Pediatric Smoflipid Therapy: Patient Response and Safety Concerns

Abstract

Background: Intestinal failure-associated liver disease (IFALD) occurs in ≤85% of neonates receiving prolonged parenteral nutrition. Strategies for treatment of IFALD include alternative lipid therapies, such as Smoflipid (Fresenius Kabi). In this study, we reviewed our institutional Smoflipid use, including predictors of patient response and safety concerns. Methods: This is a retrospective chart review of all pediatric patients who received Smoflipid therapy over a 2-year period at Riley Hospital for Children. Forty-two patients (89%) had cholestasis at the start of Smoflipid therapy and were included in group analysis. We compared patients based on response to Smoflipid therapy, identifying associations and predictors of patient response. We also documented patient safety concerns, including essential fatty acid deficiency (EFAD), rapid infusion, and compatibility/access issues. Results: Sixteen patients (38%) with cholestasis had resolution with Smoflipid. Those patients with resolution were older at initiation (58 vs 33.5 days; P = .010), treated with Smoflipid for longer (85.5 vs 41 days; P = .001), and had lower direct bilirubin at the start of Smoflipid therapy (3.7 vs 5.2 mg/dL; P = .035). We identified multiple safety concerns, including EFAD (54%), rapid infusion (17%), and missed doses (51%). No patient characteristics were found to correlate with Smofllpid therapy and diagnosis of EFAD. Conclusion: In our patient population, Smoflipid therapy led to cholestasis resolution in patients with lower direct bilirubin or less-severe IFALD. Use of Smoflipid is also associated with significant safety concerns, and its use should be coupled with close monitoring in pediatric patients, particularly in neonates.

Prevalence of Parenteral Nutrition-Associated Liver Disease in Neonates With Congenital Heart Disease

“…However, in cases where this is not possible (e.g., short bowel syndrome), decreasing exposure to soybean-based lipid formulations by utilizing alternatives such as SMOFLipid® (Fresenius Kabi USA, Lake Zurich, IL) and Omegaven® (Fresenius Kabi USA, Lake Zurich, IL) is a potential alternative, as these have been demonstrated to have fewer adverse events (30), and can reverse liver injury (31). However, this must be used cautiously, as essential fatty acid deficiency can arise (32). Alternative lipid preparations and PN cycling may prevent or treat PNALD but are not fully effective.…”

Decreased liver damage in rat models of short bowel syndrome through DPP4 inhibition

“…Pure sh oil lipid emulsions are considered a treatment that can reverse IFALD, increase survival, and avoid the need for transplantation; thus, they are considered rescue therapy [10]. In contrast, SMOFlipid, which is a mixed lipid emulsion containing soybean oil and sh oil, resolves cholestasis in patients with lower direct bilirubin levels or less severe IFALD [11]. Many researchers have discussed the e cacy of lipid emulsions in SBS patients or SBS animal models; however, there are very few publications on the treatment of IFALD, except for those regarding lipid emulsions.…”

IFALD in children: What's new? A narrative review

“…When PN is required for more than 60 days, IFALD occurs in more than 75% of cases ( 11 ). Although IFALD has a multifactorial origin, it is widely accepted that soy-based lipid emulsions (SO-LEs), used for parenteral nutrition, play a primary pathogenic role due to their high phytosterol content, high ω-6 to ω-3 long-chain polyunsaturated fatty acid ratio, and low levels of α - tocopherol ( 12 ). Whereas IFALD was initially considered as a PN complication, an increasing number of evidence suggests that liver disease is not solely due to PN administration but strongly related to IF factors ( 13 ).…”

“…In 2021, a retrospective study on predictors of cholestasis or IFALD response to SMOF-LE therapy in patients with IFALD showed that 38% of the patients treated with SMOF had cholestasis resolution, 7% improvement, and 45% no response. The responders were older at the beginning of SMOF use, treated with it for longer time, with higher corrected gestational age and lower direct bilirubin levels at the start of treatment ( 12 ). Previous studies had already demonstrated that younger age, increased direct bilirubin, and signs of liver disease were associated with an increased risk of therapy failure.…”

“…Previous studies had already demonstrated that younger age, increased direct bilirubin, and signs of liver disease were associated with an increased risk of therapy failure. This work suggested that early initiation of SMOF therapy, when cholestasis is less severe, improves the likelihood of resolution ( 12 ). Regarding use of FO-LEs for IFALD treatment, Nandivada et al demonstrated that most PN-dependent infants with IFALD respond to FO therapy with the resolution of biochemical cholestasis and avoidance of liver transplantation.…”