Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease.
OBJECTIVE
Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN.


METHODS
A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree.


RESULTS
Neonates (38 studied) required a mean (+/-SD) of 33 +/- 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis (P = .56), birth weight (P = .54), gestational age (P = .18), and duration of TPN (P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 +/- 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology.


CONCLUSIONS
Total parenteral nutrition-associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.
Tsai
Susan
S
Section of Pediatric Surgery, CS Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Strouse
Peter J
PJ
Drongowski
Robert A
RA
Islam
Saleem
S
Teitelbaum
Daniel H
DH
D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D042882:Gallstones / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D011446:Prospective Studies; D012844:Sincalide / Q000627:therapeutic use*; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D002756:Cholagogues and Choleretics; D005765:Gastrointestinal Agents; D014580:Ursodeoxycholic Acid; D012844:Sincalide