Fentanyl‐induced asystole in two dogs

Fentanyl is used in small animals for perioperative analgesia during anaesthesia. Severe bradycardia and asystole were observed on bolus administration of a 3 µg/kg loading dose of fentanyl in two dogs under isoflurane anaesthesia. Premedication with 10 µg/kg glycopyrrolate did not prevent asystole in the first case; and although bradycardia was treated with 5 µg/kg glycopyrrolate administered intravenously in the second case, the heart rate continuously decreased and asystole subsequently developed. Asystole in both cases was quickly corrected by intravenous administration of 0 · 04 mg/kg atropine and closed chest compressions. This case report describes asystole induced by fentanyl administration in isoflurane anaesthetised dogs. Atropine was more effective than glycopyrrolate in the treatment of fentanyl‐induced asystole.     

Pharmacokinetics of a controlled‐release liposome‐encapsulated hydromorphone administered to healthy dogs

The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (C_MAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.     

Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) is a serious public health concern and in Australia, one that disproportionately affects Aboriginal people. Paralleling MRSA in human medicine, methicillin‐resistant S. pseudintermedius (MRSP) is an increasingly prevalent pathogen in veterinary medicine. We aimed to characterize the carriage of MRSA and MRSP in dogs and cats from predominantly Aboriginal communities in a very remote region of New South Wales (NSW), Australia. Pets (303 dogs and 80 cats) were recruited from six communities in western NSW. Three swabs were collected from each animal (anterior nares, oropharynx and perineum) and from skin lesions or wounds (if present) and cultured on selective media for methicillin‐resistant staphylococci. Human host‐adapted community‐associated MRSA representing four multilocus sequence types (ST1‐IV, ST5‐IV, ST72‐IV, ST93‐IV) were isolated from eight dogs (prevalence 2.6%, 95% confidence interval 1.3%–5.1%). Two ST5‐IV isolates from a single dog were phenotypically trimethoprim‐resistant, harbouring trimethoprim‐resistant gene dfrG within the SCCmec type IVo mobile genetic element. MRSA was not isolated from any cats and MRSP was not isolated from any dogs or cats. This study estimated a high prevalence of human host‐adapted community‐associated MRSA carriage in dogs despite an absence of MRSP. This suggests MRSA carried by dogs in remote NSW originate from human hosts. The cycle of transmission between people, dogs and common environmental sources warrants further investigation. To our knowledge, this is the first report of trimethoprim‐resistant ST5‐IV in eastern Australia and the first report of trimethoprim‐resistant ST5‐IV from a dog.     

Metabolizable energy intake of client‐owned adult dogs

A post hoc analysis of the metabolizable energy (ME) intake of privately owned pet dogs from the authors' nutrition consultation practice (Years 2007–2011) was carried out to identify if current ME recommendations are suitable for pet dogs. Data on 586 adult dogs were available (median age 5.5, median deviation from ideal weight 0.0), 55 of them were healthy; the others had various diseases. For ration calculation, a standardized questionnaire and the software diet‐check Munich^? was used. ME was predicted according to NRC (2006). Data were evaluated for the factors disease, breed, size, age, gender and type of feeding. The mean ME intake of all adult dogs amounted to 0.410 ± 0.121 MJ/kg metabolic body weight (BW^0.75) (n = 586). There was no effect of size and disease. Overweight dogs ate 0.360 ± 0.121 MJ/kg BW^0.75, and underweight dogs ate 0.494 ± 0.159 MJ/kg BW^0.75. Older dogs (>7 years, n = 149, 0.389 ± 0.105 MJ/kg BW^0.75) had a lower ME intake than younger ones (n = 313, 0.419 ± 0.121 MJ/kg BW^0.75), and intact males had a higher ME intake than the others (p < 0.001). Some breeds were above average: Jack Russell Terrier, Dalmatian, small Munsterlander and Magyar Viszla, Bearded Collies, Sight Hounds, German Boxers, English foxhounds, Rhodesian Ridgebacks and Flat‐Coated Retrievers with a mean ME intake of 0.473 ± 0.121 MJ/kg BW^0.75. The following breeds were below average: Dachshunds, Bichons, West highland White Terrier, Collies except Bearded Collies, Airedale Terriers, American Staffordshire terriers and Golden Retrievers with a mean ME intake of 0.343 ± 0.096 MJ/kg BW^0.75. The mean maintenance energy requirements of pet dogs are similar to that of kennel dogs which do not exercise very much. These results suggest that opportunity and stimulus to exercise provided for pet dogs are lower than for kennel dogs. Lower activity in pet dogs may reduce part of potential effects of breed, medical history and age groups.     

Aldosterone breakthrough with benazepril in furosemide‐activated renin‐angiotensin‐aldosterone system in normal dogs

Pilot studies in our laboratory revealed that furosemide‐induced renin‐angiotensin‐aldosterone system (RAAS) activation was not attenuated by the subsequent co‐administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin‐converting enzyme (ACE) activity and furosemide‐induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide‐induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4–6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days ?1, ?2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days ?1 and ?2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P < 0.05). Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P < 0.05) but did not significantly reduce aldosterone excretion (Group FB baseline UAldo:C = 0.35, SD 0.16; day 1 UAldo:C = 0.79, SD 0.39; day 3 UAldo:C 0.92, SD 0.48, day 7 UAldo:C = 0.99, SD 0.48, P < 0.05). Benazepril decreased plasma ACE activity but did not prevent furosemide‐induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy.     

Age‐associated changes to pathogen‐associated molecular pattern‐induced inflammatory mediator production in dogs

Objective – To determine whether older dogs will have a more pronounced pro‐inflammatory response and blunted anti‐inflammatory response to pathogen‐associated molecular patterns (PAMPs) compared with younger dogs. Design – Prospective. Setting – University teaching hospital. Animals – Thirty‐eight privately owned sexually altered dogs of various ages. Interventions – Blood was collected for HCT, WBC count, plasma biochemical analysis, and whole blood culture. Whole blood was stimulated with lipopolysaccharide (LPS) or, lipoteichoic acid or, peptidoglycan or, addition of phosphate‐buffered saline. Tumor necrosis factor (TNF), interleukin (IL)‐6, and IL‐10 production from whole blood were compared among young, middle aged, and geriatric dogs. Measurements and Main Results – LPS, lipoteichoic acid, and peptidoglycan stimulated significant TNF, IL‐6, and IL‐10 production from canine whole blood compared with phosphate‐buffered saline. Whole blood from geriatric dogs had a blunted IL‐10 response to LPS stimulation and middle‐aged dogs had increased LPS‐induced TNF production compared with the other groups. Conclusion – PAMPs from gram‐positive and gram‐negative bacteria stimulate TNF, IL‐6, and IL‐10 production from canine whole blood. The inflammatory mediator response to PAMPs from gram‐negative bacteria alters with age and may be one factor contributing to mortality in geriatric dogs with sepsis.     

A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs

Combretastatin A4 ‐Phosphate (CA4P ) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m^?2. At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low‐grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m^?2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m^?2, low‐grade hypertension and high‐grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m^?2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m^?2, although transient, does not invite to use this dose in canine oncology patients.     

Breed‐associated variability in serum biochemical analytes in four large‐breed dogs

Background: Genetic background can influence the expected values of hematologic and serum biochemical analytes in domestic animal species. Objective: The purpose of this study was to determine if there are breed‐related differences in serum biochemical variables in healthy purebred dogs of 4 breeds and to develop appropriate reference intervals. Methods: Alaskan Malamutes (n=59), Siberian Huskies (n=78), Golden Retrievers (n=90), and English Setters (n=77) were included in the study. The dogs had a median age of 42 months (range 10–112 months) and each breed included a mix of intact and neutered dogs of both sexes. Serum biochemical profiles (Olympus AU400e) were performed along with physical examinations, CBCs, and urinalyses to ensure dogs were clinically healthy. Differences in the values of biochemical analytes were assessed nonparametrically and reference intervals for all breeds combined were calculated as the central 95% percentile. Results: Significant differences were observed between breeds for all serum biochemical analytes except alkaline phosphatase, glucose, and chloride. The analyte ranges had a large degree of overlap between the different breeds. Conclusions: Although many statistically significant breed‐related differences in serum biochemical values were observed, the differences were small and unlikely to have clinical relevance or impact medical decision making.