Gas chromatography-tandem mass spectrometric analysis of metaldehyde and its metabolite acetaldehyde in initial assessment of hemodialysis abatement of toxicity in live animals.

Metaldehyde consumption by pets and other mammals constitute medical emergencies ideally requiring rapid poison removal. The purpose of this study was three-fold: 1) development of a sensitive method for metaldehyde quantitation in patient serum samples by gas chromatography combined with tandem quadrupole mass spectrometry (GC/MS/MS); 2) development of a sensitive method for quantitation of the volatile metaldehyde metabolite acetaldehyde by headspace analysis combined with GC/MS/MS; and 3) an initial assessment of the efficacy of combined dialysis and hemoperfusion treatments in diminishing toxin loads in canine victims of metaldehyde poisoning. Both mass spectrometric approaches relied on Multiple Reaction Monitoring (MRM) methodologies. Metaldehyde extracted via liquid-liquid partitioning from serum was detected with a limit of quantitation (LOQ) of 7.3 ± 1.4 ng/mL with linearity in the range 1-250 ng/mL with accuracy improved by inclusion of a deuterated metaldehyde internal standard. Acetaldehyde was determined to have an LOQ of 0.39 µg/mL with linearity in the range 1-1000 µg/mL. The developed methodologies were applied to canine samples taken over various time points during dialysis treatment. Two of three canine patients showed significant abatement of metaldehyde levels by over 50-fold from initial concentrations while a third was shown to be negative with no measureable metaldehyde. The toxic metabolite acetaldehyde was found in one of the metaldehyde-poisoned patients and the detected acetaldehyde was also reduced by roughly 200-fold during the course of treatment. The designed mass spectrometric techniques were thus successful in demonstrating the efficacy of the applied dialysis-hemoperfusion methods which may find wider applicability against other potentially lethal toxins in poisoned patients in future studies.

Successful resuscitation and neurological monitoring of a dog with out-of-hospital cardiopulmonary arrest due to pentobarbital overdose.

OBJECTIVE: To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication. CASE SUMMARY: A 10-year-old, male intact Jack Russell Terrier was referred for management of refractory status epilepticus and presented dead on arrival. After 7 minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, but the dog remained comatose, apneic, and lacked brainstem reflexes on neurological examination 6 hours following resuscitation. Magnetic resonance imaging showed polioencephalomalacia consistent with prolonged epileptiform activity, and EEG was initially concerning for electrocerebral inactivity. Following supportive care that included short-term mechanical ventilation, the dog made a full recovery and was discharged from the hospital alive 7 days postresuscitation. It was later revealed that the dog had been administered an unknown amount of pentobarbital during transportation, which likely contributed to the OHCA, clinical, and EEG findings. NEW INFORMATION PROVIDED: This is the first report to describe the full recovery and hospital discharge of a dog suffering OHCA and the first description of EEG findings in a clinical veterinary patient following cardiopulmonary arrest and successful resuscitation. Factors likely contributing to successful patient outcome and potential benefits and limitations of EEG in monitoring postcardiac arrest patients are discussed.

Hemodialysis as emergency treatment of a severe baclofen intoxication in a 3 kg dog.

OBJECTIVE: To describe the clinical efficacy and drug removal kinetics of hemodialysis (HD) as emergency treatment in a small size dog with severe baclofen intoxication. CASE DESCRIPTION: A 2-year-old dog was presented in stupor to the emergency service a few hours after ingestion of up to 25 mg of baclofen. Medical stabilisation was attempted but was unsuccessful in improving the neurological condition and the patient rapidly progressed to coma. A 4-h session of HD was performed in emergency with near complete resolution of neurological signs and only mild disorientation by the end of the treatment. No adverse side effects occurred during HD. Baclofen concentration was measured serially during the session. Drug extraction ratio, clearance and mass removal by the dialyser were calculated. Dialytic elimination rate constant (Kd ) was seven times higher than the intrinsic elimination rate constant (Kintr ) and the half-life (t½) during HD was nearly nine times shorter than the endogenous one. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case report providing pharmacokinetic data associated with HD treatment of severe baclofen intoxication in a dog.

Diagnosis of post-attenuation neurological signs syndrome in a cat with refractory status epilepticus and clinical response to therapeutic plasma exchange.

Case summary: An 8-year-old female spayed British Shorthair cat that underwent surgical portosystemic shunt (PSS) attenuation developed progressive neurological signs 7 days postoperatively. Neurological signs progressed, despite medical management, and seizure activity became rapidly refractory to anticonvulsants. The diagnosis of post-attenuation neurological signs (PANS) was made based on the timing of the occurrence of clinical signs following surgery, absence of hyperammonaemia and suggestive MRI findings of the brain. The cat developed status epilepticus that required treatment with general anaesthesia and mechanical ventilation, from which the cat could not be effectively weaned without the recurrence of seizures. Therapeutic plasma exchange (TPE) was performed as a rescue therapy for PANS and associated refractory status epilepticus. A total of two plasma volumes were processed during one single TPE session. The seizure activity resolved immediately after the TPE session, the cat showed progressive improvement of neurological signs and remained stable thereafter. No significant complications associated with the TPE were observed. The cat was discharged 11 days after admission and was fully recovered. Relevance and novel information: This is an unusual report of PANS diagnosed in a cat based on clinical and MRI findings. The cat developed refractory status epilepticus and had a positive outcome following TPE as rescue therapy. The MRI findings in this report could be useful for the diagnosis of PANS in cats. We speculate that TPE could be taken into consideration as a possible therapeutic intervention in PANS syndrome.

Self-Reported Clinical Practice of Small Animal Cardiopulmonary Resuscitation and Compliance With RECOVER Guidelines Among Veterinarians in Eight Western European Regions.

Introduction: The objective of this study was to assess whether small animal veterinarians across Western Europe are compliant with the 2012 cardiopulmonary resuscitation (CPR) guidelines by the Reassessment Campaign on Veterinary Resuscitation (RECOVER). Methods: A previously published online questionnaire from Switzerland was adapted and translated into 7 languages, corresponding to national languages in Austria, France, Germany, Ireland, Italy, Liechtenstein, Netherlands, Portugal, Spain, and the United Kingdom. The survey was distributed via respective national veterinary organizations and social media outlets. A subset of questions was analyzed to evaluate respondent demographics, RECOVER guideline awareness, and to allocate composite compliance scores for CPR preparedness, basic life support (BLS) and advanced life support (ALS). Percentages of group total (95% confidence interval) were calculated. Multivariable logistic regression was used to evaluate the effects of region of practice, gender, age, specialty training, and guideline awareness on compliance. Odds ratios (95% confidence interval) were generated and significance set at P < 0.05. Results: Nine-hundred and thirty respondents were included in analysis. Awareness of and compliance with RECOVER guidelines varied widely across regions. Compliance with all assessed RECOVER guideline recommendations was highest in Germany/Austria [14% (7- 27%)] and lowest in France and Portugal [0% (0-3%)]. CPR preparedness compliance was higher in participants aware of RECOVER guidelines [OR 10.1 (5.2-19.5)], those practicing in Germany/Austria [OR 4.1 (1.9-8.8)] or UK/Ireland [OR 2.2 (1.3-3.7)], and lower in those practicing in Portugal [OR 0.2 (0.1-0.9)]. Specialty training [OR 1.8 (1.1-2.9)], guideline awareness [OR 5.2 (3.2-8.6)], and practice in Germany/Austria [OR 3.1 (1.5-6.5)], UK/Ireland [OR 2.6 (1.7-4.1)], or the Netherlands [OR 5.3 (2.0-14.2)] were associated with increased BLS compliance. ALS compliance was higher in participants with guideline awareness [OR 7.0 (2.9-17.0)], specialty training [OR 6.8 (3.8-12.1)], those practicing in Germany/Austria [OR 3.5 (1.3-9.6)], UK/Ireland [OR 4.0 (1.9-8.3)], or Spain [OR 3.2 (1.2-8.3)] and in younger survey participants [OR 0.9 (0.9-1.0)]. Conclusions: Awareness and compliance with RECOVER guidelines varied widely among countries surveyed, however overall compliance scores in all countries were considered low. Further research may highlight factors surrounding poor guideline awareness and compliance so targeted efforts can be made to improve veterinary CPR in Europe.

Acute nephrotic-range glomerular proteinuria following ibuprofen intoxication in two cats.

Case series summary: In this report we describe the origin of protein loss and development of acute kidney injury after ibuprofen intoxication in two cats. Two 13-month-old neutered male domestic shorthair siblings were presented with acute kidney injury (AKI) and severe glomerular proteinuria following witnessed ibuprofen intoxication 3 days prior. Both cats presented with severe azotaemia (creatinine >900 µmol/l [>10 mg/dl]) and severe proteinuria (urine protein:creatinine [UPC] >20, normal <0.5). Urine protein electrophoresis upon presentation revealed mainly albumin and primary glomerular protein losses. The proteinuria and azotaemia resolved completely within 5 days of hospital treatment (8 days after ingestion). Urine protein electrophoresis, once the azotaemia and proteinuria resolved (UPC 0.11; normal <0.5), had a similar pattern to the one from admission. Both cats made a full recovery with supportive care. Relevance and novel information: This is the first clinical report of AKI with nephrotic-range protein losses following ibuprofen intoxication in cats. We propose that this finding is due to idiosyncratic glomerular injury, as described in humans.

A prospective randomized open-label trial on the comparative effects of 6% hydroxyethyl starch 130/0.4 versus polyionic isotonic crystalloids on coagulation parameters in dogs with spontaneous hemoperitoneum.

OBJECTIVE: To evaluate the effects of 6% hydroxyethyl starch 130/0.4 (HES) and a polyionic isotonic crystalloid (CRYS) on standard coagulation tests and rotational thromboelastometry (ROTEM) in dogs with spontaneous hemoperitoneum (SHP). DESIGN: Prospective randomized open-label clinical study. SETTING: University teaching hospital. ANIMALS: Forty-two client-owned dogs presented with SHP. INTERVENTIONS: Dogs diagnosed with SHP and hypovolemic shock were randomly allocated to receive HES (10 mL/kg, n = 22) or CRYS (30 mL/kg, n = 20) intravenously over 20 minutes for hemodynamic stabilization. MEASUREMENTS AND MAIN RESULTS: Parameters measured before (T0 ) and after (T1 ) treatment were HCT, platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and extrinsic activated (EXTEM), intrinsic activated (INTEM), and extrinsic activated with platelet inhibition ROTEM assays. Data were analyzed as absolute values and as the percentage change from T0 to T1 . No significant differences between groups were detected in any variable at T0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T1 . Clot formation time in EXTEM was significantly prolonged (P = 0.037), and maximum clot firmness was significantly decreased (P = 0.038) in the HES group compared to the CRYS group at T1 . The percentage change in EXTEM clotting time (P = 0.012) and INTEM clot formation time (P = 0.031) was greater after HES than CRYS. Lysis indices remained at 100% for all ROTEM assays in both groups. CONCLUSION: Compared to a 3-fold volume of CRYS, administration of HES was associated with impairment in ROTEM parameters in dogs with SHP, but no evidence of hyperfibrinolysis was detected.

Striate Artery Infarct After Bilateral Carotid Artery Ligation (BCAL) in a Dog: A Multimodal MRI Study.

Bilateral carotid artery ligation has been reported as a lifesaving procedure to control severe hemorrhage. However, reports are sparse and little information is available regarding the potential risks associated with this procedure. We report an ischemic brain infarct as a complication after vascular surgery. A 3-year old, male intact border collie was presented for acute onset of forebrain signs 5 days after bilateral carotid artery ligation. Multimodal brain MRI including morphologic sequences, MR angiography, diffusion- and perfusion-weighted images were performed. MRI revealed a well-defined intra-axial lesion of the left caudate nucleus, with increased T2 and decreased T1 signal intensity and moderate heterogeneous peripheral contrast enhancement. The cerebral blood flow was reduced relative to the contralateral caudate nucleus. Images were consistent with a subacute lacunar ischemic infarct of the left striate artery. Additionally, multiple arterio-arterial anastomosis arising from the vertebral arteries were visible in the angiography sequences. Ischemic infarct due to thromboembolism should be considered as a possible complication associated with bilateral carotid artery ligation. Collateral blood supply can develop as early as 5 days after surgery.