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Background The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity ( p  = 0.64) or country income ( p  = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011.

The debate on replacing coagulation factors and its effect on the final outcome of the patients with acute traumatic coagulopathy (ATC) in need of transfusion is still ongoing. Therefore, the present study is designed with the aim of comparing the outcome of patients with acute traumatic coagulopathies receiving fibrinogen and fresh frozen plasma (FFP). In this quasi-experimental randomized controlled study, patients with severe blunt trauma (ISS>16) and in need of packed cells transfusion were divided into 3 groups of receiving fibrinogen, receiving FFP, and control, and their final outcome was compared. 90 patients with the mean age of 33.16±16.32years were randomly allocated to one of the 3 study groups (82.2% male). The 3 groups were similar regarding baseline characteristics. Patients receiving fibrinogen needed significantly less packed cells (p=0.044) and intravenous fluid in the initial 24h of hospitalization (p=0.022). In addition, mortality rate (p=0.029), need for admission to intensive care unit (p=0.020) and duration of hospitalization (p=0.045) were also lower in the group receiving fibrinogen. The number of sepsis cases in patients receiving fibrinogen and control group was lower than those who received FFP (p=0.001). The number of multiple organ failure cases in patients receiving fibrinogen was about one fourth of the other 2 groups (p=0.106), and a fewer number of them needed mechanical ventilation (p=0.191). No case of venous thrombosis was detected in any of the 3 groups. Multiple trauma patients in need of transfusion who received fibrinogen along with packed cells had significantly better outcomes regarding mortality, sepsis, need for admission to the intensive care unit, need for receiving packed cells, need for receiving intravenous fluids in the initial 24h, and duration of hospitalization.

Venous thromboembolism (VTE) is a leading cause of death in multisystem trauma patients; the importance of VTE prevention is well recognized. Presently, standard dose enoxaparin (30 mg BID) is used as chemical prophylaxis, regardless of weight or physiologic status. However, evidence suggests decreased bioavailability of enoxaparin in critically ill patients. Therefore, we hypothesized that a weight-based enoxaparin dosing regimen would provide more adequate prophylaxis (as indicated by antifactor Xa levels) for patients in our trauma intensive care unit (TICU).These data were prospectively collected in TICU patients admitted over a 5-month period given twice daily 0.6 mg/kg enoxaparin (actual body weight). Patients were compared with a historical cohort receiving standard dosing. Anti-Xa levels were collected at 11.5 hours (trough, goal ≥0.1 IU/mL) after each evening administration. Patient demographics, admission weight, dose, and daily anti-Xa levels were recorded. Patients with renal insufficiency or brain, spine, or spinal cord injury were excluded. Data were collected from 26 patients in the standard-dose group and 37 in the weight-based group. Sixty-four trough anti-Xa measurements were taken in the standard dose group and 74 collected in the weight-based group. Evaluating only levels measured after the third dose, the change in dosing of enoxaparin from 30 to 0.6 mg/kg resulted in an increased percentage of patients with goal antifactor Xa levels from 8 per cent to 61 per cent ( P < 0.0001). Examining all troughs, the change in dose resulted in an increase in patients with a goal anti-Xa level from 19 to 59 per cent ( P < 0.0001). Weight-based dosing of enoxaparin in trauma ICU patients yields superior results with respect to adequate anti-Xa levels when compared with standard dosing. These findings suggest that weight-based dosing may provide superior VTE prophylaxis in TICU patients. Evaluation of the effects of this dosing paradigm on actual VTE rate is ongoing at our institution.

Multiple trauma can cause an increase in creatine phosphokinase (CPK) and subsequently rhabdomyolysis and acute kidney injury (AKI). This study was designed to evaluate the effect of vitamin D3 on the serum CPK level and the incidence of rhabdomyolysis-induced AKI in patients with multiple trauma. Patients with serum CPK levels <1000 IU/L were followed as the control 1 group. Subjects with serum CPK levels ≥1000 IU/L were randomly allocated to the control 2 or intervention group at Imam Hossein Medical Center, Tehran, Iran in 2020. Patients in the intervention group received a single dose of vitamin D3 (300,000 units) on the recruitment day. The serum level of CPK was recorded every 3 days for 14 days. Parametric and non-parametric tests were used to compare the CPK values between groups. Forty-six patients, consisting of 16, 15, and 15 in control 1, control 2, and intervention arms of the study were recruited, respectively. Unlike control groups, the significant steadily decreasing trend was seen only in the intervention group (P<0.001). This significant decrease in the intervention arm was observed on days 5 to 7 (P=0.001) and on days 8 to 10 (P<0.001) compared to the baseline. Patients in the intervention group had a lower number of AKI or need for dialysis (P=0.869 and P=0.670 for AKI and dialysis, respectively) than control group 2, although the differences were not significant. The current study revealed that vitamin D3, could prevent the increasing trend of CPK during the first days and accelerate the normalization of CPK in patients with elevated CPK due to multiple trauma. IRCT20120703010178N23.

Background Since probiotics are considered to exert beneficial health effects by enhancing the host’s immune response, we investigated the benefits of a synbiotics treatment on the rate of infections, systemic inflammatory response syndrome (SIRS), severe sepsis, and mortality in critically ill, mechanically ventilated, multiple trauma patients. Length of stay in the intensive care unit (ICU) and number of days under mechanical ventilation were also evaluated. Method Sixty‐five patients were randomized to receive once daily for 15 days a synbiotic formula (Synbiotic 2000Forte, Medipharm, Sweden) or maltodextrin as placebo. The synbiotic preparation consisted of a combination of four probiotics (1011 CFU each):Pediococcus pentosaceus 5–33:3, Leuconostocmesenteroides 32–77:1, L.paracasei ssp.paracasei 19; and L. plantarum 2,362; and inulin, oat bran, pectin, and resistant starch as prebiotics. Infections, septic complications, mortality, days under ventilatory support, and days of stay in ICU were recorded. Results Synbiotic‐treated patients exhibited a significantly reduced rate of infections (P = 0.01), SIRS, severe sepsis (P = 0.02), and mortality. Days of stay in the ICU (P = 0.01) and days under mechanical ventilation were also significantly reduced in relation to placebo (P = 0.001). Conclusion The administration of this synbiotic formula in critically ill, mechanically ventilated, multiple trauma patients seems to exert beneficial effects in respect to infection and sepsis rates and to improve the patient’s response, thus reducing the duration of ventilatory support and intensive care treatment.

To determine how immediate enteral nutrition (EN) affects gut permeability and the development of multiple organ failure (MOF) in multiply injured patients. Prospective, randomised clinical trial. 20-bed surgical intensive care unit (ICU), university hospital. 28 consecutive multiply injured patients, admitted in shock and stabilised in 6 h. Patients were randomly assigned to EN started not later than 6 h after admission to the ICU (group A), and to EN started later than 24 h after admission (group B). The lactulose/mannitol (L/M) test was performed in patients on days 2 and 4 after trauma, and in 5 healthy volunteers. MOF scores were calculated daily. The mean MOF score from day 4 onwards was 1.84 in group A versus 2.81 in group B (p < 0.002), and was correlated with the time of initiation of EN after injury and the L/M ratio on day 2. The median L/M ratio on day 2 was 0.029 for group A and 0.045 for group B, while on day 4 it was 0.020 and 0.060, respectively. On day 2 after trauma, the L/M ratio was significantly higher in group B (p < 0.05) than in normal volunteers (median 0.014) and was positively correlated with the time of starting EN. In contrast with normal volunteers, the patients started on EN later than 24 h after admission to the ICU demonstrated increased intestinal permeability on the second day after sustaining multiple injury. Also, they had a more severe form of MOF than the group placed on EN immediately upon admission. However, early EN had no influence on the length of ICU stay or the time of mechanical ventilation.

Background Many studies have established intravenous corticosteroid as an effective prophylactic therapy in fat embolism syndrome (FES). However, its use is limited among surgeons because of systemic side effects. Inhalational steroids have least systemic effects and are widely used for several chest conditions (i.e., asthma), but their effectiveness in FES has not been established. Question/purpose This study was sought to evaluate the (1) efficacy and (2) safety of inhalational Ciclesonide (CIC) in prevention of FES and treatment of hypoxemia in isolated skeletal trauma victims. Methods A nonrandomized prospective control trial was designed in which all patients between 18 and 40 years with isolated skeletal injury who presented within 8 h of injury were allocated to either Trial group or control group. Trial group patients received 640 mcg of inhalational CIC with a metered-dose inhaler at the time of admission, and at 24 h. Control group patients did not receive any prophylactic therapy. Both groups were evaluated for development of FES (Gurd’s criteria) and hypoxemia (PaO 2 <70 mmHg) for 72 h. The complications related to CIC administration were evaluated in trial group patients during their hospital stay. Results Of 35 patients in each group, two patients in Trial group and nine patients in control group developed FES ( P  = 0.022). Eight patients in Trial group had hypoxemia at the time of admission, six of them improved and one additional patient developed hypoxemia after inhalational CIC administration. In control group, ten patients had hypoxia at the time of admission, only one of them improved and remaining nine patients had persistent hypoxemia even after 72 h. Additionally, three patients developed hypoxemia. A significant improvement in hypoxemia and a significant decrease in the incidence of FES were observed in Trial group ( P  < 0.05) compared to control group. None of the patients presented with any complications or adverse effects of steroid in Trial group. Conclusion Inhalational CIC is a safe and effective therapy for prevention of FES and also an effective drug for treatment of hypoxemia in orthopedic trauma victims. Level of evidence Level III, therapeutic study.

Early accurate assessment of the clinical status of severely injured patients is crucial for guiding the surgical treatment strategy. Several scales are available to differentiate between risk categories. They vary between expert recommendations and scores developed on the basis of patient data (level II). We compared four established scoring systems in regard to their predictive abilities for early (e.g., hemorrhage-induced mortality) versus late (Multiple Organ Failure (MOF), sepsis, late death) in-hospital complications. A database from a level I trauma center was used. The inclusion criteria implied an injury severity score (ISS) of ≥16 points, primary admission, and a complete data set from admission to hospital-day 21. The following four scales were tested: the clinical grading scale (CGS; covers acidosis, shock, coagulation, and soft tissue injuries), the modified clinical grading scale (mCGS; covers CGS with modifications), the polytrauma grading score (PTGS; covers shock, coagulation, and ISS), and the early appropriate care protocol (EAC; covers acid-base changes). Admission values were selected from each scale and the following endpoints were compared: mortality, pneumonia, sepsis, death from hemorrhagic shock, and multiple organ failure. Shapiro-Wilk test for normal distribution, Pearson Chi square, odds ratios (OR) for all endpoints, 95% confidence intervals. Fitted, generalized linear models were used for prediction analysis. Krippendorff was used for comparison of CGS and mCGS. Alpha set at 0.05. In total, 3668 severely injured patients were included (mean age, 45.8±20 years; mean ISS, 28.2±15.1 points; incidence of pneumonia, 19.0%; incidence of sepsis, 14.9%; death from hem. shock, 4.1%; death from multiple organ failure (MOF), 1.9%; mortality rate, 26.8%). Our data show distinct differences in the prediction of complications, including mortality, for these scores (OR ranging from 0.5 to 9.1). The PTGS demonstrated the highest predictive value for any late complication (OR = 2.0), sepsis (OR = 2.6, p = 0.05), or pneumonia (OR = 2.0, p = 0.2). The EAC demonstrated good prediction for hemorrhage-induced early mortality (OR = 7.1, p<0.0001), but did not predict late complications (sepsis, OR = 0.8 and p = 0.52; pneumonia, OR = 1.1 and p = 0.7) CGS and mCGS are not comparable and should not be used interchangeably (Krippendorff α = 0.045). Our data show that prediction of complications is more precise after using values that covers different physiological systems (coagulation, hemorrhage, acid-base changes, and soft tissue damage) when compared with using values of only one physiological system (e.g., acidosis). When acid-base changes alone were tested in terms of complications, they were predictive of complications within 72 hours but failed to predict late complications. These findings should be considered when performing early assessment of trauma patients or for the development of new scores.

Minimal literature correlates stroke rates in blunt cerebrovascular injury (BCVI) to bilaterality, multi-vessel injury, or multifocal injury. We hypothesized that a synchronous cerebrovascular injury and a higher-grade injury would increase stroke rates. A single-center retrospective (1/2016-12/2023) review was conducted identifying patients with BCVI. Injury characteristics, clinical features, and demographic data were collected and statistically modeled in relation to stroke risk. Stroke rate in our cohort was 3.7 ​%. Higher-grade injuries increased the odds of stroke in carotid and vertebral BCVIs. The odds of stroke also increased with combined carotid and vertebral BCVIs versus isolated vertebral injury (OR 3.9 [1.4–10.2]), but not with bilateral carotid (OR 1.5 [0.5–3.9]) or vertebral injuries (OR 1.0 [0.3–2.8]). Our findings support previous data on the relationship between BCVI grade and stroke risk; however, combined vertebral and carotid injuries may also increase the risk. •Higher-grade injuries increase the odds of stroke in both carotid and vertebral BCVI.•Combined carotid and vertebral BCVI increase the odds of stroke.•Bilaterality of carotid or vertebral BCVI does not impact stroke risk.•Antiplatelet/anticoagulant prophylaxis may help prevent strokes in patients with carotid BCVI.

Background Accidental hypothermia is a known predictor for worse outcomes in trauma patients, but has not been comprehensively assessed in a meta-analysis so far. The aim of this systematic review and meta-analysis was to investigate the impact of accidental hypothermia on mortality in trauma patients overall and patients with traumatic brain injury (TBI) specifically. Methods This is a systematic review and meta-analysis using the Ovid Medline/PubMed database. Scientific articles reporting accidental hypothermia and its impact on outcomes in trauma patients were included in qualitative synthesis. Studies that compared the effect of hypothermia vs. normothermia at hospital admission on in-hospital mortality were included in two meta-analyses on (1) trauma patients overall and (2) patients with TBI specifically. Meta-analysis was performed using a Mantel–Haenszel random-effects model. Results Literature search revealed 264 articles. Of these, 14 studies published 1987–2018 were included in the qualitative synthesis. Seven studies qualified for meta-analysis on trauma patients overall and three studies for meta-analysis on patients with TBI specifically. Accidental hypothermia at admission was associated with significantly higher mortality both in trauma patients overall (OR 5.18 [95% CI 2.61–10.28]) and patients with TBI specifically (OR 2.38 [95% CI 1.53–3.69]). Conclusions In the current meta-analysis, accidental hypothermia was strongly associated with higher in-hospital mortality both in trauma patients overall and patients with TBI specifically. These findings underscore the importance of measures to avoid accidental hypothermia in the prehospital care of trauma patients.