Manual plasma exchange to treat an accidental overdose of intravenous lipid emulsion in a dog with baclofen toxicosis

Abstract

CASE DESCRIPTION An approximately 2-year-old sexually intact male German Shorthair Pointer was presented for treatment of baclofen toxicosis. CLINICAL FINDINGS The dog had signs of severe baclofen toxicosis (no gag reflex, intermittent vocalization, and stupor) and received intravenous lipid emulsion (142 mL/kg) as a constant rate infusion over 11 hours. Severe hypertriglyceridemia (29,221 mg/dL; reference interval, 19 to 133 mg/dL) developed, followed by cardiovascular depression (poor peripheral perfusion, hyperlactatemia, and hypertension), severe hypoglycemia (26 mg/dL), acute kidney injury (serum creatinine, 3.6 mg/dL), intravascular hemolysis, and coagulopathy (hypocoagulable thromboelastogram and marked bilateral epistaxis). TREATMENT AND OUTCOME Therapeutic plasma exchange was performed in 4 stages to treat the hypertriglyceridemia. For each stage, an approximately 500-mL aliquot of blood (22 mL/kg) was removed and centrifuged, and the patient’s RBCs and allogenic fresh-frozen plasma were returned to the dog. Approximately 1.2 times the dog’s plasma volume was exchanged, reducing the serum triglyceride concentration to 1,349 mg/dL and improving the dog’s cardiovascular function and coagulation. Hours after the procedure was completed, the dog regurgitated and developed acute respiratory distress as a result of presumptive aspiration pneumonia, and the owner elected to have the dog euthanized. CLINICAL RELEVANCE Veterinarians should be aware of possible complications associated with administration of intravenous lipid emulsion, and veterinary-specific guidelines for the maximum dose of intravenous lipid emulsion should be developed to help prevent adverse effects. TPE appears to be an effective method for treating iatrogenic hypertriglyceridemia in dogs.

Successful treatment of bifenthrin toxicosis using therapeutic plasma exchange

“…17 Although no adverse effects attributable to lipid therapy were noted in this case report, adverse effects reported in veterinary medicine include hypertriglyceridemia, pancreatitis, coagulation disturbances, intraocular lipid deposits, and respiratory distress. 4 The severe hypocalcemia reported in this case is likely the cause of CPA given the exposure to citrate, severe sinus bradycardia, lack of calcium supplementation during TPE, and return of spontaneous circulation after calcium gluconate administration, although the severity of bifenthrin toxicosis could also have caused CPA. Bunker et al 18 reported cardiac arrest in dogs after IV citrate administration, with ionized calcium concentrations ranging from 0.16 to 0.55 mmol/L.…”

“…The postmortem analysis was performed using gas chromatography-mass spectrometry, which confirmed high concentrations of bifenthrin in the liver and kidney. 1 Epstein et al 4 performed manual TPE on a patient with an iatrogenic intralipid emulsion overdose in an attempt to treat the patient's baclofen toxicosis. They saw no appreciable decrease in plasma baclofen concentrations, but their method was highly successful in removing intralipids by documenting a decrease in serum triglycerides by more than 77%.…”

“…Baclofen is a drug that, like bifenthrin, also has a large volume of distribution, but perhaps other more favorable pharmacokinetic parameters of bifenthrin made it a more amenable compound to TPE. 4 It remains unclear as to whether TPE could have had a synergistic effect on bifenthrin elimination after multiple intralipid infusions. There has been conflicting evidence reported in the human literature regarding the use of TPE with various drug overdoses, such as phenytoin and vancomycin, due to minimal drug concentrations in the plasmapheresate despite a decline in serum drug concentrations.…”

“…[14][15][16] The principle theory behind the beneficial effect of intralipids is the creation of a lipid sink in which lipophilic drugs move into the intravascular compartment due to their high partition coefficient, thereby facilitating elimination. 4 The Log P of bifenthrin is ∼7, making it a highly lipophilic compound and suitable for intralipid emulsion therapy. 14,15 The high serum concentration of bifenthrin detected prior to TPE could have been influenced by recent intralipid therapy (∼4 h prior to blood collection).…”

“…2 Therapeutic plasma exchange (TPE) is an extracorporeal technique that has been used in veterinary medicine for nonsteroidal antiinflammatory toxicoses, immune-mediated disorders, myasthenia gravis, and other disease states. [4][5][6][7] This modality is usually best suited for large, highly plasma protein-bound molecules, drugs with low volumes of distribution, and long elimination half-lives. [6][7][8] During TPE, the patient's blood is separated into its cellular components with the use of centrifugation or filtration through a semipermeable membrane.…”