained within normal limits during the experiment and no behavioural changes were associated with DPH administration. The IV protocol was chosen for the clinical phase 2 under anesthesia, due to a shorter time to maximal concentrations (Tmax) of 6.0 ± 0.3 min versus 45 ± 5.1 min for the IM group. During the clinical phase 2, plasma concentrations of DPH remained above concentrations considered therapeutic (25 ng/mL) in humans until the end of surgery. Despite the lack of statistical differences in histamine concentrations throughout anesthesia between groups, higher histamine concentrations were measured during maximal manipulation of the tumour. Mean arterial and diastolic blood pressures were significantly lower in DPH than in the saline group during surgical excision of the tumour. These results contradict the assumption that hypotension is more likely in dogs undergoing MCT excision that have not received DPH. Values for cardio-respiratory parameters in both groups were considered within acceptable limits for anesthetized dogs. In dogs, DPH can be administered by either IV or IM routes at 1 mg/kg and 2 mg/kg, respectively, to yield plasma concentrations that exceed therapeutic concentrations in humans without noticeable adverse behavioural or cardio-respiratory side effects. The administration of DPH prior to surgical removal of MCT in dogs did not have clear clinical anesthetic differences related to cardio-respiratory responses compared to dogs receiving a saline placebo. Ontario Veterinary College Pet Trust