Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.

BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.

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.

A Novel Cooling Device for Targeted Brain Temperature Control and Therapeutic Hypothermia: Feasibility Study in an Animal Model.

BACKGROUND: Therapeutic hypothermia (i.e., temperature management) is an effective option for improving survival and neurological outcome after cardiac arrest and is potentially useful for the care of the critically ill neurological patient. We analyzed the feasibility of a device to control the temperature of the brain by controlling the temperature of the blood flowing through the neck. METHODS: A lumped parameter dynamic model, with one-dimensional heat transfer, was used to predict cooling effects and to test experimental hypotheses. The cooling system consisted of a flexible collar and was tested on 4 adult sheep, in which brain and body temperatures were invasively monitored for the duration of the experiment. RESULTS: Model-based simulations predicted a lowering of the temperature of the brain and the body following the onset of cooling, with a rate of 0.4 °C/h for the brain and 0.2 °C/h for the body. The experimental findings showed comparable cooling rates in the two body compartments, with temperature reductions of 0.6 (0.2) °C/h for the brain and 0.6 (0.2) °C/h for the body. For a 70 kg adult human subject, we predict a temperature reduction of 0.64 °C/h for the brain and 0.43 °C/h for the body. CONCLUSIONS: This work demonstrates the feasibility of using a non-invasive method to induce brain hypothermia using a portable collar. This device demonstrated an optimal safety profile and represents a potentially useful method for the administration of mild hypothermia and temperature control (i.e., treatment of hyperpyrexia) in cardiac arrest and critically ill neurologic patients.

Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke.

BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). RESULTS: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 µg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 µg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 µg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 µg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001). CONCLUSIONS: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.

My paper 20 years later: cerebral venous oxygen saturation studied with bilateral samples in the internal jugular veins.

INTRODUCTION: Jugular oxygen saturation monitoring was introduced in neurointensive care after severe traumatic brain injury (TBI) to explore the adequacy of brain perfusion and guide therapeutic interventions. The brain was considered homogeneous, and oxygen saturation was taken as representative of the whole organ. We investigated whether venous outflow from the brain was homogeneous by measuring oxygen saturation simultaneously from the two jugular veins. METHODS: In 32 comatose TBI patients both internal jugular veins (IJs) were simultaneously explored using intermittent samples; hemoglobin saturation was also recorded continuously by fiber-optic catheters in five patients. In five cases long catheters were inserted bilaterally upstream, up to the sigmoid sinuses. MAIN FINDINGS: On average, measurements from the two sides were in agreement (mean and standard deviation of the differences between the saturation of the two IJs were respectively 5.32 and 5.15). However, 15 patients showed differences of more than 15 % in hemoglobin saturation at some point; three others showed differences larger than 10 %. No relationship was found between the computed tomographic scan data and the hemoglobin saturation pattern. DISCUSSION/CONCLUSION: Several groups have confirmed differences between oxygen saturation in the two jugular veins. After years of enthusiasm, interest for jugular saturation has decreased and more modern methods, such as tissue oxygenation monitoring, are now available. Jugular saturation monitoring has low sensitivity, with the risk of missing low saturation, but high specificity; moreover it is cheap, when used with intermittent sampling. Monitoring the adequacy of brain perfusion after severe TBI is essential. However the choice of a specific monitor depends on local resources and expertise.

Risk of perioperative seizures in patients undergoing craniotomy with intraoperative brain mapping.

BACKGROUND: The identification of risk factors associated with perioperative seizures would be of great benefit to the anesthesiologist in managing brain tumor patients undergoing craniotomy with intraoperative brain mapping. METHODS: A series of 316 supratentorial craniotomies for tumor resection, in which intraoperative brain mapping was used, were analyzed. From January 2005 to December 2010 the occurrence of intraoperative and immediate postoperative clinical seizures was prospectively recorded into a database. Demographic data, tumor characteristics, preoperative seizure control, intraoperative events and anesthetic management were evaluated as risk factors for intraoperative clinical seizures. Additionally, the association between intraoperative clinical seizures and immediate postoperative seizures was evaluated. In order to determine the best predictors of intraoperative and immediate postoperative clinical seizures, a multivariable analysis by logistic regression was performed. RESULTS: Younger age, location of the tumor in the frontal and parietal lobe, brain mapping conducted under general anesthesia and non physiologic values of arterial carbon dioxide (PaCO2) during brain mapping were independent positive risk factors for the development of intraoperative clinical seizures. Location of tumor in the frontal lobe, antiepileptic polytherapy, intraoperative seizures requiring pharmacologic treatment during brain mapping, and blood on postoperative CT scan were independent positive risk factors for the development of immediate postoperative seizures. CONCLUSION: Clinical seizures are common intraoperative and postoperative complications of supratentorial craniotomies with intraoperative brain mapping. The identification of those patients at higher risk of seizures may guide intraoperative and postoperative medical management.

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

Heart-fatty acid-binding and tau proteins relate to brain injury severity and long-term outcome in subarachnoid haemorrhage patients.

BACKGROUND: Vasospasm and other secondary neurological insults may follow subarachnoid haemorrhage (SAH). Biomarkers have the potential to stratify patient risk and perhaps serve as an early warning sign of delayed ischaemic injury. METHODS: Serial cerebrospinal fluid (CSF) samples were collected from 38 consecutive patients with aneurysmal SAH admitted to the neurosurgical intensive care unit. We measured heart-fatty acid-binding protein (H-FABP) and tau protein (τ) levels in the CSF to evaluate their association with brain damage, and their potential as predictors of the long-term outcome. H-FABP and τ were analysed in relation to acute clinical status, assessed by the World Federation of Neurological Surgeons (WFNS) scale, radiological findings, clinical vasospasm, and 6-month outcome. RESULTS: H-FABP and τ increased after SAH. H-FABP and τ were higher in patients in poor clinical status on admission (WFNS 4-5) compared with milder patients (WFNS 1-3). Elevated H-FABP and τ levels were also observed in patients with early cerebral ischaemia, defined as a CT scan hypodense lesion visible within the first 3 days after SAH. After the acute phase, H-FABP, and τ showed a delayed increase with the occurrence of clinical vasospasm. Finally, patients with the unfavourable outcome (death, vegetative state, or severe disability) had higher peak levels of both proteins compared with patients with good recovery or moderate disability. CONCLUSIONS: H-FABP and τ show promise as biomarkers of brain injury after SAH. They may help to identify the occurrence of vasospasm and predict the long-term outcome.

Intensive care for pediatric traumatic brain injury.

PURPOSES: The aims of this study are to describe a cohort of head-injured pediatric patients, focusing on current practice for intracranial pressure (ICP) monitoring and treatment and to verify the relationship between clinical and radiological parameters and the six-month outcome in a multivariable statistical model. METHODS: A retrospective review was done of a prospectively collected database considering patients younger than 19 years admitted to three neuro-intensive care units (ICU). Patients were divided into four age groups: 0-5 (infant), 6-12 (children), 13-16 (pre-adolescent) and 17-18 years (adolescent). The ICP and cerebral perfusion pressure (CPP) were analyzed calculating average data and values exceeding thresholds for more than 5 min. Outcome was assessed 6 months after trauma using the Glasgow Outcome Score. RESULTS: There were 199 patients, 155 male, included. Sixty percent had extracranial injuries. Pupils were abnormal in 38 %. Emergency evacuation of intracranial hematomas was necessary in 81 cases. The ICP was monitored in 117 patients; in 87 cases ICP was higher than 20 mmHg, with no differences among age groups. All but six patients received therapy to prevent raised ICP; barbiturates, deep hyperventilation or surgical decompression were used in 31 cases. At 6 months, mortality was 21 % and favorable outcome was achieved by 72 %. Significant predictors of outcome in the multivariable model were the Glasgow Coma Scale (GCS) motor score, pupils and ICP. CONCLUSIONS: Pediatric head injury is associated with a high incidence of intracranial hypertension. Early surgical treatment and intensive care may achieve favorable outcome in the majority of cases.

Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage.

PURPOSE: The contribution of axonal injury to brain damage after aneurysmal subarachnoid haemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesised that patients with aSAH would have elevated cerebrospinal fluid (CSF) NF-L levels and sought to explore the clinical correlates of CSF NF-L dynamics. METHODS: Serial ventricular CSF (vCSF) samples were collected from 35 patients with aSAH for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analysed in relation to acute clinical status, radiological findings and 6-month outcomes. RESULTS: vCSF NF-L concentrations were elevated in all patients with aSAH. Patients with early cerebral ischaemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial haemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischaemia or 6-month Glasgow Outcome Scale. CONCLUSIONS: Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with ECI. However, our results suggest that axonal injury after aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long-term clinical outcomes.

Traumatic brain injury in pediatric patients.

Traumatic brain injury (TBI) in children is frequent, sometimes lethal, and may have life-long consequences in survivors. Prevention at school and in sports, including both kids and families, is of paramount importance. Scarce data are available in terms of epidemiology, physiopathology, management and prognosis. This non-systematic review suggests that rational organization of rescue and transport to designated hospitals, linked with early diagnosis/removal of surgical masses and comprehensive monitoring and intensive care, offer the best chances for reducing mortality and morbidity in severe cases. After the acute phase rehabilitation and families play a fundamental role.

Awake neurosurgery: an update.

Intraoperative brain mapping has the goal of aiding with maximal surgical resection of brain tumors while minimizing functional sequelae. Retrospective randomized studies on large populations have shown that this technique can optimize the surgical approach while reducing postoperative morbidity. During direct electrical stimulation of the language areas adjacent to the tumor, the patient should be collaborative and be able to speak to participate in language testing. Different anesthesiological protocols have been proposed to allow intraoperative brain mapping, which range from local anesthesia to conscious sedation or general anesthesia, with or without airway instrumentation. The most common intraoperative complications are seizure, respiratory depression, and patients' stress and discomfort. Since awake craniotomy carries both benefits and potential risks, the following factors are crucial in the management of patients: 1) careful selection of the patients and 2) communication between the anesthesiological and surgical teams. To date, there remains no consensus about the optimal anesthesiological regimen to use. Only prospective, multicentre randomized studies focused on evaluating the role of different anesthesiological techniques on intraoperative monitoring, postoperative deficits, and intraoperative complications can answer the question of which anesthesiological approach should be chosen when intraoperative brain mapping is requested.

Hypothermia for brain protection in the non-cardiac arrest patient.

This review focuses on the potential application of hypothermia in adults suffering traumatic brain injury (TBI). Hypothermia is neuroprotective, reducing the damaging effects of trauma to the brain in a variety of experimental situations, such as brain ischemia and brain injury, but it has failed to demonstrate outcome improvement in a major controlled, randomized trial. The evidence for the use of hypothermia as a protective procedure is scarce and contradictory. However, evidence does suggest that hypothermia is effective in reducing intracranial hypertension after head injury. Since hypothermia has important side effects, further work is necessary before introducing this procedure into clinical practice for TBI.

Intracranial pressure monitoring for traumatic brain injury: available evidence and clinical implications.

Following traumatic brain injury, uncontrollable intracranial hypertension remains the most frequent cause of death. Despite general agreement on the deleterious effects of elevated intracranial pressure (ICP), however, the evidence supporting the use of ICP monitoring has recently been questioned. The aim of this review was to evaluate the pros and cons of ICP monitoring and to discuss the hypothetical desirability and feasibility of a trial testing the benefits of ICP monitoring.