Diuretic Exposure in Premature Infants from 1997 to 2011

Abstract

Objective Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia (BPD). We examined their use and safety in this group. Study Design Retrospective cohort study of infants <32 weeks gestation and <1500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997–2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and FiO2 on the first day of each course of diuretic use were identified. Results Thirty-seven percent (39,357/107,542) of infants were exposed to at least 1 diuretic; furosemide was the most commonly used (93% with ≥1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. Seventy-four percent were exposed to 1 diuretic at a time, 19% to 2 diuretics simultaneously, and 6% to 3 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 1000 infant-days for any diuretic and 35 per 1000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia. Conclusion Despite no 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.

Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review

“…A cohort study from more than 300 NICUs in the U.S. found that furosemide was the fifth most common drug used between the years 2005 to 2010 in premature infants with birth weights < 1000 g, with approximately 50% of these infants exposed to at least one dose of furosemide during their initial hospitalization [ 51 ]. Although other diuretic medications are used in the NICU for similar indications, furosemide is by far the most commonly used diuretic in the NICU, accounting for 93% of diuretic use [ 52 ]. Furosemide is also variably used in the NICU setting.…”

“…A cohort study of infants with birth weights < 1500 g from more than 200 U.S. NICUs over a 15 year period found considerable variability in the percentage of infants exposed to at least one dose of furosemide at each particular site, with a median exposure by site of 33% and a range of 0 to 75%. The observations from this study emphasize the lack of a universally accepted standard governing when to expose an infant in the NICU to furosemide and indicate that at some centers, no exposure to furosemide is an option [ 52 ].…”

The Randomized, Controlled Trial of Late Surfactant: Effects on Respiratory Outcomes at 1-Year Corrected Age

“…Thus, the effect of late surfactant may be more specific to the perturbed lung development of ELGAN. Diuretics similarly are more common is this population, although we failed to show a significant benefit of late surfactant on diuretic exposure (32). Notably, the results of the current study represent the effects of late surfactant in infants receiving iNO, which, when administered by this protocol in the NO CLD study, decreased home oxygen use and respiratory medication exposure from all drug classes.…”

Monitoring neonates for ototoxicity

“…Loop diuretics are also associated with hearing loss. Many NICU admissions (~30%, or ~120,000 neonates annually) receive loop diuretics, like furosemide and bumetanide, for fluid overload in both acute and chronic disease states, including sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, meconium aspiration syndrome, cardiac defects and congenital diaphragmatic hernia (Pacifici, 2012; Laughon et al, 2015). The most commonly-reported side effect of loop diuretic administration in neonates is thrombocytopenia (Laughon et al, 2015); however, lower doses of loop diuretics can induce transient hearing loss (most frequently), or lead to permanent hearing losses in pediatric admissions (Rybak, 1982; Saha et al, 2013).…”