Supplementary Material for: Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients - A Secondary Analysis of the RENAL Trial

Introduction: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. Methods: In a secondary analysis of the Randomized Evaluation of Normal vs. Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. Results: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7% vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5 - 16] vs. 8 [5 - 15] days; adjusted median difference [MD], 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). Conclusions: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.