Cardiovascular and respiratory implications of concurrent administration of phenylbutazone and romifidine in healthy adult horses

Abstract

Phenylbutazone is one of the most widely-used non-steroidal anti-inflammatory drugs in equine practice. According to literature, it does not have cardiorespiratory effects in healthy, standing horses, but anaesthesiologists at the Onderstepoort Veterinary Academic Hospital have experienced increased intra-operative haemodynamic instability associated with the use of the intravenous formulation directly prior to anaesthesia. Romifidine is widely used in equine practice as a sedative and adjunct to anaesthesia. It is known to have adverse cardiorespiratory effects, but these effects have only been characterised up to 2 hours after administration. The aim of this study was to characterise the cardiovascular and respiratory effects of phenylbutazone and romifidine individually over a 3-hour period and to establish whether there may be interactions between them. A blinded crossover trial was performed in 5 horses. All horses were administered saline (Plac) IV, phenylbutazone 4.4 mg/kg IV (Pbz), romifidine 80μg/kg IV (Rom) and a combination of phenylbutazone 4.4 mg/kg IV and romifidine 80 μg/kg IV (Pbz_Rom), with at least one week washout period between treatments. Heart rate, respiratory rate, arterial pressures and central venous pressure were recorded directly prior to drug administration and every 5 minutes thereafter for a 3-hour period. Arterial and venous blood-gas and electrolyte values were assessed directly prior to and at 10, 60, 120 and 180 minutes after drug administration. Electrocardiographic abnormalities, the level of sedation and frequency of urination were recorded. Data was assessed using ANOVA for the maximum change from baseline during the first 30 minutes and changes over time within groups were assessed descriptively. There were statistically significant differences between treatment groups for maximum change in central venous pressure in the first 30 minutes after treatment. All groups differed significantly from all other groups, except Rom and Pbz_Rom. Descriptive findings included a transient increase in heart rate in the Pbz group as well as a transient decrease in arterial pressures. In the Rom group, there was an initial increase in central venous pressure, peaking at 5 min, followed by a decrease to a minimum at 105 min, where after it slowly started to recover. Systolic and mean arterial pressures were decreased, reaching a minimum at 105 min. Diastolic arterial pressure showed an initial increase to a maximum at 5 min, followed by a decrease to a minimum at 105 min. All these parameters as well as heart rate, respiratory rate and PvO2 were still decreased at 175 min. Serum Ca2+ and K+ decreased during the observational period and PCO2 and HCO3- increased. Pbz_Rom showed similar trends to Rom, but the depressant effect on heart rate, arterial pressure and central venous pressure was less severe, and the decrease in serum Ca2+ and K+ more severe than Pbz or Rom. We conclude that romifidine’s depressant cardiorespiratory effects are prolonged beyond 175 min. No interaction between phenylbutazone and romifidine was found. This is a pilot study and larger studies are required to establish whether the observed changes in this trial are statistically significant. Copyright