Hemofiltration in sepsis: where do we go from here?

Hemofiltration as an adjunct to therapy for sepsis is now 10 years old. Despite early successes and significant theoretical advantages, the treatment remains experimental. Although feasibility has been established, efficacy has proved to be much more difficult. Clinical as well as technical difficulties remain important considerations to future studies. These issues are discussed and the brief history of hemofiltration in sepsis is reviewed

Effectiveness of the Medical Emergency Team: the importance of dose

Up to 17% of hospital admissions are complicated by serious adverse events unrelated to the patients presenting medical condition. Rapid Response Teams (RRTs) review patients during early phase of deterioration to reduce patient morbidity and mortality. However, reports of the efficacy of these teams are varied. The aims of this article were to explore the concept of RRT dose, to assess whether RRT dose improves patient outcomes, and to assess whether there is evidence that inclusion of a physician in the team impacts on the effectiveness of the team. A review of available literature suggested that the method of reporting RRT utilization rate, (RRT dose) is calls per 1,000 admissions. Hospitals with mature RRTs that report improved patient outcome following RRT introduction have a RRT dose between 25.8 and 56.4 calls per 1,000 admissions. Four studies report an association between increasing RRT dose and reduced in-hospital cardiac arrest rates. Another reported that increasing RRT dose reduced in-hospital mortality for surgical but not medical patients. The MERIT study investigators reported a negative relationship between MET-like activity and the incidence of serious adverse events. Fourteen studies reported improved patient outcome in association with the introduction of a RRT, and 13/14 involved a Physician-led MET. These findings suggest that if the RRT is the major method for reviewing serious adverse events, the dose of RRT activation must be sufficient for the frequency and severity of the problem it is intended to treat. If the RRT dose is too low then it is unlikely to improve patient outcomes. Increasing RRT dose appears to be associated with reduction in cardiac arrests. The majority of studies reporting improved patient outcome in association with the introduction of an RRT involve a MET, suggesting that inclusion of a physician in the team is an important determinant of its effectiveness

How to improve the care of patients with acute kidney injury

Non peer reviewe

Pro/con clinical debate: Is high-volume hemofiltration beneficial in the treatment of septic shock?

Although there have been exciting advances in the management of sepsis and septic shock, mortality still remains high. Recent data suggest that high-volume hemofiltration (HVHF) may play a role in these patients. In contrast to the usual rate of hemofiltration, HVHF is felt to be better able to remove the inflammatory mediators associated with sepsis and septic shock. Such an approach is currently incapable of selectively removing specific mediators. This may be a problem when one considers that several mediators may in fact be beneficial. When determining whether HVHF should be instituted in a patient with septic shock, one need remember that its role is far from clear and its usefulness remains the subject of much debate. Although early data is encouraging, it is clear that additional data is required before HVHF becomes standard management. The authors of this pro/con debate, which is based on a clinical scenario, first describe their own position and then respond to their opponent's position

Clinical review: Anticoagulation for continuous renal replacement therapy - heparin or citrate?

Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate

Pharmacological Management of Cardiorenal Syndromes

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pharmacological management of Cardiorenal syndromes may be complicated by unanticipated or unintended effects of agents targeting one organ on the other. Hence, a thorough understanding of the pathophysiology of these disorders is paramount. The treatment of cardiovascular diseases and risk factors may affect renal function and modify the progression of renal injury. Likewise, management of renal disease and associated complications can influence heart function or influence cardiovascular risk. In this paper, an overview of pharmacological management of acute and chronic Cardiorenal Syndromes is presented, and the need for high-quality future studies in this field is highlighted

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 (ADQI) Group

INTRODUCTION: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at ) CONCLUSION: Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology

Economics of dialysis dependence following renal replacement therapy for critically ill acute kidney injury patients

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 dependence among critically ill AKI survivor

Cost of acute renal replacement therapy in the intensive care unit: results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Study

INTRODUCTION: Severe acute kidney injury (AKI) can be treated with either continuous renal replacement therapy (CRRT) or intermittent renal replacement therapy (IRRT). Limited evidence from existing studies does not support an outcome advantage of one modality versus the other, and most centers around the word use both modalities according to patient needs. However, cost estimates involve multiple factors that may not be generalizable to other sites, and, to date, only single-center cost studies have been performed. The aim of this study was to estimate the cost difference between CRRT and IRRT in the intensive care unit (ICU). METHODS: We performed a post hoc analysis of a prospective observational study among 53 centers from 23 countries, from September 2000 to December 2001. We estimated costs based on staffing, as well as dialysate and replacement fluid, anticoagulation and extracorporeal circuit. RESULTS: We found that the theoretic range of costs were from $3,629.80/day more with CRRT to$378.60/day more with IRRT. The median difference in cost between CRRT and IRRT was $289.60 (IQR 830.8-116.8) per day (greater with CRRT). Costs also varied greatly by region. Reducing replacement fluid volumes in CRRT to <or= 25 ml/min (approximately 25 ml/kg/hr) would result in$67.20/day (23.2%) mean savings. CONCLUSIONS: Cost considerations with RRT are important and vary substantially among centers. We identified the relative impact of four cost domains (nurse staffing, fluid, anticoagulation, and extracorporeal circuit) on overall cost differences, and hospitals can look to these areas to reduce costs associated with RRT