A lipid emulsion (Intralipid) 20%
|Trade names||Intralipid, Nutrilipid, others|
|Other names||Fat emulsion, lipid emulsion therapy, lipid resuscitation therapy|
|Main uses||Parenteral nutrition, certain overdoses|
|Typical dose||100 ml dose of 20% emulsion (overdose)|
|AHFS/Drugs.com||FDA Professional Drug Information|
Lipid emulsion, sold under the brand name Intralipid among others, is a oil based solution for intravenous use. They are traditionally used as part of parenteral nutrition. They are also used to treat a number of toxicities including local anesthetic, beta-blocker, calcium channel blocker, organophosphate, and antipsychotic.
Side effects are generally few, though may include allergies, pancreatitis and adult respiratory distress syndrome. Use may be complicated by certain fungal infections. How it works in toxicity is not entirely clear.
Lipid emulsions became available for medical use in 1961. It use for toxicity began in 1998. Different versions are made from different source. Common sources include soy bean, coconut, olive, eggs, and fish. In the United States it costs about 47 USD per 250 ml of 20% emulsion as of 2021.
Intralipid and other balanced lipid emulsions provide essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid. The emulsion is used as a component of intravenous nutrition for people who are unable to get nutrition via an oral diet.
Local anaesthetic toxicity
Vehicle for other medications
The dose for anesthetic toxicity in those over 70 kg is 100 mL bolus of 20% lipid emulsion followed by another 200 to 250 mL infusion over 15 to 20 minutes. For those below 70 kg, a rapid 1.5 mL/kg bolus of 20% lipid emulsion followed by a 0.25 mL/kg/minute infusion is recommended.
Intravenous lipid emulsions have been used experimentally since at least the 19th century. An early product marketed in 1957 under the name Lipomul was briefly used in the United States but was subsequently withdrawn due to side effects. Intralipid was invented by the Swedish physician and nutrition researcher Arvid Wretlind, and was approved for clinical use in Sweden in 1962. In the United States, the Food and Drug Administration initially declined to approve the product due to prior experience with another fat emulsion. It was approved in the United States in 1972.
Intralipid is also widely used in optical experiments to simulate the scattering properties of biological tissues. Solutions of appropriate concentrations of intralipid can be prepared that closely mimic the response of human or animal tissue to light at wavelengths in the red and infrared ranges where tissue is highly scattering but has a rather low absorption coefficient.
Intralipid is currently being studied for its potential use as a cardioprotective agent, specifically as a treatment for ischemic reperfusion injury. The rapid return of myocardial blood supply is critical in order to save the ischemic heart, but it also has the potential to create injury due to oxidative damage (via reactive oxygen species) and calcium overload. Myocardial damage with the resumption of blood flow after an ischemic event is termed “reperfusion injury”.
The mitochondrial permeability transition pore (mPTP) is normally closed during ischemia, but calcium overload and increased reactive oxygen species (ROS) with reperfusion open mPTP allowing hydrogen ions to flow from the mitochondrial matrix into the cytosol. The hydrogen flux disrupts the mitochondrial membrane potential and results in mitochondrial swelling, outer membrane rupture, and the release of pro-apoptotic factors. These changes impair mitochondrial energy production and drive cardiac myocyte apoptosis.
Intralipid (5mL/kg) provided five minutes before reperfusion delays the opening of mPTP in vivo rat models, making it a potential cardioprotective agent Lou et al. (2014) found that the cardioprotection aspect of Intralipid is initiated by the accumulation of acylcarnitines in the mitochondria and involves inhibition of the electron transport chain, an increase in ROS production during early (3 min) reperfusion, and activation of the reperfusion injury salvage kinase pathway (RISK). The mitochondrial accumulation of acylcarnitines (primarily palmitoyl-carnitine) inhibits the electron transport chain at complex IV, generating protective ROS. The effects of ROS are both “site” and “time” sensitive, meaning that both will ultimately determine whether the ROS are beneficial or detrimental. The generated ROS, which are formed from electrons leaking from the electron transport chain of the mitochondria, first act directly on mPTP to limit opening. ROS then activate signalling pathways that act on the mitochondria to decrease mPTP opening and mediate protection. Activation of the RISK pathway by ROS increases the phosphorylation of other pathways, such as phosphatidylinositol 3-kinase/Akt and extracellular-regulated kinase (ERK) pathways, both of which are found in pools localized at the mitochondria. The Akt and ERK pathways converge to alter glycogen synthase kinase-3 beta (GSK-3β) activity. Specifically, Akt and ERK phosphorylate GSK-3β, inactivating the enzyme, and inhibiting the opening of mPTP. The mechanism by which GSK-3β inhibits the opening of the mPTP is controversial. Nishihara et al. (2007) proposed that it is achieved through interaction of GSK-3β with ANT subunit of mPTP, inhibiting the Cyp-D–ANT interaction, resulting in the inability of the mPTP to open.
In a study by Rahman et al. (2011) Intralipid-treated rat hearts were found to required more calcium to open mPTP during ischemia-reperfusion. The cardiomyocytes are therefore, better able to tolerate the calcium overload, and increase the threshold for opening of the mPTP with the addition of Intralipid.
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- "Intralipid Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 14 April 2021. CS1 maint: discouraged parameter (link)
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- Li J, Iorga A, Sharma S, Youn JY, Partow-Navid R, Umar S, Cai H, Rahman S, Eghbali M (October 2012). "Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A". Anesthesiology. 117 (4): 836–46. doi:10.1097/ALN.0b013e3182655e73. PMC 3769111. PMID 22814384.
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- Rahman S, Li J, Bopassa JC, Umar S, Iorga A, Partownavid P, Eghbali M (August 2011). "Phosphorylation of GSK-3β mediates intralipid-induced cardioprotection against ischemia/reperfusion injury". Anesthesiology. 115 (2): 242–53. doi:10.1097/ALN.0b013e318223b8b9. PMC 3322241. PMID 21691195.
- Lou PH, Lucchinetti E, Zhang L, Affolter A, Schaub MC, Gandhi M, Hersberger M, Warren BE, Lemieux H, Sobhi HF, Clanachan AS, Zaugg M (2014). "The mechanism of Intralipid®-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases". PLOS ONE. 9 (1): e87205. Bibcode:2014PLoSO...987205L. doi:10.1371/journal.pone.0087205. PMC 3907505. PMID 24498043.
- Perrelli MG, Pagliaro P, Penna C (June 2011). "Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species". World Journal of Cardiology. 3 (6): 186–200. doi:10.4330/wjc.v3.i6.186. PMC 3139040. PMID 21772945.
- Martel C, Huynh L, Garnier A, Ventura-Clapier R, Brenner C (2012). "Inhibition of the Mitochondrial Permeability Transition for Cytoprotection: Direct versus Indirect Mechanisms". Biochemistry Research International. 2012: 1–13. doi:10.1155/2012/213403. PMC 3364550. PMID 22675634.
- Nishihara M, Miura T, Miki T, Tanno M, Yano T, Naitoh K, Ohori K, Hotta H, Terashima Y, Shimamoto K (November 2007). "Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection". Journal of Molecular and Cellular Cardiology. 43 (5): 564–70. doi:10.1016/j.yjmcc.2007.08.010. PMID 17931653.
- Lipid rescue (intralipid as antidote)