[Show abstract][Hide abstract] ABSTRACT: Purpose Dysglycemia is a characteristic feature of critical illness associated with adverse outcome. Whether dysglycemia contributes to brain dysfunction during critical illness and long-term neurological complications is unclear. We give an overview of glucose metabolism in the brain and review the literature on critical illness-induced dysglycemia and the brain. Methods Medline database search using relevant search terms on dysglycemia, critical illness, acute brain injury/dysfunction, and randomized controlled trial. Results Hyperglycemia has been associated with deleterious effects on the nervous system. Underlying mechanisms in critical illness remain largely speculative and are often extrapolated from knowledge in diabetes mellitus. Increased hyperglycemia-induced blood–brain barrier permeability, oxidative stress, and microglia activation may play a role and compromise neuronal and glial cell integrity. Hypoglycemia is feared as critically ill patients cannot recognize or communicate hypoglycemic symptoms, which furthermore are masked by sedation and analgesia. However, observational data on the impact of brief hypoglycemia on the brain in critical illness are controversial. Secondary analysis of two large randomized studies suggested neuroprotection by strict glycemic control with insulin during intensive care, with lowered intracranial pressure, reduction of seizures, and better long-term rehabilitation in patients with isolated brain injury, and reduced incidence of critical illness polyneuromyopathy in the general critically ill patient population. Several subsequent studies failed to reproduce neurological benefit, likely explained by methodological issues, which include divergent achieved glucose levels and inaccurate glucose monitoring tools. Conclusions Preventing hyperglycemia during critical illness holds promise as a neuroprotective strategy to preserve brain cell viability and prevent acute brain dysfunction and long-term cognitive impairment in survivors.
Intensive Care Medicine 12/2014; · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: La sindrome di Guillain-Barré è la prima causa di paralisi acuta estensiva nei paesi industrializzati dopo la scomparsa della poliomielite. La sua diagnosi resta essenzialmente clinica. Dal momento che la malattia è evolutiva, un esame neurologico preciso e ripetuto permette, il più delle volte, di confermare la diagnosi e di giudicare l’evolutività e la potenziale gravità. Gli esami complementari sono utili soprattutto per escludere un’altra patologia, in particolare una meningoradicolite attraverso la puntura lombare e una lesione midollare attraverso una risonanza magnetica (RM). Un elemento essenziale della gestione è l’identificazione dei pazienti a rischio di sviluppare un’insufficienza respiratoria acuta. L’altro risvolto terapeutico è la scelta terapeutica tra gli scambi plasmatici e le immunoglobuline endovenose.
[Show abstract][Hide abstract] ABSTRACT: El síndrome de Guillain-Barré es la primera causa de parálisis aguda extensa en los países desarrollados desde la desaparición de la poliomielitis. Su diagnóstico se basa esencialmente en la clínica. Se trata de una patología evolutiva, por lo que una exploración neurológica minuciosa y repetida permite confirmar el diagnóstico y valorar su posible evolución y gravedad potencial. Las pruebas complementarias son útiles para descartar otras patologías, especialmente la meningorradiculitis, por punción lumbar, y la afectación medular, por resonancia magnética (RM). Un elemento esencial del tratamiento es la identificación del paciente con riesgo de desarrollar insuficiencia respiratoria aguda. Otro punto importante del tratamiento es la elección entre la plasmaféresis y la terapia con inmunoglobulinas intravenosas.
[Show abstract][Hide abstract] ABSTRACT: “Brain Disorders in Critical Illness”, edited by Robert Stevens, Tarek Sharshar and Wes Ely, offers an overview of critical illness brain dysfunction (delirium, coma, encephalopathy), a major problem in intensive care with potentially debilitating long-term consequences. Chapters on epidemiology, outcomes, relevant behavioral neurology and biological mechanisms of acute brain dysfunction are written by an interdiscplinary panel of leading experts in the field.
07/2014; Cambridge University Press., ISBN: 9781107029194
[Show abstract][Hide abstract] ABSTRACT: Many patients admitted to the intensive care unit (ICU) have pre-existing or acquired neurological disorders which significantly affect their short-term and long-term outcomes. The ESICM NeuroIntensive Care Section convened an expert panel to establish a pragmatic approach to neurological examination (NE) of the critically ill patient.
The group conducted a comprehensive review of published studies on the NE of patients with coma, delirium, seizures and neuromuscular weakness in critically ill patients. Quality of data was rated as high, moderate, low, or very low, and final recommendations as strong, weak, or best practice. The group made the following recommendations: (1) NE should be performed in all patients admitted to ICUs; (2) NE should include an assessment of consciousness and cognition, brainstem function, and motor function; (3) sedation should be managed to maximize the clinical detection of neurological dysfunction, except in patients with reduced intracranial compliance in whom withdrawal of sedation may be deleterious; (4) the need for additional tests, including neurophysiological and neuroradiological investigations, should be guided by the NE; (5) selected features of the NE have prognostic value which should be considered in well-defined patient populations.
European Journal of Intensive Care Medicine 02/2014; · 5.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SUMMARY The role of Campylobacter jejuni as the triggering agent of Guillain-Barré syndrome (GBS) has not been reassessed since the end of the 1990s in France. We report that the number of C. jejuni-related GBS cases increased continuously between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0·007).
Epidemiology and Infection 10/2013; · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sepsis-associated brain dysfunction has been linked to white matter lesions (leucoencephalopathy) and ischemic stroke. Our objective was to assess the prevalence of brain lesions in septic shock patients requiring magnetic resonance imaging (MRI) for an acute neurological change.
Seventy-one septic shock patients were included in a prospective observational study. Patients underwent daily neurological examination. Brain MRI was obtained in patients who developed focal neurological deficit, seizure, coma, or delirium. Electroencephalogy was performed in case of coma, delirium or seizure. Leucoencephalopathy was graded and considered present when white matter lesions were either confluent or diffuse. Patient outcome was evaluated at 6 months using the Glasgow Outcome Scale (GOS).
We included 71 patients with a median age of 65 yrs (56-76) and new simplified acute physiology score (SAPS II) at admission of 49 (38-60). MRI was indicated upon focal neurological sign in 13 (18%), seizure in 7 (10%), coma in 33 (46%) and delirium in 35 (49%). MRI was normal in 37 patients (52%) and showed cerebral infarcts in 21(29%), leucoencephalopathy in 15 (21%), and mixed lesions in 6 (8%). EEG malignant pattern was more frequent in patients with ischemic stroke or leukoencephalopathy. Ischemic stroke was independently associated with disseminated intravascular coagulation (DIC), focal neurological signs, increased mortality and worse GOS at six months.
Brain MRI in septic shock patients who developed acute brain dysfunction can reveal leukoencephalopathy and ischemic stroke, which is associated with DIC and increased mortality.
Critical care (London, England) 09/2013; 17(5):R204. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurological assessment of critically ill patients requires physical examination although coexisting cognitive impairment, sedative or paralytic medication, endotracheal intubation, mechanical ventilation, neuromuscular weakness, injuries or surgery involving extracranial tissues may limit sensitivity and specificity of findings. Notwithstanding these constraints, neurological signs and syndromes are valuable indicators of severity of illness and prognosis. Common neurologic syndromes in ICU patients include disturbances in the level of arousal and in cognition, delirium, seizures, generalized weakness, and focal neurological deficits. Whenever possible, neurological examination should include an assessment of mental status, attention, cranial nerves, motor and sensory findings. If there is persisting diagnostic uncertainty additional testing should be sought. Computed tomography of the head should be obtained whenever there is a new onset of seizures, focal neurologic deficits, alteration of mental status or loss of consciousness which are not immediately reversible or explainable. Magnetic resonance imaging has greater sensitivity for demyelinating and inflammatory diseases, hyperacute ischemic stroke, microhemorrhagic lesions, anoxic-ischemic damage, and disorders affecting the white matter and the brainstem. Electroencephalography is needed if seizures or status epilepticus are suspected as a cause or consequence of acute brain dysfunction. Somatosensory evoked potentials, best studied in patients with anoxic brain injury may help with prognostication following cardiac arrest. Electromyography and nerve conduction velocities should be obtained when neuromuscular weakness is severe or cannot be assessed clinically.
Brain Disorders in Critical Illness, 1 edited by Robert D Stevens, Tarek Sharshar, E Wesley Ely, 09/2013: chapter Diagnosis of Brain Dysfunction: pages 219-228; Cambridge University Press., ISBN: 9781107029194
[Show abstract][Hide abstract] ABSTRACT: We investigated effects of transcranial direct-current stimulation (tDCS) on the diaphragmatic corticospinal pathways in healthy human. Anodal, cathodal, and sham tDCS were randomly applied upon the left diaphragmatic motor cortex in twelve healthy right-handed men. Corticospinal pathways excitability was assessed by means of transcranial magnetic stimulation (TMS) elicited motor-evoked-potential (MEP). For each tDCS condition, MEPs were recorded before (Pre) tDCS then after 10minutes (Post1, at tDCS discontinuation in the anodal and cathodal sessions) and 20minutes (Post2). As result, both anodal and cathodal tDCS significantly decreased MEP amplitude of the right hemidiaphragm at both Post1 and Post2, versus Pre. MEP amplitude was unchanged versus Pre during the sham condition. The effects of cathodal and anodal tDCS applied to the diaphragm motor cortex differ from those observed during tDCS of the limb motor cortex. These differences may be related to specific characteristics of the diaphragmatic corticospinal pathways as well as to the diaphragm's functional peculiarities compared with the limb muscles.
[Show abstract][Hide abstract] ABSTRACT: Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood--brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke's encephalopathy. Modulation of microglial activation, prevention of blood--brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.
[Show abstract][Hide abstract] ABSTRACT: Sepsis is a major cause of mortality and morbidity in intensive care units (ICU). Acute and longterm brain dysfunctions have been demonstrated both in experimental models and septic patients. Sepsis-associated encephalopathy (SAE) is an early and frequent manifestation, but is under diagnosed, due to the absence of specific biomarkers and to confounding factors such as sedatives used in the ICU. SAE may have acute and long-term consequences including development of autonomic dysfunction, delirium and cognitive impairment. The mechanisms of SAE involve mitochondrial and vascular dysfunctions, oxidative stress, neurotransmission disturbances, inflammation and cell death. Here we review specific evidence that links bioenergetics, mitochondrial dysfunction and oxidative stress in the setting of brain dysfunctions associated to sepsis.
[Show abstract][Hide abstract] ABSTRACT: The scientific community has agreed upon developing accurate monitoring of tissue perfusion and oxygenation to improve the management of subjects with sepsis. This pilot study aimed to investigate the feasibility of targeting tissue oxygen saturation (StO(2)) in addition to the currently recommended resuscitation goals, central venous pressure, mean arterial pressure and central venous oxygen saturation, in patients with severe sepsis or septic shock. A pilot, single-centre, randomised, non-blinded trial recruited 30 subjects with severe sepsis upon intensive care unit admission at an academic medical centre in France. Subjects were randomly assigned to a 6 h resuscitation strategy following the Surviving Sepsis Campaign guidelines with (experimental) or without (control) StO(2). StO(2) was measured over several muscles (masseter, deltoid and pectoral or thenar muscles), and a StO(2) above 80 % over at least 2 muscles was the therapeutic goal. The primary outcome was evaluated as follows: 7-day mortality or worsening of SOFA score between day 7 and study onset, i.e., DSOFA > 0). Thirty subjects were included in the study over a period of 40 weeks. Fifteen subjects were included in each group. Monitoring of StO(2) over three areas was performed in the experimental group. However, measures over the pectoral muscle provided poor results. At study day 7, there were 5/15 (33.3 %) subjects who died or had a DSOFA > 0 in the experimental arm and 4/15 (26.6 %) who died or had a DSOFA > 0 in the control arm (p = 1.00). This pilot study was the first randomised controlled trial using an algorithm derived from the SSC recommendations, which included StO(2) as a treatment goal. However, the protocol showed no clear trend for or against targeting StO(2).
International Journal of Clinical Monitoring and Computing 02/2013;
[Show abstract][Hide abstract] ABSTRACT: Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.
[Show abstract][Hide abstract] ABSTRACT: Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required.
Critical care (London, England) 01/2013; 17(1):201. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock.
Prospective interventional study.
Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals.
Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock.
Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes.
Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted.
More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.
PLoS ONE 01/2013; 8(11):e80190. · 3.53 Impact Factor