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1.
Characterization and Analysis of Chitosan-Gelatin Composite-Based Biomaterial Effectivity as Local Hemostatic Agent: A Systematic Review
Herliana H, Yusuf HY, Laviana A, Wandawa G, Cahyanto A
Polymers. 2023;15(3)
Abstract
Chitosan and gelatin were the most widely used natural materials in pharmaceutical and medical fields, especially as local hemostatic agents, independently or as a composite material with the addition of other active substances. Chitosan and gelatin have excellent properties in biocompatibility, biodegradability, non-toxicity and water absorption capacity. The objective of this review was to analyze the characteristics of chitosan-gelatin (CG) composite-based biomaterial and its effectivity as a local hemostatic agent. We used PRISMA guidelines and the PICO framework to compile this review. The findings demonstrated that the CG composite-based biomaterial had excellent physical, chemical, mechanical properties and local hemostatic agent activity by adding other active substances such as oxidized fibers (OF), silica nanoparticles (SiNPs), calcium (Ca) and biphasic calcium phosphate (BCP) or by setting the CG composite proportion ratio.
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2.
Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis
Hmidan Simsam M, Delorme L, Grimm D, Priestap F, Bohnert S, Descoteaux M, Hilsden R, Laverty C, Mickler J, Parry N, et al
Injury. 2023
Abstract
BACKGROUND Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. METHODS We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). CONCLUSION When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. LEVEL OF EVIDENCE Systematic review and meta-analysis, level IV.
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3.
Impact of time and distance on outcomes following tourniquet use in civilian and military settings: A scoping review
Joarder M, Noureddine El Moussaoui H, Das A, Williamson F, Wullschleger M
Injury. 2023
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Editor's Choice
Abstract
BACKGROUND The last two decades have seen the reintroduction of tourniquets into guidelines for the management of acute limb trauma requiring hemorrhage control. Evidence supporting tourniquet application has demonstrated low complication rates in modern military settings involving rapid evacuation timeframes. It is unclear how these findings translate to patients who have prolonged transport times from injury in rural settings. This scoping review investigates the relationship between time and distance on metabolic complications, limb salvage and mortality following tourniquet use in civilian and military settings. METHODS A systematic search strategy was conducted using PubMed, Embase, and SafetyLit databases. Study characteristics, setting, mechanism of injury, prehospital time, tourniquet time, distance, limb salvage, metabolic response, mortality, and tourniquet removal details were extracted from eligible studies. Descriptive statistics were recorded, and studies were grouped by ischemia time (< 2 h, 2-4 h, or > 4 h). RESULTS The search identified 3103 studies, from which 86 studies were included in this scoping review. Of the 86 studies, 55 studies were primarily in civilian environments and 32 were based in military settings. One study included both settings. Blast injury was the most common mechanism of injury sustained by patients in military settings (72.8% [5968/8200]) followed by penetrating injury (23.5% [1926/8200]). In contrast, in civilian settings penetrating injury was the most common mechanism (47.7% [1633/3426]) followed by blunt injury (36.4% [1246/3426]). Tourniquet time was reported in 66/86 studies. Tourniquet time over four hours was associated with reduced limb salvage rates (57.1%) and higher mortality rates (7.1%) compared with a tourniquet time of less than two hours. The overall limb salvage and mortality rates were 69.6% and 6.7% respectively. Metabolic outcomes were reported in 28/86 studies with smaller sample sizes and inconsistencies in which parameters were reported. CONCLUSION This scoping review presents literature describing comparatively safe tourniquet application when used for less than two hours duration. However, there is limited research describing prolonged tourniquet application or when used for protracted distances, such that the impact of tourniquet release time on metabolic outcomes and complications remains unclear. Prospective studies utilizing the development of an international database to provide this dataset is required.
PICO Summary
Population
Patients in civilian and military settings who had a tourniquet applied for the management of acute limb trauma (86 studies).
Intervention
Scoping review investigating the relationship between time and distance on metabolic complications, limb salvage and mortality following tourniquet use.
Comparison
Outcome
Most included studies (55) were based in civilian environments, 32 were based in military settings, and 1 included both settings. Blast injury was the most common mechanism of injury sustained by patients in military settings (72.8% [5968/8200]) followed by penetrating injury (23.5% [1926/8200]). In civilian settings, penetrating injury was the most common mechanism (47.7% [1633/3426]) followed by blunt injury (36.4% [1246/3426]). Tourniquet time was reported in 66/86 studies. Tourniquet time over four hours was associated with reduced limb salvage rates (57.1%) and higher mortality rates (7.1%) compared with a tourniquet time of less than two hours. The overall limb salvage and mortality rates were 69.6% and 6.7% respectively. Metabolic outcomes were reported in 28/86 studies with smaller sample sizes and inconsistencies in which parameters were reported.
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The Efficacy of Tranexamic Acid for the Treatment of Traumatic Hip Fractures: A Network Meta-Analysis
Bloom DA, Lin CC, Manzi JE, Mojica ES, Telgheder ZL, Chapman CB
Journal of orthopaedic trauma. 2023
Abstract
OBJECTIVES Network meta-analysis to compare the efficacy of different dosages of intravenous(IV) acid(TXA) in the treatment of traumatic hip fractures against the control group of no TXA. DATA SOURCES This study utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform a network meta-analysis on the use of TXA for the treatment of hip fractures. The study team utilized Ovid MEDLINE, Cochrane Reviews, Scopus, Embase, and Web of Science databases to perform the search. Studies were selected that were published in English between the years 2010 and 2020. STUDY SELECTION/DATA EXTRACTION For inclusion in this study, selected manuscripts were required to be randomized controlled trials with at least one control group had no anti-fibrinolytic intervention to serve as a control, IV formulations of TXA were utilized as part of the treatment group. Furthermore, all study participants must have undergone surgical intervention for traumatic hip fractures. Studies that did not immediately meet criteria for inclusion were saved for review by the full investigating team and were included based on consensus. DATA SYNTHESIS All statistical analyses conducted for this study were performed using R (R Foundation for Statistical Computing, Vienna, Austria). Network meta-analyses were conducted with a frequentist approach with a random effects model using the netmeta package version 0.9-6 in R. The frequentist equivalent to surface under the cumulative ranking (SUCRA) probabilities, termed "P-Score" was used to rank different treatments. CONCLUSION The use of TXA in the surgical management of traumatic hip fractures reduces the number of transfusions and perioperative blood loss, with minimal to no increased incidence of thrombotic events when compared to control. When comparing formulations, no route of administration is clearly superior in reducing perioperative blood loss.
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Permissive hypotension compared to fluid therapy for the management of traumatic haemorrhage: a rapid review
Clarke R, Dippenaar E
British paramedic journal. 2022;7(3):34-43
Abstract
BACKGROUND Haemorrhage and subsequent hypovolemia from traumatic injury is a potentially reversible cause of cardiac arrest, as interventions can be made to increase circulatory volume and organ perfusion. Traditionally, intravenous (IV) fluid therapy is recommended for all patients who have experienced a haemorrhagic emergency. There has been some argument, however, that this may not be the most effective treatment as isotonic fluids can dilute coagulation factors and further stimulate bleeding. Permissive hypotension, also known as hypotensive resuscitation within the context of damage control resuscitation, is a method of managing haemorrhagic trauma patients by restricting IV fluid administration to allow for a reduced blood pressure. It is important to evaluate and compare current research literature on the effects of both permissive hypotension and fluid therapy on patients suffering from traumatic haemorrhage. METHODS A rapid review was conducted by systematically searching and identifying literature to narratively compare permissive hypotension and fluid therapy. Searches were carried out across two databases to find relevant primary research containing quantitative data that provide contextual and statistical evidence to achieve the aim of this review. Papers were narratively synthesised to produce key themes for discussion. RESULTS The database searches identified 125 records, 78 from PubMed and 47 from ScienceDirect. Eleven duplicates were removed, and 114 titles screened. Ninety-four records were initially excluded and nine more after abstract review. Eleven papers were critiqued using Benton and Cormack's framework, with eight articles included in the final review. CONCLUSION Permissive hypotension may have a positive impact on 30-day mortality, when compared with fluid resuscitation methods, however there is evidence to suggest that hypotensive resuscitation may be more effective for blunt force injuries. Some studies even suggest a reduction in the treatment cost when reducing fluid volumes. Penetrating injuries are usually more likely to be a compressible source of haemorrhage within which haemorrhage control can be gained much more easily. There are recommendations for the use of permissive hypotension in both compressible and non-compressible injuries. It is difficult at this time to draw definitive conclusions for the treatment of every case related to traumatic haemorrhage given the variability and unpredictability of trauma.
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A Systematic Review of Tranexamic Acid-Associated Venous Thromboembolic Events in Combat Casualties and Considerations for Prolonged Field Care
Russo RM, Lozano R, Ruf AC, Ho JW, Strayve D, Zakaluzny SA, Keeney-Bonthrone TP
Military medicine. 2022
Abstract
INTRODUCTION Tranexamic acid (TXA) is a standard component of Tactical Combat Casualty Care. Recent retrospective studies have shown that TXA use is associated with a higher rate of venous thromboembolic (VTE) events in combat-injured patients. We aim to determine if selective administration should be considered in the prolonged field care environment. MATERIALS AND METHODS We performed a systematic review using the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Clinical trials and observational studies of combat casualties published between January 1, 1960, and June 20, 2022, were included. We analyzed survival and VTE outcomes in TXA recipients and non-recipients. We discussed the findings of each paper in the context of current and future combat environments. RESULTS Six articles met criteria for inclusion. Only one study was powered to report mortality data, and it demonstrated a 7-fold increase in survival in severely injured TXA recipients. All studies reported an increased risk of VTE in TXA recipients, which exceeded rates in civilian literature. However, five of the six studies used overlapping data from the same registry and were limited by a high rate of missingness in pertinent variables. No VTE-related deaths were identified. CONCLUSIONS There may be an increased risk of VTE in combat casualties that receive TXA; however, this risk must be considered in the context of improved survival and an absence of VTE-associated deaths. To optimize combat casualty care during prolonged field care, it will be essential to ensure the timely administration of VTE chemoprophylaxis as soon as the risk of significant hemorrhage permits.
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The role of REBOA in patients in traumatic cardiac arrest subsequent to hemorrhagic shock: a scoping review
Slot SAS, van Oostendorp SE, Schoonmade LJ, Geeraedts LMG
European journal of trauma and emergency surgery : official publication of the European Trauma Society. 2022
Abstract
PURPOSE Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a useful adjunct in treatment of patients in severe hemorrhagic shock. Hypothetically, REBOA could benefit patients in traumatic cardiac arrest (TCA) as balloon occlusion of the aorta increases afterload and may improve myocardial performance leading to return of spontaneous circulation (ROSC). This scoping review was conducted to examine the effect of REBOA on patients in TCA. METHODS This scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) Statement. PubMed, EMBASE.com and the Web of Science Core Collection were searched. Articles were included if they reported any data on patients that underwent REBOA and were in TCA. Of the included articles, data regarding SBP, ROSC and survival were extracted and summarized. RESULTS Of 854 identified studies, 26 articles met criteria for inclusion. These identified a total of 785 patients in TCA that received REBOA (presumably less because of potential overlap in patients). This review shows REBOA elevates mean SBP in patients in TCA. The achievement of ROSC after REBOA deployment ranged from 18.2% to 67.7%. Survival to discharge ranged from 3.5% to 12.1%. CONCLUSION Overall, weak evidence is available on the use of REBOA in patients in TCA. This review, limited by selection bias, indicates that REBOA elevates SBP and may benefit ROSC and potentially survival to discharge in patients in TCA. Extensive further research is necessary to further clarify the role of REBOA during TCA.
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Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury: A Systematic Review and Meta-analysis
Karl V, Thorn S, Mathes T, Hess S, Maegele M
JAMA network open. 2022;5(3):e220625
Abstract
IMPORTANCE Tranexamic acid is widely available and used off-label in patients with bleeding traumatic injury, although the literature does not consistently agree on its efficacy and safety. OBJECTIVE To examine the association of tranexamic acid administration with mortality and thromboembolic events compared with no treatment or with placebo in patients with traumatic injury in the literature. DATA SOURCES On March 23, 2021, PubMed, Embase, and the Cochrane Library were searched for eligible studies published between 1986 and 2021. STUDY SELECTION Randomized clinical trials and observational studies investigating tranexamic acid administration compared with no treatment or placebo among patients with traumatic injury and traumatic brain injury who were 15 years or older were included. Included studies were published in English or German. The electronic search yielded 1546 records, of which 71 were considered for full-text screening. The selection process was performed independently by 2 reviewers. DATA EXTRACTION AND SYNTHESIS The study followed the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 2 independent reviewers and pooled using the inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES Outcomes were formulated before data collection and included mortality at 24 hours and 28 and 30 days (1 month) as well as the incidence of thromboembolic events and the amount of blood products administered. Owing to missing data, overall mortality was added and the amount of blood products administered was discarded. RESULTS Thirty-one studies with a total of 43 473 patients were included in the systematic review. The meta-analysis demonstrated that administration of tranexamic acid was associated with a significant decrease in 1-month mortality compared with the control cohort (risk ratio, 0.83 [95% CI, 0.71-0.97]; I2 = 35%). The results of meta-analyses for 24-hour and overall mortality and thromboembolic events were heterogeneous and could not be pooled. Further investigations on clinical heterogeneity showed that populations with trauma and trial conditions differed markedly. CONCLUSIONS AND RELEVANCE These findings suggest that tranexamic acid may be beneficial in various patient populations with trauma. However, reasonable concerns about potential thromboembolic events with tranexamic acid remain.
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Effects of tranexamic acid treatment in severely and non-severely injured trauma patients
Ageron FX, Shakur-Still H, Roberts I
Transfusion. 2022
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Free full text
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Editor's Choice
Abstract
BACKGROUND Urgent treatment with tranexamic acid (TXA) reduces bleeding deaths but there is disagreement about which patients should be treated. We examine the effects of TXA treatment in severely and non-severely injured trauma patients. STUDY DESIGN AND METHODS We did an individual patient data meta-analysis of randomized trials with over 1000 trauma patients that assessed the effects of TXA on survival. We defined the severity of injury according to characteristics at first assessment: systolic blood pressure of less than 90 mm Hg and a heart rate greater than 120 beats per minute or Glasgow Coma Scale score of less than nine or any GCS with one or more fixed dilated pupils. The primary measure was survival on the day of the injury. We examined the effect of TXA on survival in severely and non-severely injured patients and how these effects vary with the time from injury to treatment. RESULTS We obtained data for 32,944 patients from two randomized trials. Tranexamic acid significantly increased survival on the day of the injury (OR = 1.22, 95% CI 1.11-1.34; p < .01). The effect of tranexamic acid on survival in non-severely injured patients (OR = 1.25, 1.03-1.50) was similar to that in severely injured patients (OR = 1.22, 1.09-1.37) with no significant heterogeneity (p = .87). In severely and non-severely injured pateints, treatment within the first hour after injury was the most effective. DISCUSSION Early tranexamic acid treatment improves survival in both severely and non-severely injured trauma patients. Its use should not be restricted to the severely injured.
PICO Summary
Population
Severely and non-severely injured trauma patients enrolled in the two large randomised controlled trials: CRASH-2 and CRASH-3 (n= 32,944).
Intervention
Tranexamic acid (n= 16,499).
Comparison
Placebo (n= 16,445).
Outcome
Tranexamic acid significantly increased survival on the day of the injury (odd ratio (OR)= 1.22). The effect of tranexamic acid on survival in non-severely injured patients (OR= 1.25) was similar to that in severely injured patients (OR= 1.22) with no significant heterogeneity. In severely and non-severely injured patients, treatment within the first hour after injury was the most effective.
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The efficacy of tranexamic acid treatment with different time and doses for traumatic brain injury: a systematic review and meta-analysis
Huang H, Xin M, Wu X, Liu J, Zhang W, Yang K, Zhang J
Thrombosis journal. 2022;20(1):79
Abstract
OBJECTIVE Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment. METHODS PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence. RESULTS Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92-1.06), adverse events (RR 0.93, 95% Cl 0.76-1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94-1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82-1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89-1.38), or rebleeding (RR 0.97, 95% Cl 0.82-1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]). CONCLUSION TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out. TRIAL REGISTRATION The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).
