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1.
Management of bleeding in major burn surgery
Welling H, Ostrowski SR, Stensballe J, Vestergaard MR, Partoft S, White J, Johansson PI
Burns : Journal of the International Society for Burn Injuries. 2018
Abstract
Major burn surgery is often associated with excessive bleeding and massive transfusion, and the development of a coagulopathy during major burn surgery is associated with increased morbidity and mortality. The aim of this study was to review the literature on intraoperative haemostatic resuscitation of burn patients during necrectomy to reveal strategies applied for haemostatic monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies published in the period 2006-2017 concerning bleeding issues related to burn surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a broad search, a total of 1375 papers were identified. 124 of these fulfilled the inclusion criteria, and six of these were included for review. The literature confirmed that transfusion requirements increases with burn injury severity and that haemostatic monitoring by TEG((R)) (thrombelastography) or ROTEM((R)) (rotational thromboelastometry) significantly decreased intraoperative transfusions and was useful in predicting and goal-directing haemostatic therapy during excision surgery. Resuscitation of bleeding during major burn surgery in many instances was neither standardized nor haemostatic. We suggest that resuscitation should aim for normal haemostasis during the bleeding phase through close haemostatic monitoring and resuscitation. Randomised controlled trials are highly warranted to confirm the benefit of this concept.
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2.
Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients: a systematic review with meta-analysis and Trial Sequential Analysis
Rygard SL, Jonsson AB, Madsen MB, Perner A, Holst LB, Johansson PI, Wetterslev J
Intensive Care Medicine. 2018;44((2):):204-217
Abstract
PURPOSE Patients in the intensive care unit (ICU) are often transfused with red blood cells (RBC). During storage, the RBCs and storage medium undergo changes, which may have clinical consequences. Several trials now have assessed these consequences, and we reviewed the present evidence on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients. METHODS We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue blood. RESULTS We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97-1.11; 7349 patients; TSA-adjusted CI 0.93-1.15), adverse events (1.26, 0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required information size was reached for mortality for a relative risk change of 20%. CONCLUSIONS We may be able to reject a clinically meaningful effect of RBC storage time on mortality in transfused adult ICU patients as our trial sequential analyses reject a 10% relative risk change in death when comparing fresher versus older blood for transfusion.
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3.
The use of viscoelastic haemostatic assays in goal-directing treatment with allogeneic blood products - a systematic review and meta-analysis
Fahrendorff M, Oliveri RS, Johansson PI
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2017;25((1)):39.
Abstract
BACKGROUND Management of the critically bleeding patient can be encountered in many medical and surgical settings. Common for these patients is a high risk of dying from exsanguination secondary to developing coagulopathy. The purpose of this meta-analysis was to systematically review and assess randomised controlled trials (RCTs) performed on patients in acute need for blood transfusions due to bleeding to evaluate the effect of viscoelastic haemostatic assay (VHA) guidance on bleeding, transfusion requirements and mortality. METHODS PubMed and EMBASE were searched for RCTs that 1) randomised patients into receiving transfusions based on either a VHA-guided (thromboelastography [TEG] or rotational thromboelastometry [ROTEM]) algorithm (intervention group) or at the clinician's discretion and/or based on conventional coagulation tests (control group) and 2) adequately reported on the outcomes bleeding and/or transfusions and/or mortality. Data on bleeding, transfusions and mortality were extracted from each trial and included in a meta-analysis. RESULTS Fifteen RCTs (n = 1238 patients) were included. Nine trials referred to cardiothoracic patients, one to liver transplantation, one to surgical excision of burn wounds and one to trauma. One trial was conducted with cirrhotic patients, one with patients undergoing scoliosis surgery while one trial randomised treatment in post-partum females presenting with bleeding. The amount of transfused red blood cells (RBCs), fresh frozen plasma (FFP) and bleeding volume was found to be significantly reduced in the VHA-guided groups, whereas no significant difference was found for platelet transfusion requirements or mortality.
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4.
Hemostatic resuscitation with plasma and platelets in trauma
Johansson PI, Oliveri RS, Ostrowski SR
Journal of Emergencies Trauma & Shock. 2012;5((2):):120-5.
Abstract
BACKGROUND Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists although recently, the concept of hemostatic resuscitation, i.e., providing large amount of blood products to critically injured patients in an immediate and sustained manner as part of an early massive transfusion protocol has been introduced. The aim of the present review was to investigate the potential effect on survival of proactive administration of plasma and/or platelets (PLT) in trauma patients with massive bleeding. MATERIALS AND METHODS English databases were searched for reports of trauma patients receiving massive transfusion (10 or more red blood cell (RBC) within 24 hours or less from admission) that tested the effects of administration of plasma and/or PLT in relation to RBC concentrates on survival from January 2005 to November 2010. Comparison between highest vs lowest blood product ratios and 30-day mortality was performed. RESULTS Sixteen studies encompassing 3,663 patients receiving high vs low ratios were included. This meta-analysis of the pooled results revealed a substantial statistical heterogeneity (I(2) = 58%) and that the highest ratio of plasma and/or PLT or to RBC was associated with a significantly decreased mortality (OR: 0.49; 95% confidence interval: 0.43-0.57; P<0.0001) when compared with lowest ratio. CONCLUSION Meta-analysis of 16 retrospective studies concerning massively transfused trauma patients confirms a significantly lower mortality in patients treated with the highest fresh frozen plasma (FFP) and/or PLT ratio when compared with the lowest FFP and/or PLT ratio. However, optimal ranges of FFP: RBC and PLT RBC should be established in randomized controlled trials.
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5.
Fibrinogen concentrates for bleeding trauma patients: what is the evidence?
Meyer MA, Ostrowski SR, Windelov NA, Johansson PI
Vox Sanguinis. 2011;101((3):):185-90.
Abstract
Introduction: A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions. Objective: To provide a review of the literature covering the application of fibrinogen concentrates in trauma care. Methods: PubMed and Cochrane database search, 'fibrinogen' and ('concentrate' or 'trauma'), not 'congenital', 10[em space]years. Results: Only four papers were identified. None were randomized controlled trials. The main conclusion of these papers was that administration of fibrinogen sometimes together with prothrombin complex concentrate might improve haemostasis in trauma patients resuscitated with synthetic colloids. Conclusion: Evidence for the use of fibrinogen concentrate to trauma patients with massive bleeding is lacking. Well-designed prospective, randomized, double-blinded studies evaluating the effect of fibrinogen concentrate, as the only intervention, are urgently needed. Copyright 2011 The Author(s). Vox Sanguinis Copyright 2011 International Society of Blood Transfusion.
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6.
Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders
Johansson PI, Ostrowski SR
Drug Design, Development & Therapy. 2010;4:107-16.
Abstract
BACKGROUND Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX. OBJECTIVE To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders. PATIENTS AND METHODS English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs) evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders. RESULTS Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies. CONCLUSION The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual's ability to generate thrombin and form a clot, and not on the patient's weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.
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7.
Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets--a review of the current literature
Johansson PI, Stensballe J
Transfusion. 2010;50((3):):701-10.
Abstract
BACKGROUND Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists. Recent studies indicate a possible survival benefit in patients receiving a higher ratio of plasma and platelets (PLTs) to red blood cells (RBCs) than what is recommended in current transfusion guidelines. STUDY DESIGN AND METHODS English databases were searched for reports of patients receiving massive transfusion that tested the effects of administration of plasma and/or PLTs in relation to RBCs on survival from January 1990 to March 2009. RESULTS Fourteen retrospective studies involving 4594 patients were identified. Six tested the effect on survival in relation to fresh-frozen plasma (FFP)-to-RBC ratio, and five investigated FFP- and PLT-to-RBC ratios. Two studies evaluated implementation of massive transfusion protocols with preemptive FFP and PLT administration; one study based transfusion therapy on the result of the thrombelastograph (TEG) analysis versus historic controls. All studies reviewed demonstrate a survival benefit for patients who receive more FFP and PLT as part of the hemostatic resuscitation. When TEG was used to guide transfusion therapy an increase in FFP and PLT was also seen when compared to historic controls and this was associated with improved survival. CONCLUSIONS High FFP- and PLT-to-RBC ratios seem to improve survival in patients with massive bleeding. Randomized studies evaluating TEG-guided transfusion therapy versus fixed ratios of plasma and PLTs to RBCs in massively bleeding patients is highly warranted.
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8.
Hemostatic strategies for minimizing mortality in surgery with major blood loss
Johansson PI
Transfusion Alternatives in Transfusion Medicine. 2010;11((Suppl 2):):8. Abstract No. S14.