The ethical and legal aspects of palliative sedation in severely brain-injured patients: a French perspective

To fulfill their crucial duty of relieving suffering in their patients, physicians may have to administer palliative sedation when they implement treatment-limitation decisions such as the withdrawal of life-supporting interventions in patients with poor prognosis chronic severe brain injury. The issue of palliative sedation deserves particular attention in adults with serious brain injuries and in neonates with severe and irreversible brain lesions, who are unable to express pain or to state their wishes. In France, treatment limitation decisions for these patients are left to the physicians. Treatment-limitation decisions are made collegially, based on the presence of irreversible brain lesions responsible for chronic severe disorders of consciousness. Before these decisions are implemented, they are communicated to the relatives. Because the presence and severity of pain cannot be assessed in these patients, palliative analgesia and/or sedation should be administered. However, palliative sedation is a complex strategy that requires safeguards to prevent a drift toward hastening death or performing covert euthanasia. In addition to the law on patients' rights at the end of life passed in France on April 22, 2005, a recent revision of Article 37 of the French code of medical ethics both acknowledges that treatment-limitation decisions and palliative sedation may be required in patients with severe brain injuries and provides legal and ethical safeguards against a shift towards euthanasia. This legislation may hold value as a model for other countries where euthanasia is illegal and for countries such as Belgium and Netherlands where euthanasia is legal but not allowed in patients incapable of asking for euthanasia but in whom a treatment limitation decision has been made

A Modeling Approach towards Identifying Potential Bivalent Sensitizers of Neuromuscular Blocking Agents

ABSTRACT Objective: Anaphylactic reactions induced by neuromuscular blocking agents (NMBAs) can occur at first contact and might be due to cross-sensitization by other drugs or chemicals. Our aim was to investigate whether divalent molecules sharing chemical features with NMBAs might potentially cause cross-sensitization. Methods: We constructed a pharmacophore key from chemical features common to all NMBAs (two positive or ionizable features 1.0807 nm apart) and used the key to screen FDA-approved small drug molecules of the Drug Bank® database (1541 molecules). The selected molecules were categorized on the basis of the values for three main parameters (fit value, relative energy and mean polar surface area). Results: Screening from the pharmacophore key selected 13 NMBAs and 88 non-NMBA drugs. Of these 88 drugs, 42 had high-ranking parameter values and were considered preferential cross-sensitizers. These included the dopamine D2 receptor ligands aripiprazole and domperidone. Pholcodine, as well as nizatidine, ranitidine, antrafenine, cabergoline and, to some extent, chlorhexidine best fulfilled the required criteria of apolar character, bioavailability and ionization rate. Conclusion: Our data support the hypothesis that pholcodine might be a potential NMBA cross-sensitizer. They confirmed the results of inhibition tests on patient serum suggesting that dopamine D2 receptor ligands might be cross-sensitizers. They also identified chlorhexidine, a widely used disinfectant incriminated in several cases of immediate hypersensitivity reactions, as a potential cross-sensitizer. Pharmacophore modelling is an inexpensive, straightforward approach that can be used to identify potential NMBA cross-sensitizing agents

Anaphylactic Shock A Form of Distributive Shock without Inhibition of Oxygen Consumption

Background: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [PtiO 2 ] values). The PtiO 2 profile and its metabolic consequences during anaphylaxis are not known. Methods: Ovalbumin-sensitized anaphylactic shock rats (n ‫؍‬ 11) were compared to nicardipine-induced hypotension rats (n ‫؍‬ 12) for systemic hemodynamics, PtiO 2 , sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. Results: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 ؎ 6.2 ml ⅐ 100 g ؊1 ⅐ min ؊1 to 24.3

An optimized protocol for microarray validation by quantitative PCR using amplified amino allyl labeled RNA

<p>Abstract</p> <p>Background</p> <p>Validation of microarrays data by quantitative real-time PCR (qPCR) is often limited by the low amount of available RNA. This raised the possibility to perform validation experiments on the amplified amino allyl labeled RNA (AA-aRNA) leftover from microarrays. To test this possibility, we used an ongoing study of our laboratory aiming at identifying new biomarkers of graft rejection by the transcriptomic analysis of blood cells from brain-dead organ donors.</p> <p>Results</p> <p>qPCR for ACTB performed on AA-aRNA from 15 donors provided Cq values 8 cycles higher than when original RNA was used (P < 0.001), suggesting a strong inhibition of qPCR performed on AA-aRNA. When expression levels of 5 other genes were measured in AA-aRNA generated from a universal reference RNA, qPCR sensitivity and efficiency were decreased. This prevented the quantification of one low-abundant gene, which was readily quantified in un-amplified and un-labeled RNA. To overcome this limitation, we modified the reverse transcription (RT) protocol that generates cDNA from AA-aRNA as follows: addition of a denaturation step and 2-min incubation at room temperature to improve random primers annealing, a transcription initiation step to improve RT, and a final treatment with RNase H to degrade remaining RNA. Tested on universal reference AA-aRNA, these modifications provided a gain of 3.4 Cq (average from 5 genes, P < 0.001) and an increase of qPCR efficiency (from -1.96 to -2.88; P = 0.02). They also allowed for the detection of a low-abundant gene that was previously undetectable. Tested on AA-aRNA from 15 brain-dead organ donors, RT optimization provided a gain of 2.7 cycles (average from 7 genes, P = 0.004). Finally, qPCR results significantly correlated with microarrays.</p> <p>Conclusion</p> <p>We present here an optimized RT protocol for validation of microarrays by qPCR from AA-aRNA. This is particularly valuable in experiments where limited amount of RNA is available.</p

Pre-operative maintenance of angiotensin-converting enzyme inhibitors is not associated with acute kidney injury in cardiac surgery patients with cardio-pulmonary bypass: a propensity-matched multicentric analysis

Objective: We investigated the effects of the maintenance of angiotensin-converting enzyme inhibitors (ACE inhibitors) the day of the surgery on the incidence of postoperative acute kidney injury (AKI) and cardiac events in patients undergoing cardiac surgery.Methods: We performed a multicentric observational study with propensity matching on 1,072 patients treated with ACE inhibitors. We collected their baseline demographic data, comorbidities, and operative and postoperative outcomes. AKI was defined by KDIGO (Kidney Disease: Improving Global Outcome).Results: Maintenance of an ACE inhibitor was not associated with an increased risk of AKI (OR: 1.215 (CI95%:0.657–2.24), p = 0.843, 71 patients (25.1%) vs. 68 patients (24%)). Multivariate logistic regression and sensitive analysis did not demonstrate any association between ACE inhibitor maintenance and AKI, following cardiac surgery (OR: 1.03 (CI95%:0.81–1.3)). No statistically significant difference occurs in terms of incidence of cardiogenic shock (OR: 1.315 (CI95%:0.620–2.786)), stroke (OR: 3.313 (CI95%:0.356–27.523)), vasoplegia (OR: 0.741 (CI95%:0.419–1.319)), postoperative atrial fibrillation (OR: 1.710 (CI95%:0.936–3.122)), or mortality (OR: 2.989 (CI95%:0.343–26.034)). ICU and hospital length of stays did not differ (3 [2; 5] vs. 3 [2; 5] days, p = 0.963 and 9.5 [8; 12] vs. 10 [8; 14] days, p = 0.638).Conclusion: Our study revealed that maintenance of ACE inhibitors on the day of the surgery was not associated with increased postoperative AKI. ACE inhibitor maintenance was also not associated with an increased rate of postoperative major cardiovascular events (arterial hypotension, cardiogenic shock, vasopressors use, stroke and death)

Mise en place d'une ordonnance argumentée de prescriptions des antibiotiques en réanimation (évaluation des effets sur la consommation des antibiotiques)

Notre objectif était d'évaluer, par une étude avant- après, les effets de la mise en place d'une ordonnance argumentée avec arrêt automatique de la délivrance par la pharmacie des hôpitaux pour la prescription des antibiotiques dans un service de réanimation. Le critère principal de jugement était la consommation d'antibiotique en Dose DéfInie Journalière (selon l'Organisation Mondiale de la Santé) pour 1000 journées patients (DDD/1000), les critères secondaires le nombre de journées d'exposition des patients aux antibiotique pour 1000 jours d'hospitalisation (AED/I000) et la conduite thérapeutique (documentation microbiologique, réévaluation). 136 patients ont été inclus et 137 infections nosocomiales traitées. La DDD/1000 a diminué de 1029 à 827 soit 20% (P<0.001), les AED/I000 de 672 à 450 soit 34%( p<O.OOI); le taux de documentation microbiologique augmenté de 64 à 87% (p<0.01). Dans le traitement des infections nosocomiales en réanimation, une ordonnance argumentée de prescription des antibiotiques peut diminuer leur consommation et l'exposition des patients à ces molécules.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L' allo-immunisation anti-érythrocytaire post-transfusionnelle au CHU de Nancy en 2007 (Analyse et suivi immunologique de patients receveurs de concentrés érythrocytaires (étude préliminaire))

Les allo-immunisations anti-érythrocytaires, complications immunologiques retardées, peuvent être générées par la transfusion sanguine. Le pourcentage d'allo-immunisations antiérythrocytaires sans traduction clinique, ni biologique d'hémolyse varie de 1,4 à 1,8% selon les études. Elles sont dépistées par le suivi immunologique post-transfusionnel réalisé à 3 mois de l'épisode transfusionnel. Nous nous sommes intéressés à l'allo-immunisation anti-érythrocytaire post transfusionnelle au CHU de Nancy en 2007 à travers différents aspects : La description des allo-immunisations générées par les transfusions érythrocytaires Rhésus / Kell incompatibles au CHU de Nancy en 2007 grâce aux fichiers fournis par l'établissement français du sang de Nancy: l'incidence de l'allo-immunisation de nova post-transfusionnelle est estimée à 6% au CHU de Nancy en 2007. L'existence et l'organisation du suivi immunologique en réalisant un audit de pratique dans deux services hospitaliers du CHU de Nancy (orthopédiecthépato-gastroentérologie) : seulement 31% des patients ont bénéficié d'un suivi immunologique. Le rôle du médecin généraliste dans la réalisation du suivi immunologique post-transfusionnel : ils sont peu impliqués dans la réalisation de ce suivi. L'aspect médico-légal entourant les pratiques transfusionnelles: elles sont rigides et recommandent une organisation entre praticiens afin d'effectuer ce suivi immunologique entre un et trois mois au décours de l'épisode transfusionnel. Ce travail préliminaire permet de démontrer que l'allo-imrnunisation anti-érythrocytaire générée par la transfusion sanguine demeure un problème méconnu, semblant être sous-évalué et sous-déclaré. La réalisation d'un suivi immunologique systématique au décours de chaque transfusion semble être utopique. Des mesures seraient néanmoins souhaitables afin de : sensibiliser les prescripteurs de PSL et les médecins traitants vis-à-vis du suivi immunologique de certaines catégories à risques (les femmes en âge de procréer, les polytransfusés, les transfusés chroniques). . . , centraliser les résultats des RAI post-transfusionnels à l'EFS?NANCY1-SCD Medecine (545472101) / SudocSudocFranceF

Effets de l'adrénaline et de la vasopressine sur la circulation cérébrale au cours du choc anaphylactique

REIMS-BU Santé (514542104) / SudocSudocFranceF