P E Bollaert’s research while affiliated with Centre Hospitalier Universitaire de Nancy and other places

Introduction: We aimed to describe patients with coexisting infective endocarditis (IE) and bacterial meningitis (BM). Methods: We merged two large prospective cohorts, an IE cohort and a BM cohort, with only cases of definite IE and community-acquired meningitis. We compared patients who had IE and BM concurrently to patients with IE only and BM only. Results: Among the 1030 included patients, we identified 42 patients with IE-BM (4.1%). Baseline characteristics of patients with IE-BM were mostly similar to those of patients with IE, but meningitis was the predominant presentation at admission (39/42, 92.3%). Causative pathogens were predominantly Streptococcus pneumoniae (18/42, 42.9%) and Staphylococcus aureus (14/42, 33.3%). All pneumococcal IE were associated with BM (18/18). BM due to oral and group D streptococci, Streptococcus agalactiae, and S. aureus were frequently associated with IE (14/30, 46.7%). Three-month mortality was 28.6% in patients with IE-BM, 20.5% in patients with IE, and 16.6% in patients with BM. Conclusions: Patients with pneumococcal IE or altered mental status during IE must be investigated for BM. Patients with S. aureus, oral and group D streptococcal or enterococcal BM, or unfavorable outcome in pneumococcal meningitis would benefit from an echocardiography. Patients with the dual infection have the worst prognosis. Their identification is mandatory to initiate appropriate treatment.

Objectives Intensive care unit patients undergo several nursing care procedures (NCP) every day. These procedures involve a risk for adverse events (AE). Yet, their prevalence, intensity, and predisposing risk factors remain poorly established. The main objective of the study was to measure the incidence and severity of NCP related AE. Design This prospective observational multicentre study was conducted in 9 ICUs. All NCP were recorded for four consecutive weeks. For each NCP, the following were collected: patients’ baseline characteristics, type of NCP, characteristics of the NCP, AE and therapeutic responses. Results 5849 NCP occurred in 340 patients. Among the 340 patients included, 292 (85.9%) were affected by at least one AE, and 141 (41.5%) by an SAE during a NCP. Thirty % of NCP were associated with at least one AE: hemodynamic AE in 17.1%, respiratory AE in 13.6%, agitation and pain (3.7% and 3.3%). Eight invasive devices were accidentally removed. Severe Adverse Events (SAE) occurred in 5.5% of NCP. The main risk factor associated with SAE was pain/agitation at the beginning of the NCP. Conclusion AE are frequent during NCP in ICU. We identified several risk factors, some of them preventable, that could be considered for the development of recommendations for the nursing care of critically ill patients. Trial Registration: ClinicalTrials.gov NCT02881645.

Le choc septique demeure un grave problème de santé publique en raison de son incidence élevée et du taux élevé de morbimortalité. Les recommandations internationales concernant la prise en charge hémodynamique font une place à la vasopressine en seconde ligne chez les patients « réfractaires » à la noradrénaline. L’arginine-vasopressine a obtenu l’Autorisation européenne de mise sur le marché le 31 mai 2018. Ce médicament est disponible dans de nombreux pays. Pourtant, la Haute Autorité de santé vient de refuser l’inscription de l’arginine-vasopressine dans cette indication. Cet article met en lumière la discordance d’appréciation de l’évidence scientifique entre la Haute Autorité de santé et les nombreuses sociétés savantes qui ont endossé les recommandations de la Surviving Sepsis Campaign.

Background: Although anaphylaxis has been pointed as a high priority public health issue in the allergy world community, morbidity and mortality epidemiological data are still not optimal. This first multi-centric epidemiological study performed in 7 French emergency departments for one year intended to map the key issues to substantiate the need for changes and support ongoing national and international efforts for better diagnosis, management and prevention of anaphylaxis. Methods: This is a descriptive study using data routinely reported to French institutional administrative databases reported from 7 French public health institutions of the Lorraine region from January to December 2015, based on International Classification of Diseases (ICD)-10 pre-selected anaphylaxis-related codes and clinically validated as anaphylaxis cases. Results: From the 202,079 ED admissions, 4,817 had ICD-10 anaphylaxis-related codes, 323 of those have been clinically validated as anaphylaxis cases. Although 45.8% presented severity criteria, adrenaline has been prescribed only in 32.4% of these cases. Overall 323 cases, 57.9% were subsequently referred to allergy work-up or evaluation (after or during hospitalization) and 17.3% received a prescription of auto-injectable adrenaline. Conclusion: Taken the results of this study, there is an urgent and pressing need for improved public health initiatives regarding anaphylaxis recognition and treatment. Timely, we strongly believe that this document flags key problems, which may be managed in the forthcoming years by implementing national and international actions.

Introduction La fréquence de l’anaphylaxie est en augmentation. Avec le vieillissement de la population et la médicalisation plus importante, l’impact morbide et économique lié à l’anaphylaxie iatrogène est aussi amené à croître. Méthodes Nous avons réalisé une analyse en sous-groupes des données issues de l’étude rétrospective conduite sur les anaphylaxies passées aux urgences de 4 hôpitaux lorrains en 2015. L’inclusion reposait sur le codage diagnostique (CIM-10) avec revue des cas, le recueil sur un formulaire standardisé. Nous rapportons ici les résultats du groupe d’anaphylaxies retenues d’origine iatrogène. Résultats Sur les 323 patients inclus, 86 ont présenté une anaphylaxie de cause iatrogène et ont été analysés. Le sex-ratio était de 1 et 88,4 % étaient des adultes. La réaction était sévère (grade ≥ 3) dans 43,0 % des cas, avec un recours à l’adrénaline pour 43,2 % d’entre eux. Une éviction était consignée dans 52,3 % des dossiers mais seuls 10,5 % des patients recevaient une carte à la sortie. La molécule imputable était dans 45,3 % des cas une β-lactamine et 9,3 % un autre antibiotique, 10,5 % un AINS, 16,3 % un produit de contraste (2/3 iodé, 1/3 gadoliné) et 3,5 % un allergène de désensibilisation ; 15,1 % des cas étaient reliés à une autre famille médicamenteuse ou à plusieurs molécules. Sur 86 patients, 24,4 % se savaient ou pensaient allergiques à la molécule identifiée et 25,6 % des réactions faisaient suite à une exposition en structure de soins. Discussion La iatrogénie constitue une part importante et évitable d’anaphylaxie chez l’adulte, souvent secondaire à une prescription inappropriée. Le recours à l’adrénaline est sensiblement plus élevé que la moyenne, de par une meilleure identification du facteur causal, mais reste insuffisant. Trop peu consignée par écrit, l’éviction est souvent inadaptée ou mal conduite. Conclusion Outre l’amélioration du management de l’urgence anaphylactique, le recensement fin des effets indésirables allergiques graves et la prévention de la iatrogénie évitable constituent des défis du futur en termes de pharmacovigilance et de santé publique.

Résumé L’anaphylaxie est une urgence allergique dont la fréquence augmente constamment. Son management repose sur l’administration d’adrénaline et la coordination entre urgentistes et allergologues. L’objectif de l’étude était de déterminer l’incidence de l’anaphylaxie en 2015, d’en décrire les principales caractéristiques et d’évaluer les pratiques. Quatre centres hospitaliers lorrains ont été sélectionnés. Les dossiers médicaux informatiques des patients admis aux urgences adultes ou pédiatriques entre le 1er janvier et le 31 décembre 2015 ont été interrogés sur leurs motifs de recours et code diagnostique. Les dossiers dont le codage était susceptible de correspondre à une réaction anaphylactique (95 codes sélectionnés) étaient revus individuellement par un investigateur allergologue, puis inclus en cas de confirmation. Un questionnaire standardisé a permis le recueil des données épidémiologiques, caractéristiques cliniques et prise en charge des patients. L’anaphylaxie représente 0,16 % des passages aux urgences pour 2015, avec une incidence de 34 pour 100 000 personnes-année en Lorraine. La présentation clinique est influencée significativement par l’âge, le facteur étiologique, certains cofacteurs (asthme, comorbidité cardiovasculaire, médications), et la gravité de la réaction. En cas d’anaphylaxie sévère, le recours à l’adrénaline n’était que de 32,4 % (48/148), et 4 fois sur 10 la durée de surveillance hospitalière était inférieure à 6 heures. Une orientation vers l’allergologue était proposée chez 57,9 % (187/323) des patients. L’anaphylaxie est une cause non exceptionnelle d’admission aux urgences. Les recommandations sont encore trop peu appliquées, et une meilleure connaissance de la pathologie et de sa prise en charge est nécessaire pour les professionnels gérant l’urgence.

Introduction L’anaphylaxie est une urgence allergique dont la frequence et la morbidite augmentent. Son management repose sur l’administration precoce d’adrenaline et la coordination entre urgentiste et allergologue. Les objectifs de l’etude etaient de determiner l’incidence de l’anaphylaxie en 2015, d’en decrire les caracteristiques et d’evaluer les pratiques en Lorraine. Methodes Nous avons conduit une etude descriptive retrospective en consultant les dossiers des patients admis en 2015 aux urgences des 4 hopitaux lorrains sieges de SAMU. Les sujets ayant presente une anaphylaxie etaient inclus apres analyse des diagnostics (95 codes CIM-10 susceptibles de correspondre a une anaphylaxie) et revue des cas par un investigateur allergologue. Le recueil des donnees et l’evaluation de la prise en charge reposaient sur un formulaire standardise. Resultats Trois cent vingt-trois patients ont ete inclus. En 2015, l’anaphylaxie representait 0,16 % des passages aux urgences et son incidence etait estimee a 34 pour 100 000 personnes-annee en Lorraine. L’agent causal etait surtout alimentaire chez l’enfant (77 %), plus variable chez l’adulte. La presentation clinique etait influencee par l’âge, le facteur etiologique, certains cofacteurs (asthme, comorbidite cardiovasculaire, medications) et la gravite de la reaction. La tryptase n’etait dosee en urgence que dans 12,7 % des cas. En cas d’anaphylaxie severe (grade ≥ 3), le recours a l’adrenaline n’etait que de 32,4 % et 4 fois sur 10 la duree de surveillance hospitaliere etait inferieure a 6 heures. Un auto-injecteur etait prescrit a la sortie dans 17,3 % des cas, et une orientation vers l’allergologue proposee chez 57,9 % des patients. Discussion Les donnees de notre etude sont conformes a la litterature, et l’anaphylaxie n’est pas exceptionnelle aux urgences. Malgre l’existence de filieres de soins actives entre urgentistes et allergologues en Lorraine, il persiste des carences notamment de prescription d’adrenaline et de dosage de la tryptase dont l’interet est probablement meconnu. Conclusion Une meilleure connaissance de la pathologie et la diffusion des nouvelles recommandations (RFE 2016) sont essentielles pour ameliorer la prise en charge en urgence de l’anaphylaxie.

Background Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. Since clinical judgment is sometimes uncertain biomarkers could provide additional information likely to guide critical illness management. We evaluated the prognostic value of soluble Triggering Receptor Expressed by Myeloid cells 1 (sTREM-1), procalcitonin (PCT) and leucocyte surface expression of CD64. Methods This was a prospective cohort study, which included 190 septic patient admitted to the ICU in two hospitals. Blood samples for biomarker measurements were obtained upon admission and thereafter. The Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score were calculated. The primary outcome was all-cause death in the ICU. ResultsThe mortality rate reached 25.8 %. The best predictive value of the three biomarkers was obtained with baseline sTREM-1, although clinical scores outperformed this. Accuracy was greater in patients without prior exposure to antibiotics and in those with proven bacterial infection. Adding sTREM-1 levels to SAPS II increased its specificity to 98 %. The soluble TREM-1 level, core temperature and SAPS II value were the only independent predictors of death after adjustment for potential confounders. A decrease in sTREM-1 with time was also more pronounced in survivors than in non-survivors. ConclusionssTREM-1 was found to be the best prognostic biomarker among those tested. Both baseline values and variations with time seemed relevant. Although SAPS II outperformed sTREM-1 regarding the prediction of ICU survival, the biomarker could provide additional information.

Introduction Popularization of assisted-suicide and increase of online drug sellers could lead to resurgence of self-poisoning by a forgotten drug: pentobarbital. We report a case of self-poisoning with pentobarbital purchased on a Chinese website. Case details A 43-year old woman with a background history of borderline personality disorder ingested at home a “suicide kit” (pentobarbital sodium) purchased beforehand on the Internet, a few minutes before calling the French national emergency telephone number. Upon admission, she was comatose, Glasgow Coma Score (GCS) 3/15, symmetrical slight myosis, generalized hypotonia and hyporeflexia. Blood pressure was 96/66 mmHg, heart rate was 93/min, and body temperature was 33.3 °C. Blood gas analysis showed a metabolic acidosis and severe hypoxemia, related to an aspiration pneumonia (arterial pH 7.30, pCO2 40.7 mmHg, pO2 63.3 mmHg with FiO2 = 1). Hemodynamic instability rapidly appeared and norepinephrine infusion was started (up to 0.32 μg/kg/min). At day 2, clinical examination revealed signs consistent with brain death, i.e. bilateral mydriasis with absence of pupillary and oculo-cardiac reflexes. Electroencephalographic study found a severe diffuse slowing compatible with a sedative state. Plasma pentobarbital concentration was 19.9 μg/mL. At day 3, brain-stem reflexes reappeared, although pentobarbital concentration was still beyond lethal range, at 18.1 μg/mL. Neurological evolution was then progressively favourable. GCS was 5/15 at day 5, corresponding to a concentration of 9.4 μg/mL, and 15/15 at day 6 allowing extubation of the patient. She was finally discharged to the psychiatry department at day 10. Discussion Pentobarbital is a short-acting barbiturate, now rarely used in suicide attempt because it is no longer prescribed for medical purposes in most countries. Only a few cases have been published in the last decade, mostly among veterinarians because this drug is used as euthanasia agent. Pentobarbital is indeed the drug of choice for assisted-suicide. Pentobarbital is a weak acid with high lipid-solubility. After oral absorption, it is readily absorbed with an onset of action of 10 to 60 minutes. The degree of protein binding is about 45 to 70% and the volume of distribution is 0.5 to 1L/Kg. The plasma half-life for pentobarbital is 15 to 50 hours and appears to be dose-dependent. Renal excretion is negligible (< 1%). Pentobarbital is metabolized by the liver and excreted in the urine as inactive metabolites. Consciousness impairment, respiratory and circulatory depression are the main effects of acute poisoning. At worst, severe poisoning can mimic clinical and EEG features of brain death. Therapeutic blood levels are 1–3 μg/mL; levels are considered toxic at 5 μg/mL or more and reported lethal blood concentrations range from 10 to 169 μg/mL. Management of pentobarbital poisoning is mainly based on supportive care. Invasive mechanical ventilation, fluid loading and vasopressors are required in most severe cases. Several procedures to enhance elimination have been reported. Forced diuresis with urinary alkalinisation is not effective for short-acting barbiturates. Hemodialysis, hemoperfusion or continuous venovenous hemodiafiltration have been proposed as therapeutic options but improvement in supportive therapies make these techniques obsolete. Conclusion Pentobarbital is readily available without prescription on the Internet. Although there is little public awareness about this drug, current mediatisation of assisted-suicide could lead to an increased interest from suicide attempters. Supportive care is the cornerstone of medical management.