Parenteral Nutrition–Associated Cholestasis in Neonates: Multivariate Analysis of the Potential Protective Effect of Taurine
Ariel U. SpencerSunkyung YuThomas F. TracyMoustafa M. AouthmanyAdolfo LlanosMorton B. BrownMarilyn R. BrownRobert J. ShulmanRonald B. HirschlPatricia A. DeRussoJean T. CoxJacqueline DahlgrenPeter J. StrouseJonathan I. GronerDaniel H. Teitelbaum
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Background: Neonates receiving parenteral nutrition (PN) are at risk for PN‐associated cholestasis (PNAC); however, no preventive factors for PNAC have been clearly identified. Despite reports suggesting that taurine may prevent PNAC in neonates, such an effect of taurine has not yet been definitively demonstrated. We determined whether taurine supplementation reduces the incidence of PNAC in premature or critically ill neonates. Methods: This study was part of a prospective, randomized, multi‐institutional trial designed to assess cholecystokinin vs placebo as a potential preventive therapy of PNAC. Taurine supplementation of PN varied between institutions. The presence or absence of taurine in PN was analyzed by multivariate analysis, with a primary outcome measure of serum conjugated bilirubin (CB) as a measure of PNAC. Results: Taurine reduced PNAC in premature infants (estimated maximum CB [95% confidence interval] 0.50 mg/dL [–0.17 to 1.18] for those receiving taurine, vs 3.45 mg/dL [1.79–5.11] for neonates not receiving taurine, approaching significance, p = .07). Taurine significantly reduced PNAC in infants with necrotizing enterocolitis (NEC; estimated maximum CB 4.04 mg/dL [2.85–5.23], NEC infants receiving taurine, vs 8.29 mg/dL [5.61–10.96], NEC infants not receiving taurine, p < .01). There were too few neonates with surgical anomalies to evaluate the effect of taurine in this group. Conclusions: Within specific subgroups of neonatal patients, taurine supplementation does offer a very significant degree of protection against PNAC. Patients with NEC or severe prematurity are most likely to benefit substantially from taurine supplementation.Keywords:
Necrotizing Enterocolitis
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Blood–retinal barrier
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Osmoregulation
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SummaryThe effects of cellular hypoxia on taurine levels in rat hearts were determined. Hearts perfused with 95% N2-5% CO2 demonstrated a significant decrease in tissue taurine content when compared to control hearts perfused with 95% O2-5% CO2. The loss of taurine in oxygen-deficient hearts was time dependent over a period of 30 min. The perfusate when analyzed for taurine content contained 100% of the released taurine. Thus, metabolic conversion of taurine had no role in the disappearance of taurine from the rat heart.
Hypoxia
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Enteral administration
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This study investigated the effects of acute oral taurine ingestion on: (1) the power–time relationship using the 3-min all-out test (3MAOT); (2) time to exhaustion (TTE) 5% > critical power (CP) and (3) the estimated time to complete (Tlim) a range of fixed target intensities. Twelve males completed a baseline 3MAOT test on a cycle ergometer. Following this, a double-blind, randomised cross-over design was followed, where participants were allocated to one of four conditions, separated by 72 h: TTE + taurine; TTE + placebo; 3MAOT + taurine; 3MAOT + placebo. Taurine was provided at 50 mg kg−1, whilst the placebo was 3 mg kg−1 maltodextrin. CP was higher (P < 0.05) in taurine (212 ± 36 W) than baseline (197 ± 40 W) and placebo (193 ± 35 W). Work end power was not affected by supplement (P > 0.05), yet TTE 5% > CP increased (P < 0.05) by 1.7 min after taurine (17.7 min) compared to placebo (16.0 min) and there were higher (P < 0.001) estimated Tlim across all work targets. Acute supplementation of 50 mg kg−1 of taurine improved CP and estimated performance at a range of severe work intensities. Oral taurine can be taken prior to exercise to enhance endurance performance.
Cycle ergometer
Concomitant
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Taurine is a prominent and naturally occurring organic acid which has found its way into the diet of millions of people. Taurine is found in massive quantities within the energy drinks that have become increasingly popular in the last few decades. Though previous research has deemed taurine safe to consume, little is known about the effects of taurine in high doses or chronic doses. This study investigates the effect that various doses of taurine have on CD‐1 mice at both acute and chronic conditions. The motor coordination and activity levels of mice were observed for 20, 50, 100, and 200mg doses, which represented the acute condition, and also were observed after three weeks of ad libitum drinking of 1% or 5% taurine solution, which represented the chronic condition. The results showed that taurine has dose‐dependent effects that differ between levels of exposure. These findings indicate that acute doses of taurine may be beneficial in increasing bursts of movements, but repeated exposure to taurine may have adverse effects on coordination, overall movement time, and stereotypical movements.
Locomotor activity
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In the early days of parenteral nutrition of children liver disease resulting in steatosis and cholestasis was assumed to be an inevitable complication of the procedure. Since then, the management of parenteral nutrition has improved so much that nowadays adolescents have a fair chance of surviving more than 15 to 20 years without severe liver disease. Nevertheless, we still see cases of parenteral nutrition-associated cholestasis (PNAC) due to various conditions such as recurrent infections, inflammatory response, inappropriate composition of the nutrient mixture, contaminants of the nutrient solution, and toxic substances from infusion bags and tubes.
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In a newborn baby with Hirshsprung's disease obstructive jaundice developed following prolonged parenteral nutrition. At laparotomy, thick inspissated bile was flushed from the biliary tree and prompt resolution of the jaundice followed. To our knowledge, this is the first reported case in which inspissated bile appeared to be a complication of total parenteral nutrition. Mechanical obstruction must be recognized as an extreme in the spectrum of total parenteral nutrition cholestasis.
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