Use of Continuous‐Infusion Loop Diuretics in Critically Ill Children

Abstract

Loop diuretics are commonly used in critically ill children to achieve appropriate fluid balance. They are often administered as a continuous intravenous infusion (CI) in hemodynamically unstable children because of fewer alterations in central venous pressure, oxygen saturation, and heart rate compared with scheduled intermittent dosing. During the past few years, however, drug shortages have been reported for bumetanide, torsemide, and furosemide. Therefore, to explore the use of alternative agents for CI, we performed a literature search to identify articles evaluating the use of furosemide, bumetanide, ethacrynic acid, and torsemide CI in critically ill children. The search was limited to English-language articles in the MEDLINE (1946-December 2013), EMBASE (1980-December 2013), and International Pharmaceutical Abstracts (1970-December 2013) databases and the Cochrane Database of Systematic Reviews (2005-December 2013). Reference citations from relevant articles were also reviewed. A total of 10 reports representing 173 pediatric patients were included in the analysis. Most of the reports provided evidence for furosemide, and no reports with torsemide were identified. Wide variability in CI dosing was reported in these studies. When selecting the loop diuretic CI for critically ill patients, clinicians should consider their adverse-event profiles, compatibility with other concomitant intravenous infusions, and pharmacoeconomics. Fluid balance and urine output should be monitored routinely to ensure appropriate response. The lowest initial dose should be used to achieve an appropriate fluid balance and target urine output of 1-3 ml/kg/hour while limiting the likelihood of toxicity.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2—Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues

“…In addition to CLS, patients with VOD have a portal hypertensionlike pathophysiology, which further increases peritoneal leakage. Blood product transfusions and medication volumes alone may equal the daily maintenance fluid requirements of some patients; diuresis may be critical to establishing euvolemia in these instances [20][21][22][23][24][25]. Once FO is confirmed, an incremental diuretic approach as outlined in Figure 1 Table 1 Recommendations for Management of Fluid, Electrolyte, and Renal Dysfunction in Patients with Veno-Occlusive Disease Q 1 Avoid acute fluid overload (FO) in all patients undergoing hematopoietic stem cell transplantation (HCT); restriction of fluid and diuretics may be indicated in patients exhibiting evidence of FO at any time.…”

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement

“…Furosemide is the less potent of the two commonly used loop diuretics. In pediatric cardiac patients, hemodynamic status, renal function, and anticipated fluid shifts often dictate the route of administration and dosing regimen (intermittent vs continuous infusion, with or without a preceding bolus) (78). In infants following congenital heart surgery, initial pediatric studies comparing dosing regimens had mixed outcomes (79,80).…”

“…Bumetanide has a shorter half-life and the additional advantage of wider compatibility when administered continuously with other IV medications (77,78). Although pediatric data for bumetanide are limited and published dosing regimens vary, existing evidence and wide clinical experience with this agent support its role as a safe and effective loop diuretic, particularly in the setting of evolving furosemide resistance.…”

“…Gasping syndrome has been reported in neonates exposed to greater than 99 mg/kg/d of benzyl alcohol. As such, the lowest dose of bumetanide required to achieve desired diuretic effect is recommended (78).…”

Development of Tolerance to Chronic Intermittent Furosemide Therapy in Pediatric Patients

“…In particular, the development of long-term tolerance to furosemide has been well described in adults, but data in pediatrics are limited. 1 Long-term tolerance is defined as the need to modify therapy to achieve the same diuretic response (i.e., increase dose and/or frequency, change or add diuretics). As patients develop tolerance and reach a therapeutic "ceiling," providers are tasked with finding alternative methods to achieve fluid goals, while balancing adverse effects from medications.…”