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
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.
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
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 METHODS We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage.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.
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
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.
Patients in civilian and military settings who had a tourniquet applied for the management of acute limb trauma (86 studies).
Scoping review investigating the relationship between time and distance on metabolic complications, limb salvage and mortality following tourniquet use.
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.
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
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.
Efficacy of Tranexamic Acid in the Treatment of Massive Upper Gastrointestinal Bleeding: A Randomized Clinical Trial
Sedaghat M, Iranshahi M, Mardani M, Mesbah N
Background Upper gastrointestinal bleeding (GIB) is an important cause of emergency ward admission. Antifibrinolytic agents including tranexamic acid (TXA) have been used for controlling GIB. However, there have been concerns regarding the safety and efficacy of TXA in patients with GIB. Thus, in this study, we aimed to determine the efficacy of TXA in the treatment of massive upper GIB. Methodology This double-blind randomized clinical trial was conducted among 86 consecutive patients who were referred to Imam Hossein Hospital in Tehran, Iran from 2018 to 2019 with the chief complaint of massive upper GIB. Patients were chosen to be in the TXA or placebo groups based on a 1:1 allocation using the block randomization method. The rate of rebleeding, need for blood transfusion, hospital stay, adverse effects, and mortality rate were evaluated and compared across the groups. Results Of the 86 patients enrolled in this study, 55.8% (n = 48) were males. The mean age of all patients was 53.1 ± 10.6 years (TXA group: 54.9 ± 11.5 years, and placebo group: 51.4 ± 9.7 years). Rebleeding was seen in 11 (25.6%) patients in the TXA group and in 20 (46.5%) patients in the control group, which was statistically significant (p = 0.043). Blood transfusion was carried out in only three (7%) patients in the TXA group compared with 14 (32.6%) patients in the placebo group (p = 0.003). Six (14%) patients experienced a hospital stay of longer than five days in the TXA group and 15 (34.9%) patients in the control group, which was statistically significant (p = 0.024). There were no significant differences in the mortality rate across both groups (p > 0.05). Conclusions TXA has no effect on mortality associated with severe upper GIB. However, it was associated with a lower rate of rebleeding and hospitalization time, without significant adverse effects.
Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis
Beran A, Altorok N, Srour O, Malhas SE, Khokher W, Mhanna M, Ayesh H, Aladamat N, Abuhelwa Z, Srour K, et al
Journal of clinical medicine. 2022;11(7)
The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings.
Topical Hemostatic Agents in Burn Surgery: A Systematic Review
Battistini A, Gottlieb LJ, Vrouwe SQ
Journal of burn care & research : official publication of the American Burn Association. 2022
Acute burn surgery has long been associated with significant intra-operative bleeding. Several techniques were introduced to limit hemorrhage, including tourniquets, tumescent infiltration, and topical agents. To date, no study has comprehensively investigated the available data regarding topical hemostatic agents in burn surgery. A systematic review was performed by two independent reviewers using electronic databases (PubMed, Scopus, Web of Science) from first available to September 10, 2021. Articles were included if they were published in English and described or evaluated topical hemostatic agents used in burn excision and/or grafting. Data were extracted on the agent(s) used, their dosage, mode of delivery, hemostasis outcomes, and complications. The search identified 1982 non-duplicate citations, of which 134 underwent full-text review, and 49 met inclusion criteria. In total, 32 studies incorporated a vasoconstrictor agent, and 28 studies incorporated a procoagulant agent. Four studies incorporated other agents (hydrogen peroxide, tranexamic acid, collagen sheets, and TT-173). The most common vasoconstrictor used was epinephrine, with doses ranging from 1:1,000-1:1,000,000. The most common procoagulant used was thrombin, with doses ranging from 10-1,000 IU/mL. Among the comparative studies, outcomes of blood loss were not reported in a consistent manner, therefore meta-analysis could not be performed. The majority of studies (94%) were level of evidence III-V. Determining the optimal topical hemostatic agent is limited by low-quality data and challenges with consistent reporting of intra-operative blood loss. Given the routine use of topical hemostatic agents in burn surgery, high-quality research is essential to determine the optimal agent, dosage, and mode of delivery.
Vasoactive and/or inotropic drugs in initial resuscitation of burn injuries: A systematic review
Knappskog K, Andersen NG, Guttormsen AB, Onarheim H, Almeland SK, Beitland S
Acta anaesthesiologica Scandinavica. 2022
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BACKGROUND According to current guidelines initial burn resuscitation should be performed with fluids alone. The aims of the study were to review the frequency of use of vasoactive and/or inotropic drugs in initial burn resuscitation, and assess benefits and harms of adding such drugs to fluids. METHODS A systematic literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, UpToDate, and SveMed+ through 3 December 2021. The search included studies on critically ill burn patients receiving vasoactive and/or inotropic drugs in addition to fluids within 48 hours after burn injury. RESULTS The literature search identified 1058 unique publications that were screened for inclusion. After assessing 115 publications in full text, only two retrospective cohort studies were included. One study found that 16 out of 52 (31%) patients received vasopressor(s). Factors associated with vasopressor use were increasing age, burn depth and % total body surface area (TBSA) burnt. Another study observed that 20 out of 111 (18%) patients received vasopressor(s). Vasopressor use was associated with increasing age, Baux score and %TBSA burnt in addition to more frequent dialysis treatment and increased mortality. Study quality assessed by the Newcastle-Ottawa quality assessment scale was considered good in one study, but uncertain due to limited description of methods in the other. CONCLUSION This systematic review revealed that there is lack of evidence regarding benefits and harms of using vasoactive and/or inotropic drugs in addition to fluids during early resuscitation of patients with major burns.
Management strategies for perioperative anaemia in the severely burn-injured Jehovah's Witness patients who decline a blood transfusion: A systematic review with illustrative case reports
Jung M, Harish V, Wijewardena A, Kerridge I, Gillies R
Burns: journal of the International Society for Burn Injuries. 2022
BACKGROUND The management of severe burn-injured Jehovah's Witness patients who decline a blood transfusion poses unique challenges. The literature is scant for guiding perioperative anaemia management in these patients. We present a systematic review of this patient group, along with illustrative, consecutive case reports of our experience. METHODS A systematic review was performed on Embase, MEDLINE and PubMed databases on articles discussing the treatment of burn-injured Jehovah's Witness patients. Articles were excluded if discussing isolated inhalation injury, or if blood transfusions were permitted. RESULTS Nine articles including a total of 11 patients revealed consistent themes. A multimodal medical and surgical approach is suggested. Medical strategies are directed at reducing blood loss and optimising haematopoiesis and include rationalising blood collection, reversing coagulopathy, administering tranexamic acid and regular erythropoietin. Surgical strategies include staged aggressive debridement, tumescent adrenaline infiltration and limb tourniquets. We found that the argon beam coagulator was an effective haemostatic adjunct not previously described in literature. DISCUSSION Management of anaemia in severely burn-injured Jehovah's Witness patients is challenging. This systematic review presents a summary of strategies directed at minimising blood loss, and optimising haematopoiesis. Careful preoperative planning, meticulous surgical technique, and postoperative physiological support are caveats to success.
The Impact of Choice Architecture on Sepsis Fluid Resuscitation Decisions: An Exploratory Survey-Based Study
Mansoori JN, Clark BJ, Havranek EP, Douglas IS
MDM policy & practice. 2022;7(1):23814683221099454
BACKGROUND Discordance with well-known sepsis resuscitation guidelines is often attributed to rational assessments of patients at the point of care. Conversely, we sought to explore the impact of choice architecture (i.e., the environment, manner, and behavioral psychology within which options are presented and decisions are made) on decisions to prescribe guideline-discordant fluid volumes. DESIGN We conducted an electronic, survey-based study using a septic shock clinical vignette. Physicians from multiple specialties and training levels at an academic tertiary-care hospital and academic safety-net hospital were randomized to distinct answer sets: control (6 fluid options), time constraint (6 fluid options with a 10-s limit to answer), or choice overload (25 fluid options). The primary outcome was discordance with Surviving Sepsis Campaign fluid resuscitation guidelines. We also measured response times and examined the relationship between each choice architecture intervention group, response time, and guideline discordance. RESULTS A total of 189 of 624 (30.3%) physicians completed the survey. Time spent answering the vignette was reduced in time constraint (9.5 s, interquartile range [IQR] 7.3 s to 10.0 s, P < 0.001) and increased in choice overload (56.8 s, IQR 35.9 s to 86.7 s, P < 0.001) groups compared with control (28.3 s, IQR 20.0 s to 44.6 s). In contrast, the relative risk of guideline discordance was higher in time constraint (2.07, 1.33 to 3.23, P = 0.001) and lower in choice overload (0.75, 0.60, to 0.95, P =0.02) groups. After controlling for time spent reading the vignette, the overall odds of choosing guideline-discordant fluid volumes were reduced for every additional second spent answering the vignette (OR 0.98, 0.97, to 0.99, P < 0.001). CONCLUSIONS Choice architecture may affect fluid resuscitation decisions in sepsis regardless of patient conditions, warranting further investigation in real-world contexts. These effects should be considered when implementing practice guidelines. HIGHLIGHTS Time constrained clinical decision making was associated with increased proportion of guideline-discordant responses and relative risk of failure to prescribe guideline-recommended intravenous fluids using a sepsis clinical vignette.Choice overload increased response times and was associated with decreased proportion of guideline-discordant responses and relative risk of guideline discordance.Physician odds of choosing to prescribe guideline-discordant fluid volumes were reduced with increased deliberation as measured by response times.Clinicians, researchers, policy makers, and administrators should consider the effect of choice architecture on clinical decision making and guideline discordance when implementing guidelines for sepsis and other acute care conditions.