Dose Escalation Trial of Desulfated Heparin (ODSH) in Septic Peritonitis.

Objective: Septic peritonitis is associated with significant morbidity and mortality. As a potential therapeutic agent in the treatment of sepsis, 2-O, 3-O desulfated heparin (ODSH) reduces histones and platelet factor 4 (PF4) in mouse sepsis models. This pilot clinical trial evaluated the safety and effect of ODSH in client-owned dogs with septic peritonitis. Interventions: In an IACUC-approved, open-label, prospective, dose-escalation clinical trial in 6 dogs with spontaneous septic peritonitis, ODSH administration was initiated following surgical explore to achieve source control. Acute patient physiology and laboratory evaluation (APPLEfast and APPLEfull) scores on admission, source of septic peritonitis, requirement for vasopressors, the administration of blood products, and survival to discharge were recorded. Platelet count, cell free DNA (cfDNA) concentration, and platelet factor 4 (PF4) concentrations were measured at the time of each ODSH dosage. A dose of ODSH was administered every 8 hs for a total of 4 doses (maximum total dosage 75 mg/kg) based on a pre-determined escalation protocol. Patients were monitored in the ICU following administration for evidence of clinical hemorrhage. Main Results: The mean APPLEfast and APPLEfull scores on admission were 22 +/- 6 and 32 +/-10, respectively. Four dogs received 4 total dosages of ODSH and 2 dogs received 3 total dosages of ODSH intravenously. The mean total dosage of ODSH administered during the study period was 48.3 +/- 21.6 mg/kg. No dog required dose de-escalation or had any evidence of bleeding. Four dogs survived to discharge. Conclusions: No adverse effects of ODSH administration were documented in dogs with septic peritonitis. A randomized controlled trial is necessary to evaluate ODSH as a novel therapeutic in the treatment of septic peritonitis.

Hemolytic anemia blunts the cytokine response to transfusion of older red blood cells in mice and dogs.

BACKGROUND: Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions. STUDY DESIGN AND METHODS: C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion. RESULTS: Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p < .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs. CONCLUSION: These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.

Evaluation of subcutaneous versus intravenous administration of apomorphine for induction of emesis in dogs.

OBJECTIVE: To prospectively compare the effectiveness and any adverse effects of apomorphine administered SC or IV for induction of emesis in dogs. ANIMALS: 42 client-owned dogs. PROCEDURES: Dogs for which emesis induction was deemed appropriate by the attending clinician were prospectively randomized to receive apomorphine (0.03 mg/kg [0.01 mg/lb]) either SC (n = 20) or IV (22). Data collected included whether emesis was successfully induced, time from drug administration to emesis, number of emetic events, and adverse events (eg, sedation, protracted vomiting, or other). RESULTS: Of the 20 dogs given apomorphine SC, 16 (80%) vomited. Of the 22 dogs given apomorphine IV, 18 (82%) vomited. With regard to route of administration, the number of dogs in which emesis was induced did not differ significantly. Median time to the first emetic event was 13.5 minutes (range, 3 to 32 minutes) in the SC treatment group and 2 minutes (range, 1 to 5 minutes) in the IV treatment group; the difference was significant. There was no significant difference in the number of emetic events or frequency of adverse events between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Apomorphine administered SC or IV reliably induced emesis in dogs. Compared with SC administration of apomorphine, the time from drug administration to emesis associated with IV administration was significantly shorter, a finding that has clinical importance.

Successful Management of Severe Bromethalin Toxicosis in a Dog.

ABSTRACT The use of bromethalin rodenticides has risen since 2011, and in some states, it is the most common rodenticide ingestion reported to poison control. Although intravenous lipid emulsion (ILE) has been previously reported to lower serum desmethylbromethalin levels in an asymptomatic dog, and repeated mannitol has been investigated in a laboratory setting, there are no published reports of successful treatment of symptomatic bromethalin toxicosis in dogs. A 9 yr old castrated male Norwich terrier was evaluated for obtunded mentation, seizures, cranial nerve deficits, and tetraparesis secondary to bromethalin toxicosis. The patient was treated with ILE, mannitol, and ginkgo biloba and returned to normal neurological function. Bromethalin exposure was confirmed by serum desmethylbromethalin levels. Previous literature indicates that the prognosis for patients who suffer from symptomatic bromethalin toxicosis is poor to grave, and the return to normal neurological function after severe toxicosis has not been reported. ILE, mannitol, and ginkgo biloba are readily available and relatively inexpensive, and in combination may be of benefit in symptomatic bromethalin intoxication.

Retrospective comparison of thromboelastography results to postmortem evidence of thrombosis in critically ill dogs: 39 cases (2005-2010).

OBJECTIVE: To determine whether there is an association between thromboelastography (TEG) data and necropsy evidence of thrombosis in a cohort of critically ill dogs. DESIGN: Retrospective study (2005-2010). SETTING: University teaching hospital. ANIMALS: Thirty-nine client-owned critically ill dogs for which TEG was performed within 7 days of complete necropsy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thrombi were found in 26 (67%) dogs. Spayed females (n = 20) were significantly more likely to have thrombosis (P = 0.0127). No significant association was found between presence of thrombosis and any TEG parameter, the calculated coagulation index, results of coagulation testing, type of vascular access, or clinical diagnosis. D-dimers were significantly higher in dogs with thrombosis (P = 0.0207) and a weak positive correlation was found between D-dimer value and number of sites of thrombosis (ρ = 0.18, P = 0.0045). Dogs with WBC > 16 × 10(3) /µL were more likely to have thrombosis compared to others (odds ratio 5.56, 95% confidence interval 1.2-25.7, P = 0.025). CONCLUSIONS: This study found no association between any TEG parameter and the presence of thrombosis on postmortem examination.

Assessment of dexmedetomidine and other agents for emesis induction in cats: 43 cases (2009-2014).

OBJECTIVE: To compare the use of dexmedetomidine hydrochloride, xylazine hydrochloride, and hydrogen peroxide for emesis induction in cats. DESIGN: Retrospective case series. ANIMALS: 43 client-owned cats for which emesis induction was attempted because of known or suspected toxicant ingestion or recent ingestion of a string foreign body. PROCEDURES: Data collected from the cats' medical records included type, dose, and route of administration of emetic agent; outcome of attempted emesis induction; time until emesis or postemesis administration of a reversal agent (to counter sedative effects of the emetic agent); and adverse events. RESULTS: Emesis induction was attempted by oral administration of hydrogen peroxide (n = 3) or IM or IV administration of xylazine (25 [including 1 cat that had already received hydrogen peroxide]) or dexmedetomidine (16). No cat that received hydrogen peroxide vomited. Emesis was induced in 11 of 25 xylazine-treated cats and in 13 of 16 dexmedetomidine-treated cats. Dexmedetomidine was more likely to cause vomiting than xylazine (OR, 5.5; 95% confidence interval, 1.1 to 36). The median dose of dexmedetomidine that caused emesis was 7.0 µg/kg (3.2 µg/lb; range, 0.96 to 10.0 µg/kg [0.44 to 4.55 µg/lb]). The elapsed time until emesis or postemesis reversal agent administration was recorded for 5 xylazine-treated cats (median interval, 10 minutes [range, 5 to 175 minutes]) and 10 dexmedetomidine-treated cats (median interval, 5 minutes [range, 1 to 12 minutes]). Sedation was the only adverse effect, occurring in 2 xylazine-treated cats and 1 dexmedetomidine-treated cat. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dexmedetomidine can be used successfully to induce emesis in cats.

Presumptive central nervous system cuterebriasis and concurrent protein-losing nephropathy in a dog.

OBJECTIVE: To describe the clinical course and successful management of a dog suspected to have central nervous system (CNS) Cuterebra larval migration and concurrent protein-losing nephropathy (PLN). CASE SUMMARY: A 1-year-old castrated male mixed breed dog was diagnosed with presumptive CNS cuterebriasis based on history, progressively deteriorating mentation, seizures, and magnetic resonance images showing a tubular lesion consistent with a migrating Cuterebra tract. Additionally, serum biochemistry and urine analyses revealed the development of a severe PLN. Surgical removal of the Cuterebra was attempted unsuccessfully, and subsequently, the dog was treated with ivermectin, antihistamines, anticonvulsants, and a tapering dose of glucocorticoids. Over several weeks the dog's neurologic status improved and the PLN resolved completely. NEW OR UNIQUE INFORMATION PROVIDED: This case describes successful management of presumptive CNS cuterebriasis in a dog. It is also, to our knowledge, the first report of PLN associated with cuterebriasis in the veterinary literature.