We conducted a single-center retrospective observational study to investigate the association of the CRRT intensity with the 60-day in-hospital mortality rate in critically ill patients treated in an adult mixed ICU. Although the overall analysis showed no association of the CRRT intensity with the 60-day in-hospital mortality rate, higher CRRT intensity was associated significantly with higher 60-day in-hospital mortality, even after adjusting for confounding factors in the group of septic patients. Previous clinical studies have evaluated the beneficial effects of high CRRT intensity on AKI patients, but they failed to demonstrate its effectiveness (3, 4). Of note, these two multicenter RCTs did not show the disadvantage of higher-intensity CRRT. Although this study was conducted in an observational manner, the results suggest that higher CRRT intensity provides harmful effects rather than beneficial effects to AKI patients, especially those complicated with sepsis, who were expected to have been affected by overwhelming cytokine storm and therefore were assumed to be good responders of high-intensity CRRT. Another retrospective observational study conducted by Fujii et al. reported no significant difference in in-hospital mortality between the lower-intensity CRRT group (median 14.2 mL/kg/h) and the higher-intensity CRRT group (median 20.0 mL/kg/h) (10). However, multiple logistic regression analysis revealed that higher CRRT intensity is significantly associated with increased in-hospital mortality rate in accordance with our present study. It is noteworthy that the proportions of sepsis complications in these studies are similar (38% in this study; 55% in Fujii et al.'s study).
Our study entails several limitations which might have affected the results. First, this study was conducted at a single center. The number of patients analyzed was insufficiently large. One previous retrospective study conducted in a single center showed the different results from the present study; a lower delivered intensity contributed to predict higher mortality in a septic AKI cohort (18). Evaluations in multicenter ICUs with larger cohorts should be conducted to verify our findings. Second, this is a retrospective observational study that incorporates biases inherent in this study design. Because the CRRT intensity was judged by the attending physicians (intensivists and nephrologists), a higher intensity might have actually been prescribed for more severely ill patients. Third, patients receiving a lower CRRT intensity had a significantly greater body weight (Table 1). Inverse correlation between obesity and mortality of patients with heart failure, pneumonia, and severe sepsis has been reported recently (19–22). Creatine is converted into creatinine by a nonenzymatic cyclization throughout the body, but especially in skeletal muscle, and creatinine production can fall because of reductions in lean body mass. Reportedly, a higher serum creatinine is paradoxically associated with better patient survival (23, 24). Although the body weight at CRRT initiation and baseline serum creatinine concentration are not associated significantly with 60-day in-hospital mortality in the Cox proportional analysis of the present study, this inverse correlation between obesity or muscle mass and mortality might affect the association between CRRT intensity and mortality. Finally, the Japanese health insurance system for ICU patients, which is not fee-for-service, but episode-of-care payment system, might have a significant impact on CRRT intensity in this study. The prescribed dose in this study was mostly larger than the recommended dose (15 L/day) by the health insurance system because ICU physicians did not have to strictly follow this limit.
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