Wet lungs, broken hearts and difficult therapies after subarachnoid hemorrhage

Pulmonary edema (PE) can occur after subarachnoid hemorrhage and can jeopardize arterial oxygenation, which is essential for a suffering brain. In some cases PE is evident in the emergency room, being the direct consequence of intracranial bleeding, which causes an immediate and overwhelming catecholamine discharge. In the following days, PE can occur because of cardiac failure, often related to initial cardiac damage, concurrent therapies with fluid overload and vasopressors, infections, or pre-existing co-morbidities. The causes of PE need to be identified for appropriate treatment

Rethinking neuroprotection in severe traumatic brain injury : toward bedside neuroprotection

Neuroprotection after traumatic brain injury (TBI) is an important goal pursued strenuously in the last 30 years. The acute cerebral injury triggers a cascade of biochemical events that may worsen the integrity, function, and connectivity of the brain cells and decrease the chance of functional recovery. A number of molecules acting against this deleterious cascade have been tested in the experimental setting, often with preliminary encouraging results. Unfortunately, clinical trials using those candidate neuroprotectants molecules have consistently produced disappointing results, highlighting the necessity of improving the research standards. Despite repeated failures in pharmacological neuroprotection, TBI treatment in neurointensive care units has achieved outcome improvement. It is likely that intensive treatment has contributed to this progress offering a different kind of neuroprotection, based on a careful prevention and limitations of intracranial and systemic threats. The natural course of acute brain damage, in fact, is often complicated by additional adverse events, like the development of intracranial hypertension, brain hypoxia, or hypoperfusion. All these events may lead to additional brain damage and worsen outcome. An approach designed for early identification and prompt correction of insults may, therefore, limit brain damage and improve results

Report of a Consensus Meeting on Human Brain Temperature After Severe Traumatic Brain Injury: Its Measurement and Management During Pyrexia

Temperature disturbances are common in patients with severe traumatic brain injury. The possibility of an adaptive, potentially beneficial role for fever in patients with severe brain trauma has been dismissed, but without good justification. Fever might, in some patients, confer benefit. A cadre of clinicians and scientists met to debate the clinically relevant, but often controversial issue about whether raised brain temperature after human traumatic brain injury (TBI) should be regarded as “good or bad” for outcome. The objective was to produce a consensus document of views about current temperature measurement and pyrexia treatment. Lectures were delivered by invited speakers with National and International publication track records in thermoregulation, neuroscience, epidemiology, measurement standards and neurocritical care. Summaries of the lectures and workshop discussions were produced from transcriptions of the lectures and workshop discussions. At the close of meeting, there was agreement on four key issues relevant to modern temperature measurement and management and for undergirding of an evidence-based practice, culminating in a consensus statement. There is no robust scientific data to support the use of hypothermia in patients whose intracranial pressure is controllable using standard therapy. A randomized clinical trial is justified to establish if body cooling for control of pyrexia (to normothermia) vs moderate pyrexia leads to a better patient outcome for TBI patients

Intracranial pressure monitoring in intensive care: clinical advantages of a computerized system over manual recording

INTRODUCTION: The presence of intracranial hypertension (HICP) after traumatic brain injury (TBI) affects patient outcome. Intracranial pressure (ICP) data from electronic monitoring equipment are usually calculated and recorded hourly in the clinical chart by trained nurses. Little is known, however, about how precisely this method reflects the real patterns of ICP after severe TBI. In this study, we compared hourly manual recording with a validated and continuous computerized reference standard. METHODS: Thirty randomly selected patients with severe TBI and HICP admitted to the neuroscience intensive care unit (Policlinico University Hospital, Milan, Italy) were retrospectively studied. A 24-hour interval with ICP monitoring was randomly selected for each patient. The manually recorded data available for analysis covered 672 hours corresponding to 36,492 digital data points. The two methods were evaluated using the correlation coefficient and the Bland and Altman method. We used the proportion test to analyze differences in the number of episodes of HICP (ICP > 20 mm Hg) detected with the two methods and the paired t test to analyze differences in the percentage of time of HICP. RESULTS: There was good agreement between the digitally collected ICP and the manual recordings of the end-hour values. Bland and Altman analysis confirmed a mean difference between the two methods of 0.05 mm Hg (standard deviation 3.66); 96% of data were within the limits of agreement (+7.37 and -7.28). The average percentages of time of ICP greater than 20 mm Hg were 39% calculated from the digital measurements and 34% from the manual observations. From the continuous digital recording, we identified 351 episodes of ICP greater than 20 mm Hg lasting at least five minutes and 287 similar episodes lasting at least ten minutes. Conversely, end-hour ICP of greater than 20 mm Hg was observed in only 204 cases using manual recording methods. CONCLUSION: Although manually recorded end-hour ICP accurately reflected the computerized end-hour and mean hour values, the important omission of a number of episodes of high ICP, some of long duration, results in a clinical picture that is not accurate or informative of the true pattern of unstable ICP in patients with TBI

Neuroprotection in traumatic brain injury : mesenchymal stromal cells can potentially overcome some limitations of previous clinical trials

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In the last 30 years several neuroprotective agents, attenuating the downstream molecular and cellular damaging events triggered by TBI, have been extensively studied. Even though many drugs have shown promising results in the pre-clinical stage, all have failed in large clinical trials. Mesenchymal stromal cells (MSCs) may offer a promising new therapeutic intervention, with preclinical data showing protection of the injured brain. We selected three of the critical aspects identified as possible causes of clinical failure: the window of opportunity for drug administration, the double-edged contribution of mechanisms to damage and recovery, and the oft-neglected role of reparative mechanisms. For each aspect, we briefly summarized the limitations of previous trials and the potential advantages of a newer approach using MSCs

Ethics roundtable: 'Open-ended ICU care: Can we afford it?'

The patient is a 27-year-old previously healthy male with a diagnosis of viral encephalitis with a lymphocytic pleocytosis on cerebrospinal fluid examination. For 3 months, he has been in status epilepticus (SE) on high doses of barbiturates, benzodiazepines, and ketamine and a ketogenic feeding-tube formula. He remains in burst suppression on continuous electroencephalography (EEG). He is trached and has a percutaneous endoscopic gastrostomy (PEG) feeding tube. He has been treated several times for pneumonia, and he is on a warming blanket and is on vasopressors to maintain his blood pressure. His vitals are stable and his lab work is within limits. The sedation is decreased under EEG guidance every 72 hours, after which he goes back into SE and heavy sedation is resumed. The latest magnetic resonance imaging (MRI) shows edema but otherwise no obvious permanent cortical damage. The family wants a realistic assessment of the likely outcome. The neurologist tells them the literature suggests the outlook is poor but not 100% fatal. As long as all of his other organs are functioning on life support, there is always a chance the seizures will stop at some time in the future, and so the neurologist recommends an open-ended intensive care unit (ICU) plan and hopes for that outcome. © 2010 BioMed Central Ltd

Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM

Objectives: Recommendations for EEG monitoring in the ICU are lacking. The Neurointensive Care Section of the ESICM assembled a multidisciplinary group to establish consensus recommendations on the use of EEG in the ICU. Methods: A systematic review was performed and 42 studies were included. Data were extracted using the PICO approach, including: (a) population, i.e. ICU patients with at least one of the following: traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, stroke, coma after cardiac arrest, septic and metabolic encephalopathy, encephalitis, and status epilepticus; (b) intervention, i.e. EEG monitoring of at least 30min duration; (c) control, i.e. intermittent vs. continuous EEG, as no studies compared patients with a specific clinical condition, with and without EEG monitoring; (d) outcome endpoints, i.e. seizure detection, ischemia detection, and prognostication. After selection, evidence was classified and recommendations developed using the GRADE system. Recommendations: The panel recommends EEG in generalized convulsive status epilepticus and to rule out nonconvulsive seizures in brain-injured patients and in comatose ICU patients without primary brain injury who have unexplained and persistent altered consciousness. We suggest EEG to detect ischemia in comatose patients with subarachnoid hemorrhage and to improve prognostication of coma after cardiac arrest. We recommend continuous over intermittent EEG for refractory status epilepticus and suggest it for patients with status epilepticus and suspected ongoing seizures and for comatose patients with unexplained and persistent altered consciousness. Conclusions: EEG monitoring is an important diagnostic tool for specific indications. Further data are necessary to understand its potential for ischemia assessment and coma prognosticatio

Univariate comparison of performance of different cerebrovascular reactivity indices for outcome association in adult TBI: a CENTER-TBI study.

BACKGROUND: Monitoring cerebrovascular reactivity in adult traumatic brain injury (TBI) has been linked to global patient outcome. Three intra-cranial pressure (ICP)-derived indices have been described. It is unknown which index is superior for outcome association in TBI outside previous single-center evaluations. The goal of this study is to evaluate indices for 6- to 12-month outcome association using uniform data harvested in multiple centers. METHODS: Using the prospectively collected data from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, the following indices of cerebrovascular reactivity were derived: PRx (correlation between ICP and mean arterial pressure (MAP)), PAx (correlation between pulse amplitude of ICP (AMP) and MAP), and RAC (correlation between AMP and cerebral perfusion pressure (CPP)). Univariate logistic regression models were created to assess the association between vascular reactivity indices with global dichotomized outcome at 6 to 12 months, as assessed by Glasgow Outcome Score-Extended (GOSE). Models were compared via area under the receiver operating curve (AUC) and Delong's test. RESULTS: Two separate patient groups from this cohort were assessed: the total population with available data (n = 204) and only those without decompressive craniectomy (n = 159), with identical results. PRx, PAx, and RAC perform similar in outcome association for both dichotomized outcomes, alive/dead and favorable/unfavorable, with RAC trending towards higher AUC values. There were statistically higher mean values for the index, % time above threshold, and hourly dose above threshold for each of PRx, PAx, and RAC in those patients with poor outcomes. CONCLUSIONS: PRx, PAx, and RAC appear similar in their associations with 6- to 12-month outcome in moderate/severe adult TBI, with RAC showing tendency to achieve stronger associations. Further work is required to determine the role for each of these cerebrovascular indices in monitoring of TBI patients.Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA).DKM was also supported by funding from the National Institute for Health Research (NIHR, UK) through a Senior Investigator award and the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. The study also received additional support from the NIHR Clinical Research network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. FAZ has received salary support for dedicated research time, during which this project was completed. Such salary support came from: the Cambridge Commonwealth Trust Scholarship, the University of Manitoba Clinician Investigator Program, and the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery

Descriptive analysis of low versus elevated intracranial pressure on cerebral physiology in adult traumatic brain injury: a CENTER-TBI exploratory study

BackgroundTo date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP.MethodsThe Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP  20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts.Results185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p ConclusionsLow versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results.</p

Descriptive analysis of low versus elevated intracranial pressure on cerebral physiology in adult traumatic brain injury: a CENTER-TBI exploratory study.

BACKGROUND: To date, the cerebral physiologic consequences of persistently elevated intracranial pressure (ICP) have been based on either low-resolution physiologic data or retrospective high-frequency data from single centers. The goal of this study was to provide a descriptive multi-center analysis of the cerebral physiologic consequences of ICP, comparing those with normal ICP to those with elevated ICP. METHODS: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High-Resolution Intensive Care Unit (HR-ICU) sub-study cohort was utilized. The first 3 days of physiologic recording were analyzed, evaluating and comparing those patients with mean ICP  20 mmHg. Various cerebral physiologic parameters were derived and evaluated, including ICP, brain tissue oxygen (PbtO2), cerebral perfusion pressure (CPP), pulse amplitude of ICP (AMP), cerebrovascular reactivity, and cerebral compensatory reserve. The percentage time and dose above/below thresholds were also assessed. Basic descriptive statistics were employed in comparing the two cohorts. RESULTS: 185 patients were included, with 157 displaying a mean ICP below 15 mmHg and 28 having a mean ICP above 20 mmHg. For admission demographics, only admission Marshall and Rotterdam CT scores were statistically different between groups (p = 0.017 and p = 0.030, respectively). The high ICP group displayed statistically worse CPP, PbtO2, cerebrovascular reactivity, and compensatory reserve. The high ICP group displayed worse 6-month mortality (p < 0.0001) and poor outcome (p = 0.014), based on the Extended Glasgow Outcome Score. CONCLUSIONS: Low versus high ICP during the first 72 h after moderate/severe TBI is associated with significant disparities in CPP, AMP, cerebrovascular reactivity, cerebral compensatory reserve, and brain tissue oxygenation metrics. Such ICP extremes appear to be strongly related to 6-month patient outcomes, in keeping with previous literature. This work provides multi-center validation for previously described single-center retrospective results