Effect of Indomethacin on Cerebral Blood Flow Velocity of Premature Newborns

Laudignon, N; Chemtob, Sylvain; Bard, Harry; Aranda, Jacob V.

doi:10.1159/000242860

Cited by 57 publications

(32 citation statements)

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“…The minimal decrease in PG concentrations 1 h after the lower dose of indomethacin (3 mg/kg) was administered is in agreement with similar reported changes in brain PG levels up to 4 h after the same drug dose (23). The effects of indomethacin we observed are also in accord with previous reports, indicating a very rapid and similar decrease (within 2 min) in CBF in the animal (6,15,22) and human neonate (19) as well as a decrease in CBF velocity of the human newborn (16)(17)(18) before any changes in arterial or cerebral PG occur (23,24). Moreover, our findings are consistent with the action of this drug on various other major vascular beds.…”

Section: -----------supporting

confidence: 92%

“…However, the extremely fast onset of action of indomethacin on the cerebral circulation (15)(16)(17)(18)(19)22) does not coincide with its effects on the cerebral and vascular levels (23,24) and the disposition (25,26) of PG.…”

Section: O(mentioning

confidence: 99%

“…However, the significance of PG in the regulation of basal CBF remains controversial (1 [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In most studies ex-…”

mentioning

confidence: 99%

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Differences in the Effects in the Newborn Piglet of Various Nonsteroidal Antiinflammatory Drugs on Cerebral Blood Flow but Not on Cerebrovascular Prostaglandins

et al. 1991

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ABSTRACT. To characterize the role of prostaglandins (PG) in the regulation of basal cerebral blood flow (CBF) in the newborn, we determined the effects of four nonsteroidal antiinflammatory drugs, indomethacin (3 mg/kg, n = 8 and 10 mglkg, n = 5), aspirin (65 mg/kg, n = 6), ibuprofen (30 mg/kg, n = 8), and naproxen (15 mg/kg, n = 6), on CBF, cerebral metabolism, and cerebrovascular PG in conscious 1-to 3-d-old piglets. Drugs and vehicle (n = 8) were injected i.v., and measurements were made 5 min before and 20 and 60 min after injections. Neither the vehicle nor any of the nonsteroidal antiinflammatory drugs exerted significant effects on mean arterial blood pressure and on blood gases and pH. All four drugs, with the exception of indomethacin at the lower dose (3 mg/kg), decreased PG to nearly undetectable levels within 20 min; the low dose of indomethacin caused a small decrease (18-32%) in PG at 60 min. However, the effects of these agents on CBF were diverse. CBF increased after the administration of aspirin, decreased to almost the same extent after both low and high doses of indomethacin, and did not change after the administration of ibuprofen and naproxen. Cerebral metabolic rate for oxygen was increased by aspirin but was unaltered by the other drugs. The data suggest that PG may not play a critical role in the regulation of basal CBF in the newborn animal and that certain nonsteroidal antiinflammatory drugs may have additional actions unrelated to the inhibition of PG synthesis. (Pediatr Res 30: 106-111,1991) Abbreviations PG, prostaglandin CBF, cerebral blood flow BP, blood pressure NSAID, nonsteroidal antiinflammatory drugThe role of PG in the regulation of CBF during various hemodynamic disturbances, such as hypertension, hypotension, hypoxia, and asphyxia, has been reported by various investigators (1-14). However, the significance of PG in the regulation of basal CBF remains controversial (1 5-19). In most studies ex-

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confidence: 92%

Section: O(mentioning

confidence: 99%

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Differences in the Effects in the Newborn Piglet of Various Nonsteroidal Antiinflammatory Drugs on Cerebral Blood Flow but Not on Cerebrovascular Prostaglandins

et al. 1991

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“…The lack of a CBF response to repeated doses of indomethacin was explained by Laudignon ct ul. (35) as the following: cerebrovascular contraction was observed after the first dose of indomethacin, which persisted because of the prolonged half-life, thus preventing contraction from being observed with a repeated dose. However, a recent study by Bottu a/.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

et al. 1994

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“…6,7 Treatment with indomethacin, however, may be associated with adverse reactions, such as reduced renal, 8 mesenteric, 9,10 and cerebral perfusion. [11][12][13][14] Decreased perfusion to these vascular beds may lead to renal dysfunction, NEC, gastrointestinal hemorrhage, and IVH or periventricular leukomalacia. Ibuprofen, another prostaglandin synthesis inhibitor, has been shown to be as effective as indomethacin in ductal closure by several investigators who administered it intravenously.…”

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confidence: 99%

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

et al. 2003

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ABSTRACT. Objective. Patent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants with respiratory distress syndrome.Methods. Twenty-two preterm newborns (gestational age: 27.5 ؎ 1.75 [range: 23.9 -31 weeks]; weight: 979 ؎ 266 [range: 380-1500 g]) with PDA and respiratory distress syndrome were studied prospectively. They received oral ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the second day of life. Echocardiography was performed before treatment and 24 hours after each dose. Every child underwent cranial ultrasonography before and after each ibuprofen dose. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical courses were recorded.Results. Ductal closure was achieved in all newborns except for 1 (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant required surgical ligation of the ductus. There was no reopening of the ductus after closure had been achieved. Fourteen newborns were treated with 1 dose of ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3 doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants died from the following causes: 1 who was born at 24 weeks' gestation with a birth weight of 380 g died as a result of extreme prematurity complications, necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular hemorrhage was observed in 7 infants. The classification was changed from grade 2 to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was observed in the study group, and there was no case of tendency to bleed. There were no significant differences in the levels of serum creatinine before and after treatment with oral ibuprofen.Conclusions. Oral ibuprofen suspension may be an effective and safe alternative for PDA closure in premature infants with PDA. However, larger comparative studies are warranted. Pediatrics 2003;112:e354 -e358. URL: http://www.pediatrics.org/cgi/content/full/112/5/ e354; oral ibuprofen, patent ductus arteriosus, premature newborns.ABBREVIATIONS. PDA, patent ductus arteriosus; RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis.T he incidence of patent ductus arteriosus (PDA) in premature infants who weigh between 500 and 1500 g at birth is appr...

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Effect of Indomethacin on Cerebral Blood Flow Velocity of Premature Newborns

Cited by 57 publications

References 2 publications

Differences in the Effects in the Newborn Piglet of Various Nonsteroidal Antiinflammatory Drugs on Cerebral Blood Flow but Not on Cerebrovascular Prostaglandins

Differences in the Effects in the Newborn Piglet of Various Nonsteroidal Antiinflammatory Drugs on Cerebral Blood Flow but Not on Cerebrovascular Prostaglandins

Cerebral Blood Flow Responses to Indomethacin in Awake Newborn Pigs

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

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