The Effect of 15‐Hour Fat Infusions of Varying Dosage on Bilirubin Binding to Albumin

Abstract

Intravenous fat emulsions (1, 2, and 3 g/kg) were administered over 15 hr to 20 appropriate for gestational age premature infants with physiologic hyperbilirubinemia to determine the effect of fat infusions on the serum free fatty acid:albumin molar ratio (F/A) and on unbound bilirubin. Significant increases (p < 0.05) in F/A occurred with each increase in lipid dose in infants < 30 wk gestation, but not in infants ≥ 30 wk gestation. There was a direct linear correlation (r = 0.65, p < 0.001) between F/A ratio and unbound bilirubin (estimated fluorometrically by the ratio of albumin‐bound bilirubin/reserve bilirubin binding capacity, B/R). The largest increases in unbound bilirubin (albumin‐bound bilirubin/reserve bilirubin binding capacity) were seen in infants with F/ A > 4.0. The gestational age of infants with F/A > 4.0 was significantly less (p < 0.01) than infants with F/A < 4.0 (28.7 ± 0.47 us. 31.1 ± 0.40 wk, mean ± SEM). In 10/58 infusions there was a fall in unbound bilirubin, unrelated to birthweight, gestational age, postnatal age, however, during these infusions the end‐infusion F/A was ≥ 3.0. We conclude that 1 g/kg of lipid emulsion infused over a 15‐hr period has minimal risk of decreasing bilirubin binding in premature infants < 30 wk gestation. As doses of 2 or 3 g/kg are used, these infants may be at risk of decreased bilirubin binding, due to elevations in the F/A ratio. Monitoring of the F/A ratio may identify infants at risk for decreased bilirubin binding during lipid infusion and provide guidelines for determining the appropriate lipid dose. (Journal of Parenteral and Enteral Nutrition 9:144–147, 1985)

Fluorescence Sensor for the Quantification of Unbound Bilirubin Concentrations

“…Neonatal HSA concentrations depend on gestational age, ranging from 280 to 470 mol/L (30 ). In neonates receiving Intralipid, FFA concentrations increase severalfold, resulting in substantial displacement of bilirubin from HSA and, therefore, large increases in B f concentrations (23,26,27 ). This variability in bilirubin-binding capacity can result in patients having similar plasma B T but different B f .…”

Feeding Very-Low-Birth-Weight Infants: Our Aspirations versus the Reality in Practice

“…Early lipid administration has been associated with chronic lung disease [19,20], whereas in other trials, no adverse effects were found [21,22,23,24]and even beneficial effects of lipids on lung development have been described [25]. It has also been hypothesized that fatty acids competitively bind to albumin and therefore cause an increase in free bilirubin or medication to dangerously high levels [26,27]. However, a small recent study shows that early lipid administration is safe and well tolerated.…”

Postnatal serum concentrations of endogenous free fatty acids in newborns admitted to the neonatal intensive care unit: effects on unbound bilirubin

“…Although previous studies have reported the postnatal concentrations of endogenous serum FFA in newborns, 7,8,29,30 little was known about serum FFA concentrations at 4-5 days of age, when serum TB peaks. We found that serum FFA and FFA/Alb ratio at 4 and 5 days of age were significantly lower at 1 day of age in term patients.…”

“…31,32 Although the impact of endogenous FFA has not been assessed directly, increased FFA has bilirubin displacing effects, especially in premature newborns receiving intravenous lipid supplementation for nutrition and growth. 7,9,10,28,33 At an FFA/Alb ratio 54, FFAs compete with bilirubin at the bilirubin binding site, resulting in the displacement of bilirubin. 7,8,10,27,28 We found that endogenous FFAs did not affect Alb binding of bilirubin, resulting in elevations of UB, since none of the sera, from both term and preterm infants, had FFA/Alb ratios 54.…”