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Critical Care Nephrology: Update in Critical Care for the Nephrologist

      Like the tide, over the past 15 years critical care has changed—back and forth and back again. In 2001, the pivotal PROWESS (Protein C Worldwide Evaluation in Severe Sepsis) clinical trial led to the approval of the first targeted therapy in patients with sepsis and a high risk of death, activated protein C (APC).
      • Bernard G.R.
      • Vincent J.L.
      • Laterre P.F.
      • et al.
      Efficacy and safety of recombinant human activated protein C for severe sepsis.
      However, subsequent negative studies led to the PROWESS-SHOCK trial,
      • Ranieri V.M.
      • Thompson B.T.
      • Barie P.S.
      • et al.
      Drotrecogin alfa (activated) in adults with septic shock.
      a randomized clinical trial mandated by the European Medicines Agency, Europe's equivalent of the US Food and Drug Administration. The PROWESS-SHOCK study showed no benefit of APC therapy and resulted in the withdrawal of APC from the clinical market. Along the same lines, the landmark article of Van den Berghe and colleagues demonstrating significant benefit to intensive glycemic control in surgical intensive care unit (ICU) patients
      • Van den Berghe G.
      • Wouters P.
      • Weekers F.
      • et al.
      Intensive insulin therapy in the critically ill patient.
      resulted in the widespread implementation of intensive glycemic control, only to have a number of subsequent clinical trials suggest that there is no significant benefit and potential harm with intensive glycemic control.
      • Brunkhorst F.M.
      • Engel C.
      • Bloos F.
      • et al.
      Intensive insulin therapy and pentastarch resuscitation in severe sepsis.
      • Finfer S.
      • Chittock D.R.
      • Su S.Y.
      • et al.
      Intensive versus conventional glucose control in critically ill patients.
      • Qaseem A.
      • Humphrey L.L.
      • Chou R.
      • et al.
      Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians.
      At the same time, the field of acute kidney injury (AKI) has flourished. The widespread adaptation of consensus definitions for AKI
      • Bellomo R.
      • Ronco C.
      • Kellum J.
      • et al.
      Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative Group.
      • Mehta R.L.
      • Kellum J.A.
      • Shah S.V.
      • et al.
      Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.
      The KDIGO AKI Workgroup
      KDIGO Clinical Practice Guideline for Acute Kidney Injury.
      has greatly improved the epidemiology of AKI. Furthermore, the increasing recognition of the close pathophysiologic and epidemiologic link between AKI and CKD and ESRD makes understanding AKI of significant relevance to all nephrology practitioners.
      In this issue, we review recent updates in critical care as well as updates in ICU nephrology. With regard to the critical care setting, we first begin with a review of sepsis by Venkataraman and Kellum, which focuses on “best practices” in the care of the critically ill patient with sepsis. As will be the theme for a number of the critical care updates, this article also highlights the impact of AKI on mortality in patients with sepsis. Next, we turn to the acute respiratory distress syndrome (ARDS), in which large-scale clinical trials have led to significant improvements in ventilator management
      Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.
      and substantial reductions in mortality. Seeley reviews recent changes to the definition of ARDS
      • Ranieri V.M.
      • Rubenfeld G.D.
      • Thompson B.T.
      • et al.
      Acute respiratory distress syndrome: the Berlin Definition.
      as well as current evidence-based management of the patient with ARDS. The third article, by Busse and colleagues, focuses on hemodynamic monitoring in the ICU, where it has become clear that interventions that were widespread in clinical practice several years ago, such as pulmonary artery catheterization, have limited benefit
      • Wheeler A.P.
      • Bernard G.R.
      • Thompson B.T.
      • et al.
      Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.
      • Sandham J.D.
      • Hull R.D.
      • Brant R.F.
      • et al.
      A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients.
      and where a number of new technologies to provide relatively noninvasive hemodynamic monitoring are emerging.
      Continuing on the critical care theme, we turn next to the role of transfusion in the ICU. As discussed by Afshar and Netzer, transfusions may have deleterious impacts on patients, including transfusion-related acute lung injury and transfusion-associated circulatory overload. Similarly, in the critical care context, no benefit and potential harm has been suggested with the use of erythropoiesis-stimulating agents; the data in support of these statements is reviewed here. Hirsch and Josephson review the rapidly growing field of neurocritical care, including acute electrolyte issues that may arise in neurologically injured patients and considerations for patients with ESRD, who are at higher risk for certain neurologic complications, including stroke.
      The current issue turns next to fluid and diuretic management in patients with AKI. Recent data suggest that although patients with septic shock benefit from early fluid resuscitation,
      • Rivers E.
      • Nguyen B.
      • Havstad S.
      • et al.
      Early goal-directed therapy in the treatment of severe sepsis and septic shock.
      patients with ARDS without shock benefit from a restrictive fluid management strategy.
      • Wiedemann H.P.
      • Wheeler A.P.
      • Bernard G.R.
      • et al.
      Comparison of two fluid-management strategies in acute lung injury.
      Since many of these patients have concomitant AKI, the data for fluid and diuretic management in these patients are relevant and are reviewed by Nadeau-Fredette and Bouchard. Next, Cruz reviews the recently proposed classification scheme for cardiorenal syndromes,
      • Ronco C.
      • Haapio M.
      • House A.A.
      • et al.
      Cardiorenal syndrome.
      which divides these syndromes based on the chronicity of the cardiac and renal conditions and the proposed directionality of the interaction. The overall intent of the new classification system is to refine the pathogenesis and treatment of these distinct conditions. The next review focuses on perioperative AKI, an entity associated with significant postoperative morbidity and mortality. Thakar succinctly reviews this large body of literature and cardiac surgery–associated AKI, which has been relatively well characterized and in which the major insult presumably occurs in the ischemic and proinflammatory milieu of cardiopulmonary bypass, making important distinctions throughout between other types of perioperative AKI, which are generally less well described in the literature.
      For patients with AKI, “best practice” supportive care is critical. In this regard, Palevsky reviews the current evidence base for dose, timing, and modality in patients who have severe AKI requiring renal replacement therapy (RRT). Although we have excellent data from large multicenter clinical trials to inform our practice with regard to dose,
      • Palevsky P.M.
      • Zhang J.H.
      • O'Connor T.Z.
      • et al.
      Intensity of renal support in critically ill patients with acute kidney injury.
      • Bellomo R.
      • Cass A.
      • Cole L.
      • et al.
      Intensity of continuous renal-replacement therapy in critically ill patients.
      data for timing and modality are limited. The design of trials to inform these questions is complicated by our current inability to accurately predict those patients with AKI who will go on to “need” dialysis and those patients who will recover spontaneously. A previously underappreciated aspect of supportive care in AKI that is gaining rapid acceptance and exposure in the literature is the impact of RRT on medication dosing. In particular, there is concern that RRT may increase underdosing of critical medications such as antibiotics in the septic patient. Fissell uses antibiotics as a paradigm to discuss drug dosing in patients receiving RRT and offers a number of practical suggestions for medication dosing for the practitioner.
      Along the same lines, another area of growing interest is the role of extracorporeal therapy in the treatment of overdose and intoxication. A number of nephrology societies (including the National Kidney Foundation) and critical care societies have constituted the Extracorporeal Treatments in Poisoning Workgroup to systematically review data in support of the use of extracorporeal therapy for intoxication. Here, Gosselin and Ghannoum
      • Ghannoum M.
      • Nolin T.D.
      • Lavergne V.
      • Hoffman R.S.
      Blood purification in toxicology: nephrology's ugly duckling.
      review both corporeal and extracorporeal methods to enhance poison elimination, a topic of significant relevance to nephrologists because we are frequently asked to prescribe extracorporeal therapy for critically ill intoxicated patients.
      Finally, Szamosfalvi and Yee review the care of the critically ill patient with ESRD. Given the rapidly increasing number of prevalent ESRD patients in the United States and their relatively higher overall rates of hospitalization, this group constitutes another growing population of ICU patients.
      They suggest a checklist of management issues that nephrologists should review closely with their intensivist colleagues and provide a review of newer techniques to monitor dialysis adequacy and clearance in this patient population.
      In sum, the past 15 years have been an area of great evidence-based progress in critical care, albeit with some steps forward and some backward. The articles in this issue of Advances in Chronic Kidney Disease review recent evidence-based changes in critical care, current management challenges, and new technologies in use in the ICU. Given the widespread interest in this field, hopefully the next 15 years will bring even more evidence-based improvements to the ICU and reduce mortality in this high-risk patient population.

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