A 2015 review notes that in various conditions resulting in edema and hypoalbuminemia, a combination of furosemide plus albumin has been observed to increase urine output and reduce edema in certain circumstances. However, the overall use of albumin in this setting remains controversial due to a lack of well-controlled, randomized trials. Additionally, other studies have not reported a benefit in different circumstances. It is believed that albumin may enhance furosemide's ability to reach its site of a secretion at the proximal tubules. Based on available data, another review recommends their combined use in two types of patients with nephrotic syndrome: those with intravascular hypovolemia or severe diuretic refractory edema. [1], [2]
Other limited studies have observed controversial results when combining furosemide and albumin in patients presenting with nephrotic syndrome. One study of five patients observed sustained diuretic effects for 1 week; however, another study that controlled their population of eight patients to individual therapy did not find improvement in urine and sodium excretion at 24 hours when furosemide and albumin were combined. Another study observed benefits of combination therapy through an increased effect on atrial natriuretic factor and mean arterial pressure along with increased excretion at 24 hours. Further, a study observing albumin use 60 minutes before furosemide observed a modest increase in diuresis but not in natriuresis. Two of these studies contained patients with hypoalbuminemia and are summarized in Tables 1 and 2. [1]
It is important to note the studies observed had small sample sizes and heterogeneous study designs. The doses utilized varied; furosemide doses ranged from 40 mg to 220 mg with concomitant equimolar concentrations of salt-poor albumin. The method of administration also varied, with albumin either being administered concurrently with the diuretic or before the diuretic. [1]
A 2021 meta-analysis evaluated the efficacy of furosemide and albumin co-administration (N= 422; 13 observational studies). Of the studies included, doses of albumin ranged from 6 to 40 g, and doses of 0.5 g/kg were also used in three studies. Doses of furosemide also varied. Furosemide with albumin co-administration was found to increase urine output by an average of 31.45 mL/hour (95% confidence interval [CI] 19.30 to 43.59) compared to furosemide treatment alone. Co-administration of furosemide and albumin also increased the average urinary sodium excretion rate to 1.76 mEq/hour (95% CI 0.83 to 2.69) compared to furosemide treatment alone. The diuretic effect of albumin and furosemide co-administration was increased in participants with low baseline serum albumin levels (<2.5 g/dL; p= 0.04) and high prescribed albumin infusion doses (> 30 g; p= 0.02). The effect was also more significant within 12 hours after administration (p= 0.01). The diuretic effect of co-administration was also improved in those with baseline creatinine levels > 1.2 mg/dL (p= 0.07), and the natriuretic effect of co-administration was improved in those with baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 (p= 0.1); however, these differences were not statistically significant. This meta-analysis is limited by the low quality of studies included and the high degree of heterogeneity for outcomes of diuresis and natriuresis. [3]
Another 2014 meta-analysis evaluated the effects of co-administration of albumin and loop diuretics in hypoalbuminemic patients as a strategy to overcome diuretic resistance. Ten studies were included (8 with crossover designs) for analysis. Co-administration of albumin and furosemide led to a significant increase in the amount of urine volume (231 mL; 95% CI 135.5 to 326.5) and sodium excreted (15.9 mEq; 95% CI 4.9 to 26.8) at 8 hours. However, these differences were not significant at 24 hours. While the included studies were largely heterogeneous, a transient effect of co-administration of albumin and furosemide in hypoalbuminemic patients was identified. Large-scale randomized controlled trials are needed to further evaluate these effects. [4]
A recent meta-analysis evaluated aimed to clarify the benefits of co-administration of albumin and diuretics in mechanically ventilated patients. Three randomized controlled trials (N= 129) were included for analysis. Albumin was found to reduce the risk of hypotensive events (risk ratio [RR] 0.33; 95% CI 0.15 to 0.81); however, albumin did not significantly affect the number of mechanical ventilation days or all-cause mortality. Albumin infusion did, however, improve the P/F ratio (RR 2.83; 95% CI 1.42 to 5.67). No randomized controlled trials reported the total urine output after intervention or adverse events. Certainty of evidence for the reported outcomes was low to moderate. [5]