Correction to: Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

Following publication of the original article [1], we were notified that the collaborators' names part of the "The TBI Collaborative" group has not been indexed in Pubmed. Below the collaborators names full list.

Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP). AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients. METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP. RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]. CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

Clinical characteristics and outcomes of witnessed hypothermic cardiac arrest: A systematic review on rescue collapse.

AIMS: Cardiac arrest related to accidental hypothermia may occur at temperatures below 32 °C. Our goal was to describe the clinical characteristics and outcomes of patients who suffered from witnessed hypothermic cardiac arrest (CA) and assess the occurrence of hypothermic CA as a function of patient body temperature. METHODS: We conducted a systematic review of the literature on cases of hypothermic CA due to rescue collapse. Patient information data from hypothermic CA patients were collected and combined with additional unpublished data to assess the clinical characteristics and outcome of hypothermic CA patients. RESULTS: A total of 214 patients was included in this systematic review. Of the 206 witnessed hypothermic CA patients with a recorded body temperature, the average body temperature was 23.9 ± 2.7 °C with five patients (2.4%) having a core body temperature of >28 °C. The highest temperature of a patient surviving hypothermic witnessed cardiac arrest without other associated risk factors for cardiac arrest was 29.4 °C. The first recorded cardiac rhythm was asystole in 33 of the 112 patients (30%) for whom this information was available. The survival rate at hospital discharge of these hypothermic cardiac arrest patients was 73% (153 of 210 patients) and most survivors had favourable neurological outcome (89%; 102 of 105 patients). CONCLUSIONS: CA that is solely caused by hypothermia did not occurs for patients with a body temperature >30 °C. Our findings provide valuable new information that can be incorporated into the international clinical management guidelines of accidental hypothermia.

Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations

Objective To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. Design A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. Methods Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions­using a sequential approach to avoid biases and misinterpretations­was used to generate the final consensus statement. Results The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. Conclusions We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data

Is trauma in Switzerland any different? epidemiology and patterns of injury in major trauma - a 5-year review from a Swiss trauma centre.

UNLABELLED: Switzerland, the country with the highest health expenditure per capita, is lacking data on trauma care and system planning. Recently, 12 trauma centres were designated to be reassessed through a future national trauma registry by 2015. Lausanne University Hospital launched the first Swiss trauma registry in 2008, which contains the largest database on trauma activity nationwide. METHODS: Prospective analysis of data from consecutively admitted shock room patients from 1 January 2008 to 31 December 2012. Shock room admission is based on physiology and mechanism of injury, assessed by prehospital physicians. Management follows a surgeon-led multidisciplinary approach. Injuries are coded by Association for the Advancement of Automotive Medicine (AAAM) certified coders. RESULTS: Over the 5 years, 1,599 trauma patients were admitted, predominantly males with a median age of 41.4 years and median injury severity score (ISS) of 13. Rate of ISS >15 was 42%. Principal mechanisms of injury were road traffic (40.4%) and falls (34.4%), with 91.5% blunt trauma. Principal patterns were brain (64.4%), chest (59.8%) and extremity/pelvic girdle (52.9%) injuries. Severe (abbreviated injury scale [AIS] score ≥ 3) orthopaedic injuries, defined as extremity and spine injuries together, accounted for 67.1%. Overall, 29.1% underwent immediate intervention, mainly by orthopaedics (27.3%), neurosurgeons (26.3 %) and visceral surgeons (13.9%); 43.8% underwent a surgical intervention within the first 24 hours and 59.1% during their hospitalisation. In-hospital mortality for patients with ISS >15 was 26.2%. CONCLUSION: This is the first 5-year report on trauma in Switzerland. Trauma workload was similar to other European countries. Despite high levels of healthcare, mortality exceeds published rates by >50%. Regardless of the importance of a multidisciplinary approach, trauma remains a surgical disease and needs dedicated surgical resources.

[Multimodal neuromonitoring for the critical care management of acute coma]. / Neuromonitorage après coma aigu aux soins intensifs.

Management of neurocritical care patients is focused on the prevention and treatment of secondary brain injury, i.e. the number of pathophysiological intracerebral (edema, ischemia, energy dysfunction, seizures) and systemic (hyperthermia, disorders of glucose homeostasis) events that occur following the initial insult (stroke, hemorrhage, head trauma, brain anoxia) that may aggravate patient outcome. The current therapeutic paradigm is based on multimodal neuromonitoring, including invasive (intracranial pressure, brain oxygen, cerebral microdialysis) and non-invasive (transcranial doppler, near-infrared spectroscopy, EEG) tools that allows targeted individualized management of acute coma in the early phase. The aim of this review is to describe the utility of multimodal neuromonitoring for the critical care management of acute coma.

[Therapeutic hypothermia for severe traumatic brain injury]. / Hypothermie thérapeutique en traumatologie crânienne grave.

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature.

PURPOSE: To assess the sensitivity and false positive rate (FPR) of neurological examination and somatosensory evoked potentials (SSEPs) to predict poor outcome in adult patients treated with therapeutic hypothermia after cardiopulmonary resuscitation (CPR). METHODS: MEDLINE and EMBASE were searched for cohort studies describing the association of clinical neurological examination or SSEPs after return of spontaneous circulation with neurological outcome. Poor outcome was defined as severe disability, vegetative state and death. Sensitivity and FPR were determined. RESULTS: A total of 1,153 patients from ten studies were included. The FPR of a bilaterally absent cortical N20 response of the SSEP could be calculated from nine studies including 492 patients. The SSEP had an FPR of 0.007 (confidence interval, CI, 0.001-0.047) to predict poor outcome. The Glasgow coma score (GCS) motor response was assessed in 811 patients from nine studies. A GCS motor score of 1-2 at 72 h had a high FPR of 0.21 (CI 0.08-0.43). Corneal reflex and pupillary reactivity at 72 h after the arrest were available in 429 and 566 patients, respectively. Bilaterally absent corneal reflexes had an FPR of 0.02 (CI 0.002-0.13). Bilaterally absent pupillary reflexes had an FPR of 0.004 (CI 0.001-0.03). CONCLUSIONS: At 72 h after the arrest the motor response to painful stimuli and the corneal reflexes are not a reliable tool for the early prediction of poor outcome in patients treated with hypothermia. The reliability of the pupillary response to light and the SSEP is comparable to that in patients not treated with hypothermia.

Neuromonitoring after major neurosurgical procedures.

Postoperative care of major neurosurgical procedures is aimed at the prevention, detection and treatment of secondary brain injury. This consists of a series of pathological events (i.e. brain edema and intracranial hypertension, cerebral hypoxia/ischemia, brain energy dysfunction, non-convulsive seizures) that occur early after the initial insult and surgical intervention and may add further burden to primary brain injury and thus impact functional recovery. Management of secondary brain injury requires specialized neuroscience intensive care units (ICU) and continuous advanced monitoring of brain physiology. Monitoring of intracranial pressure (ICP) is a mainstay of care and is recommended by international guidelines. However, ICP monitoring alone may be insufficient to detect all episodes of secondary brain insults. Additional invasive (i.e. brain tissue PO2, cerebral microdialysis, regional cerebral blood flow) and non-invasive (i.e. transcranial doppler, near-infrared spectroscopy, EEG) brain monitoring devices might complement ICP monitoring and help clinicians to target therapeutic interventions (e.g. management of cerebral perfusion pressure, blood transfusion, glucose control) to patient-specific pathophysiology. Several independent studies demonstrate such multimodal approach may optimize patient care after major neurosurgical procedures. The aim of this review is to evaluate some of the available monitoring systems and summarize recent important data showing the clinical utility of multimodal neuromonitoring for the management of main acute neurosurgical conditions, including traumatic brain injury, subarachnoid hemorrhage and stroke.

The Treviso Dementia (TREDEM) Study: A Biomedical, Neuroradiological, Neuropsychological and Social Investigation of Dementia in North-Eastern Italy.

BACKGROUND: The incidence of dementia increases exponentially with age but knowledge of real disease-modifying interventions is still limited. OBJECTIVES: To describe the study design and methods of a large prospective cohort study aimed at exploring the complex underlying relationships existing among cognition, frailty, and health-related events in older persons with cognitive impairment. DESIGN: Prospective cohort study of a representative population of outpatients attending the Treviso Cognitive Impairment Center between 2000 and 2010. SETTING: The TREVISO DEMENTIA (TREDEM) Study conducted in Treviso, Italy. PARTICIPANTS: 490 men and 874 women, mean age 79.1 ± 7.8 years (range 40.2-100 years). MEASUREMENTS: Physiological data, biochemical parameters, clinical conditions, neuroradiological parameters (e.g., brain atrophy and cerebral vascular lesions identified by computerized tomography scans), neuropsychological assessment, and physical function markers were measured at baseline. Patients were followed-up to 10 years. RESULTS: The final sample included in the study was predominantly composed of women and characterized by an initial physical function impairment and increased vascular risk profile. Cognitive function of the sample population showed moderate cognitive impairment (Mini Mental State Examination 20.2 ± 6.3; Clinical Dementia Rating 1.2 ± 0.7), and a prevalence of vascular dementia of 26.9%. Cortical, subcortical and hippocampus atrophy were all significantly correlated with age and cognitive function. CONCLUSION: Results obtained from the preliminary analyses conducted in the TREDEM study suggest that the database will support the accomplishment of important goals in understanding the nature of cognitive frailty and neurodegenerative diseases.

[Early neurorehabilitation in an acute university hospital: from dream to reality]. / Neurorééducation précoce au Centre hospitalier universitaire vaudois: du rêve à la réalité.

The need for an early neurorehabilitation pathway was identified in an acute university hospital. A team was formed to draw up and implement it. A neuro-sensorial, interdisciplinary and coordinated therapy program was developed, focused on tracheostomised patients as soon as they were admitted to the intermediate care in neurology and neurosurgery. The impact of this care plan was evaluated by comparing the results obtained with that pertaining to patients treated previously in the same services. The comparison showed a reduction of 48% of the mean duration of tracheostomy, of 39% in the time to inscription in a neurorehabilitation centre and of 20% in the length of stay in the intermediate care. An early neurorehabilitation care program, with an interdisciplinary and coordinated team, reduces complications and lengths of stay.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension.

BACKGROUND: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO(2)) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. METHODS: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO(2) monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO(2), ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. RESULTS: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO(2) (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO(2) (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. CONCLUSIONS: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Status epilepticus: an independent outcome predictor after cerebral anoxia.

BACKGROUND: Prognosis of status epilepticus (SE) depends on its cause, but there is uncertainty as to whether SE represents an independent outcome predictor for a given etiology. Cerebral anoxia is a relatively homogenous severe encephalopathy. Postanoxic SE is associated to a nearly 100% mortality in this setting; however, it is still unclear whether this is a severity marker of the underlying encephalopathy, or an independent factor influencing outcome. The goal of this study was to assess if postanoxic SE is independently associated with mortality after cerebral anoxia. METHODS: This was a retrospective observation of consecutive comatose survivors of cardiac arrest, including subjects treated with hypothermia. On the subgroup with EEG recordings in the first hospitalization days, univariate and multivariate analyses were applied to potential determinants of in-hospital mortality, and included the following variables: age, gender, type and length of cardiac arrest, occurrence of circulatory shock, presence of therapeutic hypothermia, and electrographic SE. RESULTS: Out of 166 postanoxic patients, 107 (64%) had an EEG (median latency from admission, 2 days); in this group, therapeutic hypothermia was administered in 59%. Death occurred in 71 (67%) patients. Postanoxic SE was associated with mortality regardless of type of acute cardiac rhythm and administration of hypothermic treatment. CONCLUSION: In this hospital-based cohort, postanoxic status epilepticus (SE) seems to be independently related to death in cardiac arrest survivors, suggesting that SE might determine a bad prognosis for a given etiology. Confirmation of these results in a prospective assessment is needed.

[Tight glucose control in the ICU: how aggressive should we be?]. / Contrôle strict de a glycémie en soins intensifs: où situer la limite ?

The issue of tight glucose control in intensive care remains controversial. Compelling evidence supports the use of intensive insulin therapy in postoperative patients, particularly those who have undergone cardiac surgery. In contrast, this strategy has been challenged in other situations, including medical, septic, post-traumatic and brain-injured critically ill patients, due to the lack of effect on mortality and to the increased risk of hypoglycemia. These data suggest that the optimal target for blood glucose needs to be better defined in critical care practice and might depend on the underlying pathology. Therefore, while awaiting the results of multi-centric studies, including a large heterogeneous cohort, a less aggressive approach for glucose control is preferable in the majority of critically ill patients.

[Merging of two intensive care units: preliminary observations]. / Fusion de deux services de médecine intensive: quelques observations préliminaires.

The merging of two intensive care units is a time of profound change, and constitutes a risk of mishaps. We report some aspects of such a project in our institution. The evaluation of various indicators reflecting the activity, patient's hospital pathways, mortality, as well as the use of specific techniques, has shown that no particular problem was observed during the first 9 months. Improvements in performance or productivity have not been demonstrated so far. The follow-up will permit to demonstrate long-term benefits. We believe that these observations may be of interest for other departmental or hospital reorganisations.

Fas ligand-induced apoptosis of infected human macrophages reduces the viability of intracellular Mycobacterium tuberculosis.

Mycobacterium tuberculosis-specific cytolytic activity is mediated mostly by CD4+CTL in humans. CD4+CTL kill infected target cells by inducing Fas (APO-1/CD95)-mediated apoptosis. We have examined the effect of Fas ligand (FasL)-induced apoptosis of human macrophages infected in vitro with M. tuberculosis on the viability of the intracellular bacilli. Human macrophages expressed Fas and underwent apoptosis after incubation with soluble recombinant FasL. In macrophages infected either with an attenuated (H37Ra) or with a virulent (H37Rv) strain of M. tuberculosis, the apoptotic death of macrophages was associated with a substantial reduction in bacillary viability. TNF-induced apoptosis of infected macrophages was coupled with a similar reduction in mycobacterial viability, while the induction of nonapoptotic complement-induced cell death had no effect on bacterial viable counts. Infected macrophages also showed a reduced susceptibility to FasL-induced apoptosis correlating with a reduced level of Fas expression. These data suggest that apoptosis of infected macrophages induced through receptors of the TNF family could be an immune effector mechanism not only depriving mycobacteria from their growth environment but also reducing viable bacterial counts by an unknown mechanism. On the other hand, interference by M. tuberculosis with the FasL system might represent an escape mechanism of the bacteria attempting to evade the effect of apoptosis.