BACKGROUND:Despite its central role in early trauma coagulopathy, abnormal fibrinolysis continues to be poorly understood. Excessive fibrinolysis is a known contributor to mortality. Recent studies ...with thromboelastography (TEG) suggest decreased fibrinolysis (or shutdown) may be just as harmful. Considering the broad use of 2 different viscoelastic assays, which are not interchangeable, we proposed for the first time to define and characterize fibrinolysis shutdown using rotational thromboelastometry (ROTEM).
METHODS:Retrospective cohort study of severely injured patients with admission ROTEM. Shutdown was defined by the best Youden index value of the maximum lysis. Fibrinolysis phenotypes were physiologic, hyperfibrinolysis, and shutdown. Multivariable logistic regression evaluated association between Injury Severity Score and the fibrinolysis phenotypes, and the association among shutdown phenotype with mortality, blood transfusion, and thrombotic events.
RESULTS:Five hundred fifty patients were included. Maximum lysis <3.5% was selected to define shutdown. Predominant phenotype was physiologic (70.7%), followed by shutdown (25.6%) and hyperfibrinolysis (3.6%). Shutdown patients had higher Injury Severity Score, lower base excess, and required more transfusions than physiologic group. Shutdown was associated with acidosis (base excessodds ratio OR for a 1 mEq/L increase, 0.93; 95% confidence interval CI, 0.88–0.98; P = .0094) and the combination of clotting derangements, higher clot firmness (maximum clot formationOR for a 2 mm increase, 1.8; 95% CI, 1.5–2.27; P < .0001), lower fibrinogen (OR for a 0.5 g/dL decrease, 1.47; 95% CI, 1.18–1.84; P = .0006), and poor clot formation dynamics (clot formation timeOR for a 5 seconds increase, 1.25; 95% CI, 1.15–1.36; P < .0001). Fibrinolysis shutdown was not independently associated with mortality (OR, 0.61; 95% CI, 0.28–1.33; P = .21), massive transfusion (OR, 2.14; 95% CI, 0.79–5.74; P = .1308), or thrombotic events (OR, 1.08; 95% CI, 0.37–3.15; P = .874). Shutdown was associated with increased 24-hour transfusion (OR, 2.24; 95% CI, 1.24–4.04; P = .007).
CONCLUSIONS:Despite higher injury burden, evidence of shock, and greater need for blood transfusions, early fibrinolysis shutdown was not associated with mortality, suggesting that it could represent an adaptive physiologic response to life-threatening trauma.
The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG®) and thromboelastometry (ROTEM®), which promptly evaluate the entire clotting process and may guide ...blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients.
We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG®/ROTEM® in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies.
Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG®/ROTEM® for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG® (n =12), ROTEM® (n = 18), TEG® (n = 23), or both TEG® and rapid TEG® (n = 2). Many TEG®/ROTEM® measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM®-based transfusion algorithm reduced blood-product transfusion, but TEG®/ROTEM®-based resuscitation was not associated with lower mortality in most studies.
Limited evidence from observational data suggest that TEG®/ROTEM® tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.
OBJECTIVE:To identify causes and timing of mortality in trauma patients to determine targets for future studies.
BACKGROUND:In trials conducted by the Resuscitation Outcomes Consortium in patients ...with traumatic hypovolemic shock (shock) or traumatic brain injury (TBI), hypertonic saline failed to improve survival. Selecting appropriate candidates is challenging.
METHODS:Retrospective review of patients enrolled in multicenter, randomized trials performed from 2006 to 2009. Inclusion criteria were as followsinjured patients, age 15 years or more with hypovolemic shock systolic blood pressure (SBP) ≤ 70 mm Hg or SBP 71–90 mm Hg with heart rate ≥ 108) or severe TBI Glasgow Coma Score (GCS) ≤ 8. Initial fluid administered was 250 mL of either 7.5% saline with 6% dextran 70, 7.5% saline or 0.9% saline.
RESULTS:A total of 2061 subjects were enrolled (809 shock, 1252 TBI) and 571 (27.7%) died. Survivors were younger than nonsurvivors 30 (interquartile range 23) vs 42 (34) and had a higher GCS, though similar hemodynamics. Most deaths occurred despite ongoing resuscitation. Forty-six percent of deaths in the TBI cohort were within 24 hours, compared with 82% in the shock cohort and 72% in the cohort with both shock and TBI. Median time to death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in patients with both. Sepsis and multiple organ dysfunction accounted for 2% of deaths.
CONCLUSIONS:Most deaths from trauma with shock or TBI occur within 24 hours from hypovolemic shock or TBI. Novel resuscitation strategies should focus on early deaths, though prevention may have a greater impact.
Viscoelastic tests (VETs), specifically thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are gaining popularity in the management of critically ill surgical patients with ...hemorrhage or thrombosis due to their comprehensive characterization of the coagulation process and point-of-care availability in comparison to conventional coagulation tests (CCTs). We review current evidence for VET use in patients in the surgical intensive care unit (SICU).
We searched PUBMED, EMBASE and the Cochrane Library through May 30, 2018 for articles that evaluated the use of VETs in patient populations and clinical scenarios germane to the surgical intensivist. Individual articles were critically evaluated for relevance and appropriate methodology using a structured technique. Information on patient characteristics, timing and methods of CCTs/VETs, and outcomes was collected and summarized in narrative form.
Of 2,589 identified articles, 36 were included. Five (14%) were interventional studies and 31 (86%) were observational. Twenty-five (69%) evaluated TEG, 11 (31%) ROTEM and 18 (50%) CCTs. Investigated outcomes included quantitative blood loss (13 (36%)), blood product transfusion (9 (25%)), thromboembolic events (9 (25%)) and mortality (6 (17%)). We identified 12 clinical scenarios with sufficient available evidence, much of which was of limited quantity and poor methodological quality. Nonetheless, research supports the use of VETs for guiding early blood product administration in severe traumatic hemorrhage and for the prediction of abstract excess bleeding following routine cardiac surgery. In contrast, evidence suggests VET-based heparin dosing strategies for venous thromboembolism prophylaxis are not superior to standard dosing in SICU patients.
While VETs have the potential to impact the care of critically ill surgical patients in many ways, current evidence for their use is limited, mainly because of poor methodological quality of most available studies. Further high-quality research, including several ongoing randomized controlled trials, is needed to elucidate the role of TEG/ROTEM in the SICU population.
Systematic review, level IV.
Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h ...post-trauma and functional outcome in patients with isolated moderate-to-severe TBI.
A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level.
At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome.
Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.
Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both ...within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome.
Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine interleukin (IL)-1β, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and chemokine IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, thymus activation regulated chemokine (TARC) concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines epinephrine (Epi), norepinephrine (NE) were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes.
Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1β, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1β, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1.
Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.
Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion ...molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.
Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL-10), tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group.
TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-alpha and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels.
These findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI.
NCT00878631.
Background
Early identification of patients who may need massive blood transfusion remains a major challenge in trauma care. This study proposed a novel and easy-to-calculate prediction score using ...clinical and point of care laboratory findings in patients with abdominal trauma (AT).
Methods
Patients with AT admitted to a trauma center in Qatar between 2014 and 2017 were retrospectively analyzed. The FASILA score was proposed and calculated using focused assessment with sonography in trauma (0 = negative, 1 = positive), Shock Index (SI) (0 = 0.50–0.69, 1 = 0.70–0.79, 2 = 0.80–0.89, and 3 ≥ 0.90), and initial serum lactate (0 ≤ 2.0, 1 = 2.0–4.0, and 2 ≥ 4.0 mmol/l). Outcome variables included mortality, laparotomy, and massive blood transfusion (MT). FASILA was compared to other prediction scores using receiver operating characteristics and areas under the curves. Bootstrap procedure was employed for internal validation.
Results
In 1199 patients with a mean age of 31 ± 13.5 years, MT, MT protocol (MTP) activation, exploratory laparotomy (ExLap), and hospital mortality were related linearly with the FASILA score, Injury Severity Score, and total length of hospital stay. Initial hemoglobin, Revised Trauma Score (RTS), and Trauma Injury Severity Score (TRISS) were inversely proportional. FASILA scores correlated significantly with the Assessment of Blood Consumption (ABC) (
r
= 0.65), Revised Assessment of Bleeding and Transfusion (RABT) (
r
= 0.63), SI (
r
= 0.72), RTS (
r
= − 0.34), and Glasgow Coma Scale (
r
= − 0.32) and outperformed other predictive systems (RABT, ABC, and SI) in predicting MT, MTP, ExLap, and mortality.
Conclusions
The novel FASILA score performs well in patients with abdominal trauma and offers advantages over other scores.
As trauma systems mature, they are expected to improve patient care, reduce in-hospital complications and optimize outcomes. Qatar has a single trauma center, at the Hamad General Hospital, which ...serves as the hub for the trauma system that was verified as a level 1 trauma system by the Accreditation Canada International Distinction program in 2014. We hypothesized that this international accreditation was a major step, in the maturation process of the Qatar trauma system, that has positively impacted patient care, reduced complications and improved outcomes of trauma patients in such a rapidly developing country.
A retrospective analysis of data was conducted for all trauma patients who were admitted between 2010 and 2018. Data were obtained from the level 1 trauma center registry at Hamad Medical Corporation. Patients were divided into Group 1- pre-accreditation (admitted from January 2010 to October 2014) and Group 2- post-accreditation (admitted from November 2014 to December 2018). Patients' characteristics and in-hospital outcomes were analyzed and compared. Data included patients' demographics; injury types, mechanism and injury severity scores, interventions, hospital stay, complications and mortality (pre-hospital and in-hospital). Time series analysis for mortality was performed using expert modeler.
Data from a total of 15,864 patients was collected and analyzed. Group 2 patients had more severe injuries in comparison to Group 1 (p<0.05). However, Group 2, had a lower complication rate (ventilator associated pneumonia (VAP)) and a shorter mean hospital length of stay (p<0.05). The overall mortality was 8%. In Group 2; the pre-hospital mortality was higher (52% vs. 41%, p = 0.001), while in-hospital mortality was lower (48% vs. 59%) compared to Group 1 (p = 0.001).
The international recognition and accreditation of the trauma center in 2014 was the key factor in the maturation of the trauma system that improved the in-hospital outcomes. Accreditation also brought other benefits including a reduction in VAP and hospital length of stay. However, further studies are required to explore the maturation process of all individual components of the trauma system including the prehospital setting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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