Gastrointestinal perforation following indomethacin therapy in very low birth weight infants

Nagaraj, Hirikati S.; Sandhu, Amarjit S.; Cook, Larry N.; Buchino, John J.; Groff, Diller B.

doi:10.1016/s0022-3468(81)80865-2

Cited by 146 publications

(46 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Prostaglandin synthetase inhibitors such as indomethacin have been used to pharmacologically close the patent ductus arteriosus in ill newborn infants (2 1). Some neonatology centers have noted an increased incidence of focal perforation of the gastrointestinal tract in infants who received indomethacin (22).…”

Section: Discussionmentioning

confidence: 99%

Indomethacin Fails to Induce Ulceration in the Gastrointestinal Tract of Newborn and Suckling Rats

Bedrick

Holtzapple

1986

Pediatr Res

View full text Add to dashboard Cite

ABSTRACT. Little is known about the role of oral prostaglandins and maintenance of intestinal epithelial cell membrane integrity in suckling animals. The presence of prostaglandins in milk suggests that they may have potential cytoprotective effects. Thus, experiments were performed to determine whether indomethacin causes inflammation in the gastrointestinal tract of suckling animals. Rats were treated with daily intraperitoneal injections of indomethacin (10 mg/kg) starting on the 1st day of life. Unlike adult animals which develop intestinal lesions within 72 h, these rats did not develop intestinal ulcerations until weaning started on days 15 to 16. Indomethacintreated suckling animals prevented from weaning did not develop intestinal lesions until they had access to solid food on day 23. Indomethacin-treated rats had large reductions in jejunal prostaglandin E2 content. In addition, prostaglandin E2 was present in rat milk in relatively large concentration as determined by radioimmunoassay. These studies suggest that exogenous prostaglandins present in milk may protect the intestine of suckling rats from indomethacin-induced inflammation; however, once weaning commences, prostaglandin insufficiency may develop lea& ing to intestinal lesions. We s~eculate that suckling rats treated with indomethacin did-not develop ulcerat6e lesions, despite a marked reduction in intestinal prostaglandin content, possibly due to prostaglandins present in milk. (Pediatr Res 20: 598-601,1986) glandin F,, have also been found in significant amounts, suggesting that milk contains the parent compounds thromboxane A2 and prostacyclin (4-6). They are also found in commercially obtained whole milk and low-fat milk (7), but not in infant formulas (6). Prostaglandin in milk has been demonstrated to be effective in promoting healing of peptic ulcers and in protecting the gastroduodenal mucosa against experimentally induced ulcers (7). In addition, administration of oral prostaglandin E2 to humans has been demonstrated to protect the gastrointestinal mucosa from blood loss induced by indomethacin (8). Thus, considerable information exists about the importance of oral prostaglandins in maintaining integrity of the gastrointestinal epithelial cell membrane in adults. However, very little is known about similar functions of prostaglandins in suckling animals. The presence of prostaglandins in milk suggest that they may play an important role in the function and adaptation of the gastrointestinal tract to extrauterine life. The significance of prostaglandin cytoprotection in the gastrointestinal tract of stressed newborns has not been determined. Exogenous prostaglandin in breast milk could have cytoprotective effects on the gastrointestinal tract. Thus, to evaluate the role of oral prostaglandins in maintenance of gastrointestinal mucosal integrity in suckling animals, experiments were performed in suckling rats to explore whether indomethacin causes inflammation in the immature gastrointestinal tract. A preliminary report has been publish...

show abstract

Section: Discussionmentioning

confidence: 99%

Indomethacin Fails to Induce Ulceration in the Gastrointestinal Tract of Newborn and Suckling Rats

Bedrick

Holtzapple

1986

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…As early as 1981, indomethacin administration for a patent ductus arteriosus (PDA) was suggested to be associated with SIP in case reports. 5 However, the largest multicenter, randomized, controlled trial of indomethacin to date (the TIPP trial) did not find the prophylactic use of indomethacin to be associated with an increased incidence of SIP ( Figure 1). 6 This trial was well-designed, but despite its size, was not sufficiently powered for the secondary outcome of SIP.…”

Section: Introductionmentioning

confidence: 99%

New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure

et al. 2005

View full text Add to dashboard Cite

Background: Spontaneous intestinal perforation (SIP) is increasingly common in the premature infant and is associated with significant morbidity. Indomethacin use has been implicated as a co-risk factor for SIP when combined with glucocorticoids, but previous evidence argued against indomethacin being an independent risk factor when used prophylactically.Objectives: (1) To establish a homogeneous cohort of SIP patients in a national data set and to contrast them to patients with surgical necrotizing enterocolitis (NEC). (2) To test the hypothesis that early postnatal indomethacin is independently associated with SIP.Methods: A large de-identified data set was retrospectively queried by diagnosis, and then multiple antenatal and post-natal variables were tested by both univariate and multivariate analysis to identify associations with SIP. Sub-analyses were also performed to look at the timing of drug administration.Results: There were 2105 patients evaluated in the data set. Patients were divided into matched controls (n ¼ 581), those with SIP without report of NEC (n ¼ 633) and those with NEC requiring surgery (n ¼ 891). Infants with SIP were more likely to have a patent ductus arteriosus and more likely to be treated with vasopressors than either control or NEC patients. Compared to infants with NEC, patients with SIP were smaller, less mature and required more support. SIP was also diagnosed earlier than NEC (median of 7 vs 15 days). Patients with SIP were more likely to be treated with indomethacin, hydrocortisone or both on days of life 0-3 than controls.Conclusions: (1) Surgical NEC and SIP have significant differences in presentation, demographics and morbidity. (2) A detailed look at drug timing revealed that early post-natal indomethacin is independently associated with SIP.

show abstract

“…The halflife of indomethacin in premature neonates (at least double than in adults) could explain the long-lasting effect of indomethacin after birth (8,9). Both prenatal and postnatal exposure to indomethacin caused increased neonatal complications including necrotizing enterocolitis (10)(11)(12). Also, it has been shown that indomethacin increased oligohydramnios, intraventricular haemorrhage, renal failure (6).…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular and developmental influences of early postnatal indomethacin in mice

Nowrouzi¹,

Azadbakht²

2017

BLL

View full text Add to dashboard Cite

OBJECTIVES: The effect of early postnatal indomethacin exposure on hepatocellular and developmental alterations in mice liver was investigated. METHODS: Pups received IP injections of 0, 25, 50 and 100 mg/kg indomethacin on P0, then killed at P21 and P60. RESULTS: Indomethacin signifi cantly suppressed body weight at P21, but liver weight signifi cantly decreased only in 25 mg/kg. In contrast, liver weight and liver to body weight ratio signifi cantly increased with increasing dose of indomethacin by P60. The restoration of liver weight was a result of proliferation, as a consequence of a signifi cant increase in the number of uni and bi-nuclear hepatocytes per fi eld in 25 mg/kg at P21 and no evidence of hepatocellular hypertrophy. Indomethacin had a dose-related decrease in number of hepatocytes as the result of hepatocellular hypertrophy confi rmed with hepatocytes presenting large cellular and nuclear size in 50 and 100 mg/kg. Moreover, proliferation contributed to the increased liver size, since bi-nuclear hepatocytes and its ratio increased at P21 at fi rst and then decreased by P60 with increasing in dose. CONCLUSION: Indomethacin has long term effect on liver development in a dose-and time-dependent manner. The hepatocytes during both the liver development and regeneration show signifi cant differences in cell and nuclear number and size (Tab. 3, Fig. 2, Ref. 48). Text in PDF www.elis.sk.

show abstract

Gastrointestinal perforation following indomethacin therapy in very low birth weight infants

Cited by 146 publications

References 18 publications

Indomethacin Fails to Induce Ulceration in the Gastrointestinal Tract of Newborn and Suckling Rats

Indomethacin Fails to Induce Ulceration in the Gastrointestinal Tract of Newborn and Suckling Rats

New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure

Hepatocellular and developmental influences of early postnatal indomethacin in mice

Contact Info

Product

Resources

About