Use of Cholecystokinin to Prevent the Development of Parenteral Nutrition‐Associated Cholestasis

Teitelbaum, Daniel H.; Han-Markey, Theresa; Drongowski, Robert A.; Coran, Arnold G.; Bayar, Bilge; Geiger, James D.; Uitvlugt, Neal; Schork, M. Anthony

doi:10.1177/0148607197021002100

Cited by 63 publications

(26 citation statements)

References 13 publications

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“…Several methods for preventing such hepatic dysfunction have been reported, such as the use of cyclic TPN 13) or the administration of ursodeoxycholic acid, 14) metronidazole, 15) gentamicin, 16) anti-TNF antibody, 17) cholecystokinin, 18,19) glutamine, [20][21][22][23] or steroids and growth hormone. Nevertheless, the problem of hepatic dysfunction in patients receiving TPN has yet to be completely overcome, and the mechanism of TPN-induced hepatic steatosis remains unclear.…”

Section: Role Of Soybean Oil Fat Emulsion In the Pre-vention Of Tpn-imentioning

confidence: 99%

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Nishimura

Yamaguchi

Naito

et al. 2006

Biological & Pharmaceutical Bulletin

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INTRODUCTIONTotal parenteral nutrition (TPN), which is recognized as one method for parenteral hyperalimentation, has been found to be an effective and relatively safe method for supplying energy and nutrients to surgical patients. Following improvements in parenteral regimens including vitamins and trace elements and in catheter techniques to reduce the septic complications associated with TPN, TPN has been widely employed to provide complete nutritional support and therapeutic benefits in a variety of pathophysiological settings in which patients are unable to eat. However, TPN-induced hepatobiliary dysfunction, which was first described by Peden et al.,1) has been recognized as a cause of severe morbidity and a life-threatening complication of TPN, especially in neonates and infants. Hepatic dysfunction with steatosis is the most common complication associated with fat-free TPN in adults, and cholestasis is more common in infants.2,3) Recently, the 3-component infusion solution containing amino acids, glucose, and soybean oil emulsion, GA-1080 (MIXID ® , Otsuka Pharmaceutical Factory, Inc.; Tokushima, Japan), has been demonstrated to be effective in overcoming such hepatic morbidity in clinical studies.4) Intravenous fat emulsions, especially soybean oil, are now available as a source of essential fatty acids in patients receiving TPN, and the "three-in-one" solution GA-1080 has been found to be clinically safe, stable, and economical. However, the multifactorial pathogenesis of TPN-induced hepatic dysfunction remains unclear, and the molecular mechanisms by which GA-1080 prevents hepatic dysfunction have not yet been identified.We have recently developed an infant rat model of hepatobiliary dysfunction.5) Using this animal model, we have clearly demonstrated the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN in infant rats. Furthermore, we have shown that including fat in the TPN regimen is very important in preventing TPN-induced hepatic dysfunction. In this review, we describe the molecular mechanisms and the clinical implications of soybean oil in TPN solutions in avoiding the hepatic complications associated with parenteral nutrition. INFANT RAT TPN MODEL WITH HEPATOBILIARY DYSFUNCTIONSince the first studies of TPN in animal models conducted in 1968 by Dudrick et al.,6) it has been known that only a limited number of species (such as the dog, cat, rabbit, and guinea pig) can tolerate the surgical procedures required for TPN, and few studies have employed rats as an animal model for TPN. In 1981, Tashiro and Meng 7) were the first to report a technique for long-term TPN in unrestrained weanling or infant (3-week-old) rats, thus establishing an animal model for pediatric TPN. Numerous studies have focused on the optimal TPN composition in mature rats, but few have addressed this issue in infant rats.We have recently developed an infant rat model with hepatic dysfunction and steatosis induced by overdose of fatfree TPN. 5) After 30 infant (3-week-ol...

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Section: Role Of Soybean Oil Fat Emulsion In the Pre-vention Of Tpn-imentioning

confidence: 99%

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Nishimura

Yamaguchi

Naito

et al. 2006

Biological & Pharmaceutical Bulletin

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“…However, to date, studies testing prophylactic strategies have not identified a consistently successful method, other than discontinuing the PN, which frequently is not a feasible option. Those studies included prophylactic administration of taurosusodeoxycholic acid, 5 cholecystokinin-octapeptide, 6,7 taurine, 8 phenobarbitol 9 and removing copper and manganese from the PN. 10,11 One problem inherent in any prophylactic strategy in the NICU is accurately predicting which neonates are at highest risk for developing the adverse outcome, so that high-risk patients can be eligible for study while low-risk patients can be excluded.…”

Section: Introductionmentioning

confidence: 99%

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

et al. 2007

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“…Surgical access to the biliary tree in many critically-ill patients or those with abdominal wall defects like our patient may not be feasible. Cholecystokinin is a gastrointestinal hormone that has been shown to promote choleresis [17,18] , and was suggested in a retrospective cohort study to prevent severe conjugated hyperbilirubinemia (defined as direct bilirubin 6 5.0 mg/dl) [19] . However, a recent large multicenter double-blind, randomized, controlled trial of cholecystokinin-octapeptide in neonates did not show any effect on conjugated bilirubin levels, incidence of biliary sludge or cholelithiasis formation [15] .…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Guided Percutaneous Cholecystostomy for Acute Neonatal Biliary Obstruction

Helin

Bhat²,

Рао³

2006

Neonatology

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Use of a percutaneously-inserted cholecystostomy drainage tube is an effective therapeutic option for acute hyperbilirubinemia in severely-ill adult patients, but to our knowledge has not been previously reported in infants. We describe an infant who developed acute extrahepatic biliary tract obstruction with marked conjugated (direct) hyperbilirubinemia, and who was determined to be an unsuitable surgical candidate. Ultrasound-guided percutaneous cholecystostomy was performed and resulted in prompt, significant, and sustained decline in serum bilirubin levels. Potential risks and benefits, as well as suggested indications for the procedure are discussed.

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Use of Cholecystokinin to Prevent the Development of Parenteral Nutrition‐Associated Cholestasis

Abstract: Levels of direct bilirubin were lower in the treated compared with the nontreated group. These findings suggest that cholecystokinin prophylaxis in high-risk neonates may help prevent the development of parenteral nutrition-associated cholestasis.

Cited by 63 publications

References 13 publications

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease

Ultrasound-Guided Percutaneous Cholecystostomy for Acute Neonatal Biliary Obstruction

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