TY - JOUR

T1 - Loop diuretics in adult intensive care patients with fluid overload

T2 - a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

AU - Wichmann, Sine

AU - Barbateskovic, Marija

AU - Liang, Ning

AU - Itenov, Theis Skovsgaard

AU - Berthelsen, Rasmus Ehrenfried

AU - Lindschou, Jane

AU - Perner, Anders

AU - Gluud, Christian

AU - Bestle, Morten Heiberg

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Background: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799). Results: We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49–1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15–3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66–0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55–1.20). Conclusions: The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.

AB - Background: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. Methods: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799). Results: We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49–1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15–3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66–0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55–1.20). Conclusions: The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.

KW - Critical care

KW - Diuretics

KW - Fluid accumulation

KW - Fluid overload

KW - Furosemide

KW - Loop diuretics

KW - Systematic review

U2 - 10.1186/s13613-022-01024-6

DO - 10.1186/s13613-022-01024-6

M3 - Review

C2 - 35696008

AN - SCOPUS:85131799823

VL - 12

JO - Annals of Intensive Care

JF - Annals of Intensive Care

SN - 2110-5820

IS - 1

M1 - 52

ER -