1132

Abstract

Introduction: Multiple case reports with avermectin, a highly lipophilic insecticide, toxicity have been published in human and veterinary medicine. Intravenous treatment with lipid emulsion has been reported as a treatment option for a variety of lipophilic drug overdoses and toxicities. Extracorporeal blood purification with conventional hemodialysis or charcoal hemoperfusion has failed for the treatment of highly lipophilic toxins. Single pass albumin dialysis (SPAD) has shown promising effect for the treatment of highly protein bound drug overdoses, but has little or no effect against highly lipid bound toxins. We present a case of severe avermectin toxicity, which was treated with single pass lipid dialysis (SPLD). We replaced the albumin part of the dialysate with a 5% lipid solution to act as a second lipid sink for the extracorporeal removal of ivermectin. Case desription: A three year old, male Australian Shepherd presented to the emergency room with severe muscle tremors, hypersalivation, stupor and history of ivermectin ingestion 2 hours ago. Pertinent blood work showed a normal CBC and chemistry profile. His arterial blood gas analysis showed a respiratory acidosis with a pCO2 of 72 and a pH of 7.12. The patient was intubated, mechanical ventilation was initiated and he was treated with intravenous lipid emulsion. Despite the intravenous lipid therapy he remained comatose and ventilator depended. Due to the persistency of clinical signs, single pass lipid dialysis (SPLD) using a Gambro Prismaflex CRRT machine and a preparation of 5% lipid solution added to the dialysate was started. A six hour treatment with a projected Kt/V of 0.7 was prescribed. Blood samples were collected before and after 6 hours of treatment and submitted for ivermectin levels. The patient remained ventilator dependent for 3 more days and was successfully weaned of the ventilator on day 4. He made a full recovery, with normal physical exam and normal motor function after 4 weeks of supportive therapy. Discussion: To our knowledge this is the first case report of single pass lipid dialysis for a treatment of toxicity with a lipophilic substance. Pre-treatment level of ivermectin was 35 ppb and a drop to 25 ppb was noted after treatment, which represents an ivermectin reduction ratio of 29 %. The addition of a 5% lipid solution to the dialysate is believed to exert its beneficial effect by acting as a lipid "sink," causing lipophilic drugs to be redistributed into the expanded plasma lipid volume and decreasing free and tissue drug levels. The patient was an Australian Shepherd, who tested positive for multi –drug resistant gene (mdr1) mutation, which codes for the P-glycoprotein membrane transport molecule. This gene mutation disables the active removal of toxins through the blood-brain–barrier in this breed, explaining the long recovery for this patient. SPLD was efficient to decrease the amount of ivermectin with a relatively small dialysis dose (Kt/V of 0.7%) by 29 %. The normal plasma clearance in dogs is 2% per hour. This patient was initially treated with intravenous lipid therapy, which might have decreased the extracorporeal ivermectin reduction ratio. SPLD was an effective way to decrease the plasma levels of ivermectin in this patient. The lack of fast clinical response to the decreased plasma levels can partly be explained by the mdr1 gene mutation, which decreased the patient's ability of actively removing the drug from the brain tissue.