Multimodal assessment improves neuroprognosis performance in clinically unresponsive critical-care patients with brain injury.

Accurately predicting functional outcomes for unresponsive patients with acute brain injury is a medical, scientific and ethical challenge. This prospective study assesses how a multimodal approach combining various numbers of behavioral, neuroimaging and electrophysiological markers affects the performance of outcome predictions. We analyzed data from 349 patients admitted to a tertiary neurointensive care unit between 2009 and 2021, categorizing prognoses as good, uncertain or poor, and compared these predictions with observed outcomes using the Glasgow Outcome Scale-Extended (GOS-E, levels ranging from 1 to 8, with higher levels indicating better outcomes). After excluding cases with life-sustaining therapy withdrawal to mitigate the self-fulfilling prophecy bias, our findings reveal that a good prognosis, compared with a poor or uncertain one, is associated with better one-year functional outcomes (common odds ratio (95% CI) for higher GOS-E: OR = 14.57 (5.70-40.32), P < 0.001; and 2.9 (1.56-5.45), P < 0.001, respectively). Moreover, increasing the number of assessment modalities decreased uncertainty (OR = 0.35 (0.21-0.59), P < 0.001) and improved prognostic accuracy (OR = 2.72 (1.18-6.47), P = 0.011). Our results underscore the value of multimodal assessment in refining neuroprognostic precision, thereby offering a robust foundation for clinical decision-making processes for acutely brain-injured patients. ClinicalTrials.gov registration: NCT04534777 .

Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase.

BACKGROUND AND PURPOSE: In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. MATERIALS AND METHODS: Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MDz). Through linear regression, we evaluated the relation between microbleed concentration and MDz in predefined structures. RESULTS: In the cerebral hemispheres, MDz at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5-69.3], P = .017; right: B = 26.3 [95% CI 5.7-47.0], P = .014). No such relation was demonstrated in the central brain. MDz in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8-75.2], P < .000). MDz in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9-47.5], P = .023). CONCLUSIONS: SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

Critical appraisal of organ procurement under Maastricht 3 condition.

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after the decision to withdraw life-supportive therapies has been taken. This type of organ donation is performed in the USA, Canada, the United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations formalizing procedures and operations. The French Society of Anesthesia and Intensive Care (Société française d'anesthésie et de reanimation [Sfar]) ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounded a note of caution regarding the applicability of this type of organ procurement in unselected patients following a decision to withdraw life-supportive therapies. According to French regulations concerning organ procurement in brain-dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain-injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. This suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians, which should help preserve population trust regarding organ procurement and provide a framework for medical decision. This text has been endorsed by the Sfar.

Long-term white matter changes after severe traumatic brain injury: a 5-year prospective cohort.

BACKGROUND AND PURPOSE: Extensive white matter damage has been documented in patients with severe traumatic brain injury, yet how this damage evolves in the long term is not well understood. We used DTI to study white matter changes at 5 years after traumatic brain injury. MATERIALS AND METHODS: There were 8 healthy control participants and 13 patients with severe traumatic brain injury who were enrolled in a prospective observational study, which included clinical assessment and brain MR imaging in the acute setting (< 6 weeks) and 2 years and 5 years after injury. Only subjects with mild to moderate disability or no disability at 1 year were included in this analysis. DTI parameters were measured in 20 different brain regions and were normalized to values obtained in an age-matched control group. RESULTS: In the acute setting, fractional anisotropy was significantly lower in the genu and body of the corpus callosum and in the bilateral corona radiata in patients compared with control participants, whereas radial diffusivity was significantly (P < .05) higher in these tracts. At 2 years, fractional anisotropy in these tracts had further decreased and radial diffusivity had increased. No significant changes were detected between 2 and 5 years after injury. The baseline radial diffusivity and fractional anisotropy values in the anterior aspect of the brain stem, genu and body of the corpus callosum, and the right and left corona radiata were significantly (P < .05) associated with neurocognitive sequelae (including amnesia, aphasia, and dyspraxia) at year 5. CONCLUSIONS: DTI changes in major white matter tracts persist up to 5 years after severe traumatic brain injury and are most pronounced in the corpus callosum and corona radiata. Limited structural change is noted in the interval between 2 and 5 years.

[Euthanasia, assisted suicide and palliative care: a review by the Ethics Committee of the French Society of Anaesthesia and Intensive Care]. / Fin de vie, euthanasie et suicide assisté : une mise au point de la Société française d'anesthésie et de réanimation (Sfar).

CONTEXT: Management of the end of life is a major social issue which was addressed in France by law, on April 22nd 2005. Nevertheless, a debate has emerged within French society about the legalization of euthanasia and/or assisted suicide (E/AS). This issue raises questions for doctors and most especially for anesthetists and intensive care physicians. OBJECTIVE: To highlight, dispassionately and without dogmatism, key points taken from the published literature and the experience of countries which have legislated for E/AS. RESULTS: The current French law addresses most of the end of life issues an intensive care physician might encounter. It is credited for imposing palliative care when therapies have become senseless and are withdrawn. However, this requirement for palliative care is generally applied too late in the course of a fatal illness. There is a great need for more education and stronger incentives for early action in this area. On the rare occasions when E/AS is requested, either by the patient or their loved-ones, it often results from a failure to consider that treatments have become senseless and conflict with patient's best interest. The implementation of E/AS cannot be reduced to a simple affirmation of the Principle of autonomy. Such procedures present genuine difficulties and the risk of drift. CONCLUSION: We deliver a message of prudence and caution. Should we address painful end of life and moral suffering issues, by suppressing the subject, i.e. ending the patient's life, when comprehensive palliative care has not first been fully granted to all patients in need of it ?

[Interaction brain-lungs]. / Interaction cerveau-poumon.

The brain and the lungs interact early and rapidly when hit by a disease process. Often well tolerated by the healthy brain, an impaired respiratory function may deteriorate further a "sick" brain. Hypoxemia is a prognostic factor in the brain-injured patients. At the opposite, an acute brain damage early impacts the lung function. Local brain inflammation spreads rapidly to the lung. It initiates an immunological process weakening the lungs and increasing its susceptibility to infection and mechanical ventilation. Sometimes this process is preceded by a swelling lesion, known as neurogenic pulmonary oedema, resulting from an sympathetic overstimulation which usually follows an intense and brutal surge of intracranial pressure. The management of brain-injured patients has to be directed toward the protection of both the brain and lung. Neuronal preservation is crucial, because of the lack of regenerative potential in the brain, unlike the lung. A compromise must be obtained between the cerebral and pulmonary treatments although they may conflict in some situations.

Effect of continuous cerebrospinal fluid drainage on therapeutic intensity in severe traumatic brain injury.

BACKGROUND: The aim of this study in patients with traumatic brain injury (TBI) was to assess the effectiveness of continuous cerebrospinal fluid (CSF) drainage in controlling intracranial pressure (ICP) and minimizing the use of other ICP-lowering interventions potentially associated with serious adverse events. METHODS: We studied 20 TBI patients. In each patient, we compared four consecutive 12-hour periods covering the 24 hours before CSF drainage (NoDr1 and NoDr2) and the 24 first hours of drainage (Dr1 and Dr2). During each period, we recorded ICP, cerebral perfusion pressure (CPP), sedation, propofol infusion rate, and number of hypertonic saline boluses. RESULTS: With continuous CSF drainage, ICP decreased significantly from 18 ± 6 mmHg (NoDr1) and 19 ± 7 mmHg (NoDr2) to 11 ± 5 mmHg (Dr1) and 12 ± 7 mmHg (Dr2). CPP increased significantly with drainage. Drainage led to a significant decrease in the number of hypertonic saline boluses required for ICP elevation, from 35 in 16 patients (80%) (NoDr1/2) to eight in five patients (25%) (Dr3/4). Drainage was not associated with changes in the midazolam or sufentanil infusion rates. The propofol infusion rate was non-significantly lower with drainage. No significant differences in serum sodium, body temperature, or PaCO(2) occurred across the four 12-hour periods. CONCLUSION: CSF drainage may not only lower ICP levels, but also decreases treatment intensity during the 24 hours following EVD placement in TBI patients. Because EVD placement may be associated with adverse event, the exact role for each of the available ICP-lowering interventions remains open to discussion.

[Critical appraisal of organ procurement under Maastricht 3 condition]. / Analyse critique du prélèvement en condition M3 de Maastricht.

The ethics committee of the French Society of Anesthesia and Intensive Care (Sfar) has been requested by the French Biomedical Agency to consider the issue of organ donation in patients after a decision of withdrawing life supporting therapies has been taken. This category of organ donation is performed in the USA, Canada, United Kingdom, the Netherlands and Belgium. The three former countries have published recommendations, which formalize procedures and operations. The Sfar ethics committee has considered this issue and envisioned the different aspects of the whole process. Consequently, it sounds a note of caution regarding the applicability of this type of organ procurement in unselected patient following a decision to withdraw life supporting therapies. According to the French regulation concerning organ procurement in brain dead patients, the committee stresses the need to restrict this specific way of procurement to severely brain injured patients, once confirmatory investigations predicting a catastrophic prognosis have been performed. It suggests that the nature of the confirmatory investigation required should be formalized by the French Biomedical Agency on behalf of the French parliamentarians. This should help preserving population trust regarding organ procurement and provide a framework to medical decision. This text has been endorsed by the Sfar.

[Circumcision in children: an organizational or an ethical challenge?]. / Circoncision chez l'enfant : une simple question d'organisation des soins ou un enjeu éthique ?

OBJECTIVES: To review society, ethical and anaesthesiological issues related to circumcision in children. STUDY DESIGN: Review. METHODS: Pubmed search and expert opinion RESULTS: Circumcision concerns 30 of male world population. Reasons are ritual, medical and hygienic. In Muslims, circumcision is usual performed before the age of six. Surgery is performed at best under sevoflurane general anaesthesia and a penile bloc. Level 1 and level 2 antalgics are used for 72 hours, once the bloc has elapsed. In Jews, circumcision is performed soon after birth, in the community. Emla is the most convenient antalgics in this case. Except in case of emergency, circumcision under general anaesthesia should be delayed after 3 months as general anaesthesia is suspect to exert cerebral toxicity. Before the age of one year, there is a risk of increased respiratory problems following general anesthesia. Therefore, circumcision under general anaesthesia should be performed after one year of age. Circumcision may represent an adjunct to limit AIDS transmission in endemic countries. CONCLUSION: The ethical point associated with circumcision is to allow best analgesia, in a way matching child's age. Analgesia, is achievable by both the surgeon and the anesthesiologist.

Probing consciousness with event-related potentials in the vegetative state.

OBJECTIVE: Probing consciousness in noncommunicating patients is a major medical and neuroscientific challenge. While standardized and expert behavioral assessment of patients constitutes a mandatory step, this clinical evaluation stage is often difficult and doubtful, and calls for complementary measures which may overcome its inherent limitations. Several functional brain imaging methods are currently being developed within this perspective, including fMRI and cognitive event-related potentials (ERPs). We recently designed an original rule extraction ERP test that is positive only in subjects who are conscious of the long-term regularity of auditory stimuli. METHODS: In the present work, we report the results of this test in a population of 22 patients who met clinical criteria for vegetative state. RESULTS: We identified 2 patients showing this neural signature of consciousness. Interestingly, these 2 patients showed unequivocal clinical signs of consciousness within the 3 to 4 days following ERP recording. CONCLUSIONS: Taken together, these results strengthen the relevance of bedside neurophysiological tools to improve diagnosis of consciousness in noncommunicating patients.

[Anaesthesia and Parkinson's disease]. / Anesthésie et maladie de Parkinson.

OBJECTIVE: The purpose of this review is to draw up a statement on current knowledge available on perioperative management of Parkinson's disease patients. STUDY DESIGN: Review. DATA SYNTHESIS: In France, approximately 150,000 persons suffer from Parkinson's disease, a neurodegenerative disorder of central nervous system. Parkinson's disease results in selective and irreversible loss of dopaminergic neurons in the substantia nigra pars compacta. Medications based on dopaminergic drugs are used to control motor symptoms and improve motor function. Development of surgical approach, especially deep brain stimulation, has revolutionized the medical management of many patients with Parkinson's disease. Anesthesia of these patients remains a challenge for the clinician. The aim of this review is to describe anaesthetic considerations of patients with Parkinson's disease and to discuss management of antiparkinsonians medications during the perioperative period.

[Inflammation and acute brain injuries in intensive care]. / Inflammation et lésions cérébrales aiguës en anesthésie réanimation.

Patients with acute brain injuries or susceptibility to post-surgery stroke are a major therapeutic challenge for intensive care and anaesthesiology medicine. The control of systemic stress involved in brain damage is necessary to reduce the frequency and severity of secondary brain lesions. Inflammation is known to be directly involved in acute brain lesions. The brain is a major participant in inflammation control through activation or inhibition effects. The exact mechanisms involved in deleterious effects following acute brain injuries due to inflammation are still unknown. This non-exhaustive study will expose the principal processes involved in inflammatory brain disease and explain the consequences of peripheral inflammation for the brain. Neuroprotection strategies in acute neuroinflammation will be reported with a focus on anaesthetic agents and the inflammation cascade.

[Superior vena cava syndrome: cause of secondary raise of intracranial pressure after traumatic brain injury]. / Syndrome cave supérieur: une cause secondaire d'élévation de la pression intracrânienne après traumatisme crânien grave.

A 41-year-old male is admitted for cranial trauma, having fallen from his own height. His state of extreme agitation imposes sedation, intubation and mechanical ventilation. A CT-scan reveals acute right hemispheric subdural haematoma, with discrete midline shift, and diffuse cerebral oedema. ICP-monitoring reveals severely increased intracranial pressure, which is responsive to routine medical neuroprotective treatment. Ten days after admission, sedation and neuroprotective treatment is gradually withdrawn. At the end of the second week, a secondary ascent in ICP is observed. The presence of a right subclavian central venous line, in combination with the strong inflammatory response and septic state of the patient, has caused bilateral thrombosis of subclavian and internal jugular veins. This superior vena cava syndrome (SVCS) impedes cerebral venous drainage, thus raising ICP. Within a few days of anticoagulant therapy, SVCS resolved. Impeded cerebral venous drainage is often forgotten or ignored as a cause of secondary elevated ICP. In face of persisting or recurring raised ICP and cerebral oedema, or apparition of communicant hydrocephalus, cerebral venous drainage should be investigated.

[Sedation and analgesia for the brain-injured patient]. / La sédation-analgésie du patient cérébrolésé.

Sedation-analgesia occupies an essential place in the specific therapeutic arsenal of the brain-injured patients. The maintenance of the perfusion of the brain, its relaxation and its protection are the fundamental objectives whose finality is to avoid the extension of the lesions and to preserve the neuronal capital. Sedation is instituted when patients are severely agitated or present a deterioration of their state of consciousness (GCS< or =8). Under cover of mechanical ventilation, sedation is the first line treatment of intracranial hypertension, a common pathway of various acute brain diseases of traumatic, vascular or other origin. The use of the combination of hypnotic and opioids is the rule. The combined action of these two classes reinforces and improves their sedative effects. Midazolam is the 2 benzodiazepine of reference. Propofol is more and more frequently added to the combination of hypnotic and opioids. The "propofol infusion syndrome" is a severe limitation to its long term administration in particular among patients presenting a severe septic or inflammatory state. Propofol will be imperatively stopped in the event of metabolic acidosis, rhabdomyolysis, acute renal insufficiency, hyperkaliemia or increase in the blood triglyceride levels. The use of thiopental is restricted to the most severe cases. Its use as a monotherapy at high doses is abandoned to the profit of a co-administration with midazolam or even with the combination of midazolam and propofol. Thiopental overdose is very frequent in the event of associated hypothermia. Etomidate does not have its place apart from induction in fast sequence. The neuro-protective effects of ketamine require to be demonstrated in man before being recommended routinely. Withdrawal of sedation can be responsible for a state of agitation which can be controlled by neuroleptics.

Does the brain become heavier or lighter after trauma?

An uncontrolled rise in intracranial pressure is probably the most common cause of death in traumatic brain-injured patients. The intracranial pressure rise is often due to cerebral oedema. Diffusion-weighted imaging has been extensively used to study cerebral oedema formation after trauma in experimental studies. Nevertheless, this technology is difficult to perform at the acute phase, especially in unstable head trauma patients. For these reasons, a safe examination allowing us to better understand the pathophysiology of cerebral oedema formation in such patients would be of great interest. Radiological attenuation is linearly correlated with estimated specific gravity in human tissue. This property gives the opportunity to measure in vivo the volume, weight and specific gravity of any tissue by computed tomography. We recently developed a software package (BrainView) for Windows workstations, providing semi-automatic tools for brain analysis from DICOM images obtained from cerebral computed tomography. In this review, we will discuss the results of the in vivo analysis of brain weight, volume and specific gravity and consider the use of this software as a new technology to improve our knowledge of cerebral oedema formation after trauma and to evaluate the severity of traumatic brain-injured patients.

[Endovascular treatment of vasospasm following subarachnoid aneurysmal haemorrhage]. / Traitements endovasculaires du vasospasme de l'hémorragie méningée anévrysmale.

An endovascular treatment of vasospasm following a subarachnoid aneurysmal haemorrhage is to be implemented if the patient presents clinical or biological symptoms arguing for brain ischemia in conjunction with increased Doppler velocities despite well controlled systemic haemodynamic. Treatment might be either pharmacological or haemodynamic. Calcium and phosphodiesterase inhibitors can be administered. The former could also provide a neuroprotective effect as compared to the latter. In Europe, nimodipine is widely used whereas nicardipine and verapamil are the major molecules administered in North America where iv nimodipine is not FDA approved. Papaverine is less used nowadays because of its short duration of action and of the risk of aggravation of raised intracranial pressure. Balloon angioplasty has a long lasting effect but can be applied only to proximal spasm. Complications of its use are rare but life threatening. In some cases, both the pharmacological approach and the mechanical approach are used in combination.

[On the difficulty of Traumatic brain injured patients end-of-life decisions]. / Traumatisés crâniens graves: jusqu'où aller?

Traumatic brain injury occurs abruptly, involves multiple specialized teams, solicits the health care system in its emergency dimension and engages the well being of the patient and his relatives for a life time period. Clinicians are faced with issues of uppermost importance: medical issues such as predicting long term neurological outcome of the comatose patient, ethical issues because of the influence of intensive care on the long term survival of patients in vegetative and minimally conscious state, legal issues as the consequence of the current law which has set a new concept of proportionality of care, social issues as the result of the very high cost of these pathologies. This review will focus on the brain explorations that are required such as CT scan, evoked potentials, electroencephalography, magnetic resonance imaging and magnetic resonance spectroscopy to provide to the clinician a multimodal assessment of the brain state to predict outcome of coma. Such assessment is mandatory to answer the crucial question of proportionality of care in these patients. However, these techniques need further validation on large series of patients before being useful on clinical practice.