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Transfusion Guidelines in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of the Currently Available Evidence
Montgomery EY, Barrie U, Kenfack YJ, Edukugho D, Caruso JP, Rail B, Hicks WH, Oduguwa E, Pernik MN, Tao J, et al
Neurotrauma reports. 2022;3(1):554-568
Abstract
Our study aims to provide a synthesis of the best available evidence on the hemoglobin (hgb) red blood cell (RBC) transfusion thresholds in adult traumatic brain injury (TBI) patients, as well as describing the risk factors and outcomes associated with RBC transfusion in this population. A systematic review and meta-analysis was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess articles discussing RBC transfusion thresholds and describe complications secondary to transfusion in adult TBI patients in the perioperative period. Fifteen articles met search criteria and were reviewed for analysis. Compared to non-transfused, TBI patients who received transfusion tended to be primarily male patients with worse Injury Severity Score (ISS) and Glasgow Coma Scale. Further, the meta-analysis corroborated that transfused TBI patients are older (p = 0.04), have worse ISS scores (p = 0.001), receive more units of RBCs (p = 0.02), and have both higher mortality (p < 0.001) and complication rates (p < 0.0001). There were no differences identified in rates of hypertension, diabetes mellitus, and Abbreviated Injury Scale scores. Additionally, whereas many studies support restrictive (hgb <7 g/dL) transfusion thresholds over liberal (hgb <10 g/dL), our meta-analysis revealed no significant difference in mortality between those thresholds (p = 0.79). Current Class B/C level III evidence predominantly recommends against a liberal transfusion threshold of 10 g/dL for TBI patients (Class B/C level III), but our meta-analysis found no difference in survival between groups. There is evidence suggesting that an intermediate threshold between 7 and 9 g/dL, reflecting the physiological oxygen needs of cerebral tissue, may be worth exploring.
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Prothrombin Complex Concentrate for Trauma Induced Coagulopathy: A Systematic Review and Meta-Analysis
Kao TW, Lee YC, Chang HT
Journal of acute medicine. 2021;11(3):81-89
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Editor's Choice
Abstract
BACKGROUND Optimal management for trauma-induced coagulopathy (TIC) is a clinical conundrum. In conjunction with the transfusion of fresh-frozen plasma (FFP), additional administration of prothrombin complex concentrate (PCC) was proposed to bring about further coagulative benefit. However, investigations evaluating the efficacy as well as corresponding side effects were scarce and inconsistent. The aim of this study was to systematically review current literature and to perform a meta-analysis comparing FFP+PCC with FFP alone. METHODS Web search followed by manual interrogation was performed to identify relevant literatures fulfilling the following criteria, subjects as TIC patients taking no baseline anticoagulants, without underlying coagulative disorders, and reported clinical consequences. Those comparing FFP alone with PCC alone were excluded. Comprehensive Meta-analysis software was utilized, and statistical results were delineated with odd ratio (OR), mean difference (MD), and 95% confidence interval (CI). I(2) was calculated to determine heterogeneity. The primary endpoint was set as all-cause mortality, while the secondary endpoint consisted of international normalized ratio (INR) correction, transfusion of blood product, and thrombosis rate. RESULTS One hundred and sixty-four articles were included for preliminary evaluation, 3 of which were qualified for meta-analysis. A total of 840 subjects were pooled for assessment. Minimal heterogeneity was present in the comparisons (I(2) < 25%). In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631; 95% CI: 0.450-0.884, p = 0.007) after pooling. Meanwhile, INR correction time was shorter under PCC + FFP (MD: -608.300 mins, p < 0.001), whilst the rate showed no difference (p = 0.230). The PCC + FFP group is less likely to mandate transfusion of packed red blood cells (p < 0.001) and plasma (p < 0.001), but not platelet (p = 0.615). The incidence of deep vein thrombosis was comparable in the two groups (p = 0.460). CONCLUSIONS Compared with FFP only, PCC + FFP demonstrated better survival rate, favorable clinical recovery and no elevation of thromboembolism events after TIC.
PICO Summary
Population
Patients with trauma induced coagulopathy (3 studies, n= 840).
Intervention
Prothrombin complex concentrate and fresh-frozen plasma (PCC + FFP).
Comparison
Fresh-frozen plasma (FFP).
Outcome
In the PCC + FFP cohort, reduced mortality rate was observed (OR: 0.631) after pooling. Meanwhile, international normalized ratio correction time was shorter under PCC + FFP (MD: -608.300 mins), whilst the rate showed no difference. The PCC + FFP group was less likely to mandate transfusion of packed red blood cells and plasma, but not platelet. The incidence of deep vein thrombosis was comparable in the two groups.
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Platelet to erythrocyte transfusion ratio and mortality in massively transfused trauma patients. A systematic review and meta-analysis
Rijnhout TWH, Duijst J, Noorman F, Zoodsma M, van Waes O, Verhofstad MHJ, Hoencamp R
The journal of trauma and acute care surgery. 2021
Abstract
BACKGROUND Platelet transfusion during major hemorrhage is important and often embedded in massive transfusion protocols. However, the optimal ratio of platelets to erythrocytes (platelet rich plasma (PLT) :RBC ratio) remains unclear. We hypothesized that high PLT:RBC ratios, as compared to low PLT:RBC ratios, are associated with improved survival in patients requiring massive transfusion. METHODS Four databases (Pubmed, CINAHL, EMBASE and Cochrane) were systematically screened for literature published up to January 21, 2021 to determine the effect of PLT:RBC ratio on the primary outcome measure mortality at 1-6 and 24 hours and at 28-30 days. Studies comparing various PLT:RBC ratios were included in meta-analysis. Secondary outcomes included intensive care unit length of stay and in-hospital length of stay and total blood component use. The study protocol was registered in PROSPERO under number CRD42020165648. RESULTS The search identified a total of 8903 records. After removing duplicates second screening of title, abstract and full text a total of 59 articles were included in the analysis. Of these articles 12 were included in meta-analysis. Mortality at 1-6, 24-hours and 28-30 days was significantly lower for high PLT:RBC ratios as compared to low PLT:RBC ratios. CONCLUSIONS Higher PLT:RBC ratios are associated with significantly lower 1-6 hours, 24 hours, 28-30 days mortality as compared to lower PLT:RBC ratios. The optimal PLT:RBC ratio for massive transfusion in trauma patients is approximately 1:1. LEVEL OF EVIDENCE Systematic review and meta-analysis, therapeutic level III.
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Hemoglobin levels as a transfusion criterion in moderate to severe traumatic brain injury: a systematic review and meta-analysis
Florez-Perdomo WA, García-Ballestas E, Martinez-Perez R, Agrawal A, Deora H, Joaquim AF, Quiñones-Ossa GA, Moscote-Salazar LR
British journal of neurosurgery. 2021;:1-7
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Editor's Choice
Abstract
BACKGROUND Several factors can influence the outcome of severe head injuries including the patient's hemoglobin levels. There has often been a dilemma regarding levels of hemoglobin at which red cell blood transfusion (RCBT) should be performed. OBJECTIVE To systematically review the literature to determine the usefulness of management protocols that have hemoglobin levels <10 g/dL vs <7 g/dL as an RCBT criterion. METHODS Following the PRISMA statement, the search was constructed using terms and descriptors of the Medical Subject Heading (MeSH), combined with Boolean operators. Full text of these articles was studied, and outcome measures at 3-6 months were considered for patients who were given a RCBT at <10 g/dL or at 7 g/dL hemoglobin levels. RESULTS A total of 4 articles were found suitable for inclusion in the meta-analysis. RCBT below 7 g/dL was not associated with an increased risk of mortality as compared to RCBT using the value of less than 10 g/dL. RCBT at lower levels of hemoglobin was also not associated with a poor neurological outcome (GOS 4-5) but rather RCBT at lower levels lead to better outcomes (GOS 1-3) and the association was significant. CONCLUSION Allogenic RCBT was associated with poorer neurological outcomes, within a wide range of reported differences in the hemoglobin threshold to decide for RCBT in TBI patients. Restrictive RCBT strategy may be useful in moderate to severe TBI cases although the risk of anemia-induced cerebral injury needs further investigation regarding the risks and complications inherent to RCBT.
PICO Summary
Population
Patients with traumatic brain injury (4 studies, n= 607).
Intervention
Liberal red cell blood transfusion (RCBT) criterion protocol of haemoglobin level <10 g/dL.
Comparison
Restrictive RCBT criterion protocol of haemoglobin level <7 g/dL.
Outcome
RCBT below 7 g/dL was not associated with an increased risk of mortality as compared to RCBT using the value of less than 10 g/dL. RCBT at lower levels of haemoglobin was also not associated with a poor neurological outcome (GOS 4-5) but rather RCBT at lower levels lead to better outcomes (GOS 1-3) and the association was significant.
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Systematic review of the efficacy of a hybrid operating theatre in the management of severe trauma
Khoo CY, Liew TYS, Mathur S
World journal of emergency surgery : WJES. 2021;16(1):43
Abstract
BACKGROUND Hybrid operating theatres (OT) allow for simultaneous interventional radiology and operative procedures, serving as a one-stop facility for the treatment of severely injured patients. Several countries have adopted the use of the hybrid OT however their clinical impact in improving efficiency and quality of care remains unclear. This study systematically reviews the clinical impact of the hybrid OT for treatment of the severely injured. METHODS A literature review of the PubMed, Embase and Cochrane databases was performed to identify all published articles in English, from 1st January 2000 to 31st December 2020, reporting on the impact of a hybrid OT for severe trauma. Articles were also reviewed for references of interest. RESULTS Five studies reporting the clinical impact of the hybrid OT, in a total of 951 patients, were shortlisted. All were cohort studies that compared patient outcomes in the hybrid OT versus a conventional group. Out of 3 studies that assessed timeliness to intervention, one reported shorter time associated with the hybrid OT, while the other two reported no difference. Mortality outcomes were reported in 4 studies and showed no significant difference associated with treatment in the hybrid OT. Two studies revealed shorter total procedure times associated with the hybrid OT. Two out of 3 studies that evaluated blood transfusion requirements reported decreased transfusion rates in the hybrid OT group. Only 1 study examined complication rates and demonstrated morbidity benefits associated with the hybrid OT. CONCLUSION Establishment of a hybrid OT requires a significant capital investment as well as a highly functioning multi-disciplinary team. The cost-benefit ratio remains unclear. Future studies, preferably in the form of clinical trials, are required to evaluate its usefulness in improving timeliness to definitive haemorrhage control and outcomes in severe trauma.
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Platelet-to-red blood cell ratio and mortality in bleeding trauma patients: A systematic review and meta-analysis
Kleinveld DJB, van Amstel RBE, Wirtz MR, Geeraedts LMG, Goslings JC, Hollmann MW, Juffermans NP
Transfusion. 2021;61 Suppl 1:S243-s251
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Editor's Choice
Abstract
BACKGROUND In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC. METHODS Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy. RESULTS In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy. CONCLUSIONS In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.
PICO Summary
Population
Bleeding trauma patients receiving platelet transfusion (5 studies, n= 1,757).
Intervention
Higher platelet-to-red blood cell (RBC) transfusion ratio.
Comparison
Lower ratio of platelet-to-RBC.
Outcome
A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio (OR) 0.69 (0.53-0.89)) and 30- day mortality (OR 0.78 (0.63-0.98)). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy.
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The effect of massive transfusion protocol implementation on the survival of trauma patients: a systematic review and meta-analysis
Consunji R, Elseed A, El-Menyar A, Sathian B, Rizoli S, Al-Thani H, Peralta R
Blood transfusion = Trasfusione del sangue. 2020
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Editor's Choice
Abstract
BACKGROUND Massive transfusion protocol (MTP) has been widely adopted for the care of bleeding trauma patients but its actual effectiveness is unclear. An earlier meta-analysis on the implementation of MTP for injured patients from 1990 to 2013 reported that only 2 out of 8 studies showed statistical improvement in survival. This study aimed to conduct an updated systematic review and meta-analysis to evaluate the effect of implementing an MTP on the mortality of trauma patients. MATERIALS AND METHODS MEDLINE, PubMed, Cochrane Library and Google scholar databases were systematically searched for relevant studies published from 1(st) January 2008 to 30(th) September 2019 using a combination of keywords and additional manual searching of reference lists. Inclusion criteria were: original study in English, study population including trauma patients, and comparison of mortality outcomes before and after institutional implementation of an MTP. Primary outcomes were 24-hour, 30-day, and overall mortality. RESULTS Fourteen studies met inclusion criteria, analysing outcomes from 3,201 trauma patients. There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients (OR 0.71 [0.56-0.90]). No significant reduction was seen in either the 24-hour mortality (OR 0.81 [0.57-1.14]) or the 30-day mortality (OR 0.73 [0.46-1.16]). However, when mortality timing was unspecified, mortality was statistically reduced (OR 0.69 [0.55-0.86]). DISCUSSION The present study found a significant reduction in mortality following MTP implementation and thus it should be recommended to all institutions managing acutely injured patients. To better identify which elements of an MTP contribute to this effect, we encourage the use of standard nomenclature, indicators, protocols and patient populations in all future MTP studies.
PICO Summary
Population
Trauma patients (14 studies, n= 3201).
Intervention
Implementation of a massive transfusion protocol (MTP) on the mortality of trauma patients.
Comparison
Outcome
There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients. No significant reduction was seen in either the 24-hour mortality or the 30-day mortality. However, when mortality timing was unspecified, mortality was statistically reduced.
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Massive Transfusion Protocols in Pediatric Trauma Population: A Systematic Review
Kinslow K, McKenney M, Boneva D, Elkbuli A
Transfus Med. 2020
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Editor's Choice
Abstract
BACKGROUND Our main objective was to review the literature to answer the following questions regarding pediatric massive transfusion (PMT) protocols: 1) How is PMT defined? 2) Which blood product ratios have been investigated and what is their effect on outcomes? 3) What evidence exists regarding PMT outcomes? METHODS The PRISMA guidelines were used. We searched PubMed, Google Scholar, Cochrane Library, EMBASE, Wiley Online Library, and Ovid. Articles were screened for inclusion based on relevance to PMT. Articles were assessed for study design, presence of established/tested PMT, PMT definition, PMT activation criteria, and Transfusion Ratios, for final determination of article inclusion. RESULTS Our search produced 3213 articles with 33 included for final review. Existing definitions of PMT are based on volume administered/kg but vary in timeframe criteria (over 4 hr vs 24 hr). Some studies have investigated "high" balanced transfusion ratios as seen in adults (1:1 FFP:pRBC) with a few showing statistically significant improvement in pediatric mortality vs lower ratios. PMT protocol implementation has not been shown to consistently reduce pediatric trauma mortality across multiple centers. However, other operational aspects such as reduced time to first transfusion are apparent benefits. CONCLUSIONS There is poor consensus over the definition of PMT. Definitions that involve early recognition have the most promise for practice and future studies. Evidence supporting an optimal blood product ratio in PMT is also lacking but trends towards supporting balanced approaches. Implementation of PMT protocols have been limited in showing significant improvement of overall pediatric trauma mortality but may reduce associated morbidity.
PICO Summary
Population
Paediatric trauma patients undergoing massive transfusions (33 studies).
Intervention
Systematic review to define paediatric massive transfusion (PMT) protocols, and to review the evidence on PMT outcomes.
Comparison
Outcome
Existing definitions of PMT are based on volume administered/kg but vary in timeframe criteria (over 4 hr vs. 24 hr). Some studies have investigated "high" balanced transfusion ratios as seen in adults (1:1 FFP:pRBC) with a few showing statistically significant improvement in paediatric mortality vs. lower ratios. PMT protocol implementation has not been shown to consistently reduce paediatric trauma mortality across multiple centers. However, other operational aspects such as reduced time to first transfusion are apparent benefits.
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Evaluation of blood product transfusion therapies in acute injury care in low- and middle-income countries: a systematic review
Yang L, Slate-Romano J, Marques CG, Uwamahoro C, Twagirumukiza FR, Naganathan S, Moretti K, Jing L, Levine AC, Stephen A, et al
Injury. 2020
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Editor's Choice
Abstract
BACKGROUND Worldwide, injuries account for approximately five million mortalities annually, with 90% occurring in low- and middle-income countries (LMICs). Although guidelines characterizing data for blood product transfusion in injury resuscitation have been established for high-income countries (HICs), no such information on use of blood products in LMICs exists. This systematic review evaluated the available literature on the use and associated outcomes of blood product transfusion therapies in LMICs for acute care of patients with injuries. METHODS A systematic search of PubMed, EMBASE, Global Health, CINAHL and Cochrane databases through November 2018 was performed by a health sciences medical librarian. Prospective and cross-sectional reports of injured patients from LMICs involving data on blood product transfusion therapies were included. Two reviewers identified eligible records (kappa=0.92); quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Report elements, patient characteristics, injury information, blood transfusion therapies provided and mortality outcomes were extracted and analyzed. RESULTS Of 3411 records, 150 full-text reports were reviewed and 17 met inclusion criteria. Identified reports came from the World Health Organization regions of Africa, the Eastern Mediterranean, and South-East Asia. A total of 6535 patients were studied, with the majority from exclusively inpatient hospital settings (52.9%). Data on transfusion therapies demonstrated that packed red blood cells were given to 27.0% of patients, fresh frozen plasma to 13.8%, and unspecified product types to 50.1%. Among patients with blunt and penetrating injuries, 5.8% and 15.7% were treated with blood product transfusions, respectively. Four reports provided data on comparative mortality outcomes, of which two found higher mortality in blood transfusion-treated patients than in untreated patients at 17.4% and 30.4%. The overall quality of evidence was either low (52.9%) or very low (41.2%), with one report of moderate quality by GRADE criteria. CONCLUSION There is a paucity of high-quality data to inform appropriate use of blood transfusion therapies in LMIC injury care. Studies were geographically limited and did not include sufficient data on types of therapies and specific injury patterns treated. Future research in more diverse LMIC settings with improved data collection methods is needed to inform injury care globally.
PICO Summary
Population
Patients with injuries requiring acute care in low and middle income countries (17 studies, n=6535).
Intervention
Systematic review on the use of blood product transfusion therapies.
Comparison
Outcome
Packed red blood cells were given to 27.0% of patients, fresh frozen plasma to 13.8%, and unspecified product types to 50.1%. Among patients with blunt and penetrating injuries, 5.8% and 15.7% were treated with blood product transfusions, respectively. Four reports provided data on comparative mortality outcomes, of which two found higher mortality in blood transfusion-treated patients than in untreated patients at 17.4% and 30.4%.
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Practical Considerations for a Military Whole Blood Program
Bahr M, Cap AP, Dishong D, Yazer MH
Mil Med. 2020
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Editor's Choice
Abstract
INTRODUCTION Prehospital care in the combat environment has always been of great importance to the U.S. military, and trauma resuscitation has remained a cornerstone. More evidence continues to demonstrate the advantages of intervention with early transfusion of blood products at the point of injury. The military has recognized these benefits; as such, the Department of Defense Joint Trauma System and the Committee on Tactical Combat Casualty Care have developed new advanced resuscitation guidelines, which now encourage the use of whole blood (WB) in the prehospital setting. MATERIALS AND METHODS This general review of peer-reviewed journal articles was performed through an extensive electronic search from the databases of PubMed Central (MEDLINE) and the Cochrane Library. RESULTS Based on this literature search, the current evidence suggests that transfusion with WB is safe and efficacious. Additionally, soldier function is preserved after donating fresh WB in the field. Currently, the collection and implementation of WB is accomplished through several different protocol-driven techniques. CONCLUSION WB has become the favored transfusion product as it provides all of the components of blood in a convenient package that is easy to store and transport. Specifically, group O WB containing low titers of anti-A and -B antibodies has become the transfusion product of choice, offering the ability to universally fluid resuscitate patients despite not knowing their blood group. This new ability to obtain low titer group O WB has transformed the approach to the management of hemorrhagic shock in the prehospital combat environment.
PICO Summary
Population
Patients from a prehospital combat environment.
Intervention
Systematic review on the use of whole blood (WB) in prehospital setting.
Comparison
Outcome
The collection and implementation of WB is accomplished through several different protocol-driven techniques. WB has become the favored transfusion product as it provides all of the components of blood in a convenient package that is easy to store and transport. Specifically, group O WB containing low titers of anti-A and -B antibodies has become the transfusion product of choice, offering the ability to universally fluid resuscitate patients despite not knowing their blood group.
