Supplementary Material for: Impact of continuous renal replacement therapy initiation on urine output and fluid balance: A multi-centre study.

Introduction The effect of continuous renal replacement therapy (CRRT) on renal function is poorly understood. However, the initiation of CRRT may induce oliguria. We aimed to investigate the impact of CRRT commencement on urine output (UO). Methods Retrospective cohort study in two intensive care units. We included all patients who underwent CRRT and collected data on hourly UO and fluid balance before and after CRRT commencement. We performed an interrupted time series analysis using segmented regression to assess the relationship between CRRT commencement and UO. Results We studied 1057 patients. Median age was 60.7 years (IQR, 48.3 – 70.6) and the median APACHE III was 95 (IQR, 76 – 115). Median time to CRRT was 17 hours (IQR, 5 - 49). With start of CRRT, the absolute difference in mean hourly urine output and mean hourly fluid balance was -27.0 mL/hr (95%CI -32.1 to -21.8; p value < 0.01) and – 129.3 mL/hr (95%CI -169.2 to -133.3), respectively. When controlling for pre-CRRT temporal trends and patient characteristics, there was a rapid post initiation decrease in urine output (-0.12 mL/kg/hr; 95%CI -0.17 to -0.08; p value <0.01) and fluid balance (-78.1 mL/hr; 95% CI -87.9 to -68.3; p value <0.01), which was sustained over the first 24 hours of CRRT. Change in urine output and fluid balance were only weakly correlated (r -0.29; 95% CI -0.35 to -0.23; p value <0.01). Conclusion Commencement of CRRT was associated with a significant decrease in urine output that could not be explained by extracorporeal fluid removal

Supplementary Material for: Patterns and Mechanisms of Artificial Kidney Failure during Continuous Renal Replacement Therapy

<b><i>Background:</i></b> We aimed to describe the previously unstudied relationship between circuit pressures and circuit clotting, here labeled as ‘artificial kidney failure' (AKF), in patients receiving continuous renal replacement therapy (CRRT). <b><i>Methods:</i></b> We performed an observational study of CRRT-treated critically ill patients to continuously record the multiple CRRT circuit pressures. <b><i>Results:</i></b> Three patterns of access outflow dysfunction (AOD) were also noted: severe, moderate and mild. Compared with circuits without AOD, circuits experiencing at least one AOD episode had shorter lifespans (14.2 ± 12.7 vs. 21.3 ± 16.5 h, p = 0.057). This effect was more obvious with moderate or severe AOD (8.7 ± 4.6 vs. 20.6 ± 15.7 h, p = 0.007). If any AOD events occurred within the first 4 h, the sensitivity and specificity in predicting early-immediate AKF were 53.4 and 94.4%, respectively. <b><i>Conclusions:</i></b> Early and intermediate AKF during CRRT is most likely dependent on AOD, which is a frequent event with variable severity

Supplementary Material for: Femoral Access and Delivery of Continuous Renal Replacement Therapy Dose

<b><i>Aims:</i></b> The study aims to describe the use of dialysis catheters in critically ill patients treated with continuous renal replacement therapy (CRRT) and to study the impact of femoral versus non-femoral access on CRRT dose. <b><i>Methods:</i></b> Statistical analysis and predictive modelling of data from the Randomized Evaluation of Normal vs. Augmented Level renal replacement therapy trial. <b><i>Results:</i></b> The femoral vein was the first access site in 937 (67%) of 1,399 patients. These patients had higher Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores (p = 0.009) and lower pH (p < 0.001) but similar mortality to patients with non-femoral access (44 vs. 45%; p = 0.63). Lower body weight was independently associated with femoral access placement (OR 0.97, 95% CI 0.96-0.98). Femoral access was associated with a 1.03% lower CRRT dose (p = 0.05), but a 4.20% higher dose was achieved with 13.5 Fr catheters (p = 0.03). <b><i>Conclusions:</i></b> Femoral access was preferred in lighter and sicker patients. Catheter gauge had greater impact than catheter site in CRRT dose delivery. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=439581

Supplementary Material for: Perioperative Hemodynamic Instability and Fluid Overload are Associated with Increasing Acute Kidney Injury Severity and Worse Outcome after Cardiac Surgery

<p><b><i>Purpose:</i></b> The study aimed to investigate patients' characteristics, fluid and hemodynamic management, and outcomes according to the severity of cardiac surgery-associated acute kidney injury (CSA-AKI). <b><i>Methods:</i></b> In a single-center, prospective cohort study, we enrolled 282 adult cardiac surgical patients. In a secondary analysis, we assessed preoperative patients' characteristics, physiological variables, and medication for intra- and postoperative fluid and hemodynamic management and outcomes according to CSA-AKI stages by the Renal risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification. Variables of fluid and hemodynamic management were further assessed with regard to the need for postoperative renal replacement therapy (RRT) and in-hospital mortality by the area under the curve for the receiver operating characteristic (AUC-ROC) and multivariate regression analysis. <b><i>Results:</i></b> Patients with worsening RIFLE stage, were significantly older, had lower estimated glomerular filtration rate and higher body mass index, more peripheral vascular and chronic obstructive pulmonary disease, atrial fibrillation, and prolonged duration of cardiopulmonary bypass (all <i>p</i> < 0.01). Patients with more severe AKI stage stayed longer in the intensive care and hospital, had higher in-hospital mortality, and requirement for RRT (all <i>p</i> < 0.001). Also, with worsening RIFLE stage, patients had lower intraoperative mean arterial pressure (MAP); <i>p</i> = 0.047, despite higher doses of norepinephrine (<i>p</i> < 0.001). The intraoperative MAP showed the best discriminatory ability (AUC-ROC: >0.8) for and was independently associated with RRT and in-hospital mortality. Moreover, with increasing AKI severity, patients received significantly more fluid infusion, and required higher dose of furosemide; nonetheless, they had increased postoperative fluid balance. <b><i>Conclusions:</i></b> In this cohort, reduced MAP and increased fluid balance were independently associated with increased mortality and need for RRT after cardiac surgery.</p

Supplementary Material for: Variation in Risk and Mortality of Acute Kidney Injury in Critically Ill Patients: A Multicenter Study

<b><i>Background:</i></b> Despite standardized definitions of acute kidney injury (AKI), there is wide variation in the reported rates of AKI and hospital mortality for patients with AKI. Variation could be due to actual differences in disease incidence, clinical course, or a function of data ascertainment and application of diagnostic criteria. Using standard criteria may help determine and compare the risk and outcomes of AKI across centers. <b><i>Methods:</i></b> In this cohort study of critically ill patients admitted to the intensive care units at six hospitals in four countries, we used KDIGO criteria to define AKI. The main outcomes were the occurrence of AKI and hospital mortality. <b><i>Results:</i></b> Of the 15,132 critically ill patients, 32% developed AKI based on serum creatinine criteria. After adjusting for differences in age, sex, and severity of illness, the odds ratio for AKI continued to vary across centers (odds ratio (OR), 2.57-6.04, p < 0.001). The overall, crude hospital mortality of patients with AKI was 27%, which also varied across centers after adjusting for KDIGO stage, differences in age, sex, and severity of illness (OR, 1.13-2.20, p < 0.001). The severity of AKI was associated with incremental mortality risk across centers. <b><i>Conclusions:</i></b> In this study, the absolute and severity-adjusted rates of AKI and hospital mortality rates for AKI varied across centers. Future studies should examine whether variation in the risk of AKI among centers is due to differences in clinical practice or process of care or residual confounding due to unmeasured factors