Kashani, Kianoush

Abstract Background Fluid overload, a critical consequence of acute kidney injury (AKI), is associated with worse outcomes. The optimal fluid removal rate per day during continuous renal replacement therapy (CRRT) is unknown. The purpose of this study is to evaluate the impact of the ultrafiltration rate on mortality in critically ill patients with AKI receiving CRRT. Methods This was a retrospective cohort study where we reviewed 1398 patients with AKI who received CRRT between December 2006 and November 2015 at the Mayo Clinic, Rochester, MN, USA. The net ultrafiltration rate (UFNET) was categorized into low- and high-intensity groups (<35 and ≥35 mL/kg/day, respectively). The impact of different UFNET intensities on 30-day mortality was assessed using logistic regression after adjusting for age, sex, body mass index, fluid balance from intensive care unit (ICU) admission to CRRT initiation, Acute Physiologic Assessment and Chronic Health Evaluation III and sequential organ failure assessment scores, baseline serum creatinine, ICU day at CRRT initiation, Charlson comorbidity index, CRRT duration and need of mechanical ventilation. Results The mean ± SD age was 62 ± 15 years, and 827 (59%) were male. There were 696 patients (49.7%) in the low- and 702 (50.2%) in the high-intensity group. Thirty-day mortality was 755 (54%). There were 420 (60%) deaths in the low-, and 335 (48%) in the high-intensity group (P < 0.001). UFNET ≥35 mL/kg/day remained independently associated with lower 30-day mortality (adjusted odds ratio = 0.47, 95% confidence interval 0.37–0.59; P < 0.001) compared with <35 mL/kg/day. Conclusions More intensive fluid removal, UFNET ≥35 mL/kg/day, among AKI patients receiving CRRT is associated with lower mortality. Future prospective studies are required to confirm this finding.

Abstract Aim The aim of this study is to assess the association between admission serum albumin and short- and long-term mortality in all hospitalized patients. Design A single-center cohort study. Methods A retrospective cohort of all adult hospitalized patients at a tertiary referral hospital between January 2009 and December 2013 were analysed. Admission serum albumin was stratified into six groups: ≤2.4, 2.5–2.9, 3.0–3.4, 3.5–3.9, 4.0–4.4 and ≥4.5 g/dl. The outcomes of interest were in-hospital mortality, length of hospital stay and 1-year mortality. Serum albumin of 4–4.4 g/dl was selected as a reference group for outcome comparison. Results A total of 14 075 patients were studied. Admission serum albumin of ≥4.5 g/dl had the lowest in-hospital and 1-year mortality with progressively increased in-hospital mortality observed with decreased admission serum albumin. In adjusted analysis, compared with serum albumin of 4.0–4.4 g/dl, serum albumin of ≤2.4, 2.5–2.9, 3.0–3.4 and 3.5–3.9 were significantly associated with increased in-hospital and 1-year mortality. In contrast, serum albumin of ≥4.5 g/dl was significantly associated with lower 1-year mortality but not in-hospital mortality. Admission serum albumin <4.0 g/dl was significantly associated with a prolonged hospital stay, while admission serum albumin of ≥4.5 g/dl was significantly associated with shorter hospital stay, compared with serum albumin of 4.0–4.4 g/dl. Conclusion Low albumin level at admission was progressively associated with increased short- and long-term mortality in all hospitalized patients even when albumin level was considered in normal range.

Abstract Background Sepsis frequently leads to acute kidney injury. In severe cases, patients may require continuous renal replacement therapy (CRRT) which involves placement of a dialysis catheter and an extracorporeal blood filtration circuit. CRRT is commonly considered to “mask” fever, though this phenomenon has not been investigated. Methods We queried an institutional database of all patients on CRRT from 2007 to 2015 for inpatient temperature data and antibiotic administration records. Receipts of piperacillin–tazobactam, a carbapenem, or a third or fourth-generation cephalosporin, indicating a serious infection, were considered intervention arm. We analyzed temperatures recorded in the intensive care unit before, during, and after CRRT. Patients were divided into groups that did not receive antibiotics as well as those who did. Temperature data were Winsorized to correct for outliers. We also performed descriptive statistics for each group. Results There were 237,988 temperature readings for 1,568 ICU patients on CRRT. 1,153 patients received broad-spectrum antibiotics in ICU. In patients who received antibiotics in ICU and were presumed to have an infection, the mean temperature was 37.2°C prior to initiation of CRRT, 36.8°C while on CRRT, and 37.2°C following discontinuation of CRRT. In the 415 patients who did not receive IV antibiotics, the mean temperature was 36.9°C prior to initiation of CRRT, 36.6°C while on CRRT, and 37.0°C following discontinuation of CRRT. During each of the periods before, during, and after CRRT, patients who received antibiotics had significantly higher temperatures than those who did not (P < 0.001). Patients receiving antibiotics were generally younger (mean 60 years vs. 64 years, P < 0.001), had longer ICU stays (mean 29 days vs. 12 days, P < 0.001) and spent more time being ventilated (mean 23 days vs. 7 days, P < 0.001). The mean SOFA score on day one was similar (mean 11.1 in the antibiotic group and 10.5 in the other group). Conclusion This investigation suggests that patients have slightly lower temperatures while on CRRT, by on average less than half a degree. A similar effect is seen in both patients with infections as well as those without. Further work will be needed to determine what constitutes a true febrile response in this population. Disclosures All authors: No reported disclosures.

Objectives: Decreased urine output and/or increased serum creatinine may herald the development of acute kidney injury or reflect normal physiology. In this secondary analysis of the Sapphire study, we examined biomarkers of cell cycle arrest in the settings of oliguria and/or azotemia to improve risk assessment when used with conventional indices in predicting severe acute kidney injury (Kidney Disease: Improving Global Outcomes 3 defined by the need for renal replacement therapy or changes in urine output, serum creatinine or both) or death. Design: Prospective, international, Sapphire study. Setting: Academic Medical Center. Patients: Patients without acute kidney injury Kidney Disease: Improving Global Outcomes stage 2 or 3. Interventions: None. Measurements and Main Results: The primary endpoint being development of severe acute kidney injury or death within 1 week. Secondary analysis examined the relationship between tissue inhibitor of metalloproteinases-2 ([TIMP-2]) and insulin growth factor binding protein 7 ([IGFBP7]) and 9-month death or dialysis conditioned on progression to stage 2–3 acute kidney injury within 1 week. Seventy-nine patients reached the primary endpoint and were more likely to be surgical, with higher nonrenal Acute Physiology and Chronic Health Evaluation III scores and more chronic kidney disease. Stage 1 urine output, serum creatinine, and urinary [TIMP-2]•[IGFBP7] greater than 2.0 were all predictive of progression to the primary endpoint independent from nonrenal Acute Physiology and Chronic Health Evaluation III score. Combinations of predictors increased the hazard ratios considerably (from 2.17 to 4.14 to 10.05, respectively). In the presence of acute kidney injury (stage 1), [TIMP-2]•[IGFBP7] greater than 2.0 leads to an increased risk of death or dialysis at 9 months even in the absence of progression of acute kidney injury (stage 2–3) within 7 days. Conclusions: Cell cycle arrest biomarkers, TIMP-2 and IGFBP7, improve risk stratification for severe outcomes in patients with stage 1 acute kidney injury by urine output, serum creatinine or both, with risk increasing with each acute kidney injury indicator. Longer term outcomes demonstrate that the associated risks of a [TIMP-2]•[IGFBP7] greater than 2.0 is equivalent to acute kidney injury progression even where no progression from stage 1 acute kidney injury is observed.

Background: Although acute kidney injury (AKI) is a frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), the incidence and impact of AKI on mortality among patients on ECMO remain unclear. We conducted this systematic review to summarize the incidence and impact of AKI on mortality risk among adult patients on ECMO. Methods: A literature search was performed using EMBASE, Ovid MEDLINE, and Cochrane Databases from inception until March 2019 to identify studies assessing the incidence of AKI (using a standard AKI definition), severe AKI requiring renal replacement therapy (RRT), and the impact of AKI among adult patients on ECMO. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018103527). Results: 41 cohort studies with a total of 10,282 adult patients receiving ECMO were enrolled. Overall, the pooled estimated incidence of AKI and severe AKI requiring RRT were 62.8% (95%CI: 52.1%–72.4%) and 44.9% (95%CI: 40.8%–49.0%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of AKI (p = 0.67) or AKI requiring RRT (p = 0.83). The pooled odds ratio (OR) of hospital mortality among patients receiving ECMO with AKI on RRT was 3.73 (95% CI, 2.87–4.85). When the analysis was limited to studies with confounder-adjusted analysis, increased hospital mortality remained significant among patients receiving ECMO with AKI requiring RRT with pooled OR of 3.32 (95% CI, 2.21–4.99). There was no publication bias as evaluated by the funnel plot and Egger’s regression asymmetry test with p = 0.62 and p = 0.17 for the incidence of AKI and severe AKI requiring RRT, respectively. Conclusion: Among patients receiving ECMO, the incidence rates of AKI and severe AKI requiring RRT are high, which has not changed over time. Patients who develop AKI requiring RRT while on ECMO carry 3.7-fold higher hospital mortality.

Abstract Aims To evaluate sex-specific disparities in acute kidney injury (AKI) complicating acute myocardial infarction-related cardiogenic shock (AMI-CS) in the United States. Methods and results This was a retrospective cohort study from 2000 to 2014 from the National Inpatient Sample (20% sample of all hospitals in the United States). Patients &gt;18 years admitted with a primary diagnosis of AMI and concomitant CS that developed AKI were included. The endpoints of interest were the prevalence, trends, and outcomes of men and women with AKI in AMI-CS. Multivariable hierarchical logistic regression was used to control for confounding, and a two-sided P &lt; 0.05 was considered statistically significant. During this 15 year period, 440 257 admissions with AMI-CS met the inclusion criteria, with AKI noted in 155 610 (35.3%). Women constituted 36.3% of the cohort and were older, of non-White race, and with higher co-morbidity compared with men. Women with AKI less often received coronary angiography (59% vs. 66%), percutaneous coronary intervention (39% vs. 43%), mechanical circulatory support (39% vs. 48%), mechanical ventilation (49% vs. 54%), and haemodialysis (9% vs. 10%) compared with men (all P &lt; 0.001). Adjusted in-hospital mortality was higher in women—odds ratio 1.16 (95% confidence interval 1.14–1.19); P &lt; 0.001—compared with men. Women had shorter lengths of stay (12 ± 14 vs. 13 ± 14 days), lower hospital costs ($150 071 ± 180 796 vs. $181 260 ± 209 674), and were less often discharged to home (19% vs. 31%) (all P &lt; 0.001). Conclusions Women with AKI in AMI-CS received fewer cardiac and non-cardiac interventions, had higher in-hospital mortality, and were less often discharged to home compared with men.

ABSTRACT Background: The use of norepinephrine may be associated with better outcomes in some patients with shock. We sought to determine whether norepinephrine was associated with lower mortality in unselected cardiac intensive care unit (CICU) patients compared with other vasopressors, and whether patterns of vasopressor and inotrope usage in the CICU have changed over time. Methods: We retrospectively evaluated consecutive adult patients admitted to a tertiary care hospital CICU from January 1, 2007 to December 31, 2015. Vasoactive drug doses were quantified using the peak Vasoactive-Inotropic Score (VIS). Temporal trends were assessed using the Cochran–Armitage trends test and multivariable logistic regression was used to determine predictors of hospital mortality. Results: We included 10,004 patients with a mean age of 67 ± 15 years; vasoactive drugs were used in 2,468 (24.7%) patients. Use of norepinephrine increased over time, whereas dopamine utilization decreased ( P < 0.001 for trends). After adjustment for illness severity and other variables, the peak VIS was a predictor of hospital mortality across the entire population (unit odds ratio [OR] 1.013, 95% confidence interval [CI], 1.009–1.017, P < 0.001) and among patients receiving vasoactive drugs (OR 1.018, 95% CI, 1.013–1.022, P < 0.001). Among patients receiving vasoactive drugs, norepinephrine was associated with a lower risk of hospital mortality (OR 0.66, 95% CI, 0.49–0.90, P = 0.008) after adjustment for illness severity and peak VIS. Conclusions: Vasoactive drug use in CICU patients has a dose-dependent association with short-term mortality. Use of norepinephrine in CICU patients is associated with decreased odds of death when compared with other vasoactive drugs.

AKI is a global concern with a high incidence among patients across acute care settings. AKI is associated with significant clinical consequences and increased health care costs. Preventive measures, as well as rapid identification of AKI, have been shown to improve outcomes in small studies. Providing high-quality care for patients with AKI or those at risk of AKI occurs across a continuum that starts at the community level and continues in the emergency department, hospital setting, and after discharge from inpatient care. Improving the quality of care provided to these patients, plausibly mitigating the cost of care and improving short- and long-term outcomes, are goals that have not been universally achieved. Therefore, understanding how the management of AKI may be amenable to quality improvement programs is needed. Recognizing this gap in knowledge, the 22nd Acute Disease Quality Initiative meeting was convened to discuss the evidence, provide recommendations, and highlight future directions for AKI-related quality measures and care processes. Using a modified Delphi process, an international group of experts including physicians, a nurse practitioner, and pharmacists provided a framework for current and future quality improvement projects in the area of AKI. Where possible, best practices in the prevention, identification, and care of the patient with AKI were identified and highlighted. This article provides a summary of the key messages and recommendations of the group, with an aim to equip and encourage health care providers to establish quality care delivery for patients with AKI and to measure key quality indicators.