Lipid emulsion dosage for treatment as an adjuvant drug in the cat

Dear Editors, I read with interest the prospective randomised clinical study entitled ‘Alpha-chloralose poisoning in 25 cats: clinical picture and evaluation of treatment with intravenous lipid emulsion’ recently published in Journal of Feline Medicine and Surgery. ¹ The authors indicate that the administration of lipid emulsion had no notable effect on the level of alpha-chloralose in the blood or on the clinical signs in cases of alpha-chloralose poisoning in cats. ¹ Lipid emulsion is commonly used to treat systemic toxicity caused by intravenously injected local anaesthetics in humans. ² Additionally, it has been documented to reduce cardiovascular and central nervous system symptoms triggered by toxic doses of non-local anaesthetic substances in humans. ² I would like to discuss the dosage of lipid emulsion administered for treating alpha-chloralose poisoning in cats.

The authors administered a lipid emulsion at a dose of 1.5 ml/kg as an initial bolus, then continued with an infusion rate of 0.25 ml/kg/min (resulting in a total of 7.5 ml/kg over 30 mins). ¹ This lipid emulsion protocol is the same as the one suggested for treating systemic toxicity from local anaesthetics in humans. ³ Since larger animals have a lower metabolic rate, slower physiological processes and require smaller doses per unit of body weight, scaling dosage based solely on body weight for both humans and animals is not a viable approach. ⁴ Thus, dose adjustments from humans to animals should take into account body surface area. ⁴ Essentially, allometric scaling allows for dosage conversion by normalising based on body surface area. ⁴ To calculate the animal equivalent dose from a human dose, the human dose (in mg/kg) is multiplied by the correction factor (Km) ratio, which is the ratio of human Km to animal Km. ⁴ The Km is calculated as body weight divided by body surface area. ⁴ As an example, a 60 kg human with a body surface area of 1.62 m² has a Km of 37 kg/m². In comparison, a 4 kg cat with a body surface area of 0.252 m² has a Km of 15.87 kg/m². Therefore, the Km ratio for a human weighing 60 kg (with a Km of 37 kg/m²) and a cat weighing 4 kg (with a Km of 15.87 kg/m²) is approximately 2.33. Based on the dosage conversion formula above between humans and cats, a lipid emulsion regimen of 1.5 ml/kg for the initial bolus, followed by a continuous intravenous infusion of 0.25 ml/kg/min, for a 60 kg human, would be equivalent to a bolus of 3.50 ml/kg and a continuous infusion rate of 0.58 ml/kg/min for a 4 kg cat. The lower lipid emulsion dosage used in the recently published study, when compared with the dosage derived through allometric scaling, could have potentially influenced the outcomes of the study.^1,4 Using an allometrically adjusted dosage of lipid emulsion would be a sensible approach to achieve clinically meaningful results. Local anaesthetic systemic toxicity generally results from intravenous injection, while drug toxicity from non-local anaesthetic substances is typically due to oral ingestion. As a result, the pharmacokinetics of systemic toxicity from local anaesthetics differ from those of non-local anaesthetic drug toxicity that occurs via the enteral route. A lipid emulsion dosing regimen to maintain 1% plasma triglyceride for non-local anaesthetic drug toxicity in humans, aimed at providing a positive inotropic and scavenging effect, is suggested as follows: an initial bolus of 1.5 ml/kg, then an infusion at 0.25 ml/kg/min for an additional 3 mins, followed by a slower infusion rate of 0.025 ml/kg/min. ⁵ Nevertheless, additional studies are required to determine the optimal dose and timing for lipid emulsion resuscitation as a supplemental treatment for non-local anaesthetic drug toxicity in veterinary medicine.

Ju-Tae Sohn

Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 Beon-gil, Jinju-si, 52727, Republic of Korea

Email: jtsohn@gnu.ac.kr

The corresponding author responds:

Thank you for your interesting thoughts on the dosing of lipid emulsion in veterinary medicine and the potential effects of the dose selected in our study, ‘Alpha-chloralose poisoning in 25 cats: clinical picture and evaluation of treatment with intravenous lipid emulsion’. ¹ The dose chosen for our study is the most commonly recommended and utilised dose in veterinary medicine, where a positive effect has been reported. ⁶ Calculated doses based on metabolic rate, as suggested, might offer a better alternative, with individually adjusted doses targeting specific plasma levels potentially representing the gold standard.

However, this approach presents a few potential challenges. First, because feline lipid metabolism might differ from that of humans, a dose correction based solely on surface area might not be optimal. Second, since the mechanism of action of lipid emulsion in toxicity is not fully understood, the optimal effective plasma lipid level in cats remains unknown. In our study, all plasma samples were grossly lipaemic at 2 h in cats receiving lipid emulsion (not published), suggesting that triglyceride levels exceeded 3.4 mmol/l. ⁷ Unfortunately, the actual levels were not quantified. If lipid emulsion had been efficacious, one would have expected an effect throughout the period that the plasma was grossly lipaemic, which in our study was at least 2 h. Neither clinical signs nor plasma levels of alpha-chloralose were affected in the study.

The concern with higher doses is the potential for side effects, such as persistent hypertriglyceridaemia^8,9 and volume overload, especially in cats. Therefore, to optimise the dosing of lipid emulsion in cats, more studies are needed to investigate both the effects of lipid emulsions and their pharmacokinetics in this species.

Sandra Lundgren DVM

AWAKE Animal Hospital, Stockholm, Sweden