Clinical Question: Does intensive renal replacement therapy, as compared with a conventional treatment strategy, affect outcomes in critically ill patients?
Background: The optimal timing for the initiation, method, and dosing of renal replacement therapy among patients with AKI remains uncertain. Previous single-center studies limited to single methods of renal replacement therapy have suggested more intensive therapy is associated with improved survival. These results, however, have been inconsistent.
Study Design: Randomized controlled trial.
Setting: Veterans Affairs hospitals and university affiliated medical centers.
Synopsis: This study randomized 1,124 of 4,340 eligible critically ill adults with AKI to receive either intensive renal replacement therapy or a less intensive, more conventional approach. The primary end point of death at day 60 from any cause was 53.6% with intensive therapy and 51.5 % with less intensive therapy (odds ratio, 1.09; 95% CI 0.86 to 1.40; p=0.47). No significant differences were found in secondary end points, including rate of recovery of kidney function, duration of renal-replacement therapy, or evolution of non-renal organ failure.
This study demonstrates providing hemodialysis more frequently than three times per week to hemodynamically stable patients, or providing continuous renal replacement therapy at an effluent flow rate of more than 20 ml/kg/hour to hemodynamically unstable patients, does not improve outcomes. It should be noted, however, the less-intensive treatment strategy in this study provides a dose of renal replacement therapy exceeding the normal dose given in usual care.
Bottom Line: No clinical benefit exists in employing intensive renal replacement over a conventional approach in critically ill patients.
Citation: Palevsky PM, Zhang JH, O’Connor TZ, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359(1):7-20.
Elderly Patients and Females with Acute Coronary Syndrome (ACS) Often Receive Excess Doses of Heparin
Clinical Question: What initial dosing of unfractionated heparin (UFH) for patients with non-ST-segment elevation (NSTE) acute coronary syndrome is most frequently used and how does it affect risk of bleeding?
Background: UFH is commonly used in clinical practice for NSTE ACS, but a wide variability continues to exist in dosing protocols. Clinical studies have shown UFH dosing based on weight provides more effective early anticoagulation. However, the relationship between increasing weight-adjusted doses of UFH and the risk of bleeding has not been well described.
Study Design: Retrospective cohort study.
Setting: 420 U.S. hospitals involved in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation) initiative.
Synopsis: This study used data from patients enrolled in the CRUSADE initiative to investigate UFH dosing amongst 24,021 patients presenting with NSTE ACS. The study showed despite a recommendation to use weight-adjusted UFH dosing for NSTE ACS, there is a continued preference for a fixed dosing regimen of 5,000 U bolus and 1,000 U/hr initial infusion.
This fixed dose means women and the elderly are more likely to receive an excess UFH dose due to their lower body weight. The study found 35% of the group received excess weight-adjusted doses of UFH.
A clear relationship is present between excess weight-adjusted UFH doses and major bleeding, with the risk of major bleeding increasing particularly when UFH dose exceeds the recommended dosing of 70 U/kg bolus and 15 U/kg per hour infusion.
These observations support the need to follow guidelines on weight-adjusted UFH dosing in order to minimize the risk of bleeding in patients with NSTE ACS.
Bottom line: The initial UFH bolus and infusion dosing used for NSTE ACS often exceeds recommended weight-adjusted dosing, leading to higher rates of bleeding, particularly among women and the elderly.