Factors associated with an unfavourable outcome in elderly intensive care traumatic brain injury patients. a retrospective multicentre study.

BACKGROUND: Changes in the epidemiology of traumatic brain injury (TBI) in older patients have received attention, but limited data are available on the outcome of these patients after admission to intensive care units (ICUs). The aim of this study was to evaluate the outcomes of patients over 65 years of age who were admitted to an ICU for TBI. METHODS: This was a multicentre, retrospective, observational study conducted from January 2013 to February 2019 in the surgical ICUs of 5 level 1 trauma centres in France. Patients aged ≥ 65 years who were hospitalized in the ICU for TBI with or without extracranial injuries were included. The main objective was to determine the risk factors for unfavourable neurological outcome at 3 months defined as an Extended Glasgow Outcome Scale (GOSE) score < 5. RESULTS: Among the 349 intensive care patients analysed, the GOSE score at 3 months was ≤ 4 and ≥ 5 in 233 (67%) and 116 (33%) patients, respectively. The mortality rate at 3 months was 157/233 (67%), and only 7 patients (2%) fully recovered or had minor symptoms. Withdrawal or withholding of life-sustaining therapies in the ICU was identified in 140 patients (40.1%). Multivariate analysis showed that age (OR 1.09, CI 95% 1.04-1.14), male sex (OR 2.94, CI95% 1.70-5.11), baseline Glasgow Coma Scale score (OR 1.20, CI95% 1.13-1.29), injury severity score (ISS; OR 1.04, CI95% 1.02-1.06) and use of osmotherapy (OR 2.42, CI95% 1.26-4.65) were associated with unfavourable outcomes (AUC = 0.79, CI 95% [0.74-0.84]). According to multivariate analysis, the variables providing the best sensitivity and specificity were age ≥ 77 years, Glasgow Coma Scale score ≤ 9 and ISS ≥ 25 (AUC = 0.79, CI 95% [0.74-0.84]). CONCLUSIONS: Among intensive care patients aged ≥ 65 years suffering from TBI, age (≥ 77 years), male sex, baseline Glasgow coma scale score (≤ 9), ISS (≥ 25) and use of osmotherapy were predictors of unfavourable neurological outcome. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04651803. Registered 03/12/2020. Retrospectively registered.

Short acting intravenous beta-blocker as a first line of treatment for atrial fibrillation after cardiac surgery: a prospective observational study.

Post-operative atrial fibrillation (POAF) defined as a new-onset of atrial fibrillation (AF) following surgery occurs frequently after cardiac surgery. For non-symptomatic patients, rate control strategy seems to be as effective as rhythm control one in surgical patients. Landiolol is a new highly cardio-selective beta-blocker agent with interesting pharmacological properties that may have some interest in this clinical situation. This is a prospective, monocentric, observational study. All consecutive adult patients (age >18 years old) admitted in the intensive care unit following cardiac surgery with a diagnosed episode of AF were eligible. Success of landiolol administration was defined by a definitive rate control from the beginning of infusion to the 72th h. We also evaluated rhythm control following landiolol infusion. Safety analysis was focused on haemodynamic, renal and respiratory side effects. From 1 January 2020 to 30 June 2021, we included 54 consecutive patients. A sustainable rate control was obtained for 49 patients (90.7%). Median time until a sustainable rate control was 4 h (1, 22). Median infusion rate of landiolol needed for a sustainable rate control was 10 µg/kg/min (6, 19). Following landiolol infusion, median time until pharmacological cardioversion was 24 h. During landiolol infusion, maintenance of mean arterial pressure target requires a concomitant very low dose of norepinephrine. We did not find any other side effects. Low dose of landiolol used for POAF treatment was effective and safe for a rapid and sustainable rate and rhythm control after cardiac surgery.

Protocol for a prospective cohort study on the use of clinical nutrition and assessment of long-term clinical and functional outcomes in critically ill adult patients.

BACKGROUND AND AIMS: Limited data are available on the impact of clinical nutrition over the course of critical illness and post-discharge outcomes. The present study aims to characterize the use of nutrition support in patients admitted to European intensive care units (ICUs), and its impact on clinical outcomes. Here we present the procedures of data collection and evaluation. METHODS: Around 100 medical, surgical, or trauma ICUs in 11 countries (Austria, Belgium, Czech Republic, Germany, France, Hungary, Italy, Poland, Spain, Sweden, United Kingdom) participate in the study. In defined months between November 2019 and April 2020, approximately 1250 patients are enrolled if staying in ICU for at least five consecutive days. Data from ICU day 1-4 are collected retrospectively, followed by a prospective observation period from day 5-90 after ICU admission. Data collection includes patient characteristics, nutrition parameters, complications, ICU and hospital length of stay, discharge status, and functional outcomes. For data analysis, the target is 1000 patients with complete data. Statistical analyses will be descriptive, with multivariate analyses adjusted for potential confounders to explore associations between nutritional balance and change in functional status, time-to-weaning from invasive mechanical ventilation, time to first clinical complication, and overall 15, 30 and 90-day survival. ETHICS AND DISSEMINATION: This non-interventional study was reviewed and approved by the ethics committee of the Medical University Vienna, Vienna, Austria (approval number 1678/2019), and the respective ethical committees from participating sites at country and/or local level, as required. Results will be shared with investigators on a country level, and a publication and results presentation at the 2021 ESPEN Congress is planned. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04143503.

Compliance with the European trauma guidelines: An observational single centre study.

OBJECTIVES: The European trauma guidelines were developed to assist clinicians in the early phase of trauma management to diagnose and treat coagulopathy and bleeding. This study aimed to determine compliance with these European trauma guidelines in a French referral trauma centre. METHODS: Medical charts of trauma patients with an injury severity score≥16 admitted between January 2013 and December 2014 were reviewed. Compliance with 21 recommendations in the first 24-hours of patient management was assessed. RESULTS: There were 145 patients with median ISS of 34 [IQR 25-41]. A good level of compliance (i.e. applied in≥80% of patients) was identified for nine recommendations, inconsistent compliance (i.e. applied in 50 to 79% of patients) for six recommendations, including fibrinogen levels at hospital admission and achievement of a target mean arterial blood pressure (MAP)>80mmHg in patients with major bleeding and TBI (55.5%), and poor compliance (i.e. applied in<50% of patients) for another six recommendations. Poorly applied recommendations included early measurement of lactate or base deficit (32%), early administration of tranexamic acid (18%), and achievement of normocapnia in patients with TBI undergoing invasive ventilation (3%). CONCLUSIONS: In a referral trauma centre, nine of the 21 evaluable recommendations in the European trauma guidelines were applied in≥80% of patients. Early diagnosis and treatment of trauma-related coagulopathy was identified as an area for significant practice improvement. In patients with TBI, efforts should be made to achieve the targeted MAP and to maintain normocapnia.

Induced mild hypothermia reduces mortality during acute inflammation in rats.

BACKGROUND: Hypothermia has been proposed as a therapeutic possibility in brain trauma, cardiac arrest and hemorrhagic shock. Experimental studies have shown that hypothermia may act by modulating the inflammatory response during endotoxemia. This study was carried out to test whether hypothermia could protect rats from endotoxemic insult. METHODS: After general anesthesia and oro-tracheal intubation, Sprague-Dawley rats were randomly assigned to either a hypothermic group or normothermic group. In each group, rats received intraperitoneal lipopolysaccharide (LPS) (10 or 20 mg/kg). Blood samples were taken prior to and 2 h after LPS injection to measure blood gases, liver enzymes, muscular enzymes, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) plasma levels. After 2 h of hypothermia, the rats were extubated and brought back to their cages. The mortality rate was observed for 7 days following endotoxemia. In a second set of experiments, hypothermia was induced 1 h after endotoxemia (10 mg/kg of intraperitoneal LPS) and the mortality rate was observed for the following 7 days. RESULTS: The survival rate was significantly increased in the hypothermic group relative to the normothermic group, regardless of LPS dose. This increased survival rate was also observed when hypothermia was induced 1 h after endotoxemia. In the hypothermic group, IL-10 and the DeltaIL-10/DeltaTNF-alpha ratio were significantly increased relative to those in the normothermic group. CONCLUSION: Induced mild hypothermia reduces mortality during endotoxemia in rats. The modulation of the inflammatory response, with an increase in anti-inflammatory cytokines, may be involved in this protective effect.

Flow cytometry's contribution to the measurement of cell functions.

Flow cytometry has important advantages over conventional techniques. It is rapid, highly sensitive and allows multi-parametric analysis and cell sorting. Potential exists for the measurement of many cell functions by flow cytometry. The technique can be used to determine cell viability, intracellular calcium and pH, membrane potential, enzyme activities, membrane fluidity and endocytosis. Numerous examples are given on the applications of flow cytometry for cell functions measurements in the fundamental and biomedical fields.

NADH-dependent dehydrogenase activity estimation by flow cytometric analysis of 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction.

MTT reduction is usually analysed by colorimetric assay to study mitochondrial dehydrogenase activity as a test of cytotoxicity. This enzymatic reaction produces dark-blue granules of formazan, which increase cell refringency. In this work, we define the conditions for MTT use in quantitative flow cytometric analysis. MTT reduction provides a non-fluorescent dye usable by this technique to study an intracellular NADH-dependent dehydrogenase activity in vital cells. We observe that formazan production increases asymptotically with cell concentration and that this temperature-dependent Michaelis enzymatic reduction is produced essentially by mitochondrial dehydrogenases. In isolated mitochondria from rat hepatocytes and in whole L1210 murine leukemia cells, the Michaelis constants (KM) observed in the presence of respiratory substrates were, respectively, 10 microM and 500 microM. The inhibition of mitochondrial protein synthesis by chloramphenicol, which induces a rise of MTT reduction due to the correlative stimulation of glycolysis (Pasteur effect), is a limit of the MTT assay as a cytotoxicity test.

Direct analysis and significance of cardiolipin transverse distribution in mitochondrial inner membranes.

The distribution of cardiolipin across the inner mitochondrial membrane was directly determined by using the ability of the fluorescent dye 10-N-nonyl-3,6-bis(dimethylamino)acridine (10-N-nonyl acridine orange) to form dimers when it interacts with the diacidic phospholipid. Two independent methods were employed: (a) a spectrophotometric measurement of 10-N-nonyl acridine orange binding to isolated rat liver mitochondria, mitoplasts and inside-out submitochondrial particles, and (b) a flow-cytometric analysis of specific red fluorescence, emitted when two dye molecules are bound to one membrane cardiolipin; the stoichiometry of 10-N-nonyl acridine orange binding to phosphatidylserine and phosphatidylinositol, 1 mol dye/mol phospholipid, prevented dye dimerisation and subsequent red-fluorescence appearance. 57% total cardiolipin was present in the outer leaflets of inner membranes of isolated organelles, a distribution confirmed by saturation measurements for mitoplasts and inside-out submitochondrial particles. The same asymmetry was directly observed in situ with mitochondrial membranes of quiescent L1210 cells, and with mitochondrial membranes of respiring yeasts. Nevertheless, alterations in ATP synthesis and inhibition of mitochondrial protein synthesis revealed that cardiolipin distribution was apparently tightly correlated with mitochondrial membrane assembly and activity.