Project description:Trauma induces a “genomic storm” of gene expression in circulating leukocytes. We hypothesized that the neutrophil contribution to this response after blunt trauma varies with the magnitude of physiologic insult and with exposure to additional and subsequent inflammatory stimuli.
Project description:BackgroundExposure to anesthetics is common in the majority of early survivors of life-threatening injuries. Whether and to what degree general anesthetics influence outcomes from major trauma is unknown. Potential confounding effects of general anesthetics on outcome measures are usually disregarded. We hypothesized that exposure to isoflurane or sevoflurane modulates the outcome from blunt trauma with traumatic brain injury (bTBI).MethodsWe tested the hypothesis in a novel model of bTBI implemented in Drosophila melanogaster. Fruit flies of the standard laboratory strain w were cultured under standard conditions. We titrated the severity of bTBI to a mortality index at 24 hours (MI24) of approximately 20% under control conditions. We administered standard doses of isoflurane and sevoflurane before, before and during, or after bTBI and measured the resulting MI24. We report the MI24 as mean ± standard deviation.ResultsIsoflurane or sevoflurane administered for 2 hours before bTBI reduced the MI24 from 22.3 ± 2.6 to 10.4 ± 1.8 (P < 10, n = 12) and from 19.3 ± 0.9 to 8.9 ± 1.1 (P < .0001, n = 8), respectively. In contrast, administration of isoflurane after bTBI increased the MI24 from 18.5% ± 4.3% to 25.3% ± 9.1% (P = .0026, n = 22), while sevoflurane had no effect (22.4 ± 7.1 and 21.5 ± 5.8, n = 22).ConclusionsIn a whole animal model of bTBI, general anesthetics were not indifferent with respect to early mortality. Therefore, collateral effects of general anesthetics should be considered in the interpretation of results obtained in vertebrate trauma models. Invertebrate model organisms can serve as a productive platform to interrogate anesthetic targets that mediate collateral effects and to inform trauma research in higher organisms about the potential impact of anesthetics on outcomes.
Project description:BackgroundBeta-blockers have been proven in multiple studies to be beneficial in patients with traumatic brain injury. Few prospective studies have verified this and no randomized controlled trials. Additionally, most studies do not titrate the dose of beta-blockers to therapeutic effect. We hypothesize that propranolol titrated to effect will confer a survival benefit in patients with traumatic brain injury.MethodsA randomized controlled pilot trial was performed during a 24-month period. Patients with traumatic brain injury were randomized to propranolol or control group for a 14-day study period. Variables collected included demographics, injury severity, physiologic parameters, urinary catecholamines, and outcomes. Patients receiving propranolol were compared with the control group.ResultsOver the study period, 525 patients were screened, 26 were randomized, and 25 were analyzed. Overall, the mean age was 51.3 years and the majority were male with blunt mechanism. The mean Injury Severity Score was 21.8 and median head Abbreviated Injury Scale score was 4. Overall mortality was 20.0%. Mean arterial pressure was higher in the treatment arm as compared with control (p=0.021), but no other differences were found between the groups in demographics, severity of injury, severity of illness, physiologic parameters, or mortality (7.7% vs. 33%; p=0.109). No difference was detected over time in any variables with respect to treatment, urinary catecholamines, or physiologic parameters. Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation scores all improved over time. GCS at study end was significantly higher in the treatment arm (11.7 vs. 8.9; p=0.044). Finally, no difference was detected with survival analysis over time between groups.ConclusionsDespite not being powered to show statistical differences between groups, GCS at study end was significantly improved in the treatment arm and mortality was improved although not at a traditional level of significance. The study protocol was safe and feasible to apply to an appropriately powered larger multicenter study.Level of evidenceLevel 2-therapeutic.
Project description:IntroductionSevere blunt trauma is a leading cause of premature death and handicap. However, the benefit for the patient of pre-hospital management by emergency physicians remains controversial because it may delay admission to hospital. This study aimed to compare the impact of medical pre-hospital management performed by SMUR (Service Mobile d'Urgences et de Réanimation) with non-medical pre-hospital management provided by fire brigades (non-SMUR) on 30-day mortality.MethodsThe FIRST (French Intensive care Recorded in Severe Trauma) study is a multicenter cohort study on consecutive patients with severe blunt trauma requiring admission to university hospital intensive care units within the first 72 hours. Initial clinical status, pre-hospital life-sustaining treatments and Injury Severity Scores (ISS) were recorded. The main endpoint was 30-day mortality.ResultsAmong 2,703 patients, 2,513 received medical pre-hospital management from SMUR, and 190 received basic pre-hospital management provided by fire brigades. SMUR patients presented a poorer initial clinical status and higher ISS and were admitted to hospital after a longer delay than non-SMUR patients. The crude 30-day mortality rate was comparable for SMUR and non-SMUR patients (17% and 15% respectively; P = 0.61). After adjustment for initial clinical status and ISS, SMUR care significantly reduced the risk of 30-day mortality (odds ratio (OR): 0.55, 95% CI: 0.32 to 0.94, P = 0.03). Further adjustments for the delay to hospital admission only marginally affected these results.ConclusionsThis study suggests that SMUR management is associated with a significant reduction in 30-day mortality. The role of careful medical assessment and intensive pre-hospital life-sustaining treatments needs to be assessed in further studies.
Project description:Noradrenergic pathways are involved in mediating the central and peripheral effects of physiological arousal. The aim of the present study was to investigate the role of noradrenergic transmission in moral decision-making. We studied the effects in healthy volunteers of propranolol (a noradrenergic beta-adrenoceptor antagonist) on moral judgement in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person) in a double-blind, placebo-controlled, parallel group design. Propranolol (40 mg orally) significantly reduced heart rate, but had no effect on self-reported mood. Importantly, propranolol made participants more likely to judge harmful actions as morally unacceptable, but only in dilemmas where harms were 'up close and personal'. In addition, longer response times for such personal dilemmas were only found for the placebo group. Finally, judgments in personal dilemmas by the propranolol group were more decisive. These findings indicate that noradrenergic pathways play a role in responses to moral dilemmas, in line with recent work implicating emotion in moral decision-making. However, contrary to current theorising, these findings also suggest that aversion to harming is not driven by emotional arousal. Our findings are also of significant practical interest given that propranolol is a widely used drug in different settings, and is currently being considered as a potential treatment for post-traumatic stress disorder in military and rescue service personnel.
Project description:Catecholamine upregulation is a core pathophysiological feature in critical illness. Sustained catecholamine β-adrenergic induction produces adverse effects relevant to critical illness management. β-blockers (βB) have proposed roles in various critically ill disease states, including sepsis, trauma, burns, and cardiac arrest. Mounting evidence suggests βB improve hemodynamic and metabolic parameters culminating in decreased burn healing time, reduced mortality in traumatic brain injury, and improved neurologic outcomes following cardiac arrest. In sepsis, βB appear hemodynamically benign after acute resuscitation and may augment cardiac function. The emergence of ultra-rapid βB provides new territory for βB, and early data suggest significant improvements in mitigating atrial fibrillation in persistently tachycardic septic patients. This review summarizes the evidence regarding the pharmacotherapeutic role of βB on relevant pathophysiology and clinical outcomes in various types of critical illness.
Project description:ObjectiveTo examine associations of patient and injury characteristics with outcomes at inpatient rehabilitation discharge and 9 months postdischarge for patients with traumatic brain injury (TBI).DesignProspective, longitudinal observational study.SettingInpatient rehabilitation centers.ParticipantsConsecutive patients (N=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation after index TBI, and divided into 5 subgroups based on rehabilitation admission FIM cognitive score.InterventionsNot applicable.Main outcome measuresRehabilitation length of stay, discharge to home, and FIM at discharge and 9 months postdischarge.ResultsSeverity indices increased explained variation in outcomes beyond that accounted for by patient characteristics. FIM motor scores were generally the most predictable. Higher functioning subgroups had more predictable outcomes then subgroups with lower cognitive function at admission. Age at injury, time from injury to rehabilitation admission, and functional independence at rehabilitation admission were the most consistent predictors across all outcomes and subgroups.ConclusionsFindings from previous studies of the relations among patient and injury characteristics and rehabilitation outcomes were largely replicated. Discharge outcomes were most strongly associated with injury severity characteristics, whereas predictors of functional independence at 9 months postdischarge included both patient and injury characteristics.
Project description:PurposeDementia, present in 20% of hip fracture patients, is associated with an almost threefold increase in postoperative mortality risk. These patients have a substantially higher incidence of cardiovascular, respiratory, and cerebrovascular mortality after hip fracture surgery compared to patients without dementia. This study aimed to investigate the association between beta-blocker therapy and postoperative mortality in patients with dementia undergoing hip fracture surgery.MethodsThis nationwide study included all patients in Sweden with the diagnosis of dementia who underwent emergency surgery for a hip fracture between January 2008 and December 2017. Cases where the hip fracture was pathological or conservatively managed were not included. Poisson regression analysis with robust standard errors was performed while controlling for confounders to determine the relationship between beta-blocker therapy and all-cause, as well as cause-specific, postoperative mortality.ResultsA total of 26,549 patients met the study inclusion criteria, of whom 8258 (31%) had ongoing beta-blocker therapy at time of admission. After adjusting for clinically relevant variables, the incidence of postoperative mortality in patients receiving beta-blocker therapy was decreased by 50% at 30 days [adj. IRR (95% CI) 0.50 (0.45-0.54), p < 0.001] and 34% at 90 days [adj. IRR (95% CI) 0.66 (0.62-0.70), p < 0.001]. Cause-specific mortality analysis demonstrated a significant reduction in the incidence of postoperative cardiovascular, respiratory, and cerebrovascular death within 30 and 90 days postoperatively.ConclusionBeta-blocker therapy is associated with decreased postoperative mortality in hip fracture patients with dementia up to 90 days after surgery. This finding warrants further investigation.
Project description:OBJECTIVE:We tested whether Cushing's sign could predict severe traumatic brain injury (TBI) requiring immediate neurosurgical intervention (BI-NSI) in children after blunt trauma. DESIGN:Retrospective cohort study using Japan Trauma Data Bank. SETTING:Emergency and critical care centres in secondary and tertiary hospitals in Japan. PARTICIPANTS:Children between the ages of 2 and 15 years with Glasgow Coma Scale motor scores of 5 or less at presentation after blunt trauma from 2004 to 2015 were included. A total of 1480 paediatric patients were analysed. PRIMARY OUTCOME MEASURES:Patients requiring neurosurgical intervention within 24 hours of hospital arrival and patients who died due to isolated severe TBI were defined as BI-NSI. The combination of systolic blood pressure (SBP) and heart rate (HR) on arrival, which were respectively divided into tertiles, and its correlation with BI-NSI were investigated using a multiple logistic regression model. RESULTS:In the study cohort, 297 (20.1%) exhibited BI-NSI. After adjusting for sex, age category and with or without haemorrhage shock, groups with higher SBP and lower HR (SBP ≥135 mm Hg; HR ≤92 bpm) were significantly associated with BI-NSI (OR 2.84, 95% CI 1.68 to 4.80, P<0.001) compared with the patients with normal vital signs. In age-specific analysis, hypertension and bradycardia were significantly associated with BI-NSI in a group of 7-10 and 11-15 years of age; however, no significant association was observed in a group of 2-6 years of age. CONCLUSIONS:Cushing's sign after blunt trauma was significantly associated with BI-NSI in school-age children and young adolescents.