A comparative analysis of tranexamic acid dosing strategies in traumatic major hemorrhage.

INTRODUCTION: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients. METHODS: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis. RESULTS: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group. CONCLUSION: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Immature platelet dynamics are associated with clinical outcomes after major trauma.

BACKGROUND: Major trauma results in dramatic changes in platelet behavior. Newly formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated. OBJECTIVES: To determine how immature platelet metrics and plasma thrombopoietin relate to clinical outcomes after major injury. METHODS: A prospective observational cohort study was performed in adult trauma patients. Platelet counts and the immature platelet fraction (IPF) were measured at admission and 24 hours, 72 hours, and 7 days after injury. Thromboelastometry was performed at admission. Plasma thrombopoietin, c-Mpl, and GPIbα were quantified in a separate cohort. The primary outcome was in-hospital mortality; secondary outcomes were venous thromboembolic events and multiple organ dysfunction syndrome (MODS). RESULTS: On admission, immature platelet counts (IPCs) were significantly lower in nonsurvivors (n = 40) than in survivors (n = 236; 7.3 × 109/L vs 10.6 × 109/L; P = .009), but IPF did not differ. Similarly, impaired platelet function on thromboelastometry was associated with lower admission IPC (9.1 × 109/L vs 11.9 × 109/L; P < .001). However, at later time points, we observed significantly higher IPF and IPC in patients who developed venous thromboembolism (21.0 × 109/L vs 11.1 × 109/L; P = .02) and prolonged MODS (20.9 × 109/L vs 11 × 109/L; P = .003) than in those who did not develop complications. Plasma thrombopoietin levels at admission were significantly lower in nonsurvivors (P < .001), in patients with MODS (P < .001), and in those who developed venous thromboembolism (P = .04). CONCLUSION: Lower levels of immature platelets in the acute phase after major injury are associated with increased mortality, whereas higher immature platelet levels at later time points may predispose to thrombosis and MODS.

Editor's Choice - Systematic Review and Meta-Analysis of Lower Extremity Vascular Complications after Arterial Access for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): An Inevitable Concern?

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporise non-compressible torso haemorrhage. Recent data have suggested that vascular access complications secondary to REBOA placement are higher than initially anticipated. This updated systematic review and meta-analysis aimed to determine the pooled incidence rate of lower extremity arterial complications after REBOA. DATA SOURCES: PubMed, Scopus, Embase, conference abstract listings, and clinical trial registries. REVIEW METHODS: Studies including more than five adults undergoing emergency REBOA for exsanguinating haemorrhage that reported access site complications were eligible for inclusion. A pooled meta-analysis of vascular complications was performed using the DerSimonian-Laird weights for the random effects model, presented as a Forest plot. Further meta-analyses compared the relative risk of access complications between different sheath sizes, percutaneous access techniques, and indications for REBOA. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool. RESULTS: No randomised controlled trials were identified, and the overall study quality was poor. Twenty-eight studies including 887 adults were identified. REBOA was performed for trauma in 713 cases. The pooled proportion rate of vascular access complications was 8.6% (95% confidence interval 4.97 - 12.97), with substantial heterogeneity (I2 = 67.6%). There was no significant difference in the relative risk of access complications between 7 and > 10 F sheaths (p = .54), or between ultrasound guided and landmark guided access (p = .081). However, traumatic haemorrhage was associated with a significantly higher risk of complications compared with non-traumatic haemorrhage (p = .034). CONCLUSION: This updated meta-analysis aimed to be as comprehensive as possible considering the poor quality of source data and high risk of bias. It suggested that lower extremity vascular complications were higher than originally suspected after REBOA. While the technical aspects did not appear to impact the safety profile, a cautious association could be drawn between REBOA use for traumatic haemorrhage and a higher risk of arterial complications.

Bouveret syndrome: a rare cause of gastric outlet obstruction.

Bouveret syndrome is a rare cause of gastric outlet obstruction. It is characterised by the presence of an obstructing gallstone in the pylorus or proximal duodenum, which has travelled to its obstructing position via an acquired fistula. Our case involves a 73-year-old man presenting to the acute surgical take with a 2-day history of right-sided abdominal pain and vomiting. His medical history included perforated cholecystitis treated with antibiotics and percutaneous gall bladder drainage, 1 year earlier. Examination and blood tests were suggestive of gastric outlet obstruction. CT abdomen and pelvis demonstrated a large gallstone obstructing the duodenum, confirming a diagnosis of Bouveret syndrome. The patient improved following gastrolithotomy, and was discharged 2 weeks postoperatively. Fistula formation is a complication of chronic cholecystitis and therefore Bouveret syndrome should be considered in patients with a background of gallstone disease presenting with gastric outlet obstruction.

Resolvin D1 Attenuates the Organ Injury Associated With Experimental Hemorrhagic Shock.

OBJECTIVE: To evaluate the potential changes in the plasma levels of resolvin D1 (RvD1) in patients with trauma and hemorrhage. Having found that trauma results in a profound reduction in plasma RvD1 in patients, we have then investigated the effects of RvD1 on the organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. BACKGROUND: HS is a common cause of death in trauma due to excessive systemic inflammation and multiple organ failure. RvD1 is a member of the resolvin family of pro-resolution mediators. METHODS: Blood samples were drawn from critically injured patients (n = 27, ACITII-prospective observational cohort study) within 2 hours of injury for targeted liquid chromatography tandem mass spectrometry. HS rats (removal of blood to reduce arterial pressure to 30 ±â€Š2 mm Hg, 90 minutes, followed by resuscitation) were treated with RvD1 (0.3 or 1 µg/kg intravenous (i.v.)) or vehicle (n = 7). Parameters of organ injury and dysfunction were determined. RESULTS: Plasma levels of RvD1 (mg/dL) were reduced in patients with trauma+HS (0.17 ±â€Š0.08) when compared with healthy volunteers (0.76 ±â€Š0.25) and trauma patients (0.62 ±â€Š0.20). In rats with HS, RvD1 attenuated the kidney dysfunction, liver injury, and tissue ischemia. RvD1 also reduced activation of the nuclear factor (NF)-κB pathway and reduced the expression of pro-inflammatory proteins such as inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. CONCLUSION: Plasma RvD1 is reduced in patients with trauma-HS. In rats with HS, administration of synthetic RvD1 on resuscitation attenuated the multiple organ failure associated with HS by a mechanism that involves inhibition of the activation of NF-κB.

The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients.

OBJECTIVE: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. METHODS: A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. RESULTS: Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. CONCLUSIONS: Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.

Platelet transfusions reduce fibrinolysis but do not restore platelet function during trauma hemorrhage.

BACKGROUND: Platelets play a critical role in hemostasis with aberrant function implicated in trauma-induced coagulopathy. However, the impact of massive transfusion protocols on platelet function during trauma hemorrhage is unknown. The aim of this study was to characterize the effects of platelet transfusion on platelet aggregation and fibrinolytic markers during hemostatic resuscitation. METHODS: Trauma patients enrolled into the prospective Activation of Coagulation and Inflammation in Trauma study between January 2008 and November 2015 who received at least four units of packed red blood cells (PRBCs) were included. Blood was drawn in the emergency department within 2 hours of injury and at intervals after every four units of PRBCs transfused. Platelet aggregation was assessed in whole blood with multiple electrode aggregometry. Plasma proteins were quantified by enzyme-linked immunosorbent assay. RESULTS: Of 161 patients who received four or more PRBCs as part of their initial resuscitation, 44 received 8 to 11 units and 28 received 12 units or more. At each timepoint during bleeding, platelet aggregation was similar in patients who had received a platelet transfusion compared with those who had only received other blood products (p > 0.05 for all timepoints). Platelet transfusion during the four PRBC intervals was associated with a decrease in maximum lysis on rotational thromboelastometry (start of interval, 6% [2-12] vs. end of interval, 2% [0-5]; p = 0.001), an increase in plasminogen activator inhibitor-1 (start of interval, 35.9 ± 14.9 vs. end of interval, 66.7 ± 22.0; p = 0.007) and a decrease in tissue plasminogen activator (start of interval, 26.2 ± 10.5 vs. end of interval, 19.0 +/- 5.1; p = 0.04). No statistically significant changes in these parameters occurred in intervals which did not contain platelets. CONCLUSION: Current hemostatic resuscitation strategies do not appear to restore platelet aggregation during active hemorrhage. However, stored platelets may attenuate fibrinolysis by providing an additional source of plasminogen activator inhibitor-1. Further investigation into the effects of early platelet transfusion on platelet function, hemostatic, and clinical outcomes during bleeding are warranted. LEVEL OF EVIDENCE: Therapeutic, level III.

Postoperative Elevation of the Neutrophil: Lymphocyte Ratio Predicts Complications Following Esophageal Resection.

BACKGROUND: Complications following esophagectomy are a significant source of morbidity. The aim of this study was to investigate the utility of the neutrophil:lymphocyte ratio (NLR) in the early identification of complications following esophagectomy, as compared to other routinely available parameters. METHODS: We performed a retrospective cohort study of patients undergoing Ivor-Lewis esophagectomy at a single centre. Baseline characteristics and complications occurring within the first 30 days of surgery were recorded. White blood cell counts and C-reactive protein (CRP) levels immediately following surgery (day 0) and over the subsequent three postoperative days were analysed. RESULTS: Sixty-five patients were included, of whom 29 (45 %) developed complications. The median NLR was similar among patients with and without a complicated recovery on day 0 (12.7 vs 13.6, p = 0.70) and day 1 (10.0 vs 9.3, p = 0.29). Patients who subsequently developed complications had a higher NLR on day 2 (11.8 vs 7.5, p < 0.001) and day 3 (9.0 vs 6.5, p = 0.001) compared to those whose recovery was uncomplicated. Receiver-operating-characteristic plots for the diagnostic performance of the NLR, neutrophil count, lymphocyte count and CRP level at each time point demonstrated that the NLR on day 2 had the greatest discriminatory ability in predicting complications, with an area under the curve of 0.83 (95 % CI 0.73-0.94). An NLR of >8.3 on day 2 had a sensitivity of 93 % and a specificity of 72 % for predicting complications. CONCLUSION: The NLR is a simple and routinely available parameter which has a high sensitivity in the early detection of complications following esophagectomy.

Near-fatal small bowel ischaemia secondary to sacrocolpopexy mesh.

A 74-year-old woman presenting with acute abdominal pain underwent surgery for suspected small bowel ischaemia. At laparotomy, a sacrocolpopexy mesh in the pelvis, which had been inserted 8 years previously, was found to be causing strangulation of a 2-m length of the small bowel. Following resection and primary anastomosis, the patient spent several days in intensive care before her eventual discharge. This unusual life-threatening complication should be considered in patients presenting with abdominal pain even many years following abdominal sacrocolpopexy.

A large ventricular septal defect complicating resuscitation after blunt trauma.

A young adult pedestrian was admitted to hospital after being hit by a car. On arrival to the Accident and Emergency Department, the patient was tachycardic, hypotensive, hypoxic, and acidotic with a Glasgow Coma Scale of 3. Despite initial interventions, the patient remained persistently hypotensive. An echocardiogram demonstrated a traumatic ventricular septal defect (VSD) with right ventricular strain and increased pulmonary artery pressure. Following a period of stabilization, open cardiothoracic surgery was performed and revealed an aneurysmal septum with a single large defect. This was repaired with a bovine patch, resulting in normalization of right ventricular function. This case provides a vivid depiction of a large VSD in a patient following blunt chest trauma with hemodynamic compromise. In all thoracic trauma patients, and particularly those poorly responsive to resuscitation, VSDs should be considered. Relevant investigations and management strategies are discussed.

Peer-mentoring junior surgical trainees in the United Kingdom: a pilot program.

BACKGROUND: Peer-mentoring has attracted substantial interest in various healthcare professions, but has not been formally integrated into postgraduate surgical training. This study aimed to assess the feasibility and acceptability of a peer-mentor scheme among junior surgical trainees in the United Kingdom. METHOD: Trainees entering the first year of core surgical training (CST) in a single postgraduate school of surgery were allocated a mentor in the second year of CST. Allocation was based on location of the initial clinical placement. An anonymised questionnaire regarding the mentorship scheme was sent to all participants in the third month following its introduction. RESULTS: 18 trainees participated in the scheme, of whom 12 (67%) responded to the questionnaire. All respondents had made contact with their allocated mentor or mentee, and no trainees had opted out of the scheme. Areas in which the mentees received guidance included examinations (83%), CV development (67%), and workplace-based assessments (67%). All respondents felt that the mentor scheme was a good addition to CST. Suggestions for improvement of the scheme included introduction of structured meetings and greater engagement with allocated mentors. CONCLUSIONS: A pilot peer-mentoring scheme was well received by junior surgical trainees. Consideration should be given to expansion of this scheme and more rigorous assessment of its value.