Research Article: Pharmacokinetics of intramuscular alfaxalone and its echocardiographic, cardiopulmonary and sedative effects in healthy dogs

Date Published: September 24, 2018

Publisher: Public Library of Science

Author(s): Inga-Catalina Cruz-Benedetti, Isabelle Bublot, Thibault Ribas, Isabelle Fourel, Claus Vogl, Claire Dubois, Mathilde Milani, Keila Kazue Ida, Karine Portier, Francesco Staffieri.


The pharmacokinetics and the effects of a single intramuscular (IM) dose of alfaxalone on sedation and cardiopulmonary and echocardiographic variables was studied in dogs. Twelve healthy adult Beagles (3 females, 9 males) were used in this prospective controlled cross-over trial. Echocardiography was performed with and without 4 mg kg-1 alfaxalone IM with a week wash-out interval. Sedation (19-point scale; 0 = no sedation), cardiopulmonary parameters, blood gas analysis and plasma concentration of alfaxalone were assessed every 5 minutes following the injection (T0). The influence of the alfaxalone plasma concentration and time on physiological variables was tested using a linear model whereas echocardiographic measurements were compared between conscious and alfaxalone-administered dogs using paired t-tests. Compared to baseline, alfaxalone administration was followed by an increase in heart rate (HR) from T5 to T30 and a decrease in mean arterial pressure (MAP) at T10, T25 and T30, in stroke volume (SV; 15 ± 5 to 11 ± 3 ml; P<0.0001), and end-diastolic volume (EDV; 24.7 ± 5.7 to 19.4 ± 4.9 ml). Cardiac output (CO) and blood gas analysis did not change significantly throughout. Mean plasma half-life was 29 ± 8 minutes, volume of distribution was 1.94 ± 0.63 L kg-1, and plasma clearance was 47.7 ± 14.1 ml kg-1 minute-1. Moderate to deep sedation was observed from T5 to T35. Ten dogs showed paddling, trembling, nystagmus and strong reaction to sound during the procedure. Although there were no significant changes in CO and oxygenation, the impact of HR, MAP, SV, EDV alterations requires further investigations in dogs with cardiac disease.

Partial Text

Interpretation of echocardiography in canine patients requires high quality images, which can only be acquired in calm animals that do not resist physical restraint. In addition, patients presented for echocardiography may have severe cardiac diseases. A chemical restraint with minimal effect on blood pressure and cardiac output (CO) often becomes necessary to ensure myocardial oxygenation in these patients [1]. Ideally, interpretation of the echocardiographic variables should not be affected by sedation. However, most sedative and anaesthetic drugs (like alpha-2 agonists, acepromazine, ketamine) influence cardiac activity and vascular tone directly [2].

Data from one dog had to be excluded from the sedation trial since it moved during injection and the drug was partially administered subcutaneously.

To our knowledge, this is the first report on the pharmacokinetics and echocardiographic effect of IM alfaxalone alone in dogs. In the present study, the IM administration of 4 mg kg-1 of alfaxalone to healthy Beagles induced moderate to deep sedation for 30 minutes and was associated with a significant increase in HR and a significant decrease in SV, EDV, MAP, fR, and rectal temperature. The CO and systemic oxygenation remained unchanged after IM alfaxalone. Adverse reactions such as an increased reactivity to sound, trembling, paddling and nystagmus were observed during sedation.

Although the duration of sedation achieved with 4 mg kg-1 alfaxalone was sufficient and changes in the echocardiographic measurements remained limited, IM alfaxalone alone may not be considered an ideal sedative drug during echocardiography due to its significant influence on HR. Further studies would be required to evaluate the effect of alfaxalone in dogs with cardiac diseases and the impact of the association between IM alfaxalone with butorphanol on the quality of sedation for echocardiography in dogs




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