bims-heshmo Biomed News
on Trauma hemorrhagic shock — molecular basis
Issue of 2021–07–11
ten papers selected by
Andreia Luís, Ludwig Boltzmann Institute
  1. Extracellular vesicle-associated procoagulant activity is highest the first 3 hours after trauma and thereafter declines substantially: A prospective observational pilot study.
  2. CAN RH+ WHOLE BLOOD BE SAFELY USED AS AN ALTERNATIVE TO RH- PRODUCT? AN ANALYSIS OF EFFORTS TO IMPROVE THE SUSTAINABILITY OF A HOSPITAL'S LOW TITER GROUP O WHOLE BLOOD PROGRAM.
  3. A Pilot Study of Stored Low Titer Group O Whole Blood + Component Therapy versus Component Therapy Only for Civilian Trauma Patients.
  4. Mortality in hypotensive trauma patients requiring laparotomy is related to degree of hypotension and provides evidence for focused interventions.
  5. Selective brain cooling achieves peripheral organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.
  6. Platelet to erythrocyte transfusion ratio and mortality in massively transfused trauma patients. A systematic review and meta-analysis.
  7. Comparison of base excess, lactate and pH predicting 72-h mortality of multiple trauma.
  8. Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury.
  9. Glycosylated Hemoglobin as a Predictor of Sepsis and All-Cause Mortality in Trauma Patients.
  10. The impact of infection complications after trauma differs according to trauma severity.
  1. J Trauma Acute Care Surg. 2021 Jul 02.
    Extracellular vesicle-associated procoagulant activity is highest the first 3 hours after trauma and thereafter declines substantially: A prospective observational pilot study.
    Ingrid Nygren Rognes, Marit Hellum, William Ottestad, Kristi Grønvold Bache, Torsten Eken, Carola Elisabeth Henriksson.
       BACKGROUND: Trauma patients have high concentrations of circulating extracellular vesicles (EVs) following injury, but the functional role of EVs in this setting is only partly deciphered. We aimed to describe in detail EV-associated procoagulant activity in individual trauma patients during the first 12 hours after injury in order to explore their putative function, and relate findings to relevant trauma characteristics and outcome.
    METHODS: In a prospective observational study of 33 convenience recruited trauma patients, citrated plasma samples were obtained at trauma centre admission and 2, 4, 6, and 8 hours thereafter. We measured thrombin generation from isolated EVs and the procoagulant activity of phosphatidylserine-exposing EVs. Correlation and multivariable linear regression analyses were used to explore associations between EV-associated procoagulant activity and trauma characteristics as well as outcome measures.
    RESULTS: EV-associated procoagulant activity was highest in the first 3 hours after injury. EV-associated thrombin generation normalised within 7-12 hours of injury, whereas the procoagulant activity of phosphatidylserine-exposing EVs declined to a level right above that of healthy volunteers. Increased EV-associated procoagulant activity at admission was associated with higher New Injury Severity Score, lower admission base excess, higher admission international normalised ratio, prolonged admission activated partial thromboplastin time, higher Sequential Organ Failure Assessment score at day 0, and fewer ventilator-free days.
    CONCLUSIONS: Our data suggest that EVs have a transient hypercoagulable function and may play a role in the early phase of haemostasis after injury. The role of EVs in trauma-induced coagulopathy and post-traumatic thrombosis should be studied bearing in mind this novel temporal pattern.
    LEVEL OF EVIDENCE: Prognostic/Epidemiologic Level V.
    DOI:  https://doi.org/10.1097/TA.0000000000003333
  2. J Trauma Acute Care Surg. 2021 Jul 06.
    CAN RH+ WHOLE BLOOD BE SAFELY USED AS AN ALTERNATIVE TO RH- PRODUCT? AN ANALYSIS OF EFFORTS TO IMPROVE THE SUSTAINABILITY OF A HOSPITAL'S LOW TITER GROUP O WHOLE BLOOD PROGRAM.
    Christopher Cameron McCoy, Kelsey Montgomery, Madeline Cotton, David E Meyer, Charles E Wade, Bryan Alan Cotton.
       BACKGROUND: Low-titer group O whole blood (LTO-WB) has recently gained popularity in trauma centers for the acute resuscitation of hemorrhagic shock. However, limited supplies of Rh- product prevent implementation and strain sustainability at many trauma centers. We set out to identify whether Rh + LTO-WB could be safely substituted for RH- product, regardless of patient's Rh status.
    METHODS: Following IRB approval, information on all trauma patients receiving prehospital or ED transfusion of uncrossed, emergency release LTO-WB (11/17-10/19) were evaluated. Patients were first divided into those who received Rh- vs. Rh + product, the assessed by Rh of the recipient. Serial hemolysis panels, transfusion reactions, and outcomes were compared.
    RESULTS: 637 consecutive trauma patients received emergency release LTO-WB. Of these, 448 received Rh + product, while 189 received Rh- LTO-WB. Patients receiving Rh + product were more likely to be male (81 vs. 70%) and have lower field blood pressure (median 99 vs. 109) and GCS (median 7 vs 12); all p < 0.05. There were no differences in blood product volume, hemolysis labs, transfusion reactions, complications, or survival. We then separated patients by Rh status (577 were Rh+, 70 were Rh-). Rh- patients were Rh- were older (median age 54 vs 39), more likely to be female (57 vs 26%), and more likely to have sustained blunt trauma than their Rh + counterparts (92 vs. 70%); all p < 0.05. There were no differences in hemolysis labs, transfusion reactions, complications, or survival between Rh + and Rh- patients, regardless of Rh product received.
    CONCLUSIONS: When Rh- whole blood is unavailable or in short supply, Rh + LTO-WB appears to be a safe alternative for the resuscitation of hemorrhagic shock, in both Rh + and Rh- patients. Use of Rh + product may help trauma centers incorporate LTO-WB into their hospital and improve sustainability of such programs.
    LEVEL OF EVIDENCE: III.
    DOI:  https://doi.org/10.1097/TA.0000000000003342
  3. J Trauma Acute Care Surg. 2021 Jul 02.
    A Pilot Study of Stored Low Titer Group O Whole Blood + Component Therapy versus Component Therapy Only for Civilian Trauma Patients.
    Anaar E Siletz, Kevin J Blair, Richelle J Cooper, N Charity Nguyen, Scott J Lewis, Amy Fang, Dawn C Ward, Nicholas J Jackson, Tyler Rodriguez, Jonathan Grotts, Jonathan Hwang, Alyssa Ziman, H Gill Cryer.
       BACKGROUND: This pilot assessed transfusion requirements during resuscitation with whole blood followed by standard component therapy versus component therapy alone, during a change in practice at a large urban level I trauma center.
    METHODS: This was a single-center prospective cohort pilot study. Male trauma patients received up to 4 units of cold-stored low anti-A, anti-B group O whole blood (LTOWB) as initial resuscitation followed by CT as needed (LTOWB + CT). A control group consisting of females, and males who presented when LTOWB was unavailable, received component therapy only (CT group). Exclusion criteria included antiplatelet or anticoagulant medication and death within 24 hours. The primary outcome was total transfusion volume at 24 hours. Secondary outcomes were mortality, morbidity, and ICU- and hospital-free days.
    RESULTS: Thirty-eight patients received LTOWB, with a median of 2.0 [IQR 1.0, 3.0] units of LTOWB transfused. Thirty-two patients received CT only. At 24 hours after presentation, the LTOWB +CT group had received a median of 2138 mL [IQR 1275-3325] of all blood products. The median for the CT group was 4225 mL [IQR 1900-5425], p = 0.06 in unadjusted analysis. When adjusted for Injury Severity Score, sex, and positive Focused Assessment with Sonography for Trauma (FAST), LTOWB +CT group patients received 3307 mL of blood products and CT group patients received 3260 mL in the first 24 hours (p = 0.95). The adjusted median ratio of plasma to red cells transfused was higher in the LTOWB + CT group (0.85 vs 0.63 at 24 hours after admission, p = 0.043. Adjusted mortality was 4.4% in the LTOWB + CT group, and 11.7% in the CT group (p = 0.19), with similar complications, ICU-, and hospital-free days in both groups.
    CONCLUSIONS: Beginning resuscitation with LTOWB results in equivalent outcomes compared to resuscitation with CT only.
    LEVEL OF EVIDENCE: Therapeutic, Level III (Prospective study with 1 negative criterion, limited control of confounding factors).
    DOI:  https://doi.org/10.1097/TA.0000000000003334
  4. Trauma Surg Acute Care Open. 2021 ;6(1): e000723
    Mortality in hypotensive trauma patients requiring laparotomy is related to degree of hypotension and provides evidence for focused interventions.
    James W Davis, Rachel C Dirks, David R Jeffcoach, Krista L Kaups, Lawrence P Sue, Jordan T Lilienstein, Mary M Wolfe, Amy M Kwok.
       Background: Mortality in hypotensive patients requiring laparotomy is reported to be 46% and essentially unchanged in 20 years. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been incorporated into resuscitation protocols in an attempt to decrease mortality, but REBOA can have significant complications and its use in this patient group has not been validated. This study sought to determine the mortality rate for hypotensive patients requiring laparotomy and to evaluate the mortality risk related to the degree of hypotension. Additionally, this study sought to determine if there was a presenting systolic blood pressure (SBP) that was associated with a sharp increase in mortality to target the appropriate patient group most likely to benefit from focused interventions such as REBOA.
    Methods: The trauma registry at a level I trauma center was reviewed for patients undergoing emergent laparotomy from January 2007 to June 2020. Data included demographics, mechanism of injury, physiological data, Injury Severity Score, blood products transfused, and outcomes. Group comparisons were based on initial SBP (0 to 50 mm Hg, 60 to 69 mm Hg, 70 to 79 mm Hg, 80 to 89 mm Hg, and ≥90 mm Hg).
    Results: During the study period, 52 016 trauma patients were treated and 1174 required laparotomy within 90 min of arrival; 424 had an initial SBP of <90 mm Hg. The overall mortality rate was 18%, but mortality increased as SBP decreased (≥90=9%, 80 to 89=20%, 70 to 79=21%, 60 to 69=48%, 0 to 59=66%). Mortality increased sharply with SBP of <70 mm Hg.
    Discussion: Mortality rate increases with worsening hypotension and increases sharply with an SBP of <70 mm Hg. Further study on focused interventions such as REBOA should target this patient group.
    Level of evidence: Therapeutic/care management, level III.
    Keywords:  hypotension; laparotomy; mortality
    DOI:  https://doi.org/10.1136/tsaco-2021-000723
  5. Int J Med Sci. 2021 ;18(13): 2920-2929
    Selective brain cooling achieves peripheral organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.
    Chien-Ming Chao, Chien-Chin Hsu, Chien-Cheng Huang, Chung-Han Wang, Mao-Tsun Lin, Ching-Ping Chang, Hung-Jung Lin, Chung-Ching Chio.
      Background: Although whole-body cooling has been reported to improve the ischemic/reperfusion injury in hemorrhagic shock (HS) resuscitation, it is limited by its adverse reactions following therapeutic hypothermia. HS affects the experimental and clinical bowel disorders via activation of the brain-gut axis. It is unknown whether selective brain cooling achieves beneficial effects in HS resuscitation via preserving the integrity of the brain-gut axis. Methods: Male Sprague-Dawley rats were bled to hypovolemic HS and resuscitated with blood transfusion followed by retrograde jugular vein flush (RJVF) with 4 °C or 36 °C normal saline. The mean arterial blood pressure, cerebral blood flow, and brain and core temperature were measured. The integrity of intestinal tight junction proteins and permeability, blood pro-inflammatory cytokines, and multiple organs damage score were determined. Results: Following blood transfusion resuscitation, HS rats displayed gut barrier disruption, increased blood levels of pro-inflammatory cytokines, and peripheral vital organ injuries. Intrajugular-based infusion cooled the brain robustly with a minimal effect on body temperature. This brain cooling significantly reduced the HS resuscitation-induced gut disruption, systemic inflammation, and peripheral vital organ injuries in rats. Conclusion: Resuscitation with selective brain cooling achieves peripheral vital organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.
    Keywords:  gut barrier; hemorrhagic shock; resuscitation; selective brain cooling
    DOI:  https://doi.org/10.7150/ijms.61191
  6. J Trauma Acute Care Surg. 2021 Jul 02.
    Platelet to erythrocyte transfusion ratio and mortality in massively transfused trauma patients. A systematic review and meta-analysis.
    Tim W H Rijnhout, Jeanette Duijst, Femke Noorman, Margreet Zoodsma, Oscar van Waes, Michael H J Verhofstad, Rigo Hoencamp.
       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.
    DOI:  https://doi.org/10.1097/TA.0000000000003323
  7. BMC Emerg Med. 2021 Jul 07. 21(1): 80
    Comparison of base excess, lactate and pH predicting 72-h mortality of multiple trauma.
    Junfang Qi, Long Bao, Peng Yang, Du Chen.
       OBJECTIVE: To compare the predictive values of base excess (BE), lactate and pH of admission arterial blood gas for 72-h mortality in patients with multiple trauma.
    METHODS: This was a secondary analysis based on a publicly shared trauma dataset from the Dryad database, which provided the clinical data of 3669 multiple trauma patients with ISS > = 16. The records of BE, lactate, pH and 72-h prognosis data without missing values were selected from this dataset and 2441 individuals were enrolled in the study. Logistic regression model was performed to calculate the odds ratios (ORs) of variables. Area under the curve (AUC) of receiver operating curve (ROC) was utilized to evaluate the predictive value of predictors for 72 h in-hospital mortality. Pairwise comparison of AUCs was performed using the Delong's test.
    RESULTS: The statistically significant correlations were observed between BE and lactate (r = - 0.5861, p < 0.05), lactate and pH (r = - 0.5039, p < 0.05), and BE and pH (r = - 0.7433, p < 0.05). The adjusted ORs of BE, lactate and pH for 72-h mortality with the adjustment for factors including gender, age, ISS category were 0.872 (95%CI: 0.854-0.890), 1.353 (95%CI: 1.296-1.413) and 0.007 (95%CI: 0.003-0.016), respectively. The AUCs of BE, lactate and pH were 0.693 (95%CI: 0.675-0.712), 0.715 (95%CI: 0.697-0.733), 0.670 (95%CI: 0.651-0.689), respectively.
    CONCLUSIONS: There are significant correlations between BE, lactate and pH of the admission blood gas, all of them are independent predictors of 72-h mortality for multiple trauma. Lactate may have the best predictive value, followed by BE, and finally pH.
    Keywords:  Base excess; Blood gas analysis; Lactate; Mortality; Multiple trauma; Predictive value; pH
    DOI:  https://doi.org/10.1186/s12873-021-00465-9
  8. J Trauma Acute Care Surg. 2021 Jul 06.
    Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury.
    Keita Nakatsutsumi, Koji Morishita, Masayuki Yagi, Sanae Doki, Arisa Watanabe, Nahoko Ikegami, Testuyuki Kobayashi, Mitsuaki Kojima, Atsushi Senda, Kouhei Yamamoto, Junichi Aiboshi, Raul Coimbra, Yasuhiro Otomo.
       BACKGROUND: Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple organ dysfunction (MOD) after hemorrhagic shock. A previous study suggested vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of MOD. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML.
    METHODS: Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 min to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 min before 10 min after SMAO (5 V, 0.5 Hz). Liquid chromatography-electrospray ionization-tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation assay. Western blotting of phospholipase A2 group IIA (PLA2-IIA) was also performed for ML and ileum samples.
    RESULTS: VNS relieved the SMAO-induced histological gut injury. The concentration of AA and level of NF-κB activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA2-IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals.
    CONCLUSIONS: The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA2-IIA expression in the gut and ML.
    DOI:  https://doi.org/10.1097/TA.0000000000003345
  9. Infect Drug Resist. 2021 ;14 2517-2526
    Glycosylated Hemoglobin as a Predictor of Sepsis and All-Cause Mortality in Trauma Patients.
    Feng Guo, Haitao Shen.
       Background and Purpose: Infection is a common comorbidity and cause of death in emergency trauma patients, especially in diabetic patients. Once the patients are admitted, they are more susceptible to further complications like sepsis and resultant increase in in-hospital mortality. Therefore, it is necessary to evaluate risk factors associated with sepsis after trauma and death in trauma patients.
    Methods: A total of 397 trauma patients were divided into 2 groups according to HbA1c level, HbA1c: <6.5% (n = 259), HbA1c: >6.5% (n = 138), and baseline clinical characteristics were collected. The independent risk factors of sepsis associated with trauma were screened using univariate and multivariate logistic regression analysis. Cox proportional hazards regression analysis was used to investigate risk factors for 30-day all-cause mortality.
    Results: The sepsis incidence (76.1% vs 35.9%, P<0.001) and mortality rate (29.7% vs 7.3%, P<0.001) were significantly higher in HbA1c>6.5% group. Multivariate logistic regression analysis revealed that the independent risk factors of sepsis after trauma were diabetes (OR: 3.1, 95% CI: 1.41-6.79), hypertension (OR: 2.55, 95% CI: 1.35-4.82), coagulation disorder (OR: 3.45, 95% CI: 1.23-9.67), creatinine (OR: 3.71, 95% CI: 1.66-8.31), urea nitrogen (OR: 0.96, 95% CI: 0.92-0.99), HbA1c%>6.5 (OR: 2.05, 95% CI: 1.65-2.54), increase in body mass index (OR: 1.08, 95% CI: 1.03-1.13) and lower initial GCS score (OR: 0.93, 95% CI: 0.88-0.99). Multivariable Cox proportional hazard analysis revealed that male (HR: 1.94, 95% CI: 1.21-3.12), HbA1c >6.5% (HR: 1.45, 95% CI: 1.32-1.6), albumin (HR: 0.54, 95% CI: 0.34-0.86), creatinine (HR: 1.02, 95% CI: 1.01-1.03), APTT (HR: 1.02, 95% CI: 1.01-1.03), SOFA score (HR: 1.2, 95% CI: 1.1-1.31), age >65 years (HR: 3.21, 95% CI: 1.95-5.3) were independent risk factor for trauma patients' mortality.
    Conclusion: The prevalence of sepsis and mortality was higher in trauma patients with HbA1c >6.5%. HbA1c was independent risk factor for sepsis and all cases of mortality in trauma patients.
    Keywords:  diabetes; emergency; glycosylated hemoglobin; mortality; sepsis; trauma
    DOI:  https://doi.org/10.2147/IDR.S307868
  10. Sci Rep. 2021 Jul 05. 11(1): 13803
    The impact of infection complications after trauma differs according to trauma severity.
    Akira Komori, Hiroki Iriyama, Takako Kainoh, Makoto Aoki, Toshio Naito, Toshikazu Abe.
      The impact of infection on the prognosis of trauma patients according to severity remains unclear. We assessed the impact of infection complications on in-hospital mortality among patients with trauma according to severity. This retrospective cohort study used a nationwide registry of trauma patients. Patients aged ≥ 18 years with blunt or penetrating trauma who were admitted to intensive care units or general wards between 2004 and 2017 were included. We compared the baseline characteristics and outcomes between patients with and without infection and conducted a multivariable logistic regression analysis to investigate the impact of infection on in-hospital mortality according to trauma severity, which was classified as mild [Injury Severity Score (ISS) < 15], moderate (ISS 15-29), or severe (ISS ≥ 30). Among the 150,948 patients in this study, 10,338 (6.8%) developed infections. Patients with infection had greater in-hospital mortality than patients without infection [1085 (10.5%) vs. 2898 (2.1%), p < 0.01]. After adjusting for clinical characteristics, in-hospital mortality differed between trauma patients with and without infection according to trauma severity [17.1% (95% CI 15.2-18.9%) vs. 2.9% (95% CI 2.7-3.1%), p < 0.01, in patients with mild trauma; 14.8% (95% CI 13.3-16.3%) vs. 8.4% (95% CI 7.9-8.8%), p < 0.01, in patients with moderate trauma; and 13.5% (95% CI 11.2-15.7%) vs. 13.7% (95% CI 12.4-14.9%), p = 0.86, in patients with severe trauma]. In conclusion, the effect of infection complications in patients with trauma on in-hospital mortality differs by trauma severity.
    DOI:  https://doi.org/10.1038/s41598-021-93314-5
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