1.
Fluid resuscitation with 5% albumin versus normal saline in early septic shock: a pilot randomized, controlled trial
McIntyre LA, Fergusson DA, Cook DJ, Rowe BH, Bagshaw SM, Easton D, Emond M, Finfer S, Fox-Robichaud A, Gaudert C, et al
Journal of Critical Care. 2012;27((3):):317.e1-6.
Abstract
PURPOSE Randomized, controlled trials of fluid resuscitation in early septic shock face many logistic challenges. We describe the Fluid Resuscitation with 5% albumin versus Normal Saline in Early Septic Shock (PRECISE) pilot trial study design and report feasibility of patient recruitment. MATERIALS AND METHODS Six Canadian academic centers enrolled adult patients with early suspected septic shock from the emergency department and intensive care unit department. Consent was deferred. Using concealed allocation, participants were randomized to either 5% albumin or 0.9% sodium chloride. Blinded fluid resuscitation started immediately and continued for 7 days in the intensive care unit. Target recruitment was established a priori at 2 patients per site per month. RESULTS Fifty-one patients were enrolled; 50 patients received study fluid. We recruited a median of 2.5 patients (interquartile range [IQR], 1.5-3.0) per site per month into the trial. Median age and Acute Physiology and Chronic Health Evaluation II scores were 64.5 (IQR, 55.0-78.0) and 25.0 (IQR, 20.0-29.0), respectively. Most patients (n = 37 [74.0%]) were enrolled from the emergency department for a median of 1.6 hours (IQR, 0.8-3.5 hours) from their first hypotensive event and received a median of 2.4 L (IQR, 1.5-3.0 L) of resuscitation fluid before inclusion. Consent was deferred for 44 patients (89.8%). CONCLUSIONS Patient recruitment into the PRECISE pilot trial met our prespecified feasibility targets, and the PRECISE team is planning the larger trial. Copyright 2012 Elsevier Inc. All rights reserved.
2.
Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis
Turgeon AF, Hutton B, Fergusson DA, McIntyre L, Tinmouth AA, Cameron DW, Hebert PC
Annals of Internal Medicine. 2007;146((3):):193-203.
Abstract
BACKGROUND Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. PURPOSE To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. DATA SOURCES MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). STUDY SELECTION All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form. DATA SYNTHESIS The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 (95% CI, 0.62 to 0.89)) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 (CI, 0.58 to 0.89)) (17 trials (n = 1865)) and blinded trials (risk ratio, 0.61 (CI, 0.40 to 0.93) (7 trials (n = 896)). Severe sepsis or septic shock (risk ratio, 0.64 (CI, 0.52 to 0.79)) (11 trials (n = 689)), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 (CI, 0.40 to 0.94)) (7 trials (n = 560)), and receiving therapy for longer than 2 days (risk ratio, 0.66 (CI, 0.53 to 0.82)) (17 trials (n = 1847)) were strongly associated with this survival benefit. LIMITATIONS Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. CONCLUSIONS A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy.