Iowa Neonatology Handbook: Pharmacology

Pharmacologic Closure of PDA

Edward F. Bell, MD and Jeffrey L. Segar, MD
Peer Review Status: Internally Peer Reviewed

1. Indomethacin (an inhibitor of prostaglandin synthesis) is sometimes used to promote the closure of a clinically significant PDA. The decision to use indomethacin MUST be discussed with the attending neonatologist.
2. Serum creatinine, BUN, and platelet count, should be obtained prior to giving indomethacin. A reduced fluid intake prior to indomethacin may improve the congestive heart failure secondary to the PDA, as well as improve chances of PDA closure. Infants should be made NPO prior to indomethacin administration because of the effect of the drug on mesenteric blood flow.
3. Contraindications:
   1. Renal Failure
   2. GI bleeding
   3. Thrombocytopenia
   4. Acute NEC
4. Dose:
   1st dose: 0.2 - 0.3 mg/kg IV
   2nd dose: 0.2 mg/kg IV 12-24 hours after 1st dose if PDA persists.
   3rd dose: 0.2 mg/kg IV 12-24 hours after 2nd dose if PDA persists.
5. Indomethacin is given IV over 30 minutes, as slower injection may avoid decreased cerebral blood flow after indomethacin.
6. Indomethacin also has a number of significant non-cardiac effects that should be kept in mind when using this drug. These include a decrease in the blood flow velocities (up to 120 minutes after administration) of the cerebral, renal, and mesenteric vascular beds, an attenuation of ET-suctioning induced increase in cerebral blood flow velocity, an inhibition of platelet aggegation and prolonged bleeding time up to 48 hours after last dose of indomethacin, interference with the oxygen consumption autoregulation mechanisms in the mesenteric circulation, renal effects including decreased GFR, urinary volume, and FENa+, and increased sytemic vascular resistance mean arterial pressure.
7. Accurate fluid intake and urinary output during therapy is important to prevent fluid overload with dramatic changes in urine output. Decreased urine output is expected and is not a contraindication for further indomethacin therapy, although administration of dose may be deferred if urine output falls to less than 0.5 ml/kg/hr. Fluid intake should normally be reduced during indomethacin treatment in anticipation of decreasing urine output. Volume expansion in response to a decreased urine output is contraindicated and will not induce a diuresis. Co-administration with dopamine at a dose of 2 - 3 mcg/kg/min. may counteract the oliguric effect of indomethacin.

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