Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study.

OBJECTIVE: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment. METHODS: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. RESULTS: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. CONCLUSION: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. PROTOCOL: The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).

Traumatic axonal injury (TAI): definitions, pathophysiology and imaging-a narrative review.

INTRODUCTION: Traumatic axonal injury (TAI) is a condition defined as multiple, scattered, small hemorrhagic, and/or non-hemorrhagic lesions, alongside brain swelling, in a more confined white matter distribution on imaging studies, together with impaired axoplasmic transport, axonal swelling, and disconnection after traumatic brain injury (TBI). Ever since its description in the 1980s and the grading system by Adams et al., our understanding of the processes behind this entity has increased. METHODS: We performed a scoping systematic, narrative review by interrogating Ovid MEDLINE, Embase, and Google Scholar on the pathophysiology, biomarkers, and diagnostic tools of TAI patients until July 2020. RESULTS: We underline the misuse of the Adams classification on MRI without proper validation studies, and highlight the hiatus in the scientific literature and areas needing more research. In the past, the theory behind the pathophysiology relied on the inertial force exerted on the brain matter after severe TBI inducing a primary axotomy. This theory has now been partially abandoned in favor of a more refined theory involving biochemical processes such as protein cleavage and DNA breakdown, ultimately leading to an inflammation cascade and cell apoptosis, a process now described as secondary axotomy. CONCLUSION: The difference in TAI definitions makes the comparison of studies that report outcomes, treatments, and prognostic factors a daunting task. An even more difficult task is isolating the outcomes of isolated TAI from the outcomes of severe TBI in general. Targeted bench-to-bedside studies are required in order to uncover further pathways involved in the pathophysiology of TAI and, ideally, new treatments.

Hyperoxia in pediatric severe traumatic brain injury (TBI): a comparison of patient classification by cutoff versus cumulative (area-under-the-curve) analysis.

OBJECTIVE: Hyperoxia is associated with adverse outcome in severe traumatic brain injury (TBI). This study explored differences in patient classification of oxygen exposure by PaO2 cutoff and cumulative area-under-the-curve (AUC) analysis. METHODS: Retrospective, explorative study including children (<18 years) with accidental severe TBI (2002-2015). Oxygen exposure analysis used three PaO2 cutoff values and four PaO2 AUC categories during the first 24 hours of Pediatric Intensive Care Unit (PICU) admission. RESULTS: Seventy-one patients were included (median age 8.9 years [IQR 4.6-12.9]), mortality 18.3% (n = 13). Patient hyperoxia classification differed depending on PaO2 cutoff vs AUC analysis: 52% vs. 26%, respectively, were classified in the highest hyperoxia category. Eleven patients (17%) classified as 'intermediate oxygen exposure' based on cumulative PaO2 analysis whereby they did not exceed the 200 mmHg PaO2 cutoff threshold. Patient classification variability was reflected by Pearson correlation coefficient of 0.40 (p-value 0.001). CONCLUSIONS: Hyperoxia classification in pediatric severe TBI during the first 24 hours of PICU admission differed depending on PaO2 cutoff or cumulative AUC analysis. We consider PaO2 cumulative (AUC) better approximates (patho-)physiological circumstances due to its time- and dose-dependent approach. Prospective studies exploring the association between cumulative PaO2, physiological parameters (e.g. ICP, PbtO2) and outcome are warranted as different patient classifications of oxygen exposure influences how its relationship to outcome is interpreted.

Correction to: Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study.

The collaborator names are inverted.

Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study.

BACKGROUND: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. METHODS: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). RESULTS: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. CONCLUSION: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.

BACKGROUND: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. METHODS: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. RESULTS: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

Causes and Consequences of Treatment Variation in Moderate and Severe Traumatic Brain Injury: A Multicenter Study.

OBJECTIVES: Although guidelines have been developed to standardize care in traumatic brain injury, between-center variation in treatment approach has been frequently reported. We examined variation in treatment for traumatic brain injury by assessing factors influencing treatment and the association between treatment and patient outcome. DESIGN: Secondary analysis of prospectively collected data. SETTING: Five level I trauma centers in the Netherlands (2008-2009). PATIENTS: Five hundred three patients with moderate or severe traumatic brain injury (Glasgow Coma Scale, 3-13). INTERVENTIONS: We examined variation in seven treatment parameters: direct transfer, involvement of mobile medical team, mechanical ventilation, intracranial pressure monitoring, vasopressors, acute neurosurgical intervention, and extracranial operation. MEASUREMENTS AND MAIN RESULTS: Data were collected on patient characteristics, treatment, and 6-month Glasgow Outcome Scale-Extended. Multivariable logistic regression models were used to assess the extent to which treatment was determined by patient characteristics. To examine whether there were between-center differences in treatment, we used unadjusted and adjusted random effect models with the seven treatment parameters as dependent variables. The influence of treatment approach in a center (defined as aggressive and nonaggressive based on the frequency intracranial pressure monitoring) on outcome was assessed using multivariable random effect proportional odds regression models in those patients with an indication for intracranial pressure monitoring. Sensitivity analyses were performed to test alternative definitions of aggressiveness. Treatment was modestly related to patient characteristics (Nagelkerke R range, 0.12-0.52) and varied widely among centers, even after case-mix correction. Outcome was more favorable in patients treated in aggressive centers than those treated in nonaggressive centers (OR, 1.73; 95% CI, 1.05-3.15). Sensitivity analyses, however, illustrated that the aggressiveness-outcome association was dependent on the definition used. CONCLUSIONS: The considerable between-center variation in treatment for patients with brain injury can only partly be explained by differences in patient characteristics. An aggressive treatment approach may imply better outcome although further confirmation is required.

Contemporary frameless intracranial biopsy techniques: Might variation in safety and efficacy be expected?

BACKGROUND: Frameless stereotactic neuronavigation has proven to be a feasible technology to acquire brain biopsies with good accuracy and little morbidity and mortality. New systems are constantly introduced into the neurosurgical armamentarium, although few studies have actually evaluated and compared the diagnostic yield, morbidity, and mortality of various manufacturer's frameless neuronavigation systems. The present study reports our experience with brain biopsy procedures performed using both the Medtronic Stealth Treon(TM) Vertek® and BrainLAB® Varioguide frameless stereotactic brain biopsy systems. PATIENTS AND METHODS: All 247 consecutive biopsies from January 2008 until May 2013 were evaluated retrospectively. One hundred two biopsies each were performed using the Medtronic (2008-2009) and BrainLAB® system (2011-2013), respectively. The year 2010 was considered a transition year, in which 43 biopsies were performed with either system. Patient demographics, perioperative characteristics, and histological diagnosis were reviewed, and a comparison was made between the two brain biopsy systems. RESULTS: The overall diagnostic yield was 94.6 %, i.e., 11 biopsies were nondiagnostic, 5 (4.9 %) with the Medtronic and 6 (5.9 %) with the BrainLAB® system. No differences besides the operating time (108 vs 120 min) were found between the two biopsy methods. On average, 6.6 tissue samples were taken with either technique. Peri- and postoperative complications were seen in 5.3 % and 12.9 %, consisting of three symptomatic hemorrhages (1.2 %). Biopsy-related mortality occurred in 0.8 % of all biopsies. CONCLUSIONS: Regarding diagnostic yield, complication rate, and biopsy-related mortality, there seems to be no difference between the frameless biopsy technique from Medtronic and BrainLAB®. In contemporary time, the neurosurgeon has many tools to choose from, all with a relatively fast learning curve and ever improving feasibility. Thus, the issue of choice involves not the results, but the familiarity, end-user friendliness, and overall comfort when operating the system.

Clinical and Imaging Characteristics, Care Pathways, and Outcomes of Traumatic Epidural Hematomas: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study.

BACKGROUND AND OBJECTIVES: Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. METHODS: This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. RESULTS: In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. CONCLUSION: Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.

Intravenous lidocaine attenuates distention of the optical nerve sheath, a correlate of intracranial pressure, during endotracheal intubation.

BACKGROUND: By preventing hypoxia and hypercapnia, advanced airway management can save lives among patients with traumatic brain injury. During endotracheal intubation (ETI), tracheal stimulation causes an increase in intracranial pressure (ICP), which may impair brain perfusion. It has been suggested that intravenous lidocaine might attenuate this ICP response. We hypothesized that adding lidocaine to the standard induction medication for general anesthesia might reduce the ICP response to ETI. Here, we measured the optical nerve sheath diameter (ONSD) as a correlate of ICP and evaluated the effect of intravenous lidocaine on ONSD during and after ETI in patients undergoing anesthesia. METHODS: This double-blinded, randomized placebo-controlled trial included 60 patients with American Society of Anesthesiologists I or II physical status that were scheduled for elective surgery under general anesthesia. In addition to the standard anesthesia medication, 30 subjects received 1.5 mg/kg 1% lidocaine (0.15 mL/kg, ONSD lidocaine) and 30 received 0.15 mL/kg 0.9% NaCl (ONSD placebo). ONSDs were measured with ultrasound on the left eye, before (T0), during (T1), and 4 times after ETI (T2-5 at 5-min intervals). RESULTS: Compared to placebo, lidocaine did not significantly affect the baseline ONSD after anesthesia induction measured at T0. During ETI, the ONSD lidocaine was significantly smaller (ß=-0.24 mm P=0.022) than the ONSD placebo. At T4 and T5, the ONSD placebo increased steadily, up to 20 min after ETI, but the ONSD lidocaine tended to return to baseline levels. CONCLUSIONS: We found that the ONSD was distended during and after ETI in anesthetized patients, and intravenous lidocaine attenuated this effect.

Factors influencing intracranial pressure monitoring guideline compliance and outcome after severe traumatic brain injury.

OBJECTIVE: To determine adherence to Brain Trauma Foundation guidelines for intracranial pressure monitoring after severe traumatic brain injury, to investigate if characteristics of patients treated according to guidelines (ICP+) differ from those who were not (ICP-), and whether guideline compliance is related to 6-month outcome. DESIGN: Observational multicenter study. PATIENTS: Consecutive severe traumatic brain injury patients (≥16 yrs, n = 265) meeting criteria for intracranial pressure monitoring. MEASUREMENTS AND MAIN RESULTS: Data on demographics, injury severity, computed tomography findings, and patient management were registered. The Glasgow Outcome Scale Extended was dichotomized into death (Glasgow Outcome Scale Extended = 1) and unfavorable outcome (Glasgow Outcome Scale Extended 1-4). Guideline compliance was 46%. Differences between the monitored and nonmonitored patients included a younger age (median 44 vs. 53 yrs), more abnormal pupillary reactions (52% vs. 32%), and more intracranial pathology (subarachnoid hemorrhage 62% vs. 44%; intraparenchymal lesions 65% vs. 46%) in the ICP+ group. Patients with a total intracranial lesion volume of ~150 mL and a midline shift of ~12 mm were most likely to receive an intracranial pressure monitor and probabilities decreased with smaller and larger lesions and shifts. Furthermore, compliance was low in patients with no (Traumatic Coma Databank score I -10%) visible intracranial pathology. Differences in case-mix resulted in higher a priori probabilities of dying (median 0.51 vs. 0.35, p < .001) and unfavorable outcome (median 0.79 vs. 0.63, p < .001) in the ICP+ group. After correction for baseline and clinical characteristics with a propensity score, intracranial pressure monitoring guideline compliance was not associated with mortality (odds ratio 0.93, 95% confidence interval 0.47-1.85, p = .83) nor with unfavorable outcome (odds ratio 1.81, 95% confidence interval 0.88-3.73, p = .11). CONCLUSIONS: Guideline noncompliance was most prominent in patients with minor or very large computed tomography abnormalities. Intracranial pressure monitoring was not associated with 6-month outcome, but multiple baseline differences between monitored and nonmonitored patients underline the complex nature of examining the effect of intracranial pressure monitoring in observational studies.

Impact of dedicated neuro-anesthesia management on clinical outcomes in glioblastoma patients: A single-institution cohort study.

BACKGROUND: Glioblastomas are mostly resected under general anesthesia under the supervision of a general anesthesiologist. Currently, it is largely unkown if clinical outcomes of GBM patients can be improved by appointing a neuro-anesthesiologist for their cases. We aimed to evaluate whether the assignment of dedicated neuro-anesthesiologists improves the outcomes of these patients. We also investigated the value of dedicated neuro-oncological surgical teams as an independent variable in both groups. METHODS: A cohort consisting of 401 GBM patients who had undergone resection was retrospectively investigated. Primary outcomes were postoperative neurological complications, fluid balance, length-of-stay and overall survival. Secondary outcomes were blood loss, anesthesia modality, extent of resection, total admission costs, and duration of surgery. RESULTS: 320 versus 81 patients were operated under the anesthesiological supervision of a general anesthesiologist and a dedicated neuro-anesthesiologist, respectively. Dedicated neuro-anesthesiologists yielded significant superior outcomes in 1) postoperative neurological complications (early: p = 0.002, OR = 2.54; late: p = 0.003, OR = 2.24); 2) fluid balance (p<0.0001); 3) length-of-stay (p = 0.0006) and 4) total admission costs (p = 0.0006). In a subanalysis of the GBM resections performed by an oncological neurosurgeon (n = 231), the assignment of a dedicated neuro-anesthesiologist independently improved postoperative neurological complications (early minor: p = 0.0162; early major: p = 0.00780; late minor: p = 0.00250; late major: p = 0.0364). The assignment of a dedicated neuro-oncological team improved extent of resection additionally (p = 0.0416). CONCLUSION: GBM resections with anesthesiological supervision of a dedicated neuro-anesthesiologists are associated with improved patient outcomes. Prospective evidence is needed to further investigate the usefulness of the dedicated neuro-anesthesiologist in different settings.

Intraoperative B-Mode Ultrasound Guided Surgery and the Extent of Glioblastoma Resection: A Randomized Controlled Trial.

BACKGROUND: Intraoperative MRI and 5-aminolaevulinic acid guided surgery are useful to maximize the extent of glioblastoma resection. Intraoperative ultrasound is used as a time-and cost-effective alternative, but its value has never been assessed in a trial. The goal of this randomized controlled trial was to assess the value of intraoperative B-mode ultrasound guided surgery on the extent of glioblastoma resection. MATERIALS AND METHODS: In this randomized controlled trial, patients of 18 years or older with a newly diagnosed presumed glioblastoma, deemed totally resectable, presenting at the Erasmus MC (Rotterdam, The Netherlands) were enrolled and randomized (1:1) into intraoperative B-mode ultrasound guided surgery or resection under standard neuronavigation. The primary outcome of this study was complete contrast-enhancing tumor resection, assessed quantitatively by a blinded neuroradiologist on pre- and post-operative MRI scans. This trial was registered with ClinicalTrials.gov (NCT03531333). RESULTS: We enrolled 50 patients between November 1, 2016 and October 30, 2019. Analysis was done in 23 of 25 (92%) patients in the intraoperative B-mode ultrasound group and 24 of 25 (96%) patients in the standard surgery group. Eight (35%) of 23 patients in the intraoperative B-mode ultrasound group and two (8%) of 24 patients in the standard surgery group underwent complete resection (p=0.036). Baseline characteristics, neurological outcome, functional performance, quality of life, complication rates, overall survival and progression-free survival did not differ between treatment groups (p>0.05). CONCLUSIONS: Intraoperative B-mode ultrasound enables complete resection more often than standard surgery without harming patients and can be considered to maximize the extent of glioblastoma resection during surgery.

Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI): study protocol for a randomized, placebo-controlled, multi-center trial.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI. OBJECTIVE: To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients. METHODS: CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis. DISCUSSION: We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58.

Towards improving the safety and diagnostic yield of stereotactic biopsy in a single centre.

BACKGROUND: Previously, we reported on our single centre results regarding the diagnostic yield of stereotactic needle biopsies of brain lesions. The yield then (1996-2006) was 89.4%. In the present study, we review and evaluate our experience with intraoperative frozen-section histopathologic diagnosis on-demand in order to improve the diagnostic yield. METHODS: One hundred sixty-four consecutive frameless biopsy procedures in 160 patients (group 1, 2006-2010) were compared with the historic control group (group 2, n = 164 frameless biopsy procedures). Diagnostic yield, as well as demographics, morbidity and mortality, was compared. Statistical analysis was performed by Student's t, Mann-Whitney U, Chi-square test and backward logistic regression when appropriate. RESULTS: Demographics were comparable. In group 1, a non-diagnostic tissue specimen was obtained in 1.8%, compared to 11.0% in group 2 (p = 0.001). Also, both the operating time and the number of biopsies needed were decreased significantly. Procedure-related mortality decreased from 3.7% to 0.6% (p = 0.121). Multivariate analysis only proved operating time (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.000-1.025; p = 0.043), a right-sided lesion (OR, 3.183; 95% CI, 1.217-8.322; p = 0.018) and on-demand intraoperative histology (OR, 0.175; 95% CI, 0.050-0.618; p = 0.007) important factors predicting non-diagnostic biopsies. CONCLUSIONS: The importance of a reliable pathological diagnosis as obtained by biopsy must not be underestimated. We believe that when performing stereotactic biopsy for intracranial lesions, next to minimising morbidity, one should strive for as high a positive yield as possible. In the present single centre retrospective series, we have shown that using a standardised procedure and careful on-demand intraoperative frozen-section analysis can improve the diagnostic yield of stereotactic brain biopsy procedures as compared to a historical series.

Refining resuscitation strategies using tissue oxygen and perfusion monitoring in critical organ beds.

BACKGROUND: Muscle tissue oxygen monitoring (PmO2) holds promise as a continuous guide to resuscitation after hemorrhagic shock, but the relationship of muscle tissue oxygen to perfusion has not been described previously. On the other hand, brain tissue oxygen PbrO2 and perfusion as measured by cerebral blood flow (CBF) are already used clinically, especially as guides to vasopressor use in cerebral perfusion targeted therapy in patients with traumatic brain injury. This laboratory study was undertaken to describe the relative contributions of muscle perfusion and arterial oxygen tension (PaO2) to muscle tissue oxygen (PmO2) levels. Second, we wanted to compare the relationship between muscle oxygen and muscle blood flow (MBF) with simultaneously measured brain tissue oxygen and perfusion during the administration of a vasopressor and during experimental hemorrhagic shock. We hypothesized that muscle perfusion would be an important contributor to PmO2, thus underscoring the need for optimal fluid resuscitation after shock. We further hypothesized that PmO2 would decrease even as PbrO2 increased when vasopressor therapy was used. METHODS: Eight pigs were anesthetized, intubated, underwent splenectomies, and were instrumented to monitor PmO2, MBF, PbrO2, and CBF. Oxygen challenges were performed by increasing PaO2 from 100 to 500 mm Hg during three different experimental phases: baseline, vasopressor administration, and hemorrhage. Mean PmO2 and MBF were compared at the beginning and end of each experimental phase and correlations between PmO2, MBF, PbrO2, CBF, and traditional endpoints of resuscitation were investigated. RESULTS: During oxygen challenges in all phases, PmO2 increased (31.2 +/- 16.6 mm Hg to 56.6 +/- 34.1 mm Hg; p < 0.01), whereas MBF did not change significantly (16.4 +/- 11.3 mL/100 g/min to 15.4 +/- 11.9 mL/100 g/min). On administration of vasopressors, MBF decreased (18 +/- 8.8 mL/100 g/min to 5.3 +/- 3 mL/100 g/min; p = 0.03), but no change in PmO2 was detected. During hemorrhage, both PmO2 and MBF declined (PmO2: 40 +/- 8.8 mm Hg to 7.7 +/- 9.6 mm Hg; p = 0.002; MBF: 9.8 +/- 5.8 mL/100 g/min to 3.3 +/- 2.4 mL/100 g/min; p = 0.046). Both PmO2 and MBF showed strong relationships with measurements of resuscitation, base deficit (PmO2 and MBF: p < 0.01), and mean arterial pressure (PmO2: p < 0.01, MBF: p = 0.02). Like PmO2 and MBF, PbrO2 and CBF decreased uniformly during hemorrhage. However, on vasopressor administration, CBF and PbrO2 increased significantly, whereas MBF decreased. CONCLUSION: PmO2 and MBF can be monitored simultaneously and continuously and correlate well with measurements of resuscitation. PmO2 values reflect both local perfusion and arterial oxygen tension. The clinical application of PmO2 as a continuous endpoint of resuscitation and its relationship to muscle perfusion warrants further study in critically injured patients and these investigations may help to refine resuscitation strategies.

Evolution of Evidence and Guideline Recommendations for the Medical Management of Severe Traumatic Brain Injury.

Brain Trauma Foundation (BTF) Guidelines for medical management of severe traumatic brain injury (TBI) have become a global standard for the treatment of TBI patients. We aim to explore the evolution of the guidelines for the management of severe TBI. We reviewed the four editions of the BTF guidelines published over the past 20 years. The 1996 and 2000 editions were merged because of minimal differences, and are referred to as the 1996 edition. We described changes in topics and recommendations over time, and analyzed predictors of survival of recommendations with logistical regression. The guidelines contained 27 recommendations on 18 topics in 2016, 35 recommendations on 15 topics in 2007, and 22 recommendations on 10 topics in 1996. Substantial delays were found between the search for evidence and the guideline publication, ranging from 18 to 34 months. The overall body of evidence comprised 189 studies on 18 topics in 2016, compared with 156 studies on 15 topics in 2007 and 180 studies on 10 topics in 1996. Over time, a total of 175 studies were discarded from the evidence base following more rigorous grading of evidence. A total of 15/23 (65%) of the 1996/2000 recommendations were discarded over time. Out of 12 new recommendations introduced in the 2007 edition, 8 (66%) were discarded in 2016. Survival of recommendations varied between 33% and 100% for level I recommendations and between 11% and 31% for level II and III recommendations. No predictors of survival of recommendations were found. Substantial delays exist between literature search and publication, and survival rate of TBI guideline recommendations is poor. These factors may adversely affect currency and adherence to guidelines. The TBI community should take responsibility for improving the quality of the evidence base and ensuring that the translation of the evidence into guidelines supports clinicians in daily clinical practice.

Ventricular Drainage Catheters versus Intracranial Parenchymal Catheters for Intracranial Pressure Monitoring-Based Management of Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Intracranial pressure (ICP) monitoring is one of the mainstays in the treatment of severe traumatic brain injury (TBI), but different approaches to monitoring exist. The aim of this systematic review and meta-analysis is to compare the effectiveness and complication rate of ventricular drainage (VD) versus intracranial parenchymal (IP) catheters to monitor and treat raised ICP in patients with TBI. Pubmed, Embase, Web of Science, Google Scholar, and the Cochrane Database were searched for articles comparing ICP monitoring-based management with VDs and monitoring with IP monitors through March 2018. Study selection, data extraction, and quality assessment were performed independently by two authors. Outcomes assessed were mortality, functional outcome, need for decompressive craniectomy, length of stay, overall complications, such as infections, and hemorrhage. Pooled effect estimates were calculated with random effects models and expressed as relative risk (RR) for dichotomous outcomes and mean difference (MD) for ordinal outcomes, with corresponding 95% confidence intervals (CI). Six studies were included: one randomized controlled trial and five observational cohort studies. Three studies reported mortality, functional outcome, and the need for a surgical decompression, and three only reported complications. The quality of the studies was rated as poor, with critical or serious risk of bias. The pooled analysis did not show a statistically significant difference in mortality (RR = 0.90, 95% CI = 0.60-1.36, p = 0.41) or functional outcome (MD = 0.23, 95% CI = 0.67-1.13, p = 0.61). The complication rate of VDs was higher (RR = 2.56, 95% CI = 1.17-5.61, p = 0.02), and consisted mainly of infectious complications; that is, meningitis. VDs caused more complications, particularly more infections, but there was no difference in mortality or functional outcome between the two monitoring modalities. However, the studies had a high risk of bias. A need exists for high quality comparisons of VDs versus IP monitor-based management strategies on patient outcomes.