Abstract
Objective Diuretics are often prescribed off-label to premature infants, particularly to prevent
or treat bronchopulmonary dysplasia. We examined their use and safety in this group.
Study Design Retrospective cohort study of infants < 32 weeks gestation and < 1,500 g birth weight
exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined
use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic
acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination.
Respiratory support and fraction of inspired oxygen on the first day of each course
of diuretic use were identified.
Results About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide
was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone,
chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients
were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6%
to three diuretics simultaneously. The most common combination was furosemide/spironolactone,
followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants
were not receiving mechanical ventilation on the first day of each new course of furosemide
(47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%).
Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per
1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any
diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory
abnormality associated with diuretic exposure was thrombocytopenia.
Conclusion Despite no Food and Drug Administration (FDA) indication and little safety data,
over one-third of premature infants in our population were exposed to a diuretic,
many with minimal respiratory support.
Keywords
bronchopulmonary dysplasia - diuretic - safety - drug
