Length of red blood cell storage and clinical outcomes in transfused critical ill adults – the Age of Blood Evaluation (ABLE) randomised controlled trial
Lacroix L, Hebert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall, JC, Clayton L, McIntyre L, Callum J, et al
Transfusion Medicine. 2015;25((Suppl. 1)):6.. Abstract No. S10
Age of transfused blood in critically ill adults
Lacroix J, Hebert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, et al
New England Journal of Medicine. 2015;372((15):):1410-8.
BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (+/-SD) of 6.1+/-4.9 days in the fresh-blood group as compared with 22.0+/-8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
Fluid resuscitation in sepsis: a systematic review and network meta-analysis
Rochwerg B, Alhazzani W, Sindi A, Heels-Ansdell D, Thabane L, Fox-Robichaud A, Mbuagbaw L, Szczeklik W, Alshamsi F, Altayyar S, et al
Annals of Internal Medicine. 2014;161((5):):347-355.
BACKGROUND Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. STUDY SELECTION Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. DATA EXTRACTION Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. DATA SYNTHESIS 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). LIMITATIONS These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. CONCLUSION Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. PRIMARY FUNDING SOURCE The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.
The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Rimmer, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, et al
Critical Care (London, England). 2014;18((6):):699.
INTRODUCTION Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n=128) and the mean age of children ranged from 0.9 to 18 years (n=66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
The efficacy and safety of therapeutic apheresis in sepsis and septic shock: a systematic review and meta-analysis
Rimmer EK, Houston BL, Kumar A, Abou-Setta A, Friesen C, Turgeon AF, Cook DJ, Houston DS, Zarychanski R
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.
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.
The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review
Hui PLY, Cook DJ, Lim W, Fraser G, Arnold DM
Blood. 2010;116((21):): Abstract No. 4664.
Avoiding transfusions in children undergoing cardiac surgery: a meta-analysis of randomized trials of aprotinin
Arnold DM, Fergusson DA, Chan AK, Cook RJ, Fraser GA, Lim W, Blajchman MA, Cook DJ
Anesthesia and Analgesia. 2006;102((3):):731-737.
Do blood transfusions improve outcomes related to mechanical ventilation?
Hebert PC, Blajchman MA, Cook DJ, Yetisir E, Wells G, Marshall J, Schweitzer I, Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group
BACKGROUND Correcting the decrease in oxygen delivery from anemia using allogeneic RBC transfusions has been hypothesized to help with increased oxygen demands during weaning from mechanical ventilation. However, it is also possible that transfusions hinder the process because RBCs may not be able to adequately increase oxygen delivery. In this study, we determined whether a liberal RBC transfusion strategy improved outcomes related to mechanical ventilation. METHODS Seven hundred thirteen patients receiving mechanical ventilation, representing a subgroup of patients from a larger trial, were randomized to either a restrictive transfusion strategy, receiving allogeneic RBC transfusions at a hemoglobin concentration of 7.0 g/dL (and maintained between 7.0 g/dL and to 9.0 g/dL), or to a liberal transfusion strategy, receiving RBCs at 10.0 g/dL (and maintained between 10.0 g/dL and 12.0 g/dL). The larger trial was designed to evaluate transfusion practice rather than weaning per se. RESULTS Baseline characteristics in the restrictive-strategy group (n = 357) and the liberal-strategy group (n = 356) were comparable. The average durations of mechanical ventilation were 8.3 +/- 8.1 days and 8.3 +/- 8.1 days (95% confidence interval [CI] around difference, - 0.79 to 1.68; p = 0.48), while ventilator-free days were 17.5 +/- 10.9 days and 16.1 +/- 11.4 days (95% CI around difference, - 3.07 to 0.21; p = 0.09) in the restrictive-strategy group vs the liberal-strategy group, respectively. Eighty-two percent of the patients in the restrictive-strategy group were considered successfully weaned and extubated for at least 24 h, compared to 78% for the liberal-strategy group (p = 0.19). The relative risk (RR) of extubation success in the restrictive-strategy group compared to the liberal-strategy group, adjusted for the confounding effects of age, APACHE (acute physiology and chronic health evaluation) II score, and comorbid illness, was 1.07 (95% CI, 0.96 to 1.26; p = 0.43). The adjusted RR of extubation success associated with restrictive transfusion in the 219 patients who received mechanical ventilation for > 7 days was 1.1 (95% CI, 0.84 to 1.45; p = 0.47). CONCLUSION In this study, there was no evidence that a liberal RBC transfusion strategy decreased the duration of mechanical ventilation in a heterogeneous population of critically ill patients.
Crystalloids vs. colloids in fluid resuscitation: a systematic review
Choi PT, Yip G, Quinonez LG, Cook DJ
Critical Care Medicine. 1999;27((1):):200-10.
OBJECTIVE To systematically review the effects of isotonic crystalloids compared with colloids in fluid resuscitation. DATA SOURCES Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION All randomized clinical trials of adult patients requiring fluid resuscitation comparing isotonic crystalloids vs. colloids were included. Pulmonary edema, mortality, and length of stay were evaluated. Independent review of 105 articles identified 17 relevant primary studies of 814 patients. Weighted c about article inclusion was high (0.76). DATA EXTRACTION Data on population, interventions, outcomes, and methodologic quality of the studies were obtained by duplicate independent review with differences resolved by consensus. Weighted ic on the validity assessment was moderate (0.54). DATA SYNTHESIS No difference was observed overall between crystalloid and colloid resuscitation with respect to mortality and pulmonary edema; however, the power of the aggregated data was insufficient to detect small but potentially clinically important differences. Subgroup analysis suggested a statistically significant difference in mortality in trauma in favor of crystalloid resuscitation (relative risk 0.39, 95% confidence intervals: 0.17 to 0.89). Several methodologic issues are noteworthy regarding the primary studies, including lack of blinding (except in three studies). The type, dose, and duration of fluid administration and outcomes measured were different across these trials. CONCLUSIONS Overall, there is no apparent difference in pulmonary edema, mortality, or length of stay between isotonic crystalloid and colloid resuscitation. Crystalloid resuscitation is associated with a lower mortality in trauma patients. Methodologic limitations preclude any evidence-based clinical recommendations. Larger well-designed randomized trials are needed to achieve sufficient power to detect potentially small differences in treatment effects if they truly exist.