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Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation

Secondary Analysis of the Acute Renal Failure Trial Network Study
  • Shilpa Sharma
    Correspondence
    CORRESPONDENCE TO: Shilpa Sharma, MD, 11301 Wilshire Blvd, Los Angeles, CA 90073
    Affiliations
    Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

    Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, CA

    Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, CA
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  • Yvelynne P. Kelly
    Affiliations
    Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
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  • Paul M. Palevsky
    Affiliations
    Renal Section, Veterans Affairs Pittsburgh Healthcare System, and the Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • Sushrut S. Waikar
    Affiliations
    Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

    Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, MA
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      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.

      Key Words

      Abbreviations:

      AKI (acute kidney injury), ATN (Acute Renal Failure Trial Network), CRRT (continuous renal replacement therapy), CVVHDF (continuous venovenous hemodiafiltration), HR (hazard ratio), IHD (intermittent hemodialysis), RRT (renal replacement therapy), SLED (sustained low-efficiency dialysis)
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