Combined treatment with a nonselective nitric oxide synthase inhibitor (l-NMMA) and indomethacin increases ductus constriction in extremely premature newborns.
Pediatr Res
; 58(6): 1216-21, 2005 Dec.
Article
en En
| MEDLINE
| ID: mdl-16306196
ABSTRACT
Studies in premature animals suggest that 1) prolonged tight constriction of the ductus arteriosus is necessary for permanent anatomic closure and 2) endogenous nitric oxide (NO) and prostaglandins both play a role in ductus patency. We hypothesized that combination therapy with an NO synthase (NOS) inhibitor [N(G)-monomethyl-L-arginine (L-NMMA)] and indomethacin would produce tighter ductus constriction than indomethacin alone. Therefore, we conducted a phase I and II study of combined treatment with indomethacin and L-NMMA in newborns born at <28 weeks' gestation who had persistent ductus flow by Doppler after an initial three-dose prophylactic indomethacin course (0.2, 0.1, 0.1 mg/kg/24 h). Twelve infants were treated with the combined treatment protocol [three additional indomethacin doses (0.1 mg/kg/24 h) plus a 72-hour L-NMMA infusion]. Thirty-eight newborns received three additional indomethacin doses (without L-NMMA) and served as a comparison group. Ninety-two percent (11/12) of the combined treatment group had tight ductus constriction with elimination of Doppler flow. In contrast, only 42% (16/38) of the comparison group had a similar degree of constriction. L-NMMA infusions were limited in dose and duration by acute side effects. Doses of 10-20 mg/kg/h increased serum creatinine and systemic blood pressure. At 5 mg/kg/h, serum creatinine was stable but systemic hypertension still limited L-NMMA dose. We conclude that combined inhibition of NO and prostaglandin synthesis increased the degree of ductus constriction in newborns born at <28 weeks' gestation. However, the combined administration of L-NMMA and indomethacin was limited by acute side effects in this treatment protocol.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Indometacina
/
Óxido Nítrico Sintasa
/
Omega-N-Metilarginina
/
Conducto Arterioso Permeable
/
Inhibidores Enzimáticos
/
Enfermedades del Prematuro
Tipo de estudio:
Clinical_trials
/
Guideline
Límite:
Female
/
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
Pediatr Res
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos