Use of IV Lipid Emulsion for Treatment of Ivermectin Toxicosis in a Cat

Introduction

IV lipid emulsions (ILEs) have been used as a component of parenteral nutrition in human medicine since the early 1960s.¹ In 1998, Weinberg et al. described the use of ILE as a resuscitation aid for bupivacaine-induced cardiotoxicity in rats.² Then, in 2003, similar encouraging results were reported in a related study involving 12 dogs with bupivacaine-induced cardiotoxicity.³ Subsequently, lipid emulsions have been considered as a possible antidote for the treatment of different toxicities in both animals and humans.^4,5 In a recently reported case, a 2 yr old dog was successfully treated with an ILE after ivermectin ingestion.⁶ The purpose of this report was to describe the treatment of a cat with ILE after ivermectin ingestion and subsequent toxicity.

Case Report

A 1 yr old castrated male domestic shorthair weighing 4.04 kg was presented for treatment of accidental ivermectin ingestion. The cat was left alone indoors for approximately 4 hr. When the owner returned, the cat was laterally recumbent and lethargic. During that time, the cat had ingested an unknown amount of an equine formulated ivermectin anthelmintic paste^a. The cat was immediately presented to the primary care veterinarian.

On presentation to the primary care veterinarian, the cat was laterally recumbent, normothermic, tachycardic, and had deep respiratory excursions (but with a normal respiratory rate). He was also noted to be hyperesthetic. A 24-gauge IV catheter^b was placed in the right cephalic vein, and a 45 mL bolus of a balanced isotonic crystalloid solution^c was administered. The cat was maintained on the balanced isotonic crystalloid solution at a rate of 6 mL/hr (36 mL/kg/day) overnight.

The patient was re-evaluated the next morning and was noted to be laterally recumbent and hypothermic. Other physical exam findings were within normal limits. The patient was warmed with an external heating device^d and IV fluid therapy was discontinued. Approximately 24 hr after initial ivermectin ingestion, the patient was transferred to a tertiary care facility.

Upon admission to the tertiary care facility, rectal temperature was 35.4°C, heart rate was 160 beats/min, respiratory rate was 36 breaths/min with extremely shallow excursions, and indirect systolic blood pressure was 130 mm Hg. O₂ saturation measured by pulse oximetry^e was 88%, but improved to 93% with flow-by O₂ supplementation. An electrocardiogram showed a normal sinus rhythm. The cat remained laterally recumbent and obtunded, but demonstrated exaggerated responses to handling. Venous blood gas showed a pH of 7.266, the partial pressure of CO₂ was 52 mm Hg, and the partial pressure of O₂ was 52.9 mm Hg. Na, potassium, chloride, ionized Ca, glucose, and lactate were within normal reference ranges. Packed red blood cell volume was 36% and total protein was 60 g/L.

Initial treatments consisted of warming with an external heating device, flow-by O₂ supplementation, and administration of ocular lubricants^f. Following initial assessment, a 16 mL (4 mL/kg) bolus of an emulsion of 20% soybean oil in water^g was administered IV. That was followed by a constant rate infusion of lipid emulsion at a rate of 12 mL/hr (3 mL/kg/hr) for 4 hr. Upon discontinuation of the lipid emulsion, IV fluid therapy was initiated with a balanced isotonic crystalloid solution at a rate of 6 mL/hr (36 mL/kg/day). Within 30 min of finishing the initial bolus of lipid emulsion and starting the constant rate infusion, the cat’s breathing pattern underwent an obvious change with the excursions becoming deeper and more regular. At that time, a marked lipemia was noted on the spun hematocrit tubes. Within 5 hr of discontinuing the lipid emulsion, approximately 35 hr after ivermectin ingestion, the cat became appropriately responsive during handling. The exaggerated flailing ceased and the cat was able to maintain a normal “curled up” position when sleeping. He remained nonambulatory at that stage.

On day 2 of treatment at the tertiary care facility, the previously placed IV catheter was noted to be flushing poorly and was removed. A 20-gauge IV catheter was then placed in the left cephalic vein. The clinical improvements noted on the previous day were maintained, and the gross lipemia on the spun hematocrit tubes had resolved. Due to incomplete resolution of clinical signs, a second infusion of lipid emulsion was administered at a rate of 12 mL/hr (3 mL/kg) for 2 hr. Following lipid administration, IV fluid therapy was continued with the balanced isotonic crystalloid solution at a rate of 6 mL/hr (36 mL/kg/day). Following the second infusion, the cat was able to swallow soft food when syringe fed and supported sternally.

On day 3 of treatment, approximately 72 hr after ingestion, the cat began righting itself and standing with mild ataxia. The cat also began eating and drinking without assistance. Approximately 96 hr after ingestion, fluid therapy was discontinued and the patient was discharged from the hospital clinically normal except for a mild ataxia. The owner reported that the cat was completely normal during a telephone follow-up conversation 5 days after being discharged.

Discussion

Ivermectin is a macrocyclic lactone that is commonly used in both small and large animal practice. It belongs to the avermectin family of compounds and originates from the bacterium Streptomyces avermitilis. Ivermectin has excellent efficacy for the prevention and treatment of internal and external parasites at low doses, which explains its wide margin of safety.⁷ Ivermectin functions by potentiating glutamate-gated chloride channels and γ-aminobutyric acid-gated chloride channels in the nervous system, which leads to abnormal function.⁸

Although it is said to be infrequent, ivermectin toxicosis in the cat does occur. Signs of toxicity mainly involve the central nervous system and include mydriasis, depression, ataxia, recumbency, and even death.⁷ Multiple reports of ivermectin toxicosis involving dogs have been published; however, there are a limited number of case reports involving cats. Approximately 25% of the cats previously reported to have ivermectin intoxication ultimately died.^9–12 Of those cases reported, only one of the cats was an adult.

ILE as a treatment of intoxication with lipid soluble drugs is a rapidly expanding area of clinical practice in both human and veterinary toxicology. Two major theories exist as to possible mechanisms of action of ILE. The first is that lipid in the form of ILE acts as an energy substrate for the myocardium. In cases of cardiovascular collapse due to, for example, local anesthetic agents, the improved provision of myocardial energy substrate improves cardiac performance.⁵ The second and more widely accepted theory is that of a “lipid sink.” After administration of supraphysiologic doses of ILE, the drug is partitioned into a lipid compartment in the blood stream based on it’s solubility in lipid.⁵

The cat described in this case report was administered ILE therapy in a similar manner to previous reports. In most other reports, patients received ILE therapy relatively quickly after either ingestion or administration of the toxin in question.^4,6 Most of those patients responded rapidly to ILE therapy; however, the cat that in this report did not receive ILE therapy until approximately 24 hr after ingestion of the ivermectin compound. Clinical signs of intoxication were evident within 4 hr of ingestion, and the animal did not respond to traditional supportive care after 24 hr. The recovery period of this cat was similar to previous reports of cats that have survived intoxicaton with ivermectin but did not receive lipid treatment. That was likely due to the fact that the lipid treatment would not directly bind the ivermectin that was already in the central nervous system.^10–12 It was expected that the clearance of the drug from the CNS would take several days to clear completely, especially in cases of ingestion of a massive dose. The cat in this report, however, demonstrated a rapid improvement in breathing pattern shortly following the initial infusion of lipid emulsion. He was initially showing signs of hypoventilation as demonstrated by extremely poor chest excursions during inspiration. Unfortunately, arterial blood gases and either routine hemogram or biochemical profiles were not performed due to financial limitations. Additionally, a marked improvement in mentation was seen within 9 hr of starting lipid emulsion therapy.

Conclusion

It is difficult to attribute the patient’s recovery to one intervention in an isolated case report. In this case, however, administration of ILE was temporally associated with improvements in clinical signs. The cat ultimately went on to make a rapid and full recovery despite being very severely affected and having a delay in definitive therapy. ILE at previously reported doses was well tolerated in this cat and other than a transient lipemia, resulted in no adverse consequences. Timely treatment with ILE may be a valuable tool in the treatment of cats with ivermectin toxicity.