Surveillance des intoxications médicamenteuses volontaires aux urgences par capnographie (présentation d une analyse intermédiaire)

Introduction : La sévérité des intoxications médicamenteuses volontaires (IMV) est difficilement prévisible, environ 5% des patients admis aux urgences sont transférés en réanimation. La capnographie non invasive (EtCO2) permet d identifier les complications respiratoires lors de la sédation aux urgences et pourrait être utile à la surveillance des patients présentant une IMV. Méthodes : Nous avons évalué, de façon prospective et en aveugle, les performances prédictives de la mesure de l EtCO2 pour la détection des complications précoces chez les patients admis aux urgences pour IMV. Nous présentons une analyse intermédiaire de cette étude. Résultats : Du 20/04/2012 au 20/02/2013, 104 patients ont été inclus dont 94 avec des mesures analysables. La concordance entre EtCO2 et PaCO2 montrait un biais moyen de -2,7 mmHg et des limites d agrément entre -11,8 mmHg et +6,5 mmHg. Quinze patients ont présenté au moins une complication. Une EtCO2>= 50mmHg permettait de prédire la survenue d une complication avec une sensibilité de 46.6% [IC95%: 22,3 ; 72,8] et une spécificité de 75.9 % [IC95%: 64.8 ; 84.6], une valeur prédictive positive de 0,27 [IC95% : 0,19 ; 0,38] et une valeur prédictive négative de 0,88 [IC95% : 0,78 ; 0,94]. L aire sous la courbe ROC (AUC) de l EtCO2 maximale au cours des 30 premières minutes d hospitalisation était de 0,74 [IC95% : 0,62;0,86]. La mesure de l EtCO2 n était pas plus performante que le score de Glasgow initial (AUC : 0,76 [IC95%: 0,61;0,91]). Conclusion : D après ces résultats intermédiaires, la mesure continue de l EtCO2 seule ne permet pas de prédire de façon satisfaisante les complications précoces des patients admis aux urgences pour IMV.Introduction: The severity of drug self-poisoning patients can be difficult to assess, and approximately 5% of patients who are admitted to the emergency department (ED) are secondarily transferred to intensive care unit (ICU). Non-invasive capnography (EtCO2) can identify respiratory complications during procedural sedation in the ED and could be useful in the monitoring of poisoned patients. Methods: This prospective and blind study was conducted in a single ED to evaluate the predictive values of EtCO2 measurements for the detection of complications in adult drug self-poisoning patients. Here we report the preliminary results of this study. Results: From 20/04/2012 to 20/02/2013, 104 patients were enrolled including 94 patients with measurable EtCO2. The correlation between EtCO2 and PaCO2 showed an estimated bias of -2,7 mmHg and limits of agreement between -11.8 mmHg and 6.5 mmHg. 15 patients exhibited at least one complication. EtCO2>=50mmHg predicted the occurrence of a complication with a sensitivity of 46.6% [95% CI: 22.3, 72.8] and a specificity of 75.9% [95% CI: 64.8, 84.6], which lead to a positive predictive value of 0.27 [95% CI: 0.19, 0.38] and a negative predictive value of 0.88 [95% CI: 0.78, 0.94]. The area under the Receiver Operating Characteristic curve (AUC) of the highest EtCO2 during the first 30 minutes of hospitalization was 0.74 [95% CI: 0.620, 0.864]. Glasgow Coma Scale at admission was as powerful as EtCO2 to detect complications (AUC: 0.76 [95% CI: 0.61, 0.91]). Conclusion: According to these preliminary results, the monitoring of EtCO2 alone cannot adequately predict early complications in self-poisoned patients referred to the ED.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Intranasal sufentanil versus intravenous morphine for acute severe trauma pain: A double-blind randomized non-inferiority study.

BACKGROUND: Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM. METHODS AND FINDINGS: In a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 μg/kg and additional doses of 0.15 μg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was -1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was -4.1 (97.5% CI -4.6 to -3.6) in the IVM group and -5.2 (97.5% CI -5.7 to -4.6) in the INS group. Non-inferiority was demonstrated (p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of -1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings. CONCLUSIONS: We confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presenting to an emergency department. The IN route, with no need to obtain a venous route, may allow early and effective analgesia in emergency settings and in difficult situations. Confirmation of the safety profile of INS will require further larger studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02095366. EudraCT 2013-001665-16

Pain and Fatty liver disease, underestimated systemic manifestations of COPD

La bronchopneumopathie chronique obstructive (BPCO) est une des maladies chroniques les plus fréquentes et constitue une des premières causes de mortalité dans le monde avec un impact sociétal majeur et des couts de santé considérables. La BPCO est aujourd’hui considérée comme une maladie multi-systémique dont le pronostic est lié en grande partie à ses comorbidités et à la survenue d’exacerbations. Les exacerbations qui vont ponctuer l’évolution de la BPCO précipitent le déclin de la fonction respiratoire et favorisent la décompensation des comorbidités et la survenue d’événements cardiovasculaires comme des infarctus du myocarde ou des accidents vasculaires cérébraux. La prise en charge moderne de la BPCO est basée sur la mise en place d’un soin intégré incluant la prise en charge des comorbidités et une meilleure détection et gestion des exacerbations.Dans ce travail de thèse nous abordons l’atteinte hépatique (stéatopathie hépatique non alcoolique - NAFLD) dans la BPCO comme une comorbidité sous-estimée (publication 1) alors qu’elle a probablement des implications pronostiques importantes (publication 2). La BPCO s'accompagne également de symptômes non respiratoires tel que des douleurs, dont les variations et localisations sont peu connues pendant et après l'exacerbation (publication 3). Le traitement de ces douleurs par des opiacés pourrait avoir un effet spécifiquement délétère dans cette population (publication 5). Les enjeux de réforme du système de santé avec une optimisation cout-efficacité incitent à développer et valider de nouvelles méthodes de prise en charge ambulatoire des exacerbations (publication 6).Dans une première partie de la thèse nous explorons les liens épidémiologiques entre BPCO et NAFLD. Nous explorerons également les conséquences d’une telle association sur le devenir cardiovasculaire des patients à moyen terme. Dans une deuxième partie, nous cherchons à définir les caractéristiques des douleurs avant et après exacerbation au cours de la BPCO, le lien entre douleur, anxiété et dépression chez ces patients et la sécurité d'emploi des morphiniques dans cette population fragile. Dans une dernière partie, nous aborderons la stratification du risque lié à une exacerbation de BPCO, et la possibilité d’une prise en charge ambulatoire extrahospitalière pour les exacerbations de sévérité modérée.Chronic Obstructive Pulmonary Disease (COPD) is one of the most common chronic diseases and is one of the leading causes of death in the world with major societal impact and considerable health costs. COPD is now considered a multi-systemic disease whose prognosis is largely related to its comorbidities and the occurrence of exacerbations. The exacerbations that punctuate the evolution of COPD precipitate the decline of respiratory function and promote the decompensation of comorbidities and the occurrence of cardiovascular events such as myocardial infarction or cerebrovascular accidents. The modern management of COPD is based on the implementation of integrated care including the management of comorbidities and better detection and management of exacerbations.In this thesis we address liver injury (non-alcoholic fatty liver disease - NAFLD) in COPD as an underestimated comorbidity (publication 1), although it probably has important prognostic implications (publication 2). COPD is also associated with non-respiratory symptoms such as pain, the variations and locations of which are poorly known during and after exacerbation (publication 3). Treatment of this pain with opiates may have a specifically deleterious effect in this population (publication 5). The challenges of health system reform with cost-effectiveness optimization encourage the development and validation of new methods of outpatient management of exacerbations (publication 6).In a first part of the thesis we explore the epidemiological links between COPD and NAFLD. We will also explore the consequences of such an association on the cardiovascular outcome of patients in the medium term. In a second part, we seek to define the characteristics of pain before and after exacerbation during COPD, the link between pain, anxiety and depression in these patients and the safety of opioids in this fragile population. In the last part, we will discuss the stratification of the risk linked to an exacerbation of COPD, and the possibility of outpatient care for exacerbations of moderate severity

A modified Sequential Organ Failure Assessment score using the Richmond Agitation-Sedation Scale in critically ill patients

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Major gastrointestinal bleeding and antithrombotics: Characteristics and management

International audienceBACKGROUND There are few reports on major gastrointestinal (GI) bleeding among patients receiving an antithrombotic. AIM To describe clinical characteristics, bleeding locations, management and in-hospital mortality related to these events.METHODS Over a three-year period, we prospectively identified 1080 consecutive adult patients admitted in two tertiary care hospitals between January 1, 2013 and December 31, 2015 for major GI bleeding while receiving an antithrombotic. The bleeding events were medically validated. Clinical characteristics, causative lesions, management and fatalities were described. The distribution of antithrombotics prescribed was compared across the bleeding lesions identified.RESULTS Of 576 patients had symptoms of upper GI bleeding and 504 symptoms of lower GI bleeding. No cause was identified for 383 (35.5%) patients. Gastro-duodenal ulcer was the first causative lesion in the upper tract (209 out of 408) and colonic diverticulum the first causative lesion in the lower tract (120 out of 289). There was a larger proportion of direct oral anticoagulant use among patients with lower GI than among those with upper GI lesion locations (P= 0.03). There was an independent association between gastro-duodenal ulcer and antithrombotic use (P= 0.03), taking account of confounders and proton pump inhibitor co-prescription. Pair wise comparisons pointed to a difference between vitamin K antagonist, direct oral anticoagulants, and antiplatelet agents in monotherapyvsdual antiplatelet agents.CONCLUSION We showed a higher rate of bleeding lesion identification and suggested a different pattern of antithrombotic exposure between upper and lower GI lesion locations and between gastro-duodenal ulcer and other identified upper GI causes of bleeding. Management was similar across antithrombotics and in-hospital mortality was low (5.95%)

Remote Monitoring for Prediction and Management of Acute Exacerbations in Chronic Obstructive Pulmonary Disease (AECOPD)

International audienceThe progression of chronic obstructive pulmonary disease (COPD) is characterized by episodes of acute exacerbation (AECOPD) of symptoms, decline in respiratory function, and reduction in quality-of-life increasing morbi-mortality and often requiring hospitalization. Exacerbations can be triggered by environmental exposures, changes in lifestyle, and/or physiological and psychological factors to greater or lesser extents depending on the individual’s COPD phenotype. The prediction and early detection of an exacerbation might allow patients and physicians to better manage the acute phase. We summarize the recent scientific data on remote telemonitoring (TM) for the prediction and management of acute exacerbations in COPD patients. We discuss the components of remote monitoring platforms, including the integration of environmental monitoring data; patient reported outcomes collected via interactive Smartphone apps, with data from wearable devices that monitor physical activity, heart rate, etc.; and data from medical devices such as connected non-invasive ventilators. We consider how telemonitoring and the deluge of data it potentially generates could be combined with electronic health records to provide personalized care and multi-disease management for COPD patient

Major bleeding risk and mortality associated with antiplatelet drugs in real-world clinical practice. A prospective cohort study

International audienceBackground - Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. Methods and findings - A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. Conclusion - The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. Trial registration - NCT02886533

Severity of Deliberate Acute Baclofen Poisoning: A Nonconcurrent Cohort Study

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Severity of Deliberate Acute Baclofen Poisoning: A Nonconcurrent Cohort Study

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Management of epistaxis associated with oral antithrombotic drugs in emergency department and impact on prescription thereafter

International audienceOBJECTIVES: To describe management, and to assess factors associated with antithrombotic prescription thereafter in patients who had epistaxis referred to emergency department (ED). DESIGN: Prospective cohort study. From EDs, clinical, biological and hospital data were collected. The clinical database was linked to the French Health Insurance Database where we retrieved antithrombotic drug deliveries in a 3-month period before and after referral. SETTING: Multicentric population-based cohort study within five well-defined areas. PARTICIPANTS: We considered 306 patients referred for epistaxis with a stable oral antithrombotic regimen before referral. MAIN OUTCOME MEASURES: We considered management, hospital outcome and case fatality. Antithrombotic prescription in a 3-month follow-up period was categorised into three classes: no change, class change, or discontinuation. During follow-up, hospitalisation for epistaxis or ischaemic events was searched. RESULTS: Among 306 adult individuals (mean age: 76 years), 166 took oral anticoagulant and 140 an antiplatelet drug. Blood transfusion was needed in 13.7% of patients and anterior packing alone in 61%. Half of the patients were hospitalised; 301 were discharged alive. Considering antithrombotic prescription thereafter we observed no change in 219 patients (72.8%), class changes in 47 patients (15.6%) and discontinuation in 35 patients (11.6%). We identified four independent predictors for antithrombotic prescription: hospitalisation (vs. returning home, p = .05), age (p = .03), haemoglobin level (p = .03) and oral anticoagulant (vs. antiplatelet agent, p &lt; .001). During the 3 months following discharge, 2 thrombotic and 15 bleeding events were identified. CONCLUSIONS: Epistaxis referred to emergency department had an impact on subsequent antithrombotic prescription. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02886533