Abstract
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.
Highlights
Interpretation of echocardiography in canine patients requires high quality images, which can only be acquired in calm animals that do not resist physical restraint
Data from one dog had to be excluded from the sedation trial since it moved during injection and the drug was partially administered subcutaneously
Tamura et al.’s studies [10,12] demonstrated that the haemodynamic effects may be more moderate with no increase in heart rate (HR) when alfaxalone at doses of 2.5, 5, 7.5 and 10 mg kg-1 was administered IM. These findings suggested that this administration route might have less deleterious effect on the cardiovascular function than the IV route, this was not confirmed by our study
Summary
Interpretation of echocardiography in canine patients requires high quality images, which can only be acquired in calm animals that do not resist physical restraint. 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]. Interpretation of the echocardiographic variables should not be affected by sedation. Alfaxalone in hydroxypropyl beta cyclodextrin, a neuroactive steroid anaesthetic, provides good short-term anaesthesia with minimal cardiorespiratory effect in unpremedicated dogs at 2–4 mg kg-1 IV [3,4,5]. According to Kim et al [6], alfaxalone IV provides an adequate sedation for echocardiographic examination with no statistical and clinical significant cardiovascular depression in healthy dogs. IM injections can be less time-consuming and expensive than IV injections for which the placement of a catheter is recommended
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