Leon N. Warne

A review of the pharmacology and clinical application of alfaxalone in cats

Alfaxalone-2-hydroxpropyl-β-cyclodextrin (alfaxalone-HPCD) was first marketed for veterinary use in Australia in 2001 and has since progressively became available throughout the world, including the USA, where in 2012 Food and Drug Administration (FDA) registration was granted. Despite the growing body of published works and increasing global availability of alfaxalone-HPCD, the accumulating evidence for its use in cats has not been thoroughly reviewed. The purpose of this review is: (1) to detail the pharmacokinetic properties of alfaxalone-HPCD in cats; (2) to assess the pharmacodynamic properties of alfaxalone-HPCD, including its cardiovascular, respiratory, central nervous system, neuromuscular, hepatic, renal, haematological, blood-biochemical, analgesic and endocrine effects; and (3) to consider the clinical application of alfaxalone-HPCD for sedation, induction and maintenance of anaesthesia in cats. Based on the published literature, alfaxalone-HPCD provides a good alternative to the existing intravenous anaesthetic options for healthy cats.

Comparison of perioperative analgesic efficacy between methadone and butorphanol in cats

OBJECTIVE To compare the perioperative analgesic effect between methadone and butorphanol in cats. DESIGN Randomized controlled clinical trial. ANIMALS 22 healthy female domestic cats. PROCEDURES Cats admitted for ovariohysterectomy were allocated to a butorphanol group (n = 10) or methadone group (12) and premedicated with butorphanol (0.4 mg/kg [0.18 mg/lb], SC) or methadone (0.6 mg/kg [0.27 mg/lb], SC), respectively, in combination with acepromazine (0.02 mg/kg [0.01 mg/lb], SC). Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. A multidimensional composite scale was used to conduct pain assessments prior to premedication and 5, 20, 60, 120, 180, 240, 300, and 360 minutes after extubation or until rescue analgesia was given. Groups were compared to evaluate isoflurane requirement, propofol requirement, pain scores, and requirement for rescue analgesia. RESULTS Propofol and isoflurane requirements and preoperative pain scores were not different between groups. During recovery, dysphoria prevented pain evaluation at 5 minutes. Pain scores at 20 minutes were significantly lower in the methadone group, and 6 of 10 cats in the butorphanol group received rescue analgesia, making subsequent pain score comparisons inapplicable. After 6 hours, only 3 of 12 cats in the methadone group had received rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE In the present study, methadone appeared to be a better postoperative analgesic than butorphanol and provided effective analgesia for 6 hours following ovariohysterectomy in most cats.

Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats

OBJECTIVE To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. DESIGN 2-phase positive-controlled randomized masked clinical trial. ANIMALS 39 healthy female cats (10 in phase 1 and 29 in phase 2). PROCEDURES Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. RESULTS Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study:

Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 µg/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann–Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0–3.0] and 2.5 [range 1.0–3.0] for A2 and A0.5, respectively) were not significantly different (P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4–7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5–2.5 mg/kg]) (P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit.

An ovine model of cerebral catheter venography for implantation of an endovascular neural interface

OBJECTIVE Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface. METHODS Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. RESULTS The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. CONCLUSIONS The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Influence of two administration rates of propofol at induction of anaesthesia on its relative potency in cats: a pilot study

Objectives This was a randomised, blinded trial to investigate the influence of administration rate on the dose of propofol required for the orotracheal intubation of cats. Methods Twenty-four female domestic cats undergoing ovariohysterectomy were premedicated with oral tramadol (6 mg/kg) or intramuscular tramadol (4 mg/kg), and intramuscular dexmedetomidine (0.007 mg/kg). Oral or intramuscular (IM) tramadol was administered 60 or 30 mins prior to induction of anaesthesia, respectively. Dexmedetomidine was administered 30 mins prior to anaesthetic induction. Sedation scores were established prior to anaesthesia induction with propofol intravenously at 4 mg/kg/min (fast) or 1 mg/kg/min (slow) to effect until orotracheal intubation was achieved without coughing. If coughing occurred, the intubation process was paused for 15 s. Four groups were determined: IM tramadol/propofol fast (GIMF, n = 6); IM tramadol/propofol slow (GIMS, n = 6); oral tramadol/propofol fast (GOF, n = 6); oral tramadol/propofol slow (GOS, n = 6). The Shapiro–Wilk test was used to evaluate for normality of residuals. Sedation scores and propofol anaesthetic induction doses were compared between GIMF and GIMS groups, and between GOF and GOS groups using the Mann–Whitney test and the t-test, respectively (P = 0.05). The presence of hypotension (mean arterial blood pressure <60 mmHg) or apnoea (no breathing for 30 s or more) within the first 15 mins postintubation was recorded. Results The median sedation scores for GIMF and GOF were not significantly different compared with those for GIMS (P = 0.94) and GOS (P = 0.70). However, the mean ± SD propofol anaesthetic induction doses were higher in GIMF (9.1 ± 1.8 mg/kg) and GOF (7.9 ± 1.7 mg/kg) than in GIMS (5.1 ± 1.5 mg/kg; P <0.01) and GOS (5.4 ± 0.3 mg/kg; P <0.01). No hypotension or apnoea were detected. Conclusions and relevance Using the slower anaesthetic induction rate resulted in an increase in propofol relative potency.

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging

Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions.