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The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials
Abuelazm, M., Rezq, H., Mahmoud, A., Tanashat, M., Salah, A., Saleh, O., Morsi, S., Abdelazeem, B.
European journal of trauma and emergency surgery : official publication of the European Trauma Society. 2024
Abstract
BACKGROUND AND OBJECTIVE Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock. METHODS We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325. RESULTS Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20). Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24 h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups. CONCLUSION Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.
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Volume replacement in the resuscitation of trauma patients with acute hemorrhage: an umbrella review
Gianola, S., Castellini, G., Biffi, A., Porcu, G., Napoletano, A., Coclite, D., D'Angelo, D., Di Nitto, M., Fauci, A. J., Punzo, O., et al
International journal of emergency medicine. 2023;16(1):87
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Editor's Choice
Abstract
BACKGROUND The use of intravenous fluid therapy in patients with major trauma in prehospital settings is still controversial. We conducted an umbrella review to evaluate which is the best volume expansion in the resuscitation of a hemorrhagic shock to support the development of major trauma guideline recommendations. METHODS We searched PubMed, Embase, and CENTRAL up to September 2022 for systematic reviews (SRs) investigating the use of volume expansion fluid on mortality and/or survival. Quality assessment was performed using AMSTAR 2 and the Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS We included 14 SRs investigating the effects on mortality with the comparisons: use of crystalloids, blood components, and whole blood. Most SRs were judged as critically low with slight overlapping of primary studies and high consistency of results. For crystalloids, inconsistent evidence of effectiveness in 28- to 30-day survival (primary endpoint) was found for the hypertonic saline/dextran group compared with isotonic fluid solutions with moderate certainty of evidence. Pre-hospital blood component infusion seems to reduce mortality, however, as the certainty of evidence ranges from very low to moderate, we are unable to provide evidence to support or reject its use. The blood component ratio was in favor of higher ratios among all comparisons considered with moderate to very low certainty of evidence. Results about the effects of whole blood are very uncertain due to limited and heterogeneous interventions in studies included in SRs. CONCLUSION Hypertonic crystalloid use did not result in superior 28- to 30-day survival. Increasing evidence supports the scientific rationale for early use of high-ratio blood components, but their use requires careful consideration. Preliminary evidence is very uncertain about the effects of whole blood and further high-quality studies are required.
PICO Summary
Population
Trauma patients with haemorrhagic shock (14 systematic reviews).
Intervention
Crystalloids, packed red blood cells, fresh frozen plasma, platelets, liquid plasma, lyophilized plasma, low titre 0-negative whole blood.
Comparison
A comparison or combination of the above (including different ratios).
Outcome
For crystalloids, inconsistent evidence of effectiveness in 28- to 30-day survival (primary endpoint) was found for the hypertonic saline/dextran group compared with isotonic fluid solutions with moderate certainty of evidence. Pre-hospital blood component infusion seems to reduce mortality, however, as the certainty of evidence ranges from very low to moderate, the authors are unable to provide evidence to support or reject its use. The blood component ratio was in favour of higher ratios among all comparisons considered with moderate to very low certainty of evidence. Results about the effects of whole blood are very uncertain due to limited and heterogeneous interventions in studies included in systematic reviews.
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Shock index as predictor of massive transfusion and mortality in patients with trauma: a systematic review and meta-analysis
Carsetti, A., Antolini, R., Casarotta, E., Damiani, E., Gasparri, F., Marini, B., Adrario, E., Donati, A.
Critical Care (London, England). 2023;27(1):85
Abstract
BACKGROUND Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. METHODS This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. RESULTS Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR-) were 4.24 [3.18-5.65] and 0.39 [0.29-0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR- were 1.39 [1.36-1.42] and 0.87 [0.85-0.89], respectively. CONCLUSIONS Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.
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Whole blood transfusion in the treatment of acute hemorrhage, a systematic review and meta-analysis
van der Horst RA, Rijnhout TWH, Noorman F, Borger van der Burg, B. L. S., van Waes, O. J. F., Verhofstad, M. H. J., Hoencamp, R.
The journal of trauma and acute care surgery. 2023
Abstract
BACKGROUND Whole blood (WB) transfusion received renewed interest after recent armed conflicts. The effectiveness as compared to blood component transfusion (BCT) is however still topic of debate. Therefore, this study investigated the effect of WB ± BCT as compared to BCT transfusion on survival in trauma patients with acute hemorrhage. METHODS Studies published up to the 16th of January 2023, including patients with traumatic hemorrhage comparing WB ± BCT and BCT were included in meta-analysis. Sub analyses were performed on the effectiveness of WB in the treatment of civilian or military trauma patients, patients with massive hemorrhage and on platelet (PLT):Red Blood Cell (RBC), plasma:RBC and WB:RBC ratios. Methodological quality of studies was interpreted using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO under number CRD42022296900. RESULTS Random effect pooled odds ratio (OR) for 24-hours mortality in civilian and military patients treated with WB as compared to BCT was 0.72 (95% CI 0.53-0.97). In sub analysis of studies conducted in civilian setting (n = 20), early (4-hours, 6-hours and Emergency Department) and 24-hours mortality was lower in WB groups compared BCT groups: OR 0.65 (95% CI 0.44 - 0.96) and OR 0.71 (0.52 - 0.98). No difference in late mortality (28-days, 30-days, in-hospital) was found. In military settings (n = 7) there was no difference in early, 24-hours or late mortality between groups. WB groups received significant higher PLT:RBC (p = 0.030) during early treatment and significant higher PLT:RBC and Plasma:RBC ratios during 24-hours of treatment (p = 0.031 and p = 0.007). The overall risk of bias in the majority of studies was judged as serious due to serious risk on confounding and selection bias, and unclear information regarding co-interventions. CONCLUSION Civilian trauma patients with acute traumatic hemorrhage treated with WB ± BCT as compared to BCT had lower odds on early and 24-hours mortality. Additionally, WB transfusion resulted in higher plt:RBC and plasma:RBC ratios. LEVEL OF EVIDENCE Level III, systematic review and meta-analysis.
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Outcomes of Transfusion With Whole Blood, Component Therapy, or Both in Adult Civilian Trauma Patients: A Systematic Review and Meta-Analysis
Ngatuvai M, Zagales I, Sauder M, Andrade R, Santos RG, Bilski T, Kornblith L, Elkbuli A
The Journal of surgical research. 2023;287:193-201
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Editor's Choice
Abstract
INTRODUCTION This systematic review and meta-analysis was conducted to compare outcomes, including transfusion volume, complications, intensive care unit length of stay, and mortality for adult civilian trauma patients transfused with whole blood (WB), components (COMP), or both (WB + COMP). METHODS A systematic review and meta-analysis were conducted using studies that evaluated outcomes of transfusion of WB, COMP, or WB + COMP for adult civilian trauma patients. A search of PubMed, Embase, and Cochrane from database inception to March 3, 2022 was conducted. The search resulted in 18,400 initial articles with 16 studies remaining after the removal of duplicates and screening for inclusion and exclusion criteria. RESULTS This study identified an increased risk of 24-h mortality with COMP versus WB + COMP (relative risk: 1.40 [1.10, 1.78]) and increased transfusion volumes of red blood cells with COMP versus WB at 6 and 24 h, respectively (-2.26 [-3.82, -0.70]; -1.94 [-3.22, -0.65] units). There were no differences in the calculated rates of infections or intensive care unit length of stay between WB and COMP, respectively (relative risks: 1.35 [0.53, 3.46]; -0.91 [-2.64, 0.83]). CONCLUSIONS Transfusion with WB + COMP is associated with lower 24-h mortality versus COMP and transfusion with WB is associated with a lower volume of red blood cells transfused at both 6 and 24 h. Based on these findings, greater utilization of whole blood in civilian adult trauma resuscitation may lead to improved mortality and reduced transfusion requirements.
PICO Summary
Population
Adult civilian trauma patients (16 studies).
Intervention
Whole blood (WB).
Comparison
Component therapy (COMP); whole blood and component therapy (WB + COMP).
Outcome
This systematic review and meta-analysis identified an increased risk of 24h mortality with COMP versus WB + COMP (relative risk: 1.40 [1.10, 1.78]) and increased transfusion volumes of red blood cells with COMP versus WB at 6 and 24h, respectively (-2.26 [-3.82, -0.70]; -1.94 [-3.22, -0.65] units). There were no differences in the calculated rates of infections or intensive care unit length of stay between WB and COMP, respectively (relative risks: 1.35 [0.53, 3.46]; -0.91 [-2.64, 0.83]).
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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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Hypocalcemia in trauma patients: A systematic review
Vasudeva, M., Mathew, J. K., Groombridge, C., Tee, J. W., Johnny, C. S., Maini, A., Fitzgerald, M. C.
The Journal of Trauma and Acute Care Surgery. 2021;90(2):396-402
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Abstract
BACKGROUND During hemorrhagic shock and subsequent resuscitation, pathways reliant upon calcium such as platelet function, intrinsic and extrinsic hemostasis, and cardiac contractility are disrupted. The objective of this systematic review was to examine current literature for associations between pretransfusion, admission ionized hypocalcemia, and composite outcomes including mortality, blood transfusion requirements, and coagulopathy in adult trauma patients. METHODS This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We searched Ovid MEDLINE and grey literature from database inception till May 3, 2020. Case series and reports were excluded. Reference lists of appraised studies were also screened for articles that the aforementioned databases might not have captured. The Newcastle-Ottawa Scale was used to assess study quality. RESULTS A total of 585 abstracts were screened through database searching and alternative sources. Six unique full-text studies were reviewed, of which three were excluded. Admission ionized hypocalcemia was present in up to 56.2% of the population in studies included in this review. Admission ionized hypocalcemia was also associated with increased mortality in all three studies, with increased blood transfusion requirements in two studies, and with coagulopathy in one study. CONCLUSION Hypocalcemia is a common finding in shocked trauma patients. While an association between admission ionized hypocalcemia and mortality, blood transfusion requirements, and coagulopathy has been identified, further prospective trials are essential to corroborating this association. LEVEL OF EVIDENCE Systematic review, level III.
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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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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.