Furosemide low dose did not prevent worsening of AKI

The use of low doses of furosemide in critically ill patients did not prevent the worsening of acute kidney injury (ARF), the researchers reported here.

In the randomized controlled trial SPARK, loop diuretic furosemide (Lasix) had no significant impact on worsening of AKI in patients in the ICU, defined as progression of RIFLE-R to a more severe stage, compared with placebo ( 43.2% vs. 37.1%, OR 1.52, 95% CI, 0.61-3.83, P = 0.60), according to Sean M. Bagshaw, MD, of the University of Alberta in Canada, and colleagues.

Similarly, diuretic use had no significant association with renal recovery (29.7% vs 42.9%, P = 0.36), use of renal replacement therapy (27.0% vs. 28.6% %, P = 0.88) (21.6% versus 31.4%, P = 0.35) in ICU patients versus placebo, Bagshaw reported in a last minute summary at the National Kidney Foundation meeting .

“SPARK’s rationale arose from two general observations,” Bagshaw told MedPage Today. “First, experimental and preclinical data have suggested that the timely use of loop diuretics in early ARF may provide a” kidney protection “mediated to a large extent through the reduction in medullary oxygen demand. Old patients with some risk of bias – suggesting that the use of loop diuretics in ARF may be associated with an increased risk of death and / or non-recovery of renal function. ”

“Second, in the LRA, loop diuretics are used very often. Surveys of health professionals and observational data suggest more than two-thirds to three-quarters of patients are exposed to diuretics in some Moment during its course, “he said. “This represents a significant misalignment between evidence and clinical practice, suggesting that there is a need to generate new evidence and knowledge that would ideally help inform best practices in the management of AKI.”

The blind and multicenter trial included 73 ICU participants with evidence of IRA, use of a urinary catheter, as well as a peripheral or central venous catheter, two or more SIRS that occurred during the first day of screening, and post-achievement of immediate resuscitation objectives.

Participants in the intervention group (n = 37) received a bolus of furosemide of 0.4 mg / kg, accompanied by a continuous infusion with an initial dose of 0.05 mg / kg / h, with a maximum infusion of 0 , 4 mg / kg / hr. During the first intervention day, the median total dose of furosemide was 1.65 mg / kg (0.7-4.8 mg / kg), while the median dose during the test period was 3.2 mg / Kg (1.4-16.1 mg / kg). The placebo group (n = 36) received an infusion of titrated 0.9% saline at the urine output per hour.

The incidence of adverse events was greater in the furosemide group compared to the placebo group – 4.4 events / patient (25 patients, 111 events) versus 2.6 events / patient (22 patients, 57 events, P <0.001), which were associated mainly with anomalies and minor electrolytic imbalances.

No significant differences were reported between the intervention group and the placebo group after adjustment for the Chronic Health Assessment (APACHE II) Acute Physiology and Assessment II score (OR 1.14, 95% CI 0.42 -3.00). The findings were also consistent after adjustment for vancomycin exposure (OR 1.08, 0.39-2.98), prior exposure to furosemide randomization (OR 1.39, 95% CI: 0 , 52-3,76), as well as the adjustment for pre-randomization oliguria (OR 1.18; CI 0.45-3.16). In an analysis between a subgroup of ICU patients with sepsis, no significant differences were reported (OR 1.28, 95% CI: 0.50-3.30).

Bagshaw noted that his research group was not particularly surprised by the findings. However, he noted that they were surprised in terms of “some of the challenges encountered in implementing the protocol in bed.”

“Although SPARK found no significant difference in the risk of worsening ARF, the use of RRT or mortality, we recognize that the trial was insufficient to report significantly on these and other patient-centered outcomes. However, the use of loop diuretics in this environment was also associated with a higher incidence of electrolyte abnormalities. ”

“SPARK had a protocol that was very difficult to implement,” Bagshaw explained. “As a consequence, we do not currently have plans to conduct a more comprehensive definitive study with this approach. However, we strongly believe, given the apparent misalignment in evidence and practice, that additional studies should focus on the optional population, Conditions for Use Loop diuretic in AKI.