Indomethacin-associated sepsis in very-low-birth-weight infants
V. C. Herson, P. J. Krause, L. I. Eisenfeld, L. Pontius and E. G. Maderazo
Department of Pediatrics, Hartford Hospital, CT 06115.
Indomethacin sodium promotes closure of the patent ductus arteriosus in
premature infants. In addition to renal and gastrointestinal side effects,
indomethacin may predispose to infection because of inhibition of
polymorphonuclear leukocyte (PMN) function. We retrospectively assessed the
incidence of sepsis in a group of 58 premature infants with patent ductus
arteriosus who received either oral indomethacin, surgery, or usual medical
management. A significant increase in the incidence of sepsis was observed
in the indomethacin-treated group compared with patients treated with
surgery or usual medical management (seven of 31 vs one of 27). All
episodes of sepsis occurred within one week of therapy. Patients in the
indomethacin group who developed sepsis were less mature, had more
gastrointestinal symptoms, and were less likely to survive than nonseptic
indomethacin-treated patients. Nine patients studied prospectively showed
no difference in PMN chemotaxis and adherence before and after indomethacin
administration. Neither adult nor neonatal cord PMN chemotaxis was
inhibited following in vitro incubation with concentrations of indomethacin
ranging from 1 to 1000 mg/L. Bactericidal activity of neonatal cord
neutrophils was also unaffected by concentrations of indomethacin from 1 to
200 mg/L. These results suggest that oral indomethacin administration may
predispose the very-low-birth-weight infant to the development of sepsis
shortly after therapy is begun although the mechanism remains unclear.
