Management Of Secondary Brain Injury Research Articles

Minocycline Attenuates Microglia/Macrophage Phagocytic Activity and Inhibits SAH-Induced Neuronal Cell Death and Inflammation

BackgroundNeuroprotective treatment strategies aiming at interfering with either inflammation or cell death indicate the importance of these mechanisms in the development of brain injury after subarachnoid hemorrhage (SAH). This study was undertaken to evaluate the influence of minocycline on microglia/macrophage cell activity and its neuroprotective and anti-inflammatory impact 14 days after aneurismal SAH in mice.MethodsEndovascular filament perforation was used to induce SAH in mice. SAH + vehicle-operated mice were used as controls for SAH vehicle-treated mice and SAH + minocycline-treated mice. The drug administration started 4 h after SAH induction and was daily repeated until day 7 post SAH and continued until day 14 every second day. Brain cryosections were immunolabeled for Iba1 to detect microglia/macrophages and NeuN to visualize neurons. Phagocytosis assay was performed to determine the microglia/macrophage activity status. Apoptotic cells were stained using terminal deoxyuridine triphosphate nick end labeling. Real-time quantitative polymerase chain reaction was used to estimate cytokine gene expression.ResultsWe observed a significantly reduced phagocytic activity of microglia/macrophages accompanied by a lowered spatial interaction with neurons and reduced neuronal apoptosis achieved by minocycline administration after SAH. Moreover, the SAH-induced overexpression of pro-inflammatory cytokines and neuronal cell death was markedly attenuated by the compound.ConclusionsMinocycline treatment may be implicated as a therapeutic approach with long-term benefits in the management of secondary brain injury after SAH in a clinically relevant time window.

Naloxone for severe traumatic brain injury: a meta-analysis.

ObjectiveThe efficiency of naloxone for the management of secondary brain injury after severe traumatic brain injury (sTBI) remains undefined. The aim of this study is to evaluate the current evidence regarding the clinical efficiency and safety of naloxone as a treatment for sTBI in mainland China.Methodology/Principal FindingsA systematic search of the China Biology Medicine disc (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Internet (CNKI), and Wan Fang Database was performed to identify randomized controlled trials (RCTs) of naloxone treatment for patients with sTBI in mainland China. The quality of the included trials was assessed, and the RevMan 5.1 software was employed to conduct this meta-analysis. Nineteen RCTs including 2332 patients were included in this study. The odds ratio (OR) showed statistically significant differences between the naloxone group and the control group (placebo) in terms of mortality at 18 months after treatment (OR, 0.51, 95%CI: 0.38–0.67; p<0.00001), prevalence of abnormal heart rates (OR, 0.30, 95%CI: 0.21–0.43; p<0.00001), abnormal breathing rate (OR, 0.25, 95%CI: 0.17–0.36; p<0.00001) at discharge, the level of intracranial pressure at discharge (OR, 2.00, 95%CI: 1.41–2.83; p = 0.0001), verbal or physical dysfunction rate (OR, 0.65, 95%CI: 0.43–0.98; p = 0.04), and severe disability rate (OR, 0.47, 95%CI: 0.30–0.73; p = 0.0001) at 18 months after the treatment. The mean difference (MD) showed statistically significant differences in awakening time at discharge (MD, −4.81, 95%CI: −5.49 to −4.12; p<0.00001), and GCS at 3 days (MD, 1.00, 95%CI: 0.70–1.30; p<0.00001) and 10 days (MD, 1.76, 95%CI: 1.55–1.97; p<0.00001) after treatment comparing naloxone with placebo group.Conclusions/SignificanceThis study indicated that applying naloxone in the early stage for sTBI patients might effectively reduce mortality, control intracranial pressure (ICP), and significantly improve the prognosis.

Intracranial pressure monitoring: fundamental considerations and rationale for monitoring.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging.

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Background and aims: Urgent craniotomy is often indicated in pediatric patients due to traumatic brain injury and occasionally for arterio-venous malformation and brain abscess. Aims: To discuss the perioperative management of urgent craniotomy in pediatric patients. Methods: Experience of our institute as well as the recently published articles in the same field. Results: Urgent craniotomy is indicated mainly to evacuate extra- or subdural hematoma causing intra-cranial mass effects. Less common indications include brain abscess and decompression after bleeding form AVM. The main perioperative goal is optimization of cerebral perfusion pressure (CPP), prevention and early management of secondary brain injury. Secondary brain injury may result from hypotension, hypovolemia, hypoxia, fever, high intra-cranial pressure (ICP), anemia, hypo- or hyperglycemia, acidosis and seizure. ICP should be monitored in patients with severe brain injury, CPP should be maintained according to the age (usually 40 -50 mmHg). Hyperosmolar therapy may be used if indicated. Hypothermia may be used in patients with TBI within 8 hours. Arterial carbon dioxide pressure should maintained within normal range and Prophylactic hyperventilation should be not be used. High ICP is managed initially with medical measures, but if it is failed or the patient has early signs of herniation decompression craniectomy should be done. Conclusions: The main therapeutic goals are limitation the effects of primary injury, prevention and aggressive management of factors which may cause secondary brain injury. Medical treatment of high ICP and maintenance of CPP are paramount. Early surgical intervention may limits the adverse effects of high ICP and mass occupying lesions.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult—after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

Brain multimodality monitoring

An important goal of neurocritical care is the management of secondary brain injury (SBI), that is pathological events occurring after primary insult that add further burden to outcome. Brain oedema, cerebral ischemia, energy dysfunction, seizures and systemic insults are the main components of SBI. We here review recent data showing the clinical utility of brain multimodality monitoring (BMM) for the management of SBI. Despite being recommended by international guidelines, standard intracranial pressure (ICP) monitoring may be insufficient to detect all episodes of SBI. ICP monitoring, combined with brain oxygen (PbtO(2)), cerebral microdialysis and regional cerebral blood flow, might help to target therapy (e.g. management of cerebral perfusion pressure, blood transfusion, glucose control) to patient-specific pathophysiology. Physiological parameters derived from BMM, including PbtO(2) and microdialysis lactate/pyruvate ratio, correlate with outcome and have recently been incorporated into neurocritical care guidelines. Advanced intracranial devices can be complemented by quantitative electroencephalography to monitor changes of brain function and nonconvulsive seizures. BMM offers an on-line comprehensive scrutiny of the injured brain and is increasingly used for the management of SBI. Integration of monitored data using new informatics tools may help optimize therapy of brain-injured patients and quality of care.

Cerebral Microdialysis: A Metabolic Sensor Inside the Closed Box

The cranial vault was regarded by Monro-Kellie doctrine as a closed box containing the three components namely: brain, blood and cerebrospinal fluid. The brain is orders of magnitude, more complex than the heart and other vital organs yet its function has been more difficult to monitor being contained in a rigid closed box. Following an acute neurological catastrophe such as traumatic brain injury (TBI) or stroke, damage to the brain can occur at the time of the initial event. This damage is termed “primary brain injury”. Regardless of the interventions performed to limit this primary injury, much of the primary damage may be irreversible. However, this primary brain injury initi¬ates a cascade of biochemical events that are potentially reversible. This process, termed “secondary brain injury”, includes structural and chemical derangement as well as alterations in cerebral blood flow and oxygen delivery. Management of secondary brain injury is of fundamental importance to the treatment of patients with TBI, ischemic and hemorrhagic stroke, and global cerebral ischemia [1].

Multimodal monitoring and neurocritical care bioinformatics

Neurocritical care bioinformatics is a new field that focuses on the acquisition, storage and analysis of physiological and other data relevant to the bedside care of patients with acute neurological conditions such as traumatic brain injury or stroke. The main focus of neurocritical care for these conditions relates to prevention, detection and management of secondary brain injury, which relies heavily on monitoring of systemic and cerebral parameters (such as blood-pressure level and intracranial pressure). Advanced neuromonitoring tools also exist that enable measurement of brain tissue oxygen tension, cerebral oxygen utilization, and aerobic metabolism. The ability to analyze these advanced data for real-time clinical care, however, remains intuitive and primitive. Advanced statistical and mathematical tools are now being applied to the large volume of clinical physiological data routinely monitored in neurocritical care with the goal of identifying better markers of brain injury and providing clinicians with improved ability to target specific goals in the management of these patients. This Review provides an introduction to the concepts of multimodal monitoring for secondary brain injury in neurocritical care and outlines initial and future approaches using informatics tools for understanding and applying these data to clinical care.

Intensive Care Unit Nurse Characteristics Impacting Judgments About Secondary Brain Injury

Although intensive care unit nurses have an integral role in preventing secondary brain injury when caring for critically ill traumatic brain injury patients, nursing practice varies and little research has examined if individual nurse characteristics affect judgments about secondary brain injury. The purpose of this study was to investigate how intensive care unit nurse characteristics influence judgments when managing secondary brain injury. A factorial survey research design was used to administer surveys to intensive care nurses from 2 level I trauma centers. Nursing shift and number of years in the intensive care unit were significant predictors of judgments. Understanding the role of nurse characteristics is important in future educational and research efforts aimed at evidence-based management of secondary brain injury.

Judgments of Critical Care Nurses About Risk for Secondary Brain Injury

Interdisciplinary care for patients with traumatic brain injury focuses on treating the primary brain injury and limiting further brain damage from secondary injury. Intensive care unit nurses have an integral role in preventing secondary brain injury; however, little is known about factors that influence nurses' judgments about risk for secondary brain injury. To investigate which physiological and situational variables influence judgments of intensive care unit nurses about patients' risk for secondary brain injury, management solely with nursing interventions, and management by consulting another member of the health care team. A multiple segment factorial survey design was used. Vignettes reflecting the complexity of real-life scenarios were randomly generated by using different values of each independent variable. Surveys containing the vignettes were sent to nurses at 2 level I trauma centers. Multiple regression was used to determine which variables influenced judgments about secondary brain injury. Judgments about risk for secondary brain injury were influenced by a patient's oxygen saturation, intracranial pressure, cerebral perfusion pressure, mechanism of injury, and primary diagnosis, as well as by nursing shift. Judgments about interventions were influenced by a patient's oxygen saturation, intracranial pressure, and cerebral perfusion pressure and by nursing shift. The initial judgments made by nurses were the most significant variable predictive of follow-up judgments. Nurses need standardized, evidence-based content for management of secondary brain injury in critically ill patients with traumatic brain injury.

Advanced cerebral monitoring in neurocritical care

New cerebral monitoring techniques allow direct measurement of brain oxygenation and metabolism. Investigation using these new tools has provided additional insight into the understanding of the pathophysiology of acute brain injury and suggested new ways to guide management of secondary brain injury. Studies of focal brain tissue oxygen monitoring have suggested ischemic thresholds in focal regions of brain injury and demonstrated the interrelationship between brain tissue oxygen tension (P bt O 2 ) and other cerebral physiologic and metabolic parameters. Jugular venous oxygen saturation (SjVO 2 ) monitoring may evaluate global brain oxygen delivery and consumption, providing thresholds for detecting brain hypoperfusion and hyperperfusion. Furthermore, critically low values of P bt O 2 and SjVO 2 have also been predictive of mortality and worsened functional outcome, especially after head trauma. Cerebral microdialysis measures the concentrations of extracellular metabolites which may be relevant to cerebral metabolism or ischemia in focal areas of injury. Cerebral blood flow may be measured in the neurointensive care unit using continuous methods such as thermal diffusion and laser Doppler flowmetry. Initial studies have also attempted to correlate findings from advanced neuromonitoring with neuroimaging using dynamic perfusion computed tomography, positron emission tomography, and Xenon computed tomography. Additionally, new methods of data acquisition, storage, and analysis are being developed to address the increasing burden of patient data from neuromonitoring. Advanced informatics techniques such as hierarchical data clustering, generalized linear models, and heat map dendrograms are now being applied to multivariable patient data in order to better develop physiologic patient profiles to improve diagnosis and treatment.

New Approaches to Physiological Informatics in Neurocritical Care

A fundamental purpose of neurocritical care is the management of secondary brain injury. This is often accomplished by monitoring and managing individual patient parameters including physiological vital signs. Yet, the ability to record physiological data exceeds our ability to fully integrate it into patient care. We propose that advances in monitoring must be accompanied by advances in methods of high-frequency, multivariate data analysis that integrate the multiple processes occurring in critically ill patients. We describe initial work in the emerging field of physiological informatics in critical care medicine. We analyzed data on 23 patients with brain injury from our Neurotrauma and Critical Care Database, which contains more than 20 physiological parameters recorded automatically at one-minute intervals via bedside monitors connected to standard personal computers. We performed exploratory data analysis, studied two patient cases in detail, and implemented a data-driven classification approach using hierarchical clustering. In this study, we present challenges and opportunities for high-frequency multimodal monitoring to quantitatively detect secondary brain insults, and develop clustering methodology to construct multivariate physiological data "profiles" to classify patients for diagnosis and treatment. Recording of many physiological variables across multiple patients is feasible and can lead to new clinical insights. Computational and analytical methods previously used primarily for basic science may have clinical relevance and can potentially be adapted to provide physicians with improved ability to integrate complex information for decision making in neurocritical care.

Options for Cerebral Protection After Penetrating Head Injury

The medical management of secondary brain injury is entering a new era in which the fruits of labor in the laboratory are paying off in the form of legitimate agents for use in human trials. As more about pathophysiology of traumatic-ischemic brain injury becomes known, more effective means for pharmacologic intervention and neuronal salvage will emerge, and optimism is high that we are approaching an era that will witness improvements in functional survival that have been heretofore unwitnessed.