Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation: Secondary Analysis of the Acute Renal Failure Trial Network Study

Abstract

Background: Randomized clinical trials have failed to show benefit from increasing intensity of renal replacement therapy (RRT) for acute kidney injury, but continue to be frequently used. In addition, intensive RRT is associated with an increase in adverse events potentially secondary to small solute losses, such as phosphate. We hypothesized that, compared with less-intensive RRT, intensive RRT would lead to longer duration of mechanical ventilation.

Research question: Does more-intensive renal replacement therapy in critically ill patients with acute kidney injury increase time to extubation from mechanical ventilation when compared with less-intensive therapy?

Study design and methods: The Acute Renal Failure Trial Network study was a randomized multicenter trial of more-intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 mL/kg per hour) vs less-intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 mL/kg per hour) RRT in critically ill patients with acute kidney injury. Of 1124 patients, 907 who were supported by mechanical ventilation on study initiation were included in this Cox-proportional hazards analysis. The primary outcome was the time to first successful extubation off mechanical ventilation.

Results: Patients who were assigned randomly to more-intensive RRT had a 33.3% lower hazard rate of successful extubation (hazard ratio, 0.67; 95% CI, 0.52-0.88; P < .001) when compared with patients who were assigned to less-intensive RRT. Patients who were assigned to more-intensive RRT had, on average, 2.07 ventilator-free days, compared with 3.08 days in those who were assigned to less-intensive RRT (P < .001) over 14 days from start of the study.

Interpretation: Critically ill mechanically ventilated patients who were assigned randomly to more-intensive RRT had longer duration of mechanical ventilation compared with those who were assigned to less-intensive RRT. The reasons for this, such as excessive phosphate loss from more-intensive RRT, deserve further study to optimize the safety and effectiveness of CRRT delivery. This was a post hoc analysis of the Acute Renal Failure Trial Network study; clinical trial registration of the original trial is NCT00076219.

Keywords: acute kidney injury; critical care; mechanical ventilation; renal replacement therapy intensity.

Published by Elsevier Inc.

Figures

Figure 1

Kaplan-Meier survival estimates for time to extubation from mechanical ventilation according to treatment intensity. Time to extubation was shorter in the less-intensive arm (blue dashed lines) than the more-intensive arm (red solid lines); the table shows the number of participants who were at-risk.

Figure 2

Daily phosphate concentrations from day 1 through day 14 according to renal replacement therapy intensity (less intensive is indicated in blue; more intensive is indicated in red); upper and lower lines of the box represent the 75th percentile and 25th percentiles; upper and lower lines represent maximum and minimum values; the Table shows the number of participants with available data on serum phosphate by study day.