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Background/Introduction In France, the law defines and prohibits “unreasonable obstinacy” and provides a framework for the subsequent decision to limit or to cease treatment. It also gives the person the right to appoint a trusted person and to draft advance directives regarding this issue. There have been few studies of neurosurgeons’ involvement in decision-making in regard to treatment limitation after severe traumatic brain injury. Aim of the study The first aim of the study was to assess French neurosurgeons’ adherence to the law on patients’ rights and end of life which governs such decision-making. The second aim was to assess the prognostic and decision-making criteria applied by neurosurgeons. Methods A declarative practice and opinion survey, using a self-administered questionnaire emailed to all practising neurosurgeons members of the French Society of Neurosurgery, was conducted from April to June 2016. Results Of the 197 neurosurgeons contacted, 62 filled in the questionnaire. Discussions regarding treatment limitation were in all cases collegial, as required under the law, and the patient's neurosurgeon was always involved. The trusted person and/or family were always informed and consulted, but their opinions were not consistently taken into account. Advance directives were most often lacking (68%) [56; 80] or inappropriate (27%) [16; 38]. The most frequently used prognostic criteria were clinical parameters, intracranial pressure, cerebral perfusion pressure, and imaging, with significant interindividual variation in their use. The main decision-making criteria were foreseeable disability, expected future quality of life, and age. Conclusions Neurosurgeons showed good compliance with legal requirements, except in the matter of calling for the opinion of an external consultant. Furthermore, this survey confirmed variability in the use of prognosis predictors, and the need for further clinical research so as to achieve more-standardized practices to minimise the subjectivity in decision-making.

Points essentiels Devant des signes cliniques d’hemorragie sous-arachnoidienne (HSA), le diagnostic positif est realise par une tomodensitometrie encephalique sans injection. Le diagnostic etiologique d’une HSA repose sur l’angioscanner cerebral qui permet d’identifier l’anevrysme et d’etudier ses rapports anatomiques avant traitement. En phase aigue, la reanimation de complications cardiovasculaires et/ou respiratoires ne doit pas retarder le traitement du sac anevrysmal de plus de 12 a 24 heures. La securisation du sac anevrysmal doit etre realisee le plus precocement possible, au mieux dans les 24 premieres heures suivant l’admission. Si elle est necessaire, une derivation ventriculaire externe doit etre mise en place avant embolisation. La principale complication apres HSA est l’ischemie cerebrale retardee (ICR), qui reconnait plusieurs etiologies, dont le vasospasme. La detection du vasospasme repose sur l’examen clinique et sur la realisation reguliere de Doppler transcraniens. Le diagnostic d’ICR repose sur une technique d’imagerie de la perfusion cerebrale, soit scanner de perfusion soit imagerie par resonance magnetique. La prevention de l’ICR repose sur la nimodipine administree par voie orale ou intraveineuse. Le traitement de l’ICR repose sur le maintien d’une pression de perfusion cerebrale (PAM ≥ 100 mmHg) et la neuroradiologie interventionnelle (angioplastie medicamenteuse par milrinone ou mecanique).

International audience; BACKGROUND:Enterocolitis is a rare, but serious gastrointestinal complication associated with docetaxel-based chemotherapy in patients with cancer. The incidence, clinical presentation and outcome of enterocolitis in patients with cancer treated with docetaxel-based chemotherapy was assessed in this study Patients and Methods: All patients treated with docetaxel for cancer between January 2010 and December 2014 at the University Hospital of Besançon were identified and their medical records reviewed.RESULTS:During this period, 1,227 patients received docetaxel chemotherapy and gastrointestinal events occurred in 381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal events was associated with a higher dose of docetaxel (≥75 mg/m2) (odds ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65 (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%) patients, respectively; 54 patients (14.2%) were hospitalized. Computed tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients presented radiological signs of enterocolitis. Three deaths (0.8%) related to enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120 patients (31.5%).CONCLUSION:Gastrointestinal events in patients treated with docetaxel may be a potential sign of fatal enterocolitis and require particular attention. Dose reduction at the first cycle may reduce the risk of such events.

International audience

Background and Purpose: Providing non-therapeutic intensive care for some patients in hopeless condition after cerebrovascular stroke in order to protect their organs for possible post-mortem organ donation after brain death is an effective but ethically tricky strategy to increase organ grafting. Finding out the feelings and opinion of the involved healthcare professionals and assessing the training needs before implementing such a strategy is critical to avoid backlash even in a presumed consent system. Participants and methods: A single-centre opinion survey of healthcare professionals was conducted in 2013 in the potentially involved wards of a French University Hospital: the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Unit and the Emergency Department. A questionnaire with multiple-choice questions and one open-ended question was made available in the different wards between February and May 2013. Ethical considerations: The project was approved by the board of the Lorraine University Diploma in Medical Ethics. Results: Of a total of 340 healthcare professionals, 51% filled the form. Only 21.8% received a specific education on brain death, and only 18% on potential donor’s family approach and support. Most healthcare professionals (93%) think that non-therapeutic intensive care is the continuity of patient’s care. But more than 75% of respondents think that the advance patient’s consent and the consent of the family must be obtained despite the presumed consent rule regarding post-mortem organ donation in France. Conclusion: The acceptance by healthcare professionals of non-therapeutic intensive care for brain death organ donation seems fairly good, despite a suboptimal education regarding brain death, non-therapeutic intensive care and families’ support. But they ask to require previously expressed patient’s consent and family’s approval. So, it seems that non-therapeutic intensive care should only remain an ethically sound mean of empowerment of organ donors and their families to make post-mortem donation happen as a full respect of individual autonomy.

Background: Advance announcement of forthcoming brain death has developed to enable intensivists and organ procurement organisation coordinators to more appropriately, and separately from each other, explain to relatives brain death and the subsequent post-mortem organ donation opportunity. Research aim: The aim was to assess how potentially involved healthcare professionals perceived ethical issues surrounding the strategy of advance approach. Research design: A multi-centre opinion survey using an anonymous self-administered questionnaire was conducted in the six-member hospitals of the publicly funded East of France regional organ and tissue procurement network called ‘Prélor’. Participants: The study population comprised 460 physicians and nurses in the Neurosurgical, Surgical and Medical Intensive Care Units, the Stroke Units and the Emergency Departments. Ethical considerations: The project was approved by the board of the Lorraine University Diploma in Medical Ethics and the Prélor Network administrators. Main findings: A slight majority of 53.5% of respondents had previously participated in an advance relatives approach: 83% of the physicians and 42% of the nurses. A majority of healthcare professionals (68%) think that the main justification for advance relatives approach is the comprehensive care of the dying patient and the research of his or her most likely opinion (74%). The misunderstanding of the related issues by relatives is an obstacle for 47% of healthcare professionals and 51% think that the answer given by the relatives regarding the most likely opinion of the person regarding post-mortem organ donation really corresponds to the person opinion in only 50% of the cases or less. Conclusion: Time given by advance approach should be employed to help and enable relatives to authentically bear the values and interests of the potential donor in the post-mortem organ donation discussion. Nurses’ attendance of advance relatives approach seems necessary to enable them to optimally support the families facing death and post-mortem organ donation issues.

International audience; The chronic worldwide lack of organs for transplantation and the continuing improvement of strategies for _in situ_ organ preservation have led to renewed interest in elective non-therapeutic ventilation of potential organ donors. Two types of situation may be eligible for elective intensive care: patients definitely evolving towards brain death and patients suitable as controlled non-heart beating organ donors after life-supporting therapies have been assessed as futile and withdrawn. Assessment of the ethical acceptability and the risks of these strategies is essential. We here offer such an ethical assessment using the four principles of medical ethics of Beauchamp and Childress applying them in their broadest sense so as to include patients and their families, their caregivers, other potential recipients of intensive care, and indeed society as a whole. The main ethical problems emerging are the definition of beneficence for the potential organ donor, the dilemma between the duty to respect a dying patient's autonomy and the duty not to harm him/her, and the possible psychological and social harm for families, caregivers other potential recipients of therapeutic intensive care, and society more generally. Caution is expressed about the ethical acceptability of elective non-therapeutic ventilation, along with some proposals for precautionary measures to be taken if it is to be implemented. ER - End of Reference

Summary Introduction Stroke is presently the first cause of brain death in France. In this context, the question of elective non-therapeutic ventilation and resuscitation arises, aiming at enabling the patients for whom a decision to stop all the therapeutics has been made to evolve towards brain death and organ donation. In 2010, the French society of intensive care has released guidelines regarding stroke management including strategy on this topic. The question has also been referred to the Ethics Committee of Nancy university hospital by a chief-nurse of our hospital and we report here its conclusions and propositions. Method A workgroup was appointed and has tackled the major issues: the justification, the risks for the patient and the society, the expression of the patient's consent, the legality of this care benefiting only a third party, and the practical details. Conclusions and propositions Elective intensive care following decision to stop any treatment after severe stroke seems to be justified with regard to public health as well as individual or collective ethics, providing the patient has expressed his/her consent or his/her non-opposition before stroke occurrence. In France there is no legal frame regulating this practice, no information of the general public, and a public debate has yet to be initiated. Regarding the practical details, a priori agreement of the organ procurement organisation, patient's consent, and approval of the consultant required by the law of April 22, 2005 relating to Patients’ rights and to the end of life to rule out any conflict of interest, have to be checked before referring the patient to ICU. Advance directives drafting must be developed and their scope extended to organ donation and elective resuscitation. Therefore, fair information of the general public and clarity and transparency of the procedures are needed. The prolongation of the French moratorium on Maastricht III type non-heart beating organ donation - grounded on fears of possible conflicts on interest - seems obsolete with regard to the increasing respect of the patient's autonomy and to the risk of harmfulness entailed by elective resuscitation before death.

Electrolyte disturbances are frequent after brain injuries, especially dysnatremia and dyskalemia. In neurological patients, usual clinical signs of hyponatremia are frequently confounded with clinical signs of the underlying disease. Natremia absolute value is less important than speed of onset of the trouble. Most often, hyponatremia is associated with hypotonicity and intracellular hyperhydration, which may exacerbate a cerebral edema. Distinction between inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSWS) may be difficult and is mainly based on assessment of patient's volemia, SIADH being associated with normal or hypervolemia and CSWS with hypovolemia. After subarachnoid haemorrhage, the most common disorder is CSWS. In this case, fluid restriction is strictly prohibited. Treatment of CSWS needs to compensate for the natriuresis and may justify the use of mineralocorticoid. It is important to avoid excessively rapid correction of hypernatremia, with a maximal speed of correction of 0.5 m mol/l/h. Serum sodium monitoring should be mandatory for the first ten postoperative days after pituitary adenoma surgery. Therapeutic barbiturate may be responsible for life threatening dyskalemia.

Refractory shock from anaphylaxis can occur after induction of general anesthesia. We report two cases of fatal cardiac arrest with increased blood tryptase and immunoglobulin E values after succinylcholine administration. Tryptase and immunoglobulin E assays may help to identify anaphylactic reactions when cardiac arrest occurs at induction of anesthesia.

Resume La fievre est une agression cerebrale secondaire d’origine systemique, susceptible d’aggraver le pronostic des patients de neuroreanimation. En reponse a une agression immunologique, la fievre associe plusieurs reponses physiologiques, dont la plus facilement mesurable est l’hyperthermie. La definition de celle-ci est variable, mais le seuil le plus frequemment utilise est 37,5 °C. Chez l’animal, l’hyperthermie, appliquee avant, au moment ou apres une ischemie cerebrale, augmente le volume des lesions. Le mecanisme de cet effet serait lie a une augmentation de permeabilite de la barriere hematoencephalique, a une liberation accrue d’acides amines excitateurs et a une majoration de la production de radicaux libres. En clinique, l’hyperthermie est tres frequente, touchant entre 20 et 30 % des patients au cours des 72 premieres heures d’hospitalisation, ce chiffre atteignant 40 a 50 % en cas d’accident vasculaire cerebral (AVC) hemorragique. Cette hyperthermie est rattachee a une infection dans la moitie des cas, mais dans plus de 25 % des cas elle serait d’origine centrale. Au cours de l’AVC ischemique, une hyperthermie au cours des 72 premieres heures est associee a une augmentation de la taille de l’infarctus, une augmentation de la morbidite et de la mortalite. Cette aggravation du pronostic est egalement retrouvee au cours de l’hemorragie sous-arachnoidienne. Apres traumatisme crânien grave, la fievre ne semble pas influencer la mortalite, mais est associee a une augmentation de morbidite. Bien qu’aucune relation causale entre fievre et aggravation du pronostic ne soit etablie, il parait raisonnable de traiter l’hyperthermie. Chez le patient cerebrolese, les antipyretiques sont faiblement efficaces. En cas d’echec, ils doivent etre remplaces par des techniques de refroidissement physique.

Neurogenic pulmonary edema (NPE) is usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. It has been reported regularly for a long time in numerous and various injuries of the central nervous system in both adults and children, but remains poorly understood because of the complexity of its pathophysiologic mechanisms involving hemodynamic and inflammatory aspects. NPE seems to be under-diagnosed in acute neurologic injuries, partly because the prevention and detection of non-neurologic complications of acute cerebral insults are not at the forefront of the strategy of physicians. The presence of NPE should be high on the list of diagnoses when patients with central neurologic injury suddenly become dyspneic or present with a decreased P(a)o(2)/F(i)o(2) ratio. The associated mortality rate is high, but recovery is usually rapid with early and appropriate management. The treatment of NPE should aim to meet the oxygenation needs without impairing cerebral hemodynamics, to avoid pulmonary worsening and to treat possible associated myocardial dysfunction. During brain death, NPE may worsen myocardial dysfunction, preventing heart harvesting.

Paralytic ileus is a major concern in the acute phase of spinal cord injury. Classical treatment with neostigmine is often ineffective. Continuous intravenous (i.v.) lidocaine infusion has been previously proposed intra and post-operatively in order to decrease the duration of post-operative ileus after abdominal surgery. We report the cases of seven patients suffering from complete paralytic spinal cord injury-related ileus with colectasy resistant to neostigmine, who were treated by i.v. lidocaine infusion.

International audience; Logo Cerebrovascular DiseasesOriginal PaperGene Expression Profile of Blood Cells for the Prediction of Delayed Cerebral Ischemia after Intracranial Aneurysm Rupture: A Pilot Study in HumansBaumann A.a · Devaux Y.i · Audibert G.a · Zhang L.i · Bracard S.b · Colnat-Coulbois S.e · Klein O.e · Zannad F.f, g · Charpentier C.c · Longrois D.h · Mertes P.-M.dAuthor affiliationsServices de aRéanimation Neurochirurgicale, bNeuroradiologie Diagnostique et Thérapeutique, cRéanimation Chirurgicale and dAnesthésie-Réanimation Chirurgicale, eDépartement de Neurochirurgie and fINSERM Unité 961, Centre Hospitalier Universitaire de Nancy, Hôpital Central, and gDepartment of Cardiology, Nancy University, Nancy, and hService d'Anesthésie Réanimation Chirurgicale, Groupe Hospitalier Bichat - Claude Bernard, Paris, France; iLaboratory of Cardiovascular Research, Public Research Centre for Health (CRP-Santé), Luxembourg, LuxembourgKeywords: AneurysmsGenomicsIntracranial aneurysmSubarachnoid hemorrhageDelayed cerebral ischemiaCerebrovasc Dis 2013;36:236-242https://doi.org/10.1159/000354161 Abstract Get article FullText PDF Login / RegisterAbstractBackground: Delayed cerebral ischemia (DCI) is a potentially devastating complication after intracranial aneurysm rupture and its mechanisms remain poorly elucidated. Early identification of the patients prone to developing DCI after rupture may represent a major breakthrough in its prevention and treatment. The single gene approach of DCI has demonstrated interest in humans. We hypothesized that whole genome expression profile of blood cells may be useful for better comprehension and prediction of aneurysmal DCI. Methods: Over a 35-month period, 218 patients with aneurysm rupture were included in this study. DCI was defined as the occurrence of a new delayed neurological deficit occurring within 2 weeks after aneurysm rupture with evidence of ischemia either on perfusion-diffusion MRI, CT angiography or CT perfusion imaging, or with cerebral angiography. DCI patients were matched against controls based on 4 out of 5 criteria (age, sex, Fisher grade, aneurysm location and smoking status). Genome-wide expression analysis of blood cells obtained at admission was performed by microarrays. Transcriptomic analysis was performed using long oligonucleotide microarrays representing 25,000 genes. Quantitative PCR: 1 µg of total RNA extracted was reverse-transcribed, and the resulting cDNA was diluted 10-fold before performing quantitative PCR. Microarray data were first analyzed by ‘Significance Analysis of Microarrays' software which includes the Benjamini correction for multiple testing. In a second step, microarray data fold change was compared using a two-tailed, paired t test. Analysis of receiver-operating characteristic (ROC) curves and the area under the ROC curves were used for prediction analysis. Logistic regression models were used to investigate the additive value of multiple biomarkers. Results: A total of 16 patients demonstrated DCI. Significance Analysis of Microarrays software failed to retrieve significant genes, most probably because of the heterogeneity of the patients included in the microarray experiments and the small size of the DCI population sample. Standard two-tailed paired t test and C-statistic revealed significant associations between gene expression and the occurrence of DCI: in particular, the expression of neuroregulin 1 was 1.6-fold upregulated in patients with DCI (p = 0.01) and predicted DCI with an area under the ROC curve of 0.96. Logistic regression analyses revealed a significant association between neuroregulin 1 and DCI (odds ratio 1.46, 95% confidence interval 1.02-2.09, p = 0.02). Conclusions: This pilot study suggests that blood cells may be a reservoir of prognostic biomarkers of DCI in patients with intracranial aneurysm rupture. Despite an evident lack of power, this study elicited neuroregulin 1, a vasoreactivity-, inflammation- and angiogenesis-related gene, as a possible candidate predictor of DCI. Larger cohort studies are needed but genome-wide microarray-based studies are promising research tools for the understanding of DCI after intracranial aneurysm rupture.

International audience; 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.

Hyponatremia is often associated with, and worsens, the prognosis of severe aneurysmal subarachnoid hemorrhage (SAH). Several possible endocrine perturbations of variable severity and variable sodium and water intake have been described in SAH. However, a comprehensive study of the different hormonal systems involved in sodium and water homeostasis and circulating blood volume modifications is still needed. Our aim was to assess water and sodium regulation after severe SAH by investigating blood volume and several hormonal regulatory systems in the context of hyponatremia prevention by controlled sodium intake.Nineteen mechanically ventilated patients with severe SAH, were prospectively studied. Replacement of sodium was at least 4.5 mmol x kg(-1) x d(-1) and adjusted on natriuresis. Hormones involved in electrolyte and water homeostasis: vasopressin, renin, angiotensin, aldosterone, and natriuretic peptides were assessed every 3 days for 12 days. Red blood cell volume was measured by the isotopic method (technetium-labeled red blood cells), in the first 48 h after admission and at day 7. Cardiac function was assessed using electrocardiogram, transthoracic echocardiography, and troponin Ic (cTnI). Outcome was assessed at 3 mo.After SAH onset, hyponatremia, but not decreased circulating blood volume, was prevented by high sodium and water infusion adapted to renal excretion. The hormonal profiles were characterized by an increase in renin, angiotensin II, natriuretic peptide concentrations associated with increased troponin Ic, stable low levels of vasopressin, and the absence of increased aldosterone concentrations. There were no correlations between hormone concentrations and natriuresis.After severe SAH, in the context of multiple clinical interventions, increased natriuresis and low blood volume are consistent with cerebral salt wasting syndrome, probably related to the sequence of severe SAH, highly increased sympathetic tone, hyperreninemic hypoaldosteronism syndrome, and increased natriuretic peptides release.

French law 2005-370 of April 22, 2005 (Leonetti's law) brings new rights to patients and clarifies medical practices regarding end of life care. This new law prohibits unreasonable obstinacy in investigations or therapeutics and authorizes the withholding or withdrawal of treatments when they appear "useless, disproportionate or having no other effect than solely the artificial preservation of life". Relief from pain is a fundamental right of patients. With regard to pain control, the law also allows doctors to dispense to patients "in an advanced or final phase of a serious and incurable affliction" anti-pain treatments as needed, even if these treatments, as a side effect, hasten their death. The drafting of advance directives regarding end of life constitutes a new right of patients. The decision to withdraw or withhold a treatment from a patient unable to express their will has to take into account the wishes they might have expressed through advance directives, and/or the wishes of a trusted person or, lastly, of the family. Before making any decision, physicians should respect a collegial medical procedure. Euthanasia defined as the act of terminating one's life on a patient's explicit request remains illegal.

Seven hundred patients were investigated prospectively before undergoing chemonucleolysis. A past history of allergy and/or previous exposure to papain, either in food, beverages or drugs, was sought, and a skin-prick test with chymopapain was performed. Based on the results obtained, the subjects were classified into four groups: Group I--225 non-atopic non-papain-exposed subjects; Group II--285 non-atopic papain-exposed subjects; Group III--69 atopic non-papain-exposed subjects; and Group IV--121 atopic papain-exposed subjects. Latent sensitization to papain was observed in 0.4% of subjects in Group I, 3.16% in Group II, 5.8% in Group III and 7.4% in Group IV. The odds ratios were 13.8 for atopy and 7.3 for exposure to papain. Interaction between atopy and papain exposure did not result in a significantly greater risk. Neither sex nor age nor a history of a previous drug reaction were risk factors. Only one patient out of the 23 who were sensitive to papain had no risk factor. The 677 skin-test negative patients then underwent chemonucleolysis and none of them had an anaphylactic reaction. This was significantly less frequent: (P = 0.04) than the incidence in a random population (0.45%). Prick tests performed 6 weeks and 6 months after chemonucleolysis revealed newly acquired sensitization in 36% of the patients. Atopy was not a risk factor for this event.(ABSTRACT TRUNCATED AT 250 WORDS)