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Systematic Review and Meta-Analysis of Effects of Transfusion on Hemodynamic and Oxygenation Variables
Cavalcante Dos Santos E, Orbegozo D, Mongkolpun W, Galfo V, Nan W, Gouvea Bogossian E, Taccone FS, Vallet B, Creteur J, Vincent JL
Critical care medicine. 2020;48(2):241-248
Abstract
OBJECTIVES RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. DATA SOURCES PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. STUDY SELECTION All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. DATA EXTRACTION Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. DATA SYNTHESIS We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were -0.0 L/min/m (-0.1 to 0.1 L/min/m) (p = 0.86) for cardiac index; -1.8 beats/min (-3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m (71.1-122.5 mL/min/m) (p < 0.01) for oxygen delivery index; 2.9% (2.2-3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; -3.7% (-4.4% to -3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m (0.9-9.0 mL/min/m) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m (2.3-14.5 mL/min/m; p = 0.01). CONCLUSIONS Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis.
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Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients
Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L
Critical Care (London, England). 2017;21((1)):213.
Abstract
BACKGROUND Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients. METHODS This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng/kg/minute (n = 19), 3.75 ng/kg/minute (n = 2), or placebo (n = 21) until shock resolution or a maximum of 7 days. If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added. Co-primary endpoints were maintenance of MAP >60 mmHg without norepinephrine, norepinephrine dose, and proportion of patients maintaining MAP >60 mmHg with or without norepinephrine over 7 days. Secondary endpoints included cumulative fluid balance, organ dysfunction, pharmacokinetics, and safety. RESULTS A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01). The 7-day cumulative doses of norepinephrine were 761, 659, and 249 mug/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01). Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 mug/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001). Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05). The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02). Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group. CONCLUSIONS In septic shock patients, selepressin 2.5 ng/kg/minute was able to rapidly replace norepinephrine while maintaining adequate MAP, and it may improve fluid balance and shorten the time of mechanical ventilation. TRIAL REGISTRATION ClinicalTrials.gov, NCT01000649 . Registered on September 30, 2009.
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A liberal strategy of red blood cell transfusion reduces cardiogenic shock in elderly patients undergoing cardiac surgery
Nakamura RE, Vincent JL, Fukushima JT, Almeida JP, Franco RA, Lee Park C, Osawa EA, Pinto Silva CM, Costa Auler JO Jr, Landoni G, et al
Journal of Thoracic & Cardiovascular Surgery. 2015;150((5)):1314-20.
Abstract
OBJECTIVE The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a liberal transfusion strategy. METHODS This is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS) randomized controlled trial. In this subgroup analysis, we separated patients into those aged 60 years or more (elderly) and those aged less than 60 years randomized to a restrictive or a liberal strategy of red blood cell transfusion. The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity. RESULTS Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60 years or more and 242 (48.2%) were aged less than 60 years and were included in this study. The primary end point occurred in 11.9% of patients in the liberal strategy group and 16.8% of patients in the restrictive strategy group (P = .254) for those aged 60 years or more and in 6.8% of patients in the liberal strategy group and 5.6% of patients in the restrictive strategy group for those aged less than 60 years (P = .714). However, in the older patients, cardiogenic shock was more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P = .031). Thirty-day mortality, acute respiratory distress syndrome, and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups. CONCLUSIONS Although there was no difference between groups regarding the primary outcome, a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients.Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Crystalloids versus colloids: exploring differences in fluid requirements by systematic review and meta-regression
Orbegozo Cortes D, Gamarano Barros T, Njimi H, Vincent JL
Anesthesia & Analgesia. 2015;120((2):):389-402.
Abstract
BACKGROUND Positive fluid balance has been associated with worse outcomes, and knowledge of differences in the amounts of different types of fluid needed to achieve the same end points may have important clinical implications. Large molecules persist longer in the blood vessels than smaller molecules, such that less IV colloid may be needed to achieve similar hemodynamic end points compared with crystalloid. Recent clinical data have, however, challenged this physiological concept, with investigators reporting lower-than-expected crystalloid/colloid ratios in various populations. METHODS We performed a systematic search in MEDLINE, EMBASE, and CENTRAL up to December 18, 2013, to retrieve all studies comparing (any) crystalloid with (any) colloid in all types of patients. The crystalloid/colloid ratio was calculated for each study. Descriptive analysis was performed for all studies, and a meta-analysis was performed in those studies reporting full data (in terms of means and standard deviations) of infused fluid volumes. Studies were grouped according to study and population characteristics. A meta-regression analysis was then performed to evaluate some of the possible reasons for differences in crystalloid/colloid ratios across studies. RESULTS From 976 studies, 48 were retained for the final analysis; 24 of the studies had sufficient data for meta-analysis. The crystalloid/colloid ratio across all the studies included in the meta-analysis was 1.5 (95% confidence interval, 1.36-1.65) with marked heterogeneity among studies (I = 94%). From the meta-regression analysis, decade of publication across all publications (P = 0.001) and concentration (tonicity) in the subgroup of albumin studies (P = 0.001) were associated with the administered crystalloid/colloid ratio. The reduction in heterogeneity among studies for all publications in the meta-regression was minimal, with the maximal decrease obtained when decade of publication was considered (R = 12%). CONCLUSIONS Greater fluid volumes are required to meet the same targets with crystalloids than with colloids, with an estimated ratio of 1.5 (1.36-1.65), but there is marked heterogeneity among studies. The crystalloid/colloid ratio seems to have decreased over the years, and differences in ratios are correlated with the concentration of albumin solutions; however, the main reasons behind the high heterogeneity among studies remain unclear.
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Transfusion requirements in surgical oncology patients: a prospective, randomized controlled trial
Pinheiro de Almeida J, Vincent JL, Barbosa Gomes Galas FR, Pinto Marinho de Almeida E, Fukushima JT, Osawa EA, Bergamin F, Lee Park C, Nakamura RE, Fonseca SM, et al
Anesthesiology. 2015;122((1):):29-38.
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Abstract
BACKGROUND Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. METHODS In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration <7 g/dl) was superior to a liberal one (transfusion when hemoglobin concentration <9 g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. RESULTS A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). CONCLUSION A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.
Clinical Commentary
What is known?
Thresholds for red cell transfusion are currently under much scrutiny with a growing number of randomised controlled trials (RCTs) supporting the safety of restrictive transfusion practices in specified patient groups e.g. patients treated on the intensive care unit (TRICC) [1], following hip (FOCUS) [2] and cardiac surgery (TRACS) [3, 4], and patients with acute upper gastrointestinal bleeding [5] and sepsis (TRISS) [6]. Patients with cancer who are anaemic have poorer outcomes than those who are not [7] but there are no previous RCTs examining risks and benefits of transfusion in surgical patients with malignancy.
What did this paper set out to examine?
This paper describes 198 critically ill patients following surgery for abdominal malignancy randomised to restrictive (threshold 7 g/dl) and liberal (9 g/dl) transfusion strategies [8]. The primary outcome was a composite 30-day endpoint of all-cause mortality, cardiovascular complications, acute respiratory distress syndrome, acute kidney injury requiring renal replacement therapy, septic shock and reoperation.
What did they show?
This is the first RCT to demonstrate a worse outcome for patients assigned a restrictive threshold. There is an almost two-fold increase in the composite 30-day endpoint in the restrictive group (35.6% versus 19.6%, p=0.012). Thirty day mortality was 8.2% (liberal) versus 22.8% (restrictive), p= 0.005. The most common causes of death were septic shock and multisystem organ failure. Cardiovascular events and intra-abdominal sepsis were more frequent in the restrictive group.
The extent of the worse outcomes in the restrictive group is unexpected following larger RCTs supporting the safety of restrictive transfusion practice. The least supportive of this strategy was the recently published cardiac surgery RCT which concluded that a restrictive threshold was not superior to a liberal threshold [4]; they showed no difference in the primary outcome (serious infection or ischaemic event at 3 months). However, there was an increased mortality in the restrictive group (4.2% versus 2.6%, p=0.045).
There are significant differences in outcomes between the 2 groups in Almeida’s study and so we must consider whether these are attributable to differences in transfusion practice. Importantly, 57.7% of those even in the liberal group (79.2% in the restrictive group) were not transfused during the randomisation period. The reported difference in haemoglobin between the groups relates to the pre-transfusion haemoglobin and therefore does not include haemoglobins of those not transfused (68.9% of total study population).
Although the target thresholds were 7.0 and 9.0 g/dl, patients were transfused on average at 6.8 g/dl (restrictive group) and 7.9 g/dl (liberal). Compared to the preceding large RCTs there is a lack of separation in haemoglobin levels between groups [2, 6]. All 13 protocol deviations in the liberal group occurred when patients with haemoglobin <9.0 g/dl were not transfused; all 7 deviations in the restrictive group were for transfusions given with haemoglobin >7.0 g/dl.
The median duration for which patients remained randomised (i.e. length of ICU stay) was 4 days, compared to 11 days in the TRICC trial and until discharge or death in the Villanueva and FOCUS trials. In this study the small difference in haemoglobin between the groups only emerges at 4 days.
These factors together call into doubt whether the differences in outcomes can be attributed to differences in transfusion alone, and so an alternative explanation for the differences in outcomes must be sought. One possible reason is the small excess in major operations (oesophagectomy, gastroduodenopancreatectomy) as compared to cystectomy and hysterectomy in the restrictive group; this may also explain the excess of abdominal sepsis. There was a small, non-significant, excess of patients with diabetes, chronic obstructive pulmonary disease and congestive heart failure in the restrictive group.
The question addressed in the study is important and there are positive aspects to the trial which should be highlighted. This is the first randomised study specifically assessing post-operative patients with malignancy; the FOCUS study is the only other large RCT to include significant numbers of cancer patients (18.0 and 18.8% in the two arms) but the types, stage or remission status are not given. In the current study there were attempts to blind patients and investigators and the clinical practice described is deliverable on most ICUs. There were small numbers of protocol deviations and follow-up to the primary endpoint was complete.
What are the implications for practice and for future work?
It is important to consider the limitations of this study if its findings are to be used to inform practice. In the presence of multiple other RCT data supportive of restrictive transfusion practice we would caution against changing practice based on this research. Despite its unexpected findings, this study questions the safety of restrictive transfusion practice and it is important that future trials continue to address the safety this approach among different patient groups.
References
1. Hébert PC, et al., A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med, 1999. 340(6): 409-17.
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Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: A randomized pilot trial
Galas FR, de Almeida JP, Fukushima JT, Vincent JL, Osawa EA, Zeferino S, Camara L, Guimaraes VA, Jatene MB, Hajjar LA
Journal of Thoracic & Cardiovascular Surgery. 2014;148((4):):1647-55.
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Abstract
OBJECTIVES Acute acquired hypofibrinogenemia in children undergoing cardiac surgery is a major concern because it often results in perioperative bleeding and high rates of allogeneic blood transfusion. Fibrinogen concentrate has been proposed as an alternative to cryoprecipitate (the gold standard therapy), with minimal infectious and immunologic risks. Our objective was to investigate the efficacy and safety of fibrinogen concentrate in children undergoing cardiac surgery. METHODS In this randomized pilot study, patients were allocated to receive fibrinogen concentrate (60 mg/kg) or cryoprecipitate (10 mL/kg) if bleeding was associated with fibrinogen levels <1 g/dL after cardiopulmonary bypass weaning. The primary outcome was postoperative blood losses during the 48 hours after surgery. RESULTS A total of 63 patients were included in the study, 30 in the fibrinogen concentrate group and 33 in the cryoprecipitate group. The median 48-hour blood loss was not significantly different between the 2 groups (320 mL [interquartile range, 157-750] vs 410 mL [interquartile range, 215-510], respectively; P = .672). After treatment, plasma fibrinogen concentration increased similarly following administration of both products. There were no differences in allogeneic blood transfusion after intervention treatment. CONCLUSIONS A large trial comparing fibrinogen concentrate and cryoprecipitate in the management of children with acute acquired hypofibrinogenemia during heart surgery is feasible. The preliminary results of our study showed that the use of fibrinogen concentrate was as efficient and safe as cryoprecipitate in the management of bleeding children undergoing cardiac surgery. Copyright 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Clinical Commentary
Dr Simon Stanworth - NHS Blood & Transplant, Oxford, UK
What is known?
There are several different sources of fibrinogen for use in patients with major bleeding such as trauma or postpartum or surgery. The two main concentrated sources are fibrinogen concentrate or cryoprecipitate. Cryoprecipitate is the standard method of fibrinogen supplementation in UK. The evidence relating to the clinical effectiveness of cryoprecipitate is very limited; with very few randomised controlled trials (RCTs) completed to date. Fibrinogen concentrate (FgC) is increasingly available and a recent Cochrane review evaluating the effectiveness of FgC for patients with bleeding found limited data (six small trials, none in trauma) but reported no effect on overall mortality but did find a reduction in allogeneic transfusion.
What did this paper set out to examine?
Pilot trials are needed to inform the design of larger definitive trials which can answer fundamental questions about effectiveness of fibrinogen supplementation in patients with major bleeding. This study describes a pilot study of fibrinogen concentrate or cryoprecipitate to reduce bleeding in children undergoing cardiac surgery. Patients younger than 7 years and admitted for elective cardiac surgery and cardio-pulmonary bypass were screened and eligible for randomisation to receive fibrinogen concentrate (60mg/kg) or cryoprecipitate (10ml/kg) if they developed diffuse bleeding at wound surfaces and a fibrinogen concentration < 1g/L/.
What did they show?
A total of 63 patients were included in the pilot, 30 received fibrinogen concentrate and 33 cryoprecipitate. There were no differences in post-operative blood losses (primary outcome), and the median 48 hour blood loss was not significantly different between the two groups. Rises in plasma fibrinogen concentration were similar between the two groups, and there were no significant differences between the groups for adverse events and a range of other clinical outcomes.
What are the implications for practice and for future work?
In addition to documenting feasibility of recruitment, the pilot study supports the need for larger trials, not just to understand how different sources of fibrinogen should be used, but also to evaluate comparative differences between products. Cryoprecipitate is a pooled blood component) that has a variable, but high Fg concentration (15-20 g/L), but also contains other plasma proteins (FVIII, FXIII, von Willebrand’s factor and fibronectin) which may confer additional haemostatic benefits.
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Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial
Dutton RP, Parr M, Tortella BJ, Champion HR, Bernard GR, Boffard K, Bouillon B, Croce MA, Dimsits J, Holcomb JB, et al
The Journal of Trauma. 2011;71((1):):12-9.
Abstract
BACKGROUND Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial). METHODS Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee. RESULTS There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022). CONCLUSIONS This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.
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Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage
Hauser CJ, Boffard K, Dutton R, Bernard GR, Croce MA, Holcomb JB, Leppaniemi A, Parr M, Vincent JL, Tortella BJ, et al
The Journal of Trauma. 2010;69((3):):489-500.
Abstract
BACKGROUND Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes. METHODS We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma bundleswith formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases. RESULTS Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10. 8% vs. 27. 5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11. 0% (rFVIIa) versus 10. 7% (placebo) (p = 0. 93, blunt) and 18. 2% (rFVIIa) versus 13. 2% (placebo) (p = 0. 40, penetrating). Blunt trauma rFVIIa patients received (mean +/- SD) 7. 8 +/- 10. 6 RBC units and 19. 0 +/- 27. 1 total allogeneic units through 48 hours, and placebo patients received 9. 1 +/- 11. 3 RBC units (p = 0. 04) and 23. 5 +/- 28. 0 total allogeneic units (p = 0. 04). Thrombotic adverse events were similar across study cohorts. CONCLUSIONS rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.
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Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial
Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, Fukushima J, Kalil Filho R, Sierra DB, Lopes NH, et al
JAMA : the Journal of the American Medical Association. 2010;304((14):):1559-67.
Abstract
CONTEXT Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS Hemoglobin concentrations were maintained at a mean of 10. 5 g/dL (95% confidence interval [CI], 10. 4-10. 6) in the liberal-strategy group and 9. 1 g/dL (95% CI, 9. 0-9. 2) in the restrictive-strategy group (P < . 001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < . 001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = . 85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1. 2 [95% CI, 1. 1-1. 4]; P = . 002). CONCLUSION Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION clinicaltrials. gov Identifier: NCT01021631.
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Management of bleeding following major trauma: an updated European guideline
Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Hunt BJ, Komadina R, Nardi G, Neugebauer E, et al
Critical Care (London, England). 2010;14((2):):R52.
Abstract
INTRODUCTION Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes. METHODS The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.