Pharmacoepidemiology of Furosemide in the Neonatal Intensive Care Unit

Thompson, Elizabeth J.; Benjamin, Daniel K.; Greenberg, Rachel G.; Kumar, Karan; Zimmerman, Kanecia O.; Laughon, Matthew M.; Clark, Reese H.; Smith, P. Brian; Hornik, Christoph P.

doi:10.1159/000510657

Cited by 7 publications

(7 citation statements)

References 21 publications

(24 reference statements)

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“…A recent report from North American NICUs revealed an average daily dose was 1 mg/kg (0.88, 1.1) with a median cumulative dose of 2 mg/kg (1.0, 4.5) and a shorter duration of 2 days (1, 4). 11 However, our doses were relatively higher compared to this report, and differences in the population, and severity of illnesses could explain this difference. This also calls for improving the neonatologists’ awareness of the importance of rational use and potential de-prescription of furosemide.…”

Section: Discussioncontrasting

confidence: 66%

Cumulative Doses Predict the Risk of Furosemide-Induced Electrolyte Abnormalities in Critically Ill Neonates

Sridharan¹,

Madhoob²,

Jufairi³

2022

TCRM

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Background Furosemide has limited indications in the term neonates. Its use in preterm neonates is off-label. Considering the dearth of data, we carried out a retrospective study evaluating the furosemide use and its effects on the electrolyte abnormalities in critically ill neonates. Methods Critically ill neonates receiving at least one dose of furosemide during their stay in the NICU were recruited. The following details were obtained: demographic characteristics and furosemide details (dose, frequency, route, and duration). Urine output, body weight, serum creatinine, electrolytes (sodium, potassium, calcium, bicarbonate, chloride, and magnesium) during furosemide therapy were extracted. Results Ninety neonates were recruited. Elevated serum creatinine was observed in 21.1% of the patients, and electrolyte disturbances were observed in 52.2%. Those with electrolyte disturbances had significantly greater cumulative doses compared to those without [5.5 (1–34) vs 3.9 (0.9–30.2) mg/kg; p = 0.01]. Cumulative doses adjusted to body-weight were significantly lower in very preterm and extremely preterm neonates compared to late preterm category. A significant area-under-the-curve was observed for the cumulative dose (0.66; 95% CI: 0.54–0.78; p = 0.01) in predicting the risk of electrolyte abnormalities with a cut-off value of 4 mg/kg. Eight neonates received more than 10 mg/kg cumulative dose of furosemide of which one died. No significant differences were observed between the proportion of neonates with electrolyte disturbances with cumulative furosemide dose above 10 mg/kg ( p = 0.3) and with mortality ( p = 0.3). Conclusion We observed that our critically ill neonates received relatively higher cumulative doses of furosemide and electrolyte disturbances were observed in nearly half of the population. A cumulative dose of 4 mg/kg increases the risk of electrolyte abnormalities, particularly in preterm neonates. More diligence in the dose titration coupled with deprescribing and intense monitoring of all the potential adverse effects in this vulnerable population is needed.

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Section: Discussioncontrasting

confidence: 66%

Cumulative Doses Predict the Risk of Furosemide-Induced Electrolyte Abnormalities in Critically Ill Neonates

Sridharan¹,

Madhoob²,

Jufairi³

2022

TCRM

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“…38% of the infants invasively ventilated were on daily furosemide. This is very different than the standard use of furosemide in the Neonatal ICU, which is a median exposure of 2 days and cumulative exposure of less than 4 mg/kg (Thompson et al, 2020). Furosemide has been associated with secondary hyperparathyroidism in an infant with tracheostomy and severe BPD (Srivastava et al, 2017).…”

Section: Discussionmentioning

confidence: 93%

Pharmacoepidemiology of Drug Exposure in Intubated and Non-Intubated Preterm Infants With Severe Bronchopulmonary Dysplasia

et al. 2021

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Background: Infants with severe bronchopulmonary dysplasia (BPD) are commonly treated with off-label drugs due to lack of approved therapies. To prioritize drugs for rigorous efficacy and safety testing, it is important to describe exposure patterns in this population.Objective: Our objective was to compare rates of drug exposure between preterm infants with severe bronchopulmonary dysplasia based on respiratory support status at or beyond 36 weeks post-menstrual age.Methods: A cross-sectional cohort study was performed on October 29, 2019. Preterm infants with severe BPD were eligible and details of respiratory support and drug therapy were recorded. Wilcoxon paired signed rank test was used to compare continuous variables between the invasive and non-invasive groups. Fisher’s exact test was used to compare binary variables by respiratory support status.Results: 187 infants were eligible for the study at 16 sites. Diuretics were the drug class that most subjects were receiving on the day of study comprising 54% of the entire cohort, followed by inhaled steroids (47%) and short-acting bronchodilators (42%). Infants who were invasively ventilated (verses on non-invasive support) were significantly more likely to be receiving diuretics (p 0.013), short-acting bronchodilators (p < 0.01), long-acting bronchodilators (p < 0.01), systemic steroids (p < 0.01), systemic pulmonary hypertension drugs (p < 0.01), and inhaled nitric oxide (p < 0.01).Conclusion: Infant with severe BPD, especially those who remain on invasive ventilation at 36 weeks, are routinely exposed to multiple drug classes despite insufficient pharmacokinetic, safety, and efficacy evaluations. This study helps prioritize sub-populations, drugs and drug classes for future study.

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“…We excluded infants only prescribed single-dose or as needed furosemide, those with incomplete dosing data (e.g., missing route of administration, end date, or dose) and those receiving > 9 mg/kg/dose, as these were outlying values at risk of being reporting errors. ( 10 ) This was a convenience cohort without formal sample size calculation. This study was considered exempt from human subject research approval by the Duke University Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

“…A recent descriptive study of infants discharged from Pediatrix Medical Group NICUs identified 1 mg/kg/d as the predominant intravenous dosing approach, consistent with the FDA label recommendation. ( 8 , 10 ) Differences in dosing as a function of PMA were not described. The objective of this study was to compare furosemide dosing practices across PMA groups in very preterm infants.…”

Section: Introductionmentioning

confidence: 99%

Association between postmenstrual age and furosemide dosing practices in very preterm infants

et al. 2022

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Objective: Furosemide renal clearance is slow after very preterm (VP) birth and increases with postnatal maturation. We compared furosemide dose frequency and total daily dose between postmenstrual age (PMA) groups in VP infants. Study Design: Observational cohort study of VP infants exposed to a repeated-dose course of furosemide in Pediatrix neonatal intensive care units (NICU) from 1997 to 2016. Results: We identified 6565 furosemide courses among 4638 infants. There were no statistically significant differences between PMA groups on the odds of receiving more frequent furosemide dosing. Furosemide courses initiated at < 28 weeks PMA were associated with a higher total daily dose than those initiated at a later PMA. Conclusions: Furosemide dosing practices in the NICU are similar across PMA groups, despite maturational changes in drug disposition. Research is needed to identify and test rational dosing strategies across the PMA spectrum for this commonly used but unproven pharmacotherapy.

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Pharmacoepidemiology of Furosemide in the Neonatal Intensive Care Unit

Cited by 7 publications

References 21 publications

Cumulative Doses Predict the Risk of Furosemide-Induced Electrolyte Abnormalities in Critically Ill Neonates

Cumulative Doses Predict the Risk of Furosemide-Induced Electrolyte Abnormalities in Critically Ill Neonates

Pharmacoepidemiology of Drug Exposure in Intubated and Non-Intubated Preterm Infants With Severe Bronchopulmonary Dysplasia

Association between postmenstrual age and furosemide dosing practices in very preterm infants

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