Search

BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.

In the original version of this article, the given and family names of several of the STARRT-AKI Investigators listed in the Acknowledgements section were incorrectly structured. The correct Acknowledgements section is given below. The original article has been corrected. The authors apologize for the mistake.

BACKGROUND: Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization. METHODS: We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables. RESULTS: Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (- 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08). CONCLUSIONS: Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.

We aimed to understand the prevalence, timing of onset, resource use, and long-term outcomes of patients who developed persistent critical illness in a national dataset. Design: Retrospective cohort. Using a physiologic risk adjustment model from ICU admission, we examined the relative ability of acute (related to reason for ICU presentation) and antecedent (demographics, comorbidities) characteristics to discriminate hospital mortality models. Persistent critical illness was defined as the point during an ICU stay when, at the population-level, patients' acute diagnoses and physiologic disturbance are no longer more accurate at discriminating who survives than are baseline demographics and comorbidity. We examined the change across ICU stay in the relative discrimination of those characteristics, and short-term (in-hospital and 30 d after admission) and medium-term (90 d after admission) survival. Finally, we analyzed the changes in the population definition of persistent critical illness over time. Setting: Patients admitted as level 3 to Scottish ICUs between 2005 and 2014. Patients: Seventy-two-thousand two-hundred fifty-three adult level 3 ICU admissions in 23 ICUs across Scotland. Interventions: None. Measurements and Main Results: The onset of persistent critical illness, occurs at an average of 5.0 days (95% CI, 3.9-6.4 d) across this dataset. The crossing point increased across the decade, by an average of 0.36 days (95% CI, 0.22-0.50 d) per year. In this dataset, 24,425 (33.8%) remained in the ICU long enough to meet this greater than 5-day definition of persistent critical illness. The care of such patients involved 72.3% ICU days used by any level 3 patient; 46.5% of all Scottish ICU bed-days were after day 5. Although rates of 30 days after admission survival rose dramatically during the decade under study, these rates were similar for those with shorter or longer ICU stays, as were the rates of 90-day survival among those who survived at least 30 days.

PURPOSE: Patients with persistent critical illness may account for up to half of all intensive care unit (ICU) bed-days. It is unknown if there is hospital variation in the development of persistent critical illness and if hospital performance affects the incidence of persistent critical illness. METHODS: This is a retrospective analysis of Veterans admitted to the Veterans Administration (VA) ICUs from 2015 to 2017. Hospital performance was defined by the risk- and reliability-adjusted 30-day mortality. Persistent critical illness was defined as an ICU length of stay of at least 11 days. We used 2-level multilevel logistic regression models to assess variation in risk- and reliability-adjusted probabilities in the development of persistent critical illness. RESULTS: In the analysis of 100 hospitals which encompassed 153,512 hospitalizations, 4.9% (N = 7640/153,512) developed persistent critical illness. There was variation in the development of persistent critical illness despite controlling for patient characteristics (intraclass correlation: 0.067, 95% CI 0.049-0.091). Hospitals with higher risk- and reliability-adjusted 30-day mortality had higher probabilities of developing persistent critical illness (predicted probability: 0.057, 95% CI 0.051-0.063, p < 0.01) compared to those with lower risk- and reliability-adjusted 30-day mortality (predicted probability: 0.046, 95% CI 0.041-0.051, p < 0.01). The median odds ratio was 1.4 (95% CI 1.33-1.49) implying that, for two patients with the same physiology on admission at two different VA hospitals, the patient admitted to the hospital with higher adjusted mortality would have 40% greater odds of developing persistent critical illness. CONCLUSION: Hospitals with higher risk- and reliability-adjusted 30-day mortality have a higher probability of developing persistent critical illness. Understanding the drivers of this variation may identify modifiable factors contributing to the development of persistent critical ill

OBJECTIVE: To explore associations between frailty (Clinical Frailty Scale score of 5 or more) in very old patients in intensive care units (ICUs) and their clinical outcomes (mortality, discharge destination). DESIGN, SETTING AND PARTICIPANTS: Retrospective population cohort analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data for all patients aged 80 years or more admitted to participating ICUs between 1 January 2017 and 31 December 2018. MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality; secondary outcomes: length of stay (hospital, ICU), re-admission to ICU during the same hospital admission, discharge destination (including new chronic care or nursing home admission). RESULTS: Frailty status data were available for 15 613 of 45 773 patients aged 80 years or more admitted to 178 ICUs (34%); 6203 of these patients (39.7%) were deemed frail. A smaller proportion of frail than non-frail patients were men (47% v 57%), the mean illness severity scores of frail patients were slightly higher than those of non-frail patients, and they were more frequently admitted from the emergency department (28% v 21%) or with sepsis (12% v 7%) or respiratory complications (16% v 12%). In-hospital mortality was higher for frail patients (17.6% v 8.2%; adjusted odds ratio [OR], 1.87 [95% CI, 1.65-2.11]). Median lengths of ICU and hospital stay were slightly longer for frail patients, and they were more frequently discharged to new nursing home or chronic care (4.9% v 2.8%; adjusted OR, 1.61 [95% CI, 1.34-1.95]). CONCLUSIONS: Many very old critically ill patients in Australia and New Zealand are frail, and frailty is associated with considerably poorer health outcomes. Routine screening of older ICU patients for frailty could improve outcome prediction and inform intensive care and community health care planning.

BACKGROUND: The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. METHODS: We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. RESULTS: A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. CONCLUSIONS: Acute kidney injury is common and is associated with poor outcomes, including increased mort

Purpose of the review: Among hospitalized patients, acute kidney injury is common and associated with significant morbidity and risk for mortality. The use of electronic health records (EHR) for prediction and detection of this important clinical syndrome has grown in the past decade. The steering committee of the 15th Acute Dialysis Quality Initiative (ADQI) conference dedicated a workgroup with the task of identifying elements that may impact the course of events following Acute Kidney Injury (AKI) e-alert. Sources of information: Following an extensive, non-systematic literature search, we used a modified Delphi process to reach consensus regarding several aspects of the utilization of AKI e-alerts. Findings: Topics discussed in this workgroup included progress in evidence base practices, the characteristics of an optimal e-alert, the measures of efficacy and effectiveness, and finally what responses would be considered best practices following AKI e-alerts. Authors concluded that the current evidence for e-alert system efficacy, although growing, remains insufficient. Technology and human-related factors were found to be crucial elements of any future investigation or implementation of such tools. The group also concluded that implementation of such systems should not be done without a vigorous plan to evaluate the efficacy and effectiveness of e-alerts. Efficacy and effectiveness of e-alerts should be measured by context-specific process and patient outcomes. Finally, the group made several suggestions regarding the clinical decision support that should be considered following successful e-alert implementation. Limitations: This paper reflects the findings of a non-systematic review and expert opinion. Implications: We recommend implementation of the findings of this workgroup report for use of AKI e-alerts.

Background: Acute kidney injury (AKI) is independently associated with the development of chronic kidney disease, endstage kidney disease and increased all-cause and cardiovascular-specific mortality. The severity of the renal insult and the development of multiple AKI episodes increase the risk of occurrence of these outcomes. Despite these long-term effects, only a minority of patients receive nephrologist follow up after an episode of AKI; those that do may have improved outcomes. Furthermore, relatively simple quality improvement strategies have the potential to change this status quo. Methods: On this background, a working group of the 15th Acute Dialysis Quality Initiative (ADQI) conference applied the consensus-building process informed by review of English language articles identified through PubMed search to address questions related to the opportunities, methodological requirements and barriers for longitudinal follow-up of patients with AKI in the era of electronic health records and Big Data. Results: Four consensus statements answering the key questions identified by the working group are developed. Conclusions: We have identified minimal data elements and potential data sources necessary to trace the natural history of patients from onset of AKI to long-term outcome. Minimum infrastructure and key barriers to achieving these goals are outlined together with proposed solutions.

Purpose of review: The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field. Objectives: 1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable "communication" and "translation" within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform 'registry-based' pragmatic studies. Source of information: Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI. Setting: Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7th, 2015, Banff, Canada Patients: Hospitalized patients with AKI Key messages: The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI), its temporal trends, and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care. Methods: A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions. Results: Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to

The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI.

The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15th ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions.

BACKGROUND: The obective of this study was to perform a cost-effectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from $200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). RESULTS: Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental cost-effectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. CONCLUSIONS: Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis de

PURPOSE: Choice of renal replacement therapy (RRT) modality may affect renal recovery after acute kidney injury (AKI). We sought to compare the rate of dialysis dependence among severe AKI survivors according to the choice of initial renal replacement therapy (RRT) modality applied [continuous (CRRT) or intermittent (IRRT)]. METHODS: Systematic searches of peer-reviewed publications in MEDLINE and EMBASE were performed (last update July 2012). All studies published after 2000 reporting dialysis dependence among survivors from severe AKI requiring RRT were included. Data on follow-up duration, sex, age, chronic kidney disease, illness severity score, vasopressors, and mechanical ventilation were extracted when available. Results were pooled using a random-effects model. RESULTS: We identified 23 studies: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % confidence interval (CI) 0.78-1.68], I(2) = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IRRT as compared with CRRT (RR 1.99 [95 % CI 1.53-2.59], I (2) = 42 %). These findings were consistent with adjusted analyses (performed in 7/16 studies), which found a higher rate of dialysis dependence in IRRT-treated patients [odds ratio (OR) 2.2-25 (5 studies)] or no difference (2 studies). CONCLUSIONS: Among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT. However, this finding largely relies on data from observational trials, potentially subject to allocation bias, hence further high-quality studies are necessary.

BACKGROUND: Preliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery. METHODS AND FINDINGS: In a multicenter, double-blinded (patients, clinical and research personnel), randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg) or sodium chloride (5.1 mmol/kg). The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%]) presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p = 0.009). Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001). More patients receiving bicarbonate (83/174 [47.7%]) developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04-2.45]; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90-2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p

Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P < 0.002), none of which achieved an AUC > 0.72. Furthermore, [TIMP- 2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·

Intravenous fluids are widely administered to maintain renal perfusion and prevent acute kidney injury (AKI). However, fluid overload is of concern during AKI. Using the Pubmed database (up to October 2011) we identified all randomised controlled studies of goal-directed therapy (GDT)-based fluid resuscitation (FR) reporting renal outcomes and documenting fluid given during perioperative care. In 24 perioperative studies, GDT was associated with decreased risk of postoperative AKI (odds ratio (OR) = 0.59, 95% confidence interval (CI) = 0.39 to 0.89) but additional fluid given was limited (median: 555 ml). Moreover, the decrease in AKI was greatest (OR = 0.47, 95% CI = 0.29 to 0.76) in the 10 studies where FR was the same between GDT and control groups. Inotropic drug use in GDT patients was associated with decreased AKI (OR = 0.52, 95% CI = 0.34 to 0.80, P = 0.003), whereas studies not involving inotropic drugs found no effect (OR = 0.75, 95% CI = 0.37 to 1.53, P = 0.43). The greatest protection from AKI occurred in patients with no difference in total fluid delivery and use of inotropes (OR = 0.46, 95% CI = 0.27 to 0.76, P = 0.0036). GDT-based FR may decrease AKI in surgical patients; however, this effect requires little overall FR and appears most effective when supported by inotropic drugs.

INTRODUCTION: During critical illness, oliguria is often used as a biomarker of acute kidney injury (AKI). However, its relationship with the subsequent development of AKI has not been prospectively evaluated. METHODS: We documented urine output and daily serum creatinine concentration in patients admitted for more than 24 hours in seven intensive care units (ICUs) from six countries over a period of two to four weeks. Oliguria was defined by a urine output < 0.5 ml/kg/hr. Data were collected until the occurrence of creatinine-defined AKI (AKI-Cr), designated by RIFLE-Injury class or greater using creatinine criteria (RIFLE-I[Cr]), or until ICU discharge. Episodes of oliguria were classified by longest duration of consecutive oliguria during each day were correlated with new AKI-Cr the next day, examining cut-offs for oliguria of greater than 1,2,3,4,5,6, or 12 hr duration, RESULTS: We studied 239 patients during 723 days. Overall, 32 patients had AKI on ICU admission, while in 23, AKI-Cr developed in ICU. Oliguria of greater than one hour was significantly associated with AKI-Cr the next day. On receiver-operator characteristic area under the curve (ROCAUC) analysis, oliguria showed fair predictive ability for AKI-Cr (ROCAUC = 0.75; CI:0.64-0.85). The presence of 4 hrs or more oliguria provided the best discrimination (sensitivity 52% (0.31-0.73%), specificity 86% (0.84-0.89%), positive likelihood ratio 3.8 (2.2-5.6), P < 0.0001) with negative predictive value of 98% (0.97-0.99). Oliguria preceding AKI-Cr was more likely to be associated with lower blood pressure, higher heart rate and use of vasopressors or inotropes and was more likely to prompt clinical intervention. However, only 30 of 487 individual episodes of oliguria preceded the new occurrence of AKI-Cr the next day. CONCLUSIONS: Oliguria was significantly associated with the occurrence of new AKI-Cr, however oliguria occurred frequently compared to the small number of patients (~10%) developing AKI-Cr in

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.

BACKGROUND: Furosemide is commonly prescribed in critically ill patients with acute kidney injury (AKI). Existing data from observational studies and small clinical trials have significant limitations and have reported conflicting findings. There remains controversy on whether furosemide can impact clinical outcomes in critically ill patients with AKI; however, a survey of intensivists and nephrologists showed equipoise for high-quality evidence on this important issue. DESIGN/METHODS: This protocol summarizes the rationale and design of a phase II randomized, blinded, placebo-controlled trial of a low-dose continuous infusion of furosemide, titrated to the physiology parameter of urine output, in critically ill patients with early AKI. Two hundred sixteen adult critically ill patients with early evidence of AKI, defined by the RIFLE criteria, will be enrolled. Included patients will also have fulfilled >or=2 criteria of the systemic inflammatory response syndrome and achieved immediate goals of acute resuscitation. The primary outcome is progression in severity of kidney injury. Secondary outcomes include: safety, fluid balance, electrolyte balance, the need for renal replacement therapy, duration of AKI, rate of renal recovery, mortality and changes in novel serum and urine biomarkers of AKI. The primary analysis will be intention-to-treat. Planned recruitment will be complete by June 2011 and results available by December 2011. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00978354.

INTRODUCTION: Older age is associated with higher prevalence of chronic illness and functional impairment, contributing to an increased rate of hospitalization and admission to intensive care. The primary objective was to evaluate the rate, characteristics and outcomes of very old (age >or= 80 years) patients admitted to intensive care units (ICUs). METHODS: Retrospective analysis of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for 120,123 adult admissions for >or= 24 hours across 57 ICUs from 1 January 2000 to 31 December 2005. RESULTS: A total of 15,640 very old patients (13.0%) were admitted during the study. These patients were more likely to be from a chronic care facility, had greater co-morbid illness, greater illness severity, and were less likely to receive mechanical ventilation. Crude ICU and hospital mortalities were higher (ICU: 12% vs. 8.2%, P < 0.001; hospital: 24.0% vs. 13%, P < 0.001). By multivariable analysis, age >/= 80 years was associated with higher ICU and hospital death compared with younger age strata (ICU: odds ratio (OR) = 2.7, 95% confidence interval (CI) = 2.4 to 3.0; hospital: OR = 5.4, 95% CI = 4.9 to 5.9). Factors associated with lower survival included admission from a chronic care facility, co-morbid illness, nonsurgical admission, greater illness severity, mechanical ventilation, and longer stay in the ICU. Those aged >or= 80 years were more likely to be discharged to rehabilitation/long-term care (12.3% vs. 4.9%, OR = 2.7, 95% CI = 2.6 to 2.9). The admission rates of very old patients increased by 5.6% per year. This potentially translates to a 72.4% increase in demand for ICU bed-days by 2015. CONCLUSIONS: The proportion of patients aged >or= 80 years admitted to intensive care in Australia and New Zealand is rapidly increasing. Although these patients have more co-morbid illness, are less likely to be discharged home, and have a greater mortality

INTRODUCTION: In critical illness, the association of hypoglycemia, blood glucose (BG) variability and outcome are not well understood. We describe the incidence, clinical factors and outcomes associated with an early hypoglycemia and BG variability in critically ill patients. METHODS: Retrospective interrogation of prospectively collected data from the Australia New Zealand Intensive Care Society Adult Patient Database on 66184 adult admissions to 24 intensive care units (ICUs) from 1 January 2000 to 31 December 2005. Primary exposure was hypoglycemia (BG < 4.5 mmol/L) and BG variability (BG < 4.5 and >or= 12.0 mmol/L) within 24 hours of admission. Primary outcome was all-cause mortality. RESULTS: The cumulative incidence of hypoglycemia and BG variability were 13.8% (95% confidence interval (CI) = 13.5 to 14.0; n = 9122) and 2.9% (95%CI = 2.8 to 3.0, n = 1913), respectively. Several clinical factors were associated with both hypoglycemia and BG variability including: co-morbid disease (P < 0.001), non-elective admissions (P < 0.001), higher illness severity (P < 0.001), and primary septic diagnosis (P < 0.001). Hypoglycemia was associated with greater odds of adjusted ICU (odds ratio (OR) = 1.41, 95% CI = 1.31 to 1.54) and hospital death (OR = 1.36, 95% CI = 1.27 to 1.46). Hypoglycemia severity was associated with 'dose-response' increases in mortality. BG variability was associated with greater odds of adjusted ICU (1.5, 95% CI = 1.4 to 1.6) and hospital (1.4, 95% CI = 1.3 to 1.5) mortality, when compared with either hypoglycemia only or neither. CONCLUSIONS: In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality.

INTRODUCTION: We conducted a study to evaluate the incidence, risk factors and outcomes associated with early acute kidney injury (AKI) in sepsis. METHODS: The study was a retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were collected from 57 intensive care units (ICUs) across Australia. In total, 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis. The main outcome measures were clinical and laboratory data and outcomes. RESULTS: Of 120,123 patients admitted, 33,375 had a sepsis-related diagnosis (27.8%). Among septic patients, 14,039 (42.1%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI. For septic AKI stratified by RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease) category, 38.5% of patients belonged to the risk category, 38.8% to the injury category and 22.7% to the failure category. Septic AKI patients had greater acuity of illness (P < 0.0001), lower blood pressure (P < 0.0001), higher heart rates (P < 0.0001), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P < 0.0001), greater acidaemia (P < 0.0001) and higher white cell counts (P < 0.0001) compared with patients with nonseptic AKI. Septic AKI was also associated with greater severity of AKI (RIFLE category injury or failure) compared with nonseptic AKI. Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU (19.8% versus 13.4%; odds ratio 1.60, 95% confidence interval 1.5 to 1.7; P < 0.001) and in hospital (29.7% versus 21.6%; odds ratio 1.53, 95% confidence interval 1.46 to 1.60; P < 0.001) compared with nonseptic AKI. Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories.

INTRODUCTION: Sepsis is the most common trigger of acute kidney injury (AKI) in critically ill patients; understanding the structural changes associated with its occurrence is therefore important. Accordingly, we systematically reviewed the literature to assess current knowledge on the histopathology of septic AKI. METHODS: A systematic review of the MEDLINE, EMBASE and CINHAL databases and bibliographies of the retrieved articles was performed for all studies describing kidney histopathology in septic AKI. RESULTS: We found six studies reporting the histopathology of septic AKI for a total of only 184 patients. Among these patients, only 26 (22%) had features suggestive of acute tubular necrosis (ATN). We found four primate studies. In these, seven out of 19 (37%) cases showed features of ATN. We also found 13 rodent studies of septic AKI. In total, 23% showed evidence of ATN. In two additional studies performed in a dog model and a sheep model there was no evidence of ATN on histopathologic examination. Overall, when ATN was absent, studies reported a wide variety of kidney morphologic changes in septic AKI - ranging from normal (in most cases) to marked cortical tubular necrosis. CONCLUSION: There are no consistent renal histopathological changes in human or experimental septic AKI. The majority of studies reported normal histology or only mild, nonspecific changes. ATN was relatively uncommon.

The ideology of evidence-based medicine (EBM) has dramatically altered the way we think, conceptualize, philosophize and practice medicine. One of its major pillars is the appraisal and classification of evidence. Although important and beneficial, this process currently lacks detail and is in need of reform. In particular, it largely focuses on three key dimensions (design, [type I] alpha error and beta [type II] error) to grade the quality of evidence and often omits other crucial aspects of evidence such as biological plausibility, reproducibility, generalizability, temporality, consistency and coherence. It also over-values the randomized trial and meta-analytical techniques, discounts the biasing effect of single centre execution and gives insufficient weight to large and detailed observational studies. Unless these aspects are progressively included into systems for grading, evaluating and classifying evidence and duly empirically assessed (according to the EBM paradigm), the EBM process and movement will remain open to criticism of being more evidence-biased than evidence-based."All scientific work is incomplete--whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time". (Sir Bradford Austin Hill 1).

INTRODUCTION: There is limited information on whether the incidence of acute kidney injury (AKI) in critically ill patients has changed over time and there is controversy on whether its outcome has improved. METHODS: We interrogated the Australian New Zealand Intensive Care Society Adult Patient Database to obtain data on all adult admissions to 20 Australian intensive care units (ICUs) for >or= 24 hours from 1 January 1996 to 31 December 2005. Trends in incidence and mortality for ICU admissions associated with early AKI were assessed. RESULTS: There were 91,254 patient admissions to the 20 study ICUs, with 4,754 cases of AKI, for an estimated crude cumulative incidence of 5.2% (95% confidence interval, 5.1 to 5.4). The incidence of AKI increased during the study period, with an estimated annual increment of 2.8% (95% confidence interval, 1.0 to 5.6, P = 0.04). The crude hospital mortality was significantly higher for patients with AKI than those without (42.7% versus 13.4%; odds ratio, 4.8; 95% confidence interval, 4.5 to 5.1; P < 0.0001). There was also a decrease in AKI crude mortality (annual percentage change, -3.4%; 95% confidence interval, -4.7 to -2.12; P < 0.001), however, which was not seen in patients without AKI. After covariate adjustment, AKI remained associated with a higher mortality (odds ratio, 1.23; 95% confidence interval, 1.14 to 1.32; P < 0.001) and there was a declining trend in the odds ratio for hospital mortality. CONCLUSION: Over the past decade, in a large cohort of critically ill patients admitted to 20 Australian ICUs, there has been a significant rise in the incidence of early AKI while the mortality associated with AKI has declined.

The current approach to assessing the quality of evidence obtained from clinical trials focuses on three dimensions: the quality of the design (with double-blinded randomised controlled trials representing the highest level of such design); the statistical power (beta) and the level of significance (alpha). While these aspects are important, we argue that other significant aspects of trial quality impinge upon the truthfulness of the findings: biological plausibility, reproducibility and generalisability. We present several recent studies in critical care medicine where the design, beta and alpha components of the study are seemingly satisfactory but where the aspects of biological plausibility, reproducibility and generalisability show serious limitations. Accordingly, we argue for more reflection, definition and consensus on these aspects of the evaluation of evidence.