Critically ill patients whose course is complicated by acute kidney injury often receive renal replacement therapy (RRT). For these patients, initiation of RRT results in a considerable escalation in both the complexity and associated cost of care. While RRT is extensively used in clinical practice, there remains uncertainty about the ideal circumstances of when to initiate RRT and for what indications. The process of deciding when to initiate RRT in critically ill patients is complex and is influenced by numerous factors, including patient-specific and clinician-specific factors and those related to local organizational/logistical issues. Studies have shown marked variation between clinicians, and across institutions and countries. As a consequence, analysis of ideal circumstances under which to initiate RRT is challenging. Recognizing this limitation, we review the available data and propose a clinical algorithm to aid in the decision for RRT initiation in critically ill adult patients. The algorithm incorporates several patient-specific factors, based on evidence when available, that may decisively influence when to initiate RRT. The objective of this algorithm is to provide a starting point to guide clinicians on when to initiate RRT in critically ill adult patients. In addition, the proposed algorithm is intended to provide a foundation for prospective evaluation and the development of a broad consensus on when to initiate RRT in critically ill patients.

Acute renal failure is a common complication in the intensive care unit (ICU). Over the last 25 years, there have been significant technological advances in the delivery of renal replacement therapy, particularly as it pertains to the critically ill patient population. Despite these advances, acute renal failure in critically ill patients continues to carry a poor prognosis. In this article, we review the current literature about timing and initiation of renal replacement therapy in the ICU as well as practical considerations regarding the prescription and delivery of dialysis.

The optimal dialysis dose for acute kidney injury is a matter of great controversy. Clinical trials, predominantly single-center studies, have shown conflicting results. The Acute Renal Failure Trial Network (ATN) Study was designed to compare clinical outcomes between patients allocated to an intensive dose versus a less-intensive dose of renal replacement therapy. Recently, the results of this large randomized controlled multicenter study were published. The present article will discuss certain aspects of this trial: the overall design, the baseline patient characteristics, and comparison of the results with earlier studies. Finally, the article will address the implications of the ATN Study results for clinical practice. IntroductionSince the original formulation of the dose concept for renal replacement therapy more than 30 years ago [1] and the establishment of a link between dose and clinical outcome [2,3], individualized patient dosing based on urea clearance is now routine in end-stage renal disease (ESRD) patients. More recently, similar principles have been applied to critically ill patients with acute kidney injury (AKI) treated both with continuous renal replacement therapy (CRRT) and with intermittent modalities.Using the normalized effluent rate as a dose surrogate in postdilution continuous venovenous hemofiltration, Ronco and colleagues reported higher survival in patients receiving a dose of 35 or 45 ml/hour/kg than in patients receiving a dose of 20 ml/hour/kg [4]. A second randomized controlled trial (RCT) demonstrated higher survival and renal recovery rate in AKI patients receiving an average of six intermittent hemodialysis (IHD) treatments per week compared with patients treated an average three times per week [5]. Since these two initial studies, three additional dose/outcome RCTs in CRRT [6][7][8] and one RCT in intermittent therapy [9] have been published, producing mixed results.

BackgroundRenal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively resource-intensive and expensive technology, there remains wide practice variation in its application. This systematic review will appraise the evidence for quality indicators (QIs) of CRRT care in critically ill patients.MethodsOvid MEDLINE, Ovid EMBASE, CINAHL, and the Cochrane Library including the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), and databases from the National Information Center of Health Services Research and Health Care Technology will be searched for original studies involving QIs in CRRT. Gray literature sources will be searched for technical reports, practice guidelines, and conference proceedings. Websites of relevant organizations will be identified, and industry leaders in the development and marketing of CRRT technology and non-profit organizations that represent key opinion leads in the use of CRRT will be contacted. We will search the Agency of Healthcare Research and Quality National Quality Measures Clearinghouse for CRRT-related QIs. Studies will be included if they contain quality measures, occur in critically ill patients, and are associated with CRRT. Analysis will be primarily descriptive. Each QI will be evaluated for importance, scientific acceptability, usability, and feasibility using the four criteria proposed by the United States Strategic Framework Board for a National Quality Measurement and Reporting System. Finally, QIs will be appraised for their potential operational characteristics, for their potential to be integrated into electronic medical records, and on their affordability, if applicable.DiscussionThis systematic review will comprehensively identify and synthesize QIs in CRRT. The results of this study will fuel the development of an inventory of essential QIs to support the appropriate, safe, and efficient delivery of CRRT in critically ill patients.Systematic review registrationPROSPERO CRD42015015530.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-015-0088-1) contains supplementary material, which is available to authorized users.

Approximately one-third of cases of severe sepsis result in death. Endogenous activated protein C (ApC) plays a key role in the regulation of the inflammation, fibrinolysis and coagulation associated with severe sepsis. In a recently published phase III trial, protein C Worldwide Evaluation in Severe Sepsis (pROWESS), intravenous administration of recombinant human ApC (rhApC) 24 µg/kg/h for 96 h to patients with severe sepsis resulted in a 6.1% reduction in absolute mortality and a 19.4% reduction in the relative risk of death from any cause within 28 days (number needed to treat = 16). This dose is now being applied in clinical practice.rhApC is recommended for the treatment of severe sepsis (sepsis associated with acute organ dysfunction) occurring as a result of all types of infection (Gram-negative bacterial, Gram-positive bacterial and fungal). A panel of Canadian clinicians experienced in the treatment of severe sepsis and the management of critical care patients has developed this consensus document to assist clinicians in appropriate patient selection and management of potential challenges associated with rhApC therapy.