Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats

• Published in: Regional anesthesia and pain medicine Vol. 35; no. 2; p. 140
• Main Authors: Hiller, David B, Di Gregorio, Guido, Kelly, Kemba, Ripper, Richard, Edelman, Lucas, Boumendjel, Redouane, Drasner, Kenneth, Weinberg, Guy L
• Format: Journal Article
• Language: English
• Published: England 01.03.2010
• Subjects: Animals; Dose-Response Relationship, Drug; Emulsions - administration & dosage; Emulsions - toxicity; Fat Emulsions, Intravenous - administration & dosage; Fat Emulsions, Intravenous - toxicity; Lethal Dose 50; Male; Phospholipids - administration & dosage; Phospholipids - toxicity; Rats; Rats, Sprague-Dawley; Resuscitation; Soybean Oil - administration & dosage; Soybean Oil - toxicity
• ISSN: 1532-8651
• DOI: 10.1097/AAP.0b013e3181c6f5aa

Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.