Initial Intracranial Pressure Research Articles

Comparison of two minimally invasive surgical approaches for hypertensive intracerebral hemorrhage: a study based on postoperative intracranial pressure parameters

BackgroundIncreased intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) has been associated with poor prognosis. The transsylvian insular approach (TIA) and the transcortical (TCA) approach are applied for patients with HICH. We aimed to compare the postoperative ICP parameters of TIA and TCA to identify which procedure yields better short-term outcomes in patients with basal ganglia hematoma volumes ranging from 30 to 50 mL.MethodsEighty patients with basal ganglia hematomas 30–50 mL were enrolled in this study. Patients were implanted with ICP probes and divided into TIA and TCA groups according to the procedure. The ICP values were continuously recorded for five days at four-hour intervals. Short-term outcomes were evaluated using the length of hospitalization and postoperative consciousness recovery time.ResultsNo statistically significant differences were found in age, sex, GCS score at admission, hematoma volume, and hematoma clearance rate (p > 0.05). The results showed that postoperative initial ICP, ICP on the first postoperative day, mean ICP, DICP20 mmHg × 4 h, postoperative consciousness recovery time, the length of hospitalization, mannitol utilization rate and the mannitol dosage were lower in the TIA group than in the TCA group (p < 0.05). Postoperative consciousness recovery time was positively correlated with ICP on the first postoperative day, and the length of hospitalization was positively correlated with mean ICP.ConclusionsTIA is more effective than TCA in improving the short-term outcomes of patients with basal ganglia hematoma volumes ranging from 30 to 50 mL according to comparisons of postoperative ICP parameters.

447 Haptoglobin Treatment to Improve Outcome After Aneurysmal Subarachnoid Haemorrhage: A Consensus Perspective on Clinical Translation

Abstract Aim Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of stroke with an unmet need to improve outcome. This study focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress and arriving at a Delphi-based global consensus regarding the role of extracellular haemoglobin and research priorities for clinical translation of haemoglobin-scavenging strategies. Method A narrative review of the topic by searching PubMed with relevant keywords and through discussions with leading expert in the field of aSAH. A modified Delphi processes. Four virtual meetings were held, two prior to starting, and two during the first round. Otherwise, the study was conducted electronically. Results Clinicians (n = 72) and scientific experts (n = 28) from five continents participated in the Delphi study. Microvascular spasm, iInflammation, microvascular spasm, and initial intracranial pressure rise were deemed the most important pathophysiological pathways determining outcome. Extracellular haemoglobin was thought to play an important role mostly in iron toxicity, oxidative stress, nitric oxide homeostasis and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field to be ready for early phase trial. The highest priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics and outcome measure selection. Conclusions These results highlight the pressing need for early phase trials of intracranial haptoglobin for aSAH, and the immense value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body's first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin's anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Optic Nerve Ultrasound Evaluation in Children: A Review.

Managing patients with neurocritical illness requires monitoring and treating elevated intracranial pressure (ICP), especially in cases in children. In terms of precise and real-time measurements, invasive ICP measurements are presently the gold standard for the initial diagnosis and follow-up ICP assessments. As a rapid and non-invasive way to detect elevated ICP, point-of-care ultrasonography (POCUS) of optic nerve sheath diameter (ONSD) has been proposed. The utility of bedside POCUS of ONSD to detect elevated ICP with excellent diagnostic test accuracy in adults has already been demonstrated. Nonetheless, data on the relationship between POCUS of ONSD and ICP in children are scarce. Therefore, the purpose of this review is to point out the most recent findings from the pediatric published literature and briefly discuss what was assessed with ONSD ultrasound examination, and also to describe and discuss the diagnostic procedures available for optic nerve ultrasound appraisal. A search of the medical databases PubMed and Scopus was carried out. The terms such as "ocular ultrasonography", "ICP assessment", "children", "point-of-care ultrasound", and "POCUS" were searched. In conclusion, the use of the standardized A-scan technique coupled with the B-scan technique should be suggested to provide data that are as accurate, precise, repeatable, and objective as possible.

Non-Invasive Assessment of Intracranial Hypertension in Patients with Traumatic Brain Injury Using Computed Tomography Radiomic Features: A Pilot Study.

This study aimed to assess intracranial hypertension in patients with traumatic brain injury non-invasively using computed tomography (CT) radiomic features. Fifty patients from the primary cohort were enrolled in this study. The clinical data, pre-operative cranial CT images, and initial intracranial pressure readings were collected and used to develop a prediction model. Data of 20 patients from another hospital were used to validate the model. Clinical features including age, sex, midline shift, basilar cistern status, and ventriculocranial ratio were measured. Radiomic features-i.e., 18 first-order and 40 second-order features- were extracted from the CT images. LASSO method was used for features filtration. Multi-variate logistic regression was used to develop three prediction models with clinical (CF model), first-order (FO model), and second-order features (SO model). The SO model achieved the most robust ability to predict intracranial hypertension. Internal validation showed that the C-statistic of the model was 0.811 (95% confidence interval [CI]: 0.691-0.931) with the bootstrapping method. The Hosmer Lemeshow test and calibration curve also showed that the SO model had excellent performance. The external validation results showed a good discrimination with an area under the curve of 0.725 (95% CI: 0.500-0.951). Although the FO model was inferior to the SO model, it had better prediction ability than the CF model. The study shows that the radiomic features analysis, especially second-order features, can be used to evaluate intracranial hypertension non-invasively compared with conventional clinical features, given its potential for clinical practice and further research.

Novel application of the Rotterdam CT score in the prediction of intracranial hypertension following severe traumatic brain injury.

Severe traumatic brain injury (TBI) is associated with intracranial hypertension (ICHTN). The Rotterdam CT score (RS) can predict clinical outcomes following TBI, but the relationship between the RS and ICHTN is unknown. The purpose of this study was to investigate clinical and radiological factors that predict ICHTN in patients with severe TBI. The authors performed a single-center retrospective review of patients who, between 2018 and 2021, had an intracranial pressure (ICP) monitor placed following TBI. Radiological and clinical characteristics related to the TBI and ICP monitoring were collected. The main outcome of interest was ICHTN, which was a dichotomous outcome (yes or no) defined on a per-patient basis as an ICP > 22 mm Hg that persisted for at least 5 minutes and required an escalation of treatment. ICHTN included both elevated opening pressure on initial monitor placement and ICP elevations later during hospitalization. Multivariate logistic regression was performed to determine variables associated with ICHTN. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUROC). Seventy patients with severe TBI and an ICP monitor were included in this study. There was a predominance of male patients (94.0%), and the mean patient age was 40 years old. Most patients (67%) had an intraparenchymal catheter placed, whereas 33% of patients had a ventriculostomy catheter placed. In the multivariate logistic regression analysis, the RS was an independent predictor of ICHTN (OR 2.0, 95% CI 1.2-3.5, p = 0.014). No instances of ICHTN were observed in patients with an RS of 2 or less and no sulcal effacement. The AUROC of the RS and sulcal effacement was higher than the AUROC of the RS alone for predicting ICHTN (0.76 vs 0.71, p = 0.003, z-test). The RS was predictive of ICHTN in patients with severe TBI, and the diagnostic accuracy of the model was improved with the inclusion of sulcal effacement at the vertex on CT of the head. Patients with a low RS and no sulcal effacement are likely at low risk for the development of ICHTN.

Group-based trajectory modeling of intracranial pressure in patients with acute brain injury: Results from multi-center ICUs, 2008-2019.

ObjectiveThe objective of the study was to characterize the longitudinal, dynamic intracranial pressure (ICP) trajectory in acute brain injury (ABI) patients admitted to intensive care unit (ICU) and explore whether it added sights over traditional thresholds in predicting outcomes.MethodsABI patients with ICP monitoring were identified from two public databases named Medical Information Mart for the Intensive Care (MIMIC)‐IV and eICU Collaborative Research Database (eICU‐CRD). Group‐based trajectory modeling (GBTM) was employed to identify 4‐h ICP trajectories in days 0–5 post‐ICU admission. Then, logistic regression was used to compare clinical outcomes across distinct groups. To further validate previously reported thresholds, we created the receiver operating characteristic (ROC) curve in our dataset.ResultsA total of 810 eligible patients were ultimately enrolled in the study. GBTM analyses generated 6 distinct ICP trajectories, differing in the initial ICP, evolution pattern, and number/proportion of spikes >20/22 mmHg. Compared with patients in “the highest, declined then rose” trajectory, those belonging to the “lowest, stable,” “low, stable,” and “medium, stable” ICP trajectories were at lower risks of 30‐day mortality (odds ratio [OR] 0.04; 95% confidence interval [CI] 0.01, 0.21), (OR 0.04; 95% CI 0.01, 0.19), (OR 0.08; 95% CI 0.01, 0.42), respectively. ROC analysis demonstrated an unfavorable result, for example, 30‐day mortality in total cohort: an area under the curve (AUC): 0.528, sensitivity: 0.11, and specificity: 0.94.ConclusionsThis study identified three ICP trajectories associated with elevated risk, three with reduced risks for mortality during ICU hospitalization. Notably, a fixed ICP threshold should not be applied to all kinds of patients. GBTM, a granular method for describing ICP evolution and their association with clinical outcomes, may add to the current knowledge in intracranial hypertension treatment.

The Relationship between Serum Sodium, Serum Osmolality, and Intracranial Pressure in Patients with Traumatic Brain Injury Treated with Hyperosmolar Therapy.

Treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI) is controversial. Hyperosmolar therapy is used to prevent cerebral edema in these patients. Many intensivists measure direct correlates of these agents-serum sodium and osmolality. We seek to provide context on the utility of using these measures to estimate ICP in TBI patients. Patients admitted with TBI who required ICP monitoring from 2008 to 2012 were included. Intracranial pressure, serum sodium, and serum osmolality were assessed prior to hyperosmotic therapy then at 6, 12, 18, 24, 48, and 72hours after admission. A linear regression was performed on sodium, osmolality, and ICP at baseline and serum sodium and osmolality that corresponded with ICP for 6-72-hour time points. 136 patients were identified. Patients with initial measures were included in the baseline analysis (n = 29). Patients who underwent a craniectomy were excluded from the 6-72-hour analysis (n = 53). Initial ICP and serum sodium were not significantly correlated (R2 .00367, P = .696). Initial ICP and serum osmolality were not significantly correlated (R2 .00734, P = .665). Intracranial pressure and serum sodium 6-72hours after presentation were poorly correlated (R2 .104, P < .0001), as were ICP and serum osmolality at 6-72hours after presentation (R2 .116, P < .0001). Our results indicate initial ICP is not correlated with serum sodium or osmolality suggesting these are not useful initial clinical markers for ICP estimation. The association between ICP and serum sodium and osmolality after hyperosmolar therapy was poor, thus may not be useful as surrogates for direct ICP measurements.

Initial intracranial pressure is an independent predictor of unfavorable functional outcomes after aneurysmal subarachnoid hemorrhage

The authors sought to evaluate whether initial intracranial pressure was associated with functional outcomes following aneurysmal subarachnoid hemorrhage. This retrospective analysis consisted of 54 consecutive patients with aneurysmal subarachnoid hemorrhage and acute symptomatic hydrocephalus requiring emergent placement of an external ventricular drain. Patient demographics, clinical data, intracranial pressure parameters, and radiographic imaging were collected. Functional outcomes were evaluated at 3 months using the modified Rankin Scale and dichotomized as favorable (modified Rankin Scale 0–2) or unfavorable (modified Rankin Scale 3–6). Univariate and multivariate logistic regression analyses were performed to investigate parameters independently associated with functional outcomes. In an adjusted multivariate logistic regression model, initial intracranial pressure (OR: 1.371, 95% CI: 1.119–1.679; p = 0.002) was found to be an independent predictor of unfavorable functional outcomes at 3 months. Receiver operating characteristic curve analysis for the prediction of unfavorable functional outcomes demonstrated that initial intracranial pressure exhibited an acceptable area under the curve (AUC = 0.901, 95% CI: 0.818–0.985; p < 0.001). The optimal predictive threshold to distinguish between favorable and unfavorable functional outcomes was identified at an initial intracranial pressure of 25 mmHg.

Evaluation of Intracranial Hypertension in Traumatic Brain Injury Patient: A Noninvasive Approach Based on Cranial Computed Tomography Features.

Background: Our purpose was to establish a noninvasive quantitative method for assessing intracranial pressure (ICP) levels in patients with traumatic brain injury (TBI) through investigating the Hounsfield unit (HU) features of computed tomography (CT) images. Methods: In this retrospective study, 47 patients with a closed TBI were recruited. Hounsfield unit features from the last cranial CT and the initial ICP value were collected. Three models were established to predict intracranial hypertension with Hounsfield unit (HU model), midline shift (MLS model), and clinical expertise (CE model) features. Results: The HU model had the highest ability to predict intracranial hypertension. In 34 patients with unilateral injury, the HU model displayed the highest performance. In three classifications of intracranial hypertension (ICP ≤ 22, 23–29, and ≥30 mmHg), the HU model achieved the highest F1 score. Conclusions: This radiological feature-based noninvasive quantitative approach showed better performance compared with conventional methods, such as the degree of midline shift and clinical expertise. The results show its potential in clinical practice and further research.

Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial.

BackgroundTherapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI).MethodsThe Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18–65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34–35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222.Findings302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91–2·64; P = 0·105) and in mortality (P = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031–3·361; P = 0·039). Long-term mild hypothermia did not increase the incidences of complications.InterpretationLong-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg.Funding: Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.

Serial Optic Nerve Sheath Diameter via Radiographic Imaging: Correlation With ICP and Outcomes.

Evaluation of optic nerve sheath diameter (ONSD) is a suggested correlation of intracranial pressure (ICP) and potential predictor of outcome after neurologic injury. Studies have evaluated sonographic measurement of ONSD; however, clinical limitations to this approach persist. Evaluation of ONSD measurements via routine brain CT imaging is less studied but offers potential for detection of increased ICP in the absence of invasive monitoring. Previous studies have used cross-sectional approaches to ONSD measurements via CT scan among patients with traumatic brain injury (TBI). No studies have evaluated serial correlations between CT ONSD measurements and ICP throughout hospitalization and across diagnosis types. The objective of this study was to investigate correlations between ONSD via serial CT imaging, ICP, and outcome at discharge among patients with neurologic injury. This is a retrospective cohort study of all adult patients admitted during a 12-month period with acute neurologic injury requiring ICP monitoring and critical care admission. N = 48. There was a strong, positive correlation between right/left ONSD across time points (r = 0.7-9, p < 0.001), suggesting a consistent bilateral response. Correlations were strongest between initial inpatient CT scan ONSD readings and ICP (r = 0.5, p < 0.05), but decreased over time. Patients with increased ICP across all diagnosis types experienced higher ONSD values on presentation to the emergency department (ED) and throughout hospitalization (range 5.7-6.4 mm, p < 0.05). Findings contribute to the utility of CT ONSD measurements as a potential indicator of increased ICP. Measurement of ONSD during serial CT brain imaging may inform clinical decisions regarding need for more invasive monitoring after neurologic injury.

P.263 Outcome of treatment in clinical practice compared to a clinical trial in treatment-resistant depression: a matched adjusted indirect comparison

For patients with TBI, traditional methods such as clinical examination and imaging data are the primary references used for deciding whether to operate or not. Intracranial pressure (ICP) monitoring based on lateral ventricles or parenchymal pressure is a more direct reflection of ICP. However, the research on whether the outcome results of ICP monitoring are better than results based on clinical signs and imaging is sparse. Therefore, we compared treatment results for patients with TBI based on ICP monitoring and traditional methods.This retrospective study included patients with TBI admitted to our collaborative hospitals between January 1, 2012, and December 31, 2013. All patients enrolled were divided into a traditional methods group and ICP monitoring group. Follow-up treatment was determined by ICP monitoring value or traditional methods in the 2 groups. Propensity matching scores were used to ensure that baseline characteristics of patients in the 2 groups were consistent.A significant association was found between the initial ICP value and neurologic deterioration (odds ratio 1.24; P < 0.001), and nonlinear correlation achieved the best fit (R2 = 0.547). Both 6-month good recovery rate and favorable outcome rate were higher in the ICP monitoring group than the traditional methods group by propensity score analysis (P < 0.05).For patients with TBI with cerebral contusion volume >20 mL, both 6-month good recovery rate and favorable outcome rate were significantly higher in the ICP monitoring group than the traditional methods group.

Pneumocephalus and air travel: an experimental investigation on the effects of aircraft cabin pressure on intracranial pressure

This study investigates the effects of aircraft cabin pressure on intracranial pressure (ICP) elevation of a pneumocephalus patient. We propose an experimental setup that simulates the intracranial hydrodynamics of a pneumocephalus patient during flight. It consists of an acrylic box (skull), air-filled balloon [intracranial air (ICA)], water-filled balloon (cerebrospinal fluid and blood) and agarose gel (brain). The cabin was replicated using a custom-made pressure chamber. The setup can measure the rise in ICP during depressurization to levels similar to that inside the cabin at cruising altitude. ΔICP, i.e. the difference between mean cruising ICP and initial ICP, was found to increase with ICA volume and ROC. However, ΔICP was independent of the initial ICP. The largest ΔICP was 5 mmHg; obtained when ICA volume and ROC were 20 ml and 1,600 ft/min, respectively. The postulated ICA expansion and the subsequent increase in ICP in pneumocephalus patients during flight were successfully quantified in a laboratory setting. Based on the quantitative and qualitative analyses of the results, an ICA volume of 20 ml and initial ICP of 15 mmHg were recommended as conservative thresholds that are required for safe air travel among pneumocephalus patients. This study provides laboratory data that may be used by doctors to advise post-neurosurgical patients if they can safely fly.

Comparison of Weight-Based Dosing versus Fixed Dosing of 23.4% Hypertonic Saline for Intracranial Pressure Reduction in Patients with Severe Traumatic Brain Injury.

Context:Hypertonic saline (HTS) is a pharmacologic therapy used in patients with severe traumatic brain injuries to decrease intracranial pressure (ICP) associated with cerebral edema.Aims:The purpose of this study was to compare ICP reduction between fixed doses of 23.4% HTS and weight-based doses.Setting and Design:This was a retrospective study that included adult patients at a level 1 trauma center who had nonpenetrating traumatic brain injury, an ICP monitor, and received at least one dose of 23.4% HTS.Subjects and Methods:Doses were classified as either high weight-based (>0.6 ml/kg), low weight-based (<0.6 ml/kg), or standard fixed dose (30 ml). Only doses given within 5 days post-injury were evaluated. Percent reduction in ICP was compared pre- and post-dose between dosing groups, and each dose was evaluated as a separate episode.Statistical Analysis:The primary and secondary endpoints for the study were analyzed using mixed-model, repeated-measures analysis of covariance.Results:A total of 97 doses of HTS were evaluated. The primary endpoint of ICP reduction showed a 42.5% decrease in ICP after the administration of a high weight-based dose, a 36.7% reduction after a low weight-based dose, and a 31.5% reduction after a fixed dose. There was no significant relationship between dose group and percent change in ICP (P = 0.25). A sub-analysis of doses received within 48 h postinjury found a significant relationship between both dose group and percent change in ICP, and initial ICP and percent change in ICP (P = 0.04, and <0.0001 respectively).Conclusions:Our data did not show a significant difference between fixed- and weight-based doses of 23.4% HTS for ICP reduction.

First Intracranial Pressure Monitoring or First Operation: Which One Is Better?

For patients with TBI, traditional methods such as clinical examination and imaging data are the primary references used for deciding whether to operate or not. Intracranial pressure (ICP) monitoring based on lateral ventricles or parenchymal pressure is a more direct reflection of ICP. However, the research on whether the outcome results of ICP monitoring are better than results based on clinical signs and imaging is sparse. Therefore, we compared treatment results for patients with TBI based on ICP monitoring and traditional methods. This retrospective study included patients with TBI admitted to our collaborative hospitals between January 1, 2012, and December 31, 2013. All patients enrolled were divided into a traditional methods group and ICP monitoring group. Follow-up treatment was determined by ICP monitoring value or traditional methods in the 2 groups. Propensity matching scores were used to ensure that baseline characteristics of patients in the 2 groups were consistent. A significant association was found between the initial ICP value and neurologic deterioration (odds ratio 1.24; P < 0.001), and nonlinear correlation achieved the best fit (R2= 0.547). Both 6-month good recovery rate and favorable outcome rate were higher in the ICP monitoring group than the traditional methods group by propensity score analysis (P < 0.05). For patients with TBI with cerebral contusion volume >20 mL, both 6-month good recovery rateand favorable outcome rate were significantly higher in the ICP monitoring group than the traditional methods group.

Incidence and Risk Factors for Developing Post-Traumatic Hydrocephalus, Analysis of a Prospective Cohort of 402 Patients

Abstract INTRODUCTION Post-traumatic hydrocephalus (PTH) is a common complication after traumatic brain injury (TBI). PTH incidence and risk factors have principally been derived from retrospective studies or those in the context of hydrocephalus following decompressive craniectomy. The goal of this study was to identify, in a large prospective cohort, the incidence and risk factors for PTH. METHODS This is a single-center retrospective review of a prospectively collected database of patients with severe TBI. PTH was defined as the need for permanent CSF diversion by shunt insertion. Patient demographics, GCS, bleeding patterns, intracranial pressure (ICP) monitoring, and the need for a decompressive craniectomy were considered as explanatory variables. An inverse probability weighted logistic regression model, which considers potential censoring induced by in-hospital mortality, was used as our primary analysis. RESULTS Of the 402 patients included, 40 required permanent CSF for a PTH cumulative incidence of 10% (95% CI: 7.3-13.6). PTH was associated with the need for a decompressive craniectomy [odds ratio (OR): 3.62 (1.62-8.07), P &lt; .01]. Neither age nor gender nor GCS nor bleeding pattern (including intraventricular hemorrhage) was associated with the occurrence of PTH. There were no differences on the initial ICP measurement (10.1 (8.8) vs 9.9 (7.9) mm Hg) or the trend of the ICP between patients who ultimately developed PTH and those who did not. CONCLUSION PTH develops in approximately 10% of patients with severe TBI. Patients who require a decompressive craniectomy are at a higher risk. Neither intracranial hypertension nor intraventricular hemorrhage was a relevant risk factor.

Predictive Factors of Intracranial Pressure Elevation in Patients with Severe Acute Subdural Hematoma

Elevated intracranial pressure(ICP)can cause secondary brain injury after severe traumatic brain injury(TBI), and ICP is the key factor that determines the outcome. Therefore, prediction of elevation of ICP during the course of the injury would allow for more effective care of patients with severe TBI. In this study, we investigated predictive factors for elevation of ICP in patients with severe acute subdural hematoma(ASDH). Twenty patients with severe isolated ASDH were admitted to our hospital between January 2009 and April 2016. The patients were divided into two groups with a maximum ICP of ≥20mmHg(elevated ICP group)and <20mmHg(normal ICP group). Age, mechanism of injury, Glasgow Coma Scale score on admission, initial head computed tomography findings, vital signs, serological and blood gas examinations, initial ICP, and clinical outcome were evaluated. The elevated ICP group had significantly higher initial ICP(5.0±3.1 vs. 30±22.4mmHg, p<0.01), arterial oxygen pressure(151.2±68.3 vs. 314.2±197.1mmHg, p<0.05), and activated partial thromboplastin time(APTT;28.17±3.1 vs. 35.96±8.0, p<0.05)at admission, and significantly lower fibrinogen level(273.3±65.1 vs. 188.1±82.4mg/dL, p<0.05)and favorable outcome rate(p<0.01). Our results show that high initial ICP, APTT, and arterial oxygen and low fibrinogen levels are associated with ICP elevation in patients with severe ASDH. These factors might be useful for the indication of therapeutic methods such as decompressive craniectomy.

Evidence for Mannitol as an Effective Agent Against Intracranial Hypertension: An Individual Patient Data Meta-analysis.

Mannitol is currently used to reduce intracranial pressure (ICP), but the evidence supporting its usefulness has been questioned. We aim to meta-analyze the effectiveness of mannitol in reducing ICP in adult patients with cerebral injuries and its dependency on baseline ICP values, comparing findings from individual patient data (IPD) and aggregated data (AD) meta-analysis performed on the same studies. We searched the Medline database, with no time limitation, through March 1, 2019. We selected studies for which IPD were available, with a before-after design, concerning adult patients with traumatic cerebral hemorrhages, subarachnoid hemorrhages, or hemorrhagic and ischemic stroke, treated with mannitol for increased intracranial hypertension. We extracted ICP values at baseline and at different time-points, and mannitol doses. We used a multilevel approach to account for multiple measurements on the same patient and for center variability. The AD meta-analysis and meta-regression were conducted using random-effects models. Three studies published IPD, and four authors shared their datasets. Two authors did not own their datasets anymore. Eight authors were unreachable, while 14 did not answer to our request. Overall, 7 studies provided IPD for 98 patients. The linear mixed-effects model showed that ICP decreased significantly after mannitol administration from an average baseline value of 22.1mmHg to 16.8, 12.8, and 9.7mmHg at 60, 120, and 180min after mannitol administration. ICP reduction was proportional to baseline values with a 0.64mmHg decrease for each unitary increment of the initial ICP value. Dose did not influence ICP reduction. The AD meta-analysis, based on data collected between 30 and 60min from mannitol administration not accounting for multiple time-point measurements, overestimated ICP reduction (10mmHg), while meta-regression provided similar results (0.66mmHg decrease for each unitary increase of initial ICP). Mannitol is effective in reducing pathological ICP, proportionally to the degree of intracranial hypertension. IPD meta-analysis provided a more precise quantification of ICP variation than the AD approach.

Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed across trajectory groups. Prospective observational cohort. Single-center academic medical center. Four-hundred four severe traumatic brain injury patients. None. We used group-based trajectory modeling to identify hourly intracranial pressure trajectories in days 0-5 post traumatic brain injury incorporating risk factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale, Disability Rating Scale, mortality) and ABCC8 tag-single-nucleotide polymorphisms associated with cerebral edema (rs2237982, rs7105832) across groups. Regression models determined whether trajectory groups predicted outcome. A six trajectory group model best fit the data, identifying cohorts differing in initial intracranial pressure, evolution, and number/proportion of spikes greater than 20 mm Hg. There were pattern differences in age, hemorrhage type, and craniectomy rates. ABCC8 polymorphisms differed across groups. GOS (p = 0.006), Disability Rating Scale (p = 0.001), mortality (p < 0.0001), and rs2237982 (p = 0.035) differed across groups. Unfavorable outcomes were surprisingly predicted by both low intracranial pressure trajectories and sustained intracranial hypertension. Intracranial pressure variability differed across groups (p < 0.001) and may reflect preserved/impaired intracranial elastance/compliance. We employed a novel approach investigating longitudinal/dynamic intracranial pressure patterns in traumatic brain injury. In a risk adjusted model, six groups were identified and predicted outcomes. If validated, trajectory modeling may be a first step toward developing a new, granular approach for intracranial pressure phenotyping in conjunction with other phenotyping tools like biomarkers and neuroimaging. This may be particularly relevant in light of changing traumatic brain injury demographics toward the elderly.