Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.

Abstract

The effects on gut blood flow velocities of parenteral indomethacin (0-2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent-or in some cases even retrograde-diastolic flow.In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fail in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7-4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantialiy less (22% compared with 47%) and later (median time to maximum fall 37-3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus.These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.Neonatal Unit,

Effects of Ibuprofen and Indomethacin on the Regional Circulation in Newborn Piglets

“…Indomethacin is associated with an increased incidence of intestinal bleeding and perforations in the preterm infant [41][42][43][44][45]. Coombs et al [2] and Van Bel et al [3] noted a significant reduction in superior mesenteric artery blood flow velocity in preterm infants receiving indomethacin. Meyers et al [4] reported that indomethacin at a dose of 0.3 mg/kg significantly reduced terminal ileal blood flow in near-term fetal lambs, and impaired the ability of the terminal ileum to autoregulate its oxygen consumption.…”

“…Furthermore, indomethacin was associated with a significant decline in the levels of oxidized cytochrome oxidase, reflecting a reduction in cerebral oxygenation [14]. Interestingly, the effects of indomethacin appear to be dependent on the rate of administration [2,[46][47][48].…”

“…However, indomethacin also affects renal, gastrointestinal and cerebral perfusion [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and may lead to a significant incidence of complications as a result. Alternative and safer treatments would be preferable.…”

Early Total Enteral Feeding versus Conventional Enteral Feeding in Stable Very-Low-Birth-Weight Infants: A Randomised Controlled Trial

“…Other factors such as significant PDA, clinical sepsis, and apnoea, which were more prevalent in the CEF group, may serve as a possible explanation. These comorbidities can impair mesenteric blood flow and hence may be detrimental to feeding [27]. The group initiated on exclusive enteral feeding had less apnoea, thus indicating that the increased feeding did not produce more apnoea.…”

Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial

“…The clinical consequences of persistent PDA are related to the degree of left-to-right shunting through the ductus and diastolic steal, leading to a redistribution of blood flow to the organs with localised vasoconstriction, reduced perfusion to the brain, gut and kidney, and Inhibiting prostaglandin synthesis with non-selective blockers of both cyclo-oxygenases 1 and 2 seems effective for the non-surgical closure of patent ductus and, since 1976, indomethacin (INDO) has been widely used with a reported efficacy of 70%-80% [9,12]. Its use raises some concern, however, regarding cerebral, gastrointestinal and renal perfusion [2,4,6,21,22], since INDO causes a decline in cerebral blood flow (CBF) velocity, reduces mitochondrial oxygenation and disrupts cerebrovascular control [7]. Moreover, side-effects such as necrotising enterocolitis or isolated bowel perforation, oliguria and transient renal failure may be encountered [10].…”