麻豆传媒

ORLANDO -- Low-dose furosemide use in critically ill patients did not prevent worsening acute kidney injury (AKI), researchers reported here.

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

Similarly, use of the diuretic did not have a significant association with kidney recovery (29.7% versus 42.9%, P=0.36), renal replacement therapy use (RRT) use (27.0% versus 28.6%, P=0.88), or 90-day mortality (21.6% versus 31.4%, P=0.35) in ICU patients versus placebo, Bagshaw reported in a late-breaking abstract at the National Kidney Foundation meeting.

"The rationale for SPARK stemmed from two general observations," Bagshaw explained to 麻豆传媒. "First, experimental and pre-clinical data have suggested the timely utilization of loop diuretics in early AKI could provide 'kidney protection' largely mediated through reduction in medullary oxygen demand. Yet, this is in apparent paradox with clinical data -- largely derived from older observational studies at some risk of bias -- suggesting use of loop diuretics in AKI may be associated with increased risk for death and/or non-recovery of kidney function."

"Second, in AKI, loop diuretics are used exceedingly often. Surveys of healthcare practitioners and observational data suggest more than two-thirds to three-quarters of patients are exposed to diuretics at some point during their course," he said. "This represents a significant misalignment between evidence and clinical practice. This would suggest there is need to generate new evidence and knowledge that would ideally help inform best practice in the management of AKI."

The blinded, multicenter trial included 73 participants in the ICU with evidence of AKI, use of a urinary catheter, as well as a peripheral or central venous catheter, two or more SIRS occurring during the first day of screening, and post-achievement of immediate resuscitation goals.

Participants in the intervention group (n=37) received a furosemide bolus on 0.4 mg/kg, accompanied by a continuous infusion with a starting dose of 0.05 mg/kg/hr, with a maximum infusion of 0.4 mg/kg/hr. During the first day of intervention, the median total dose of furosemide was 1.65 mg/kg (0.7-4.8 mg/kg), while the median dose over the trial period was 3.2 mg/kg (1.4-16.1 mg/kg). The placebo group (n=36) received 0.9% saline infusion titrated to hourly urine output.

Incidence of adverse events was higher 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 mostly associated with minor electrolyte abnormalities and imbalances.

No significant differences were reported between the intervention and placebo group after adjustment for Acute Physiology and Chronic Health Evaluation II score (APACHE II) (OR 1.14, 95% CI 0.42-3.00). Findings were also consistent following adjustment for vancomycin exposure (OR 1.08, 0.39-2.98), pre-randomization exposure to furosemide (OR 1.39, 95% CI 0.52-3.76), as well as adjustment for pre-randomization oliguria (OR 1.18, 95% CI 0.45-3.16). In an analysis among a subgroup of ICU patients with sepsis, no significant differences were reported (OR 1.28, 95% CI 0.50-3.30).

Bagshaw noted how his research group was not particularly surprised by the findings. However, he highlighted that they were surprised in terms of "some of the challenges encountered when implementing the protocol at the bed side."

"While SPARK did not find significant differences in risk of worsening AKI, utilization of RRT or mortality, we recognize the trial was underpowered to meaningfully inform about these and other patient-centered outcomes. We did see differences in secondary endpoints (i.e., fluid balance); however, use of loop diuretics in this setting was also associated with greater incidence of electrolyte abnormalities."

"SPARK had a protocol that proved quite challenging to implement," Bagshaw explained. "As a consequence, we do not currently have plans to perform a larger definitive study with this approach. However, we strongly believe, given the apparent misalignment in evidence and practice, that additional studies need to focus on the optional population, settings, and conditions for loop diuretic use in AKI."

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