Published online May 9, 2022. doi: 10.5492/wjccm.v11.i3.178
Peer-review started: January 12, 2022
First decision: February 8, 2022
Revised: February 11, 2022
Accepted: April 24, 2022
Article in press: April 24, 2022
Published online: May 9, 2022
Processing time: 114 Days and 9.6 Hours
In patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common.
To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.
We searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.
Nine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.
Based on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.
Core Tip: Loop diuretics are a cornerstone treatment to maintain fluid balance in patients with respiratory failure, but resistance is common. In the caveat of a substantial heterogeneity, this meta-analysis shows a significant increase in urine output with negative fluid balance with the combination of loop diuretics plus thiazides compared to loop diuretics alone in patients with respiratory failure. Further trials are required to confirm the safety and efficacy of such interventions in patients with respiratory failure.