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

Abstract

Furosemide is a potent loop diuretic commonly and variably used by neonatologists to improve oxygenation and lung compliance in premature infants. There are several safety concerns with use of furosemide in premature infants, specifically the risk of sensorineural hearing loss (SNHL), and nephrocalcinosis/nephrolithiasis (NC/NL). We conducted a systematic review of all trials and observational studies examining the association between these outcomes with exposure to furosemide in premature infants.We searched MEDLINE, EMBASE, CINAHL, and clinicaltrials.gov. We included studies reporting either SNHL or NC/NL in premature infants (< 37 weeks completed gestational age) who received at least one dose of enteral or intravenous furosemide. Thirty-two studies met full inclusion criteria for the review, including 12 studies examining SNHL and 20 studies examining NC/NL. Only one randomized controlled trial was identified in this review. We found no evidence that furosemide exposure increases the risk of SNHL or NC/NL in premature infants, with varying quality of studies and found the strength of evidence for both outcomes to be low. The most common limitation in these studies was the lack of control for confounding factors.The evidence for the risk of SNHL and NC/NL in premature infants exposed to furosemide is low. Further randomized controlled trials of furosemide in premature infants are urgently needed to adequately assess the risk of SNHL and NC/NL, provide evidence for improved FDA labeling, and promote safer prescribing practices.Electronic supplementary materialThe online version of this article (10.1186/s40748-018-0092-2) contains supplementary material, which is available to authorized users.

Furosemide use in Italian neonatal intensive care units: a national survey

“…Regardless, no relationship between the administration of high doses or prolonged treatment and the need to discontinue the therapy was evident. The low rate of adverse event is in line with a recent review that found low evidence for the risk of SNHL and NC/NL in premature infants [37].…”

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications

“…Sensorineuronal hearing loss is more frequent in infants born preterm vs. term, and the earlier the gestational age at birth, the greater the risk. The proposed mechanisms for the increased risk of hearing loss have largely focused on postnatal factors, such as immaturity, administration of ototoxic medications (e.g., aminoglycosides, diuretics), environmental noise, hyperbilirubinemia, and hypoxia [295][296][297][298]. However, the role of congenital factors has been known since 1897 when Aschoff described the concept of otitis media neonatorium, which was thought to be a sterile middle ear inflammation related to aspiration of amniotic fluid cellular content based on microscopic study of the temporal bone in fetuses and neonates [299].…”

Pharmacoepidemiology of Furosemide in the Neonatal Intensive Care Unit

“…In pediatric patients, recommended dosing of furosemide is 1 mg/kg/dose up to a maximum of 6 mg/kg/dose [4]. In premature infants, the maximum US Food and Drug Administration label suggested dose is 1 mg/kg/day [4, 13]. Despite these recommendations, current dose and frequency practice varies widely [11].…”