Treatment of ibuprofen intoxication with charcoal haemoperfusion in two dogs.

Case history: Two dogs presented separately to the Small Animal Hospital, University of Florida (Gainsville, FL, USA) for ingestion of ibuprofen. The first dog ingested 561.8 mg/kg ibuprofen in addition to paracetamol and caffeine and vomited prior to admission. This patient also received fluid therapy for 8 hours prior to charcoal haemoperfusion. The second dog ingested 500 mg/kg of ibuprofen and the owners induced vomiting with hydrogen peroxide prior to presentation. Due to the severity of clinical signs, both patients were treated with charcoal haemoperfusion.Clinical findings: The concentrations of ibuprofen in the blood of the dogs prior to treatment were 478 and 301 mg/L. During the treatment ibuprofen concentrations were reduced by 95.8% and 45.5%, respectively, with no treatment side effects and minimal clinical signs after treatment.Diagnosis: Toxicity due to ingestion of ibuprofen toxicity that was successfully treated with charcoal haemoperfusion.Clinical relevance: In the cases described here minimal benefit was seen after 3 hours of treatment using one haemoperfusion cartridge. This is in contrast to a previously published report in which dogs were treated for 6 hours with two charcoal haemoperfusion cartridges. This suggests that one cartridge may be sufficient. The amount of ibuprofen ingested was not a reliable predictor of the concentration in blood at the initiation of treatment. Charcoal haemoperfusion is an effective means of reducing plasma concentrations of ibuprofen, however, its use may be limited by its cost and availability.

Successful treatment of a severe 5-hydroxytrytophan intoxication using carbon hemoperfusion, hemodiafiltration, and mechanical ventilation in a dog.

OBJECTIVE: To describe the successful use of carbon hemoperfusion and hemodiafiltration in combination with mechanical ventilation (MV) to treat a severe intoxication of 5-hydroxytryptophan (5-HTP) in a dog. CASE SUMMARY: A dog ingested a minimum of 550 mg/kg of extended-release 5-HTP, resulting in serotonin syndrome that progressed to a comatose state and severe hypoventilation requiring MV. Extracorporeal carbon hemoperfusion coupled with hemodiafiltration was performed to remove 5-HTP from this patient. A carbon hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A total of 46.5 L of blood (4.89 L/kg) was processed during a 4.85-hour treatment. Serial plasma samples were obtained at 0, 60, 90, and 150 minutes during the session and 14 hours after the session. These samples were later analyzed for 5-HTP and serotonin concentrations. The extraction ratio of 5-HTP was 93.6%-98.9% through the carbon filter. The dog was weaned from MV within 8 hours after extracorporeal therapy and, after a full recovery, was successfully discharged. NEW OR UNIQUE INFORMATION PROVIDED: Despite an extensive review of the available literature, this appears to be the first reported case of using a carbon hemoperfusion, hemodiafiltration, and MV to treat severe serotonin syndrome secondary to 5-HTP intoxication in a dog. The combination of carbon hemoperfusion and hemodiafiltration can significantly reduce plasma 5-HTP concentrations after acute intoxication and may serve to decrease morbidity and mortality in patients with severe intoxication.

Use of extracorporeal hemoperfusion therapy in an adult horse with Clostridioides difficile colitis and severe systemic inflammatory response syndrome.

An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.

Synovial distribution of "systemically" administered acetylsalicylic acid in the isolated perfused equine distal limb.

BACKGROUND: This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature.Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC50 (half maximal effective concentration) determined in equine whole blood. RESULTS: The ASA concentration in the synovial fluid (n=6) reached a maximum of 4 µg/mL, the mean concentration over the entire perfusion period was 2 µg/mL. Maximum SA concentration was 17 µg/mL, the average was 14 µg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after "systemic" administration, respectively. CONCLUSIONS: ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated.

Extracorporeal blood purification in acutely intoxicated veterinary patients: A multicenter retrospective study (2011-2018): 54 cases.

OBJECTIVE: To investigate the clinical outcome and complications associated with extracorporeal blood purification (EBP) using either hemodialysis (HD), hemodialysis and hemoperfusion (HD + HP), or therapeutic plasma exchange (TPE) for the management of acute toxin ingestion in small animals. DESIGN: Retrospective, multicenter study from January 2011 to July 2018. SETTING: One university teaching hospital and one private specialty hospital. ANIMALS: Fifty-one dogs and 3 cats with a history of acute toxin exposure that could lead to severe morbidity and mortality, managed with different EBP techniques. MAIN RESULTS: Nonsteroidal anti-inflammatory drugs (38/54, 52%), baclofen (8/54, 15%), and ethylene glycol (7/54, 13%) were the most common toxicities treated with EBP. Membrane-based TPE was used most commonly (22/54, 40.7%), followed by HD (17/54, 31.5%) and then HD + HP (15/54, 27.8%). There was an 83.3% (45/54) overall survival, with 88.9% (8/9) of nonsurvivors having clinical signs prior to therapy. One third (18/54) of the patients never developed clinical signs of toxicity. Treatment complications occurred in 44.4% (24/54) of the animals, although only 18.5% (10/54) of these complications, such as mild hypotension, thrombocytopenia secondary to the HP cartridge, facial swelling after plasma transfusion for TPE, bleeding from catheter size secondary to heparinization, or clotting of the system, could be attributed to the EBP treatment. None of the nonsurvivors died because of EBP complications. CONCLUSIONS: Early initiation of EBP therapy might be considered as an alternative route of decontamination in severe acute toxicities with high potential for significant morbidity and mortality. The survival rate in small animals undergoing EBP is high despite exposure to potential lethal doses of toxins, and survival appears to be more likely if clinical signs of toxicity are not present at the time of EBP. Continued research is warranted with randomized controlled clinical trials to further evaluate the clinical efficacy and benefit of EBP.

Use of extracorporeal therapy in a dog with heatstroke.

OBJECTIVE: To describe the use of extracorporeal therapy (ECT) in the management of a dog with complications stemming from heatstroke. CASE REVIEW: A 3-year-old intact male Rhodesian Ridgeback was presented for heat-related illness following strenuous exercise. Despite intensive supportive care, the dog developed progressive and refractory hyperkalemia, hypoglycemia, neurologic dysfunction, acute kidney injury (AKI), and pulmonary dysfunction. Four ECT sessions were performed in this dog, consisting of 4 intermittent hemodialysis (HD) sessions, the first 2 of which concurrently utilized hemoperfusion with a cytokine adsorption filter. Interleukin-6 (IL-6), IL-8, IL-10, and monocyte chemoattractant protein-1 were detected in samples collected during the first ECT session. Despite an initial decrease in their concentration, the concentrations of these cytokines ultimately rose over the course of the ECT session. Rapid and sustained glycemic and electrolyte control were achieved after the first ECT session, although AKI and muscle injury persisted. The dog survived to discharge and was nonazotemic 3 months following initial management. NEW OR UNIQUE INFORMATION PROVIDED: Heatstroke is a common, potentially catastrophic, occurrence in dogs. To the authors' knowledge, this represents the first clinical use of ECT consisting of HD and cytokine adsorption in the management of severe heat-related illness in a dog. The use of ECT for the management of complications from severe heatstroke in dogs warrants further investigation.

Efficacy of a single session in-series hemoperfusion and hemodialysis in the management of carprofen overdose in two dogs.

OBJECTIVE: To describe the efficacy of in-series hemoperfusion and hemodialysis in 2 dogs with carprofen overdose. CASE SUMMARY: This report describes the treatment of 2 dogs following accidental carprofen overdoses who underwent a single in-series hemoperfusion and hemodialysis session. Serial serum carprofen concentrations were measured before, during, and after the session. The first patient's session lasted 5 hours, with the largest decrease in serum carprofen concentrations occurring during the first hour of treatment. The carprofen clearance during the following 4 hours of treatment decreased substantially compared to the first hour and was not different from the patient's intrinsic clearance of carprofen after the session was completed. Based on the findings from the first case, the second patient was treated with a 1 hour single hemoperfusion and hemodialysis session. Our results support the hypothesis that carprofen is not effectively removed by conventional hemodialysis and the efficacy of hemoperfusion is short lived due to rapid saturation of the charcoal filter. Once filter saturation occurs, the extracorporeal session is no longer efficacious. Using in-series hemoperfusion and hemodialysis is of benefit to correct the side effects seen with hemoperfusion alone, and hourly charcoal filter replacement may extend the efficacy of treatment in removing carprofen. NEW OR UNIQUE INFORMATION PROVIDED: This is the first published report of in-series hemoperfusion and hemodialysis being used to treat carprofen overdose in a dog. In these 2 cases, the intrinsic clearances of the patients were shown to be equivalent to that of standard hemodialysis alone, indicating that hemodialysis does not produce any advantage in carprofen clearance. In this limited report, we suggest that the efficacy of hemoperfusion in removing carprofen is short-lived, and extending the treatment beyond the first hour does not produce any therapeutic benefit. In order to extend the efficacy of hemoperfusion, hourly replacement of the charcoal filter should be considered.

Successful treatment of a severe cannabinoid toxicity using extracorporeal therapy in a dog.

OBJECTIVE: To describe the use of extracorporeal therapy (ECT) to treat severe cannabinoid intoxication in a dog with severe hyperlipidemia. CASE SUMMARY: A 7-month-old female intact Labrador Retriever presented with seizures and severe hyperesthesia that were refractory to multiple anticonvulsant medications and required induction of general anesthesia with propofol and mechanical ventilation. The dog's urine yielded a strong positive signal for delta-9-tetrahydrocannabinol (THC) on urine drug test and exposure to THC oil was confirmed by the owner. Bloodwork revealed severe hyperlipidemia such that IV lipid emulsion was considered contraindicated. The dog was treated with a 3-hour ECT session, using charcoal hemoperfusion and hemodialysis in series. Neurologic signs improved during the session and mechanical ventilation was discontinued. Immediately after the session, the dog's mentation was significantly improved and seizures and hyperesthesia had ceased, although the dog remained moderately ataxic. The dog was hospitalized for 36 hours following the ECT session for continued monitoring. The dog fully recovered and was successfully discharged. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first published report to document ECT to treat THC intoxication in veterinary medicine. ECT may be considered as a treatment option for severe THC intoxication that is refractory to standard therapy or where severe hyperlipidemia precludes use of IV lipid emulsions.

Use of charcoal hemoperfusion and hemodialysis in the treatment of methotrexate toxicosis in a dog.

OBJECTIVE: To describe the successful use of charcoal hemoperfusion (HP) and hemodialysis (HD) in a dog in the treatment of methotrexate (MTX) toxicosis. CASE SUMMARY: An American Pit Bull Terrier accidentally ingested 56.8 mg/m2 of MTX. The patient's initial serum MTX concentration was 0.11 µmol/L. At this dosage, myelosuppression and gastrointestinal epithelial necrosis have been reported. Charcoal HP and HD in series were used to enhance elimination of MTX. Serial serum samples were obtained during the session at 0, 30, 60, 90, 120, 150, and 180 minutes and 12 hours after the session. These were later analyzed for MTX concentrations. Clearance of MTX was 73% and extraction ratio was 63% within the first 30 minutes of HP/HD. A 3-hour session eliminated all detectable traces of MTX. The dog tolerated the session well and did not develop any clinical signs of MTX toxicosis. NEW OR UNIQUE INFORMATION PROVIDED: HP and HD together were highly effective in enhancing elimination of MTX from this patient. The prompt use of extracorporeal techniques decreased toxic concentrations of MTX to safer values, which prevented myelosuppression and gastrointestinal injury. HP and HD in conjunction or in place of traditional therapy may be a viable option for the treatment of acute toxic exposures to MTX.

Treatment of acute kidney injury associated with cyclosporine overdose in a dog using hemodialysis and charcoal hemoperfusion.

OBJECTIVE: To describe the management of cyclosporine overdose using hemodialysis and hemoperfusion in a dog. CASE SUMMARY: A 6-year-old, spayed female Australian Shepherd was presented for treatment of cyclosporine overdose and acute kidney injury. Five days prior to presentation, the dog had been diagnosed by its referring veterinarian with immune-mediated thrombocytopenia. Treatment was initiated with prednisone, but since no response was noted, azathioprine (50 mg PO q 24 h) and cyclosporine (6 mg/kg IV q 24 h) were added. On day 4, an overdose of cyclosporine (33 mg/kg IV) was administered accidentally. Upon presentation, serum biochemistry panel revealed azotemia [creatinine, 521.6 µmol/L (5.9 mg/dL); BUN, 59.3 mmol/L (166 mg/dL)], increased activities of liver enzymes, and hyperbilirubinemia. Due to the presumed diagnosis cyclosporine overdose and acute kidney injury, a combined hemodialysis and charcoal hemoperfusion treatment was planned. Hemosorba CH-350 charcoal hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A 3-hour treatment was performed and a total of 0.74 L/kg of blood was processed. Pretreatment blood cyclosporine concentration was 960 nmol/L (1154 ng/mL) and decreased to 440 nmol/L (529 ng/mL) posttreatment (54% fractional reduction, 18% per hour). Thirty-one hours following treatment, blood cyclosporine concentration was 220 nmol/L (265 ng/mL; 1.5% decrease per hour). Twelve days following presentation to our hospital, the dog was euthanized due to lack of response to medical management. NEW OR UNIQUE INFORMATION PROVIDED: Combined hemodialysis and charcoal hemoperfusion treatment can significantly reduce blood cyclosporine concentrations following acute intoxication or overdosage, and should be considered as an option for decontamination in such cases.

Evaluation of the in vitro efficacy of hemodialysis, hemoperfusion, and the combined approach on the removal of metaldehyde from canine plasma.

OBJECTIVE: To evaluate the effect of hemodialysis, hemoperfusion, and a combined approach on the removal of metaldehyde from canine plasma. DESIGN: In vitro study. SETTING: University veterinary teaching hospital laboratory. ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Metaldehyde-fortified canine plasma was prepared. Hemodialysis (HD), charcoal hemoperfusion (HP), and in-series hemodialysis and charcoal hemoperfusion (HD/HP) were applied in triplicate to eliminate metaldehyde from plasma. Plasma samples were obtained before starting the procedure and subsequently after every processed total plasma volume until plasma had been processed 10 times. Plasma metaldehyde concentration was quantitatively assayed by gas chromatography-mass spectrometry. Statistical analysis was performed using one-way ANOVA, repeated measures ANOVA, and Bonferroni post hoc test, and by calculating the coefficient of variation from duplicate measurements, binomial distribution, and by Bland-Altman analysis. Statistically significant reduction in metaldehyde concentration was reached by all 3 techniques. Reduction of metaldehyde concentration of more than 95% was achieved after processing the plasma volume 4 times applying HD, 8 times applying HP, and 2 times applying HD/HP. Efficacy in reduction of metaldehyde concentration differed significantly between the 3 procedures (P < 0.001). In-series hemodialysis and charcoal hemoperfusion was more effective in metaldehyde removal than HD (P = 0.003) and HP (P < 0.001), and HD was more effective than HP (P = 0.002). CONCLUSIONS: Metaldehyde was effectively removed by all applied extracorporeal blood purification techniques in vitro. However, the combination of both techniques was more effective than HD or HP alone. Further clinical studies are warranted to confirm therapeutic benefits in patients.

Treatment of ibuprofen toxicity with serial charcoal hemoperfusion and hemodialysis in a dog.

OBJECTIVE: To describe the efficacy of serial charcoal hemoperfusion and hemodialysis in removing ibuprofen from a dog with severe clinical signs of toxicity. CASE SUMMARY: A dog ingested a minimum of 2,200 mg/kg of ibuprofen resulting in progressive neurologic dysfunction that progressed to a comatose state by the time of presentation. Extracorporeal charcoal hemoperfusion coupled serially with hemodialysis was performed to remove ibuprofen from this patient. Serial charcoal hemoperfusion and hemodialysis therapy resulted in complete reversal of the neurologic dysfunction in this dog. No evidence of acute kidney or hepatic injury was observed. Serum ibuprofen concentrations confirmed the efficacy of this treatment. NEW INFORMATION PROVIDED: This report details the technique for extracorporeal extraction of ibuprofen, a methodology that could be employed for other toxicities due to substances with similar pharmacokinetics. Complications and limitations (eg, saturation of the charcoal cartridge) of the therapy are discussed.

Amanita mushroom poisoning: efficacy of aggressive treatment of two dogs.

Amatoxins, the primary toxins found in mushrooms of the genus Amanita, are very toxic to dogs. Acute fulminant liver failure and death can occur within a few days of ingestion. By their curious nature, dogs, especially young dogs, are prone to ingest mushrooms. Early identification of suspect mushrooms, and prompt emergency measures aimed at decreasing absorption of the toxins can improve the chance of survival. Knowing the major clinical syndromes associated with Amanita mushroom toxicosis can help direct the treatment and supportive care of affected animals and improve survival rates. We describe 2 cases in dogs with confirmed ingestion of Amanita phalloides and Amanita ocreata resulting in fulminant liver failure. Death occurred in 1 dog despite aggressive treatment measures including hemoperfusion, while aggressive measures resulted in a favorable outcome in the other dog.

Comportamento clínico e perfil hematológico de cães intoxicadosexperimentalmente com carbamato (Aldicarb) e submetidosà hemodiálise e hemoperfusão / Clinical evaluation and blood profile of dogs experimentally intoxicated by carbamate (Aldicarb) and submitted to hemodialysis and hemoperfusion

Técnicas dialíticas são estudadas a fim de se verificar suas reais contribuições no tratamento das mais diversas formas deintoxicações. Esta pesquisa foi realizada com o objetivo de avaliar o comportamento clínico e o perfil hematológico de cãesintoxicados com cabamato (Aldicarb) e submetidos a duas diferentes técnicas dialíticas: hemodiálise e hemoperfusão. Quinzecães adultos, sem raça definida foram intoxicados experimentalmente com 4,97mg/kg de peso vivo de Aldicarb, por via oral.Todos os animais, para controle dos efeitos clínicos provocados pela droga, foram medicados 30 minutos e uma hora após aingestão, com sulfato de atropina e benzodiazepínico (Diazepam), ambos na dose de 1mg/kg. Esses cães foram divididos emtrês grupos experimentais, compostos de cinco animais cada, denominados grupos I, II e III. Os animais do grupo II e do grupoIII, três horas após administração do Aldicarb foram submetidos a sessões de duas horas de hemodiálise e de hemoperfusão,respectivamente. Os animais do grupo I serviram de controle, não tendo sido submetidos a nenhum tratamento dialítico. Aintoxicação provocada pelo aldicarb foi capaz de causar alterações clínicas manifestadas por vômito, sialorréia, diarréia,incontinência urinária, fasciculações e alterações no perfil hematológico relacionadas principalmente a hemoconcentração.Houve leucocitose e aumento no número absoluto de neutrófilos em todos os animais 30 minutos após administração docarbamato. Não foram observadas diferenças clínicas entre os animais do grupo controle e os animais tratados por hemodiáliseou hemoperfusão. Após a sessão de hemoperfusão ocorreu discreta redução no número dos leucócitos, com diminuição dosvalores absolutos de eosinófilos, basófilos, monócitos e linfócitos. Nenhuma das técnicas foi efetiva em retirar o Aldicab doorganismo.

The aim of this work was to study the contribution of dialysis techniques, hemodialysis and hemoperfusion, after poisoning byAldicarb (carbamate), an anticholinesterasic compound, in dogs. Fifteen adult mongrel dogs were experimentally intoxicated by4.97mg/kg of Aldicarb orally. All animals, to prevent and treatment of clinical signs received a standard treatment with atropinesulfate (1mg/kg) and benzodiazepine (1mg/kg), administered endovenously 30 minutes and one hour after poisoning. Thedogs were separated in three groups: group I (control), group II (hemodialysis) and group III (hemoperfusion) with five animalsin each. Hemodialysis and hemoperfusion were performed three hours after poisoning, through a double lumen catheterimplanted in the jugular vein. Symptoms like vomiting, diarrhea, urinary incontinence and muscle fasciculation were observedafter poisoning in all groups. It was observed increase of leucocytes and neutrophils, 30 minutes after carbamate administration.Any clinical difference was observed after therapy with hemodialysis and hemoperfusion. After hemoperfusion occurred decreaseof total leukocyte, eosinophil, basophile, monocyte and lymphocyte. None of the techniques were effective to withdraw theAldicarb compound from the organism.