What is SMOFlipid (SMOF lipid), including its composition, dosing, indications, benefits, and contraindications?

What is SMOFlipid?

SMOFlipid is a fourth-generation composite intravenous lipid emulsion for parenteral nutrition that combines four different oil sources: soybean oil (30%), medium-chain triglycerides/MCT from coconut oil (30%), olive oil (25%), and fish oil (15%), designed to provide a balanced fatty acid profile with reduced omega-6 to omega-3 ratio (2.5:1) compared to traditional soybean-based emulsions. 1, 2

Composition and Rationale

SMOFlipid represents a multi-component approach to intravenous lipid delivery that addresses limitations of older single-oil emulsions 1:

• Soybean oil component (30%) provides essential fatty acids (linoleic and linolenic acid) required to prevent essential fatty acid deficiency 1
• Medium-chain triglycerides/MCT (30%) from coconut oil offer rapid oxidation and energy provision with less dependence on carnitine for metabolism 1
• Olive oil (25%) contributes monounsaturated fatty acids with potentially lower inflammatory effects 1
• Fish oil (15%) supplies omega-3 long-chain polyunsaturated fatty acids (EPA and DHA) with anti-inflammatory properties and a favorable impact on immune function 1, 2

Clinical Benefits and Evidence

Parenteral Nutrition-Associated Cholestasis (PNAC/PNALD)

In randomized controlled trials comparing SMOFlipid with soybean-based emulsions, the fish-oil containing SMOF emulsion proved safe and more effective in reducing bilirubin levels and oxidative stress in pediatric patients. 1

• SMOFlipid significantly reduces cholestasis risk (relative risk 0.65,95% CI 0.48-0.87) compared to other lipid emulsions in neonates 3
• In preterm infants <1,500g, SMOFlipid reduced PNAC incidence from 13% to 6% (p=0.022) and lowered peak direct bilirubin levels (3.2 vs 7.1 mg/dL, p=0.018) compared to traditional emulsions 4
• The relative risk of developing direct hyperbilirubinemia with older emulsions was 2.22 times higher than with SMOFlipid (NNT=14) 4

Oxidative Stress Reduction

SMOFlipid demonstrates beneficial effects in reducing oxidative stress by lowering lipid peroxidation levels in high-risk preterm neonates. 2

• F2-isoprostane levels (lipid peroxidation markers) were significantly reduced in the SMOFlipid group compared to baseline 2
• Eicosapentaenoic acid (EPA) and vitamin E levels were significantly increased with SMOFlipid 2

Metabolic Advantages

SMOFlipid is eliminated significantly faster than standard soybean oil emulsions, with shorter triglyceride half-life. 5

• At the end of infusion, mean serum triglyceride concentration was significantly lower with SMOFlipid (p<0.05) 5
• This faster elimination is potentially beneficial in patients with limited triglyceride clearance capacity 5

Dosing Recommendations

Standard Dosing

For adults with suspected PNALD, lipid emulsions with a reduced omega-6 to omega-3 ratio (such as SMOFlipid) can be used at conventional lipid doses. 1

Pediatric Dosing

In infants and children with PNAC, lipid emulsions enriched with omega-3 fatty acids (including SMOFlipid) can be used. 1

• Conventional doses of 2-3 g/kg/day are appropriate for most pediatric patients 6
• Lipid reduction strategies with SMOFlipid should be avoided, as doses of 1 g/kg/day increase the risk of essential fatty acid deficiency (EFAD) 6

Critical Caveat on Dose Reduction

A major pitfall is reducing SMOFlipid dosage below 2 g/kg/day in an attempt to manage cholestasis, as this can paradoxically cause EFAD while being unnecessary for cholestasis resolution. 6

• One case report documented moderate EFAD and slow weight gain in an infant managed with SMOFlipid reduction to 1 g/kg/day 6
• Once dosage was increased to 2-3 g/kg/day, EFA levels normalized, adequate growth resumed, and cholestasis resolved 6

Indications

SMOFlipid is indicated for parenteral nutrition in patients requiring intravenous lipid supplementation 1:

• Preterm and term neonates requiring parenteral nutrition, particularly those at risk for PNAC 3, 4
• Pediatric patients with intestinal failure requiring long-term parenteral nutrition 1
• Adults with intestinal failure-associated liver disease (IFALD) or PNALD 1
• Patients requiring essential fatty acid supplementation who cannot tolerate enteral nutrition 1

Special Population: Extremely Premature Infants

In extremely premature infants (<28 weeks gestational age), SMOFlipid reduces the incidence of patent ductus arteriosus (PDA) (RR 0.88,95% CI 0.79-0.99, p=0.04) 3

Contraindications and Precautions

General Contraindications

Standard contraindications for intravenous lipid emulsions apply 1:

• Severe hyperlipidemia or disorders of lipid metabolism
• Severe liver insufficiency with existing coagulopathy
• Acute phase of myocardial infarction or stroke

Monitoring Requirements

Monitor serum triglyceride concentrations during SMOFlipid infusion, particularly in patients with limited triglyceride clearance. 5

• Consider decreasing lipid intake in conditions of severe thrombocytopenia or coagulopathy (e.g., sepsis, disseminated intravascular coagulopathy) 1
• Do not routinely reduce SMOFlipid dosage below 2 g/kg/day to manage cholestasis, as this increases EFAD risk without additional benefit 6

Storage and Administration

SMOFlipid requires appropriate storage under refrigeration at 2-8°C prior to use, but should be gently warmed before administration. 1

Comparison to Other Lipid Strategies

Versus Pure Fish Oil Emulsions

Pure fish oil emulsions (100% fish oil) are not recommended for general use in pediatric patients but may be considered for short-term rescue treatment in patients with progression to severe IFALD. 1

• The evidence comparing pure fish oil to SMOFlipid remains limited, with most studies using different total lipid doses that confound interpretation 1
• SMOFlipid offers the advantage of providing adequate essential fatty acids at conventional doses (2-3 g/kg/day) while still delivering omega-3 benefits, whereas pure fish oil emulsions are typically limited to 1 g/kg/day to prevent EFAD 1, 6

Versus Soybean Oil Emulsions

SMOFlipid demonstrates superior outcomes compared to traditional soybean oil emulsions in terms of cholestasis prevention, oxidative stress reduction, and triglyceride clearance. 3, 2, 4, 5

Safety Profile

SMOFlipid demonstrates good systemic and local tolerance with no evidence of infusion-related abnormalities in clinical trials. 5

• Both SMOFlipid and comparator emulsions were well tolerated without adverse events in randomized trials 2
• No significant differences in mortality, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, or intraventricular hemorrhage compared to other emulsions 3
• Length of hospital stay was shorter in the SMOFlipid group (51 vs 60 days, p=0.019) in one study 4