Évaluation des hémostatiques chirurgicaux au CHU de Nantes (de l'analyse in vitro à la synthèse pratique)

Les hémostatiques chirurgicaux représentent une classe vaste et hétérogène. Leur évaluation est souvent limitée. Malgré la multiplication des produits commercialisés, il n'existe pas de consensus permettant d'orienter le choix d'un hémostatique en fonction de l indication. L'objet de ce travail est de proposer une démarche d'évaluation argumentée des agents hémostatiques chirurgicaux, de façon à amorcer une discussion sur leur bon usage. Après un état des lieux des hémostatiques chirurgicaux actuellement commercialisés et une évaluation de leur consommation au CHU de Nantes, une comparaison des indications revendiquées au regard de la littérature a été réalisée. Cette étape a été suivie d une analyse de la performance in vitro d'une sélection d'hémostatiques chirurgicaux référencés dans l'établissement. Ceci a abouti à une proposition de classement selon des critères prédéfinis d'évaluation. Les résultats montrent des discordances entre la consommation réelle au CHU de Nantes et les scores obtenus pour chacun des hémostatiques. Il résulte de ce travail que l'usage de ces produits reste subjectif au regard de leurs performances. Cette modélisation va permettre d'amorcer une discussion au sein de la COMEDIMS dans le but d'aboutir à des critères de choix objectifs et rationnels.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Évaluation visuelle de la compatibilité physique de la naloxone avec d’autres médicaments intraveineux usuels

Résumé Objectif : Déterminer visuellement la compatibilité physique de la naloxone avec d’autres médicaments intraveineux dont l’administration simultanée en dérivé est fréquente. Méthodes : L’évaluation de la compatibilité physique consiste à mélanger 1 ml de naloxone à une concentration de 0,4 mg/mL avec 1 ml de chacun des 94 médicaments à tester. Aucun des médicaments ne subit de dilution supplémentaire. L’évaluation est réalisée sous éclairage normal, à température ambiante, en duplicata. Après avoir agité mécaniquement le mélange, deux personnes l’observent à l’oeil nu, puis à l’aide d’une loupe comportant un grossissement de trois fois, aux temps 0 minute, 15 minutes, 1 heure et 4 heures. Résultats : La grande majorité des médicaments testés n’ont démontré aucune incompatibilité, à l’exception de la cyclosporine, du diazépam, de l’indométhacine, du lorazépam, de la nitroglycérine, du pantoprazole, de la phénytoïne et du thiopental pour lesquels nous ne pouvons recommander l’administration concomitante en dérivé avec la naloxone en raison de l’incompatibilité physique qui a été observée. Des résultats contradictoires sont notés entre la naloxone et l’acyclovir, l’aminophylline, l’amphotéricine et la céfazoline. Des tests plus exhaustifs seraient à réaliser pour ces quatre médicaments. Conclusion : Malgré les limites inhérentes aux tests de compatibilité physique, ils permettent néanmoins de fournir des données manquantes et de faciliter l’administration des médicaments intraveineux dans un contexte clinique. Il nous semble cliniquement très pertinent de réaliser ce type de test quand les données de la littérature scientifique sont absentes ou insuffisantes. Abstract Objective: To evaluate visually the physical compatibility of naloxone with other intravenous drugs during Y-site administration. Methods: Physical compatibility was tested by mixing 1 ml of naloxone 0.4 mg/mL with 1 ml of each of the 94 drugs tested. Assessment was done under standard lighting conditions, at room temperature, and in duplicate. Following mechanical agitation of the mixture, two people did the assessment by visual inspection and with the use of a magnifying glass, with a magnifying factor of three, at times 0 and 15 minutes and at 1 and 4 hours. Results: The majority of tested drugs did not demonstrate an incompatibility, with the exception of cyclosporine, diazepam, indomethacin, lorazepam, nitroglycerin, pantoprazole, phenytoin and thiopental. Due to the observed physical incompatibility, we cannot recommend co-administration of these with naloxone via y-site. Results were contradicting between naloxone and acyclovir, aminophylline, amphotericin and cefazolin. Conclusion: Despite the inherent limitations of physical compatibility tests, they nonetheless provide missing data and facilitate the administration of intravenous drugs in a clinical context. It seems clinically relevant to us to perform these tests when the evidence in scientific literature is either absent or incomplete. Key words: Injectable, naloxone, physical compatibility, y-site administratio

Use of clinical biological tests of haemostasis to evaluate topical haemostatics

International audienceIntroductionIn addition to traditional means, topical haemostatics are currently used to avoid haemorrhage during surgery. Although they have been reported to be effective, there is a low level of proof of their clinical efficacy, which is at odds with their levels of use. This study used two methods to better understand their in vitro mechanism of action.MethodsTwo clinical biology assays were used to measure the action of topical haemostatics on primary and secondary haemostasis. Calibrated samples of collagen sponges and polypropylene non-woven gauze were tested. Platelet aggregation was assessed using a multichannel aggregometer. A thrombin generation assay (TGA) was used with a fluorogenic readout. Tissue factor solutions were used to activate coagulation.ResultsIn terms of primary haemostasis, collagen sponges stimulated platelet aggregation, in particular between 2 and 5 min after incubation with platelet-rich plasma and with no dose effect. In regard to coagulation, the kinetics of thrombin generation was enhanced. Polypropylene non-woven gauze did not exhibit any effect on platelet aggregation, although it did have a weak effect on the kinetics of thrombin generation.ConclusionCollagen is well known to exert a haemostatic effect due to its action on platelet aggregation. By contrast, polypropylene non-woven gauze has not been shown to have any effect on platelet aggregation other than a minor impact on thrombin generation. The results obtained with the devices tested are in agreement with the literature. Platelet aggregation biological assays and TGA measurements appear to be suitable for evaluation of these medical products

Étude pilote portant sur la concordance entre l’osmolarité calculée et l’osmolalité mesurée des solutions d’alimentation parentérale

Résumé Objectif : Comparer l’osmolarité calculée et  l’osmolalité mesurée de toutes les solutions d’ali­mentation parentérale préparées durant une journée de production. Méthodologie : Il s’agit d’une étude pilote réali­sée au département de pharmacie du CHU Sainte-Justine en collaboration avec la Faculté de pharma­cie de l’Université de Montréal. L’osmolarité calculée est obtenue à partir de notre outil informatisé de gestion des ordonnances d’alimentation parentérale. L’osmolalité mesurée découle de la moyenne des deux mesures obtenues par abaissement du point de congélation (Micro-Osmette) pour chaque échan­tillon de solution parentérale préparée durant une journée de production. Résultats : Vingt-sept sacs préparés le 6 mai 2009 ont été retenus. Trente-trois pour cent des sacs de nutrition parentérale évalués ont une osmolalité fi­nale inférieure à 1000 mOsm/kg (n = 9). La différence relative entre les valeurs d’osmolarité calculées et les valeurs d’osmolalité mesurées varie entre 0 % et 48 % (médiane de 9 %). On observe que cette diffé­rence relative semble inférieure pour les solutions de moins de 1000 mOsm/kg lorsqu’on la compare aux solutions dont l’osmolalité mesurée est supé­rieure 1000 mOsm/kg. Conclusion : Cette étude pilote démontre que les valeurs d’osmolarité calculées, estimées par l’outil informatisé de gestion des ordonnances d’alimenta­tion parentérale, sont majoritairement inférieures aux valeurs d’osmolalité mesurées. L’écart observé entre les valeurs d’osmolarité calculées et d’osmola­lité mesurées varie en fonction de la composition de chaque solution. Cette différence doit être prise en compte lors de la prescription de solutions d’alimen­tation parentérale. Abstract Purpose: To compare calculated osmolarity with measured osmolality of all total parenteral nutrition solutions prepared for one day of production. Methods: This pilot study was done at the phar­macy department of the CHU Sainte-Justine, to­gether with the Université de Montréal faculty of pharmacy. Calculated osmolarity was determined using our computerized tool for management of to­tal parenteral nutrition prescriptions. Measured os­molality results from the average of the two values obtained by freezing point depression (Micro-Os­mette) for each sample of parenteral solution prepa­red during one production day. Results: Twenty-seven bags that were prepared on May 6 2009 were selected. Thirty-three percent of total parenteral nutrition bags had a final osmolality value that was less than 1000 mOsm/kg (n=9). The relative difference between calculated osmolarity values and measured osmolality values varied between 0% and 48 % (median of 9%). We observed that this relative difference seemed inferior for solu­tions with an osmolality of less than 1000 mOsm/kg, when compared to solutions with a measured osmo­lality superior to 1000 mOsm/kg. Conclusion: This pilot study demonstrates that the calculated osmolarity values that were estimated by a computerized total parenteral nutrition pres­cription management tool are largely inferior to the measured osmolality values. The observed devia­tion between calculated osmolarity and measured osmolality values varied as a function of the content of each solution. This difference must be conside­red when prescribing total parenteral nutrition solu­tions. Key words: total parenteral nutrition; osmolarity; osmolality; pediatrics; neonatolog

What do adult outpatients included in clinical trials know about the investigational drugs being assessed: A cross-sectional study in France.

This study aimed to assess patient investigational medication knowledge and to identify factors associated with medication understanding by adult outpatients included in clinical trials. A cross-sectional prospectively designed survey was conducted on consecutive volunteers at 21 university teaching hospitals (in France) from February to December 2014. Investigational medication understanding was assessed at the time of the first dispensing using a structured interviewer-administered questionnaire based on information obtained from the literature that provided an 8-point score. Demographic and other baseline data were collected using structured interviews. Of the 236 participants, 139 (58.9%) of the respondents were male, and the median age was 54.9 years (range: 18-83 years). The mean understanding score was 6.24 and 72.5% of the patients had a score of 6 or higher. In univariate analysis, the medication understanding score was negatively correlated with age (r = -0.15, p = 0.0247) and positively correlated with the level of education (r = 0.25, p = 0.0002). In multivariate analysis, prognostic factors of a higher medication understanding score were: graduation from high school or a higher level of education; HIV infection; phase II/III/IV studies; mention of the drug on the prescription form, and the dispensing of a single investigational medication. Only a quarter of the adult outpatients included in clinical trials had a maximum possible investigational medication understanding score. Being old and having a low level of education were found to be important risk factors for inadequate medication understanding. This and other data suggest that sponsors should encourage initiatives aimed at improving investigational medication understanding in adults enrolled in clinical trials

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial

International audienceEpidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia

Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial

International audienceBackground: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock.Methods: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 μg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209).Findings: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction).Interpretation: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup.Funding: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004