Management of neurological complications of infective endocarditis in ICU patients

Patients with infective endocarditis (IE) are generally referred to the intensive care unit (ICU) for one or more organ dysfunctions caused by complications of IE. Neurologic events are frequent causes of ICU admission in patients with IE. They can arise through various mechanisms consisting of stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left-sided abnormalities of native or prosthetic valves. Occlusion of cerebral arteries, with stroke or transient ischemic attack, accounts for 40% to 50% of the central nervous system complications of IE. CT scan is the most easily feasible neuroimaging in critically unstable patients. However, magnetic resonance imaging is more sensitive and when performed should follow a standardized protocol. In patients with ischemic stroke who are already receiving oral anticoagulant therapy, this treatment should be replaced by unfractionated heparin for at least 2 weeks with a close monitoring of coagulation tests. Mounting evidence shows that, for both complicated left-sided native valve endocarditis and Staphylococcus aureus prosthetic valve endocarditis, valve replacement combined with medical therapy is associated with a better outcome than medical treatment alone. In a recent series, approximately 50% of patients underwent valve replacement during the acute phase of IE before completion of antibiotic treatment. After a neurological event, most patients have at least one indication for cardiac surgery. Recent data from literature suggest that after a stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Neurologic complications of IE contribute to a severe prognosis in ICU patients. However, patients with only silent or transient stroke had a better prognosis than patients with symptomatic events. In addition, more than neurologic event per se, a better predictor of mortality is neurologic dysfunction, which is associated with location and extension of brain damage. Patients with severe neurological impairment and those with brain hemorrhage have the worse outcome

Intentional overdose with insulin: prognostic factors and toxicokinetic/toxicodynamic profiles

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Understanding brain dysfunction in sepsis

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 of 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

Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects

Additional file 1: Figure S1. Flowchart of patients included between 2012 and 2014

Hyperglycaemia and apoptosis of microglial cells in human septic shock

International audienceIntroductionThe effect of hyperglycaemia on the brain cells of septic shock patients is unknown. The objective of this study was to evaluate the relationship between hyperglycaemia and apoptosis in the brains of septic shock patients.MethodsIn a prospective study of 17 patients who died from septic shock, hippocampal tissue was assessed for neuronal ischaemia, neuronal and microglial apoptosis, neuronal Glucose Transporter (GLUT) 4, endothelial inducible Nitric Oxide Synthase (iNOS), microglial GLUT5 expression, microglial and astrocyte activation. Blood glucose (BG) was recorded five times a day from ICU admission to death. Hyperglycaemia was defined as a BG 200 mg/dL g/l and the area under the BG curve (AUBGC) > 2 g/l was assessed.ResultsMedian BG over ICU stay was 2.2 g/l. Neuronal apoptosis was correlated with endothelial iNOS expression (rho = 0.68, P = 0.04), while microglial apoptosis was associated with AUBGC > 2 g/l (rho = 0.70; P = 0.002). Neuronal and microglial apoptosis correlated with each other (rho = 0.69, P = 0.006), but neither correlated with the duration of septic shock, nor with GLUT4 and 5 expression. Neuronal apoptosis and ischaemia tended to correlate with duration of hypotension.ConclusionsIn patients with septic shock, neuronal apoptosis is rather associated with iNOS expression and microglial apoptosis with hyperglycaemia, possibly because GLUT5 is not downregulated. These data provide a mechanistic basis for understanding the neuroprotective effects of glycemic control

Changes in CRH and ACTH Synthesis during Experimental and Human Septic Shock

Context The mechanisms of septic shock-associated adrenal insufficiency remain unclear. This study aimed at investigating the synthesis of corticotropin-releasing hormone (CRH) and vasopressin (AVP) by parvocellular neurons and the antehypophyseal expression of ACTH in human septic shock and in an experimental model of sepsis. Objective To test the hypothesis that ACTH secretion is decreased secondarily to alteration of CRH or AVP synthesis, we undertook a neuropathological study of the antehypophyseal system in patients who had died from septic shock and rats with experimental faecal peritonitis. Methods Brains obtained in 9 septic shock patients were compared to 10 nonseptic patients (controls). Parvocellular expression of AVP and CRH mRNA were evaluated by in situ hybridization. Antehypophyseal expression of ACTH, vasopressin V1b and CRH R1 receptors and parvocellular expression of iNOS in the PVN were evaluated by immunohistochemistry. The same experiments were carried out in a fecal peritonitis-induced model of sepsis. Data from septic rats with (n = 6) or without (n = 10) early death were compared to sham-operated (n = 8) animals. Results In patients and rats, septic shock was associated with a decreased expression of ACTH, unchanged expression of V1B receptor, CRHR1 and AVP mRNA, and increased expression of parvocellular iNOS compared to controls. Septic shock was also characterized by an increased expression of CRH mRNA in rats but not in patients, who notably had a greater duration of septic shock. Conclusion The present study suggests that in humans and in rats, septic shock is associated with decreased ACTH synthesis that is not compensated by its two natural secretagogues, AVP and CRH. One underlying mechanism might be increased expression of iNOS in hypothalamic parvocellular neurons

Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

French Artesunate Working GroupInternational audienceArtesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate

Mastering the brain in critical conditions:an update

Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events-vascular damage in strokes and biomechanical damage in traumatic brain injuries-they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course

How valuable are your customers in the brand value co-creation process? The development of a Customer Co-Creation Value (CCCV) scale.

Despite an increasing amount of research on co-creation of value, in general, research on brand value co-creation remains limited. Particularly, how much value customers contribute to the brand value co-creation process remains unclear. This research develops in a series of eight studies the Customer Co-Creation Value (CCCV) measurement scale that helps firms assess the value of customers in the brand value co-creation process. The findings reveal that CCCV is a multidimensional construct consisting of two higher-order factors and seven dimensions: customer-owned resources (including brand knowledge, brand skills, brand creativity, and brand connectedness) and customer motivation (comprising brand passion, brand trust, and brand commitment). Further, the CCCV scale reliably and validly gauges the value customers contribute to a firm's brand. The CCCV framework helps marketing managers understand how customers can contribute to a firm's brand value cocreation efforts and how much value customers contribute to a brand in the co-creation process