Multicenter clinical evaluation of a multi-dose formulation of propofol in the dog.

BACKGROUND: Propofol is a widely used injectable anesthetic agent for induction and short-term maintenance in dogs. A multi-dose formulation of propofol (MDP) has been developed which includes 2% benzyl alcohol as a preservative. In order to document the use of the product under clinical conditions, MDP was tested in a prospective clinical trial conducted at six sites within the United States. One hundred thirty-eight healthy, client-owned dogs were assigned to one of six treatment groups based on premedicants (none, acepromazine/buprenorphine, midazolam/buprenorphine, medetomidine/buprenorphine) and maintenance agents (MDP, inhaled anesthetic). Anesthesia was induced by the intravenous administration of MDP given to effect. Physiological indices including heart rate, respiratory rate and blood pressure were monitored prior to and during anesthesia induction, maintenance and recovery. Adverse events, defined for severity by pre-established limits of these physiological values, as well as side effects, defined as any observation outside the normal range, were noted. RESULTS: The mean intubation dose was 7.6 ± 2.1 mg/kg for MDP alone and 4.7 ± 1.3, 4.0 ± 1.0 mg/kg and 3.2 ± 1.4 mg/kg when buprenorphine was used in combination with midazolam, acepromazine and medetomidine, respectively. Of the 32 adverse events, apnea (12 incidents), bradycardia (9 incidents) and hypotension (7 incidents) were most frequently recorded. Emesis, cyanosis and second degree heart block were each noted once and successfully resolved. The cause of a single death 2 days post-anesthesia was assessed as a surgical complication. CONCLUSIONS: MDP was found to be acceptable for use in healthy dogs for induction and short term maintenance of anesthesia when used alone and in combination with premedicants and inhaled anesthetics.

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis.

BACKGROUND: Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 - transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen - non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. RESULTS: Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (SR ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. CONCLUSION: Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs.

Microcirculatory effects of intravenous fluid administration in anesthetized dogs undergoing elective ovariohysterectomy.

OBJECTIVE: To assess the microcirculatory effects of IV fluid administration in healthy anesthetized dogs undergoing elective ovariohysterectomy. ANIMALS: 49 client-owned dogs. PROCEDURES: Dogs were sedated, and anesthesia was induced with propofol and diazepam and maintained with isoflurane in oxygen. Dogs received lactated Ringer's solution (LRS) IV at rates of 0, 10, or 20 mL/kg/h. Videomicroscopy was used to assess and record effects of LRS administration on microcirculation in the buccal mucosa. Measurements of microcirculatory (total vessel density, proportion of perfused vessels, microcirculatory flow index, and perfused vessel density by vessel size [< 20 µm, ≥ 20 µm, and all diameters]) and other physiologic variables (heart rate, Doppler-measured blood pressure, oxygen saturation as measured by pulse oximetry, capillary refill time, and body temperature) were compared among groups at baseline (immediately after anesthetic induction), 30 and 60 minutes afterward, and overall. RESULTS: Neither the proportion of perfused vessels nor microcirculatory flow index varied among treatment groups at any time point, regardless of vessel size. For vessels < 20 µm in diameter and for all vessels combined, total and perfused vessel density were similar among groups. For vessels ≥ 20 µm in diameter, total vessel density was significantly greater in the 20 mL/kg/h group than in other groups, and perfused vessel density was significantly greater in the 20 mL/kg/h group than in the 0 mL/kg/h group, when all time points were considered. Other physiologic variables were similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Total and perfused vessel density of vessels ≥ 20 µm in diameter (mostly venules) were greatest in dogs that received 20 mL of LRS/kg/h. Further research is required to evaluate clinical importance of these findings.