Episodes Of Intracranial Hypertension Research Articles

Using EEG total energy as a noninvasively tracking of intracranial (and cerebral perfussion) pressure in an animal model: A pilot study

Purpose: This study aims to describe the total EEG energy during episodes of intracranial hypertension (IH) and evaluate its potential as a classification feature for IH. New methods: We computed the sample correlation coefficient between intracranial pressure (ICP) and the total EEG energy. Additionally, a generalized additive model was employed to assess the relationship between arterial blood pressure (ABP), total EEG energy, and the odds of IH. Results: The median sample cross-correlation between total EEG energy and ICP was 0.7, and for cerebral perfusion pressure (CPP) was 0.55. Moreover, the proposed model exhibited an accuracy of 0.70, sensitivity of 0.53, specificity of 0.79, precision of 0.54, F1-score of 0.54, and an AUC of 0.7. Comparison with existing methods: The only existing comparable methods, up to our knowledge, use 13 variables as predictor of IH, our model uses only 3, our model, as it is an extension of the generalized model is interpretable and it achieves the same performance. Conclusion: These findings hold promise for the advancement of multimodal monitoring systems in neurocritical care and the development of a non-invasive ICP monitoring tool, particularly in resource-constrained environments.

Cerebral Lactate Uptake After Half-Molar Sodium Lactate Therapy in Traumatic Brain Injury: A Brief Report.

Exogenous sodium lactate has many advantages after traumatic brain injury, including intracranial pressure control and alternative energetic supply. It remains unclear, however, whether half-molar sodium lactate (HSL) is effectively incorporated in brain metabolism, which we can verify using the arteriovenous difference in lactate (AVDlac). Hence we compared the AVDlac in patients with severe traumatic brain injury receiving an equiosmolar bolus of sodium lactate or mannitol for intracranial hypertension (IH) treatment. We included 23 patients: 14 received HSL for 25 IH episodes, and nine received mannitol for 19 episodes (total of 44 IH episodes). We observed that the median variation in AVDlac was positive in the group that received HSL (Δ +0.1 [IQR -0.08-0.2] mmol/L), which suggests a net lactate uptake by the brain. On the other hand, it was negative in the group that received mannitol (Δ -0.0 [IQR -0.1 to 0.0] mmol/L), indicating a net lactate export. Finally, there were more positive AVDlac values in the group that received HSL and more negative AVDlac values in the group that received mannitol (Fisher exact p = 0.04). Our study reports the first evidence of a positive AVDlac, which corresponds to a net lactate uptake by the brain, in patients who received HSL for severe TBI. Our results constitute a bedside confirmation of the integration of lactate into the brain metabolism and pave the way for a wider dissemination of sodium lactate in the daily clinical care of patients with traumatic brain injury.

The role of intracranial pressure variability as a predictor of intracranial hypertension and mortality in critically ill patients.

Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07-3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77-5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04-1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10-1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.

Prediction of intracranial pressure crises after severe traumatic brain injury using machine learning algorithms.

Avoiding intracranial hypertension after traumatic brain injury (TBI) is a foundation of neurocritical care, to minimize secondary brain injury related to elevated intracranial pressure (ICP). However, this approach at best is reactive to episodes of intracranial hypertension, allowing for periods of elevated ICP before therapies can be initiated. Accurate prediction of ICP crises before they occur would permit clinicians to implement preventive strategies, minimize total time with ICP above threshold, and potentially avoid secondary injury. The objective of this study was to develop an algorithm capable of predicting the onset of ICP crises with sufficient lead time to enable application of preventative therapies. Thirty-six patients admitted to a level I trauma center with severe TBI (Glasgow Coma Scale score < 8) between April 2015 and January 2019 who underwent continuous intraparenchymal ICP monitor placement were retrospectively identified. Continuous ICP data were extracted from each monitoring period (range 4-96 hours of monitoring). An ICP crisis was treated as a binary outcome, defined as ICP > 22 mm Hg for at least 75% of the data within a 5-minute interval. ICP data preceding each ICP crisis were grouped into four total data sets of 1- and 2-hour epochs, each with 10- to 20-minute lead-time intervals before an ICP crisis. Crisis and noncrisis events were identified from continuous time-series data and randomly split into 70% for training and 30% for testing, from a subset of 30 patients. Machine learning algorithms were trained to predict ICP crises, including light gradient boosting, extreme gradient boosting, and random forest. Accuracy and area under the receiver operating characteristic curve (AUC) were measured to compare performance. The most predictive algorithm was optimized using feature selection and hyperparameter tuning to avoid overfitting, and then tested on a validation subset of 5 patients. Precision, recall, F1 score, and accuracy were measured. The random forest model demonstrated the highest accuracy (range 0.82-0.88) and AUC (range 0.86-0.88) across all four data sets. Further validation testing revealed high precision (0.76), relatively low recall (0.46), and overall strong predictive performance (F1 score 0.57, accuracy 0.86) for ICP crises. Decision curve analysis showed that the model provided net benefit at probability thresholds above 0.1 and below 0.9. The presented model can provide accurate and timely forecasts of ICP crises in patients with severe TBI 10-20 minutes prior to their occurrence. If validated and implemented in clinical workflows, this algorithm can enable earlier intervention for ICP crises, more effective treatment of intracranial hypertension, and potentially improved outcomes following severe TBI.

Intracranial Pressure and Brain Tissue Oxygen Multimodality Neuromonitoring in Gunshot Wounds to the Head in Children

Gunshot wounds to the head (GSWH) are a cause of severe penetrating traumatic brain injury (TBI). Although multimodal neuromonitoring has been increasingly used in blunt pediatric TBI, its role in the pediatric population with GSWH is not known. We report on 3 patients who received multimodal neuromonitoring as part of clinical management at our institution and review the existing literature on pediatric GSWH. We identified 3 patients ≤18 years of age who were admitted to a quaternary children's hospital from 2005 to 2021 with GSWH and received invasive intracranial pressure (ICP) and Pbto2 (brain tissue oxygenation) monitoring with or without noninvasive near-infrared spectroscopy (NIRS). We analyzed clinical and demographic characteristics, imaging findings, and ICP, Pbto2, cerebral perfusion pressure, and rSo2 (regional cerebral oxygen saturation) NIRS trends. All patients were male with an average admission Glasgow Coma Scale score of 4. One patient received additional NIRS monitoring. Episodes of intracranial hypertension (ICP ≥20 mm Hg) and brain tissue hypoxia (Pbto2 <15 mm Hg) or hyperemia (Pbto2 >35 mm Hg) frequently occurred independently of each other, requiring unique targeted treatments. rSo2 did not consistently mirror Pbto2. All children survived, with favorable Glasgow Outcome Scale-Extended score at 6 months after injury. Use of ICP and Pbto2 multimodality neuromonitoring enabled specific management for intracranial hypertension or brain tissue hypoxia episodes that occurred independently of one another. Multimodality neuromonitoring has not been studied extensively in pediatric GSWH; however, its use may provide a more complete picture of patient injury and prognosis without significant added procedural risk.

Balanced volatile sedation with isoflurane in critically ill patients with aneurysmal subarachnoid hemorrhage - a retrospective observational study.

In patients with severe aneurysmal subarachnoid hemorrhage (SAH) deep sedation is often used early in the course of the disease in order to control brain edema formation and thus intracranial hypertension. However, some patients do not reach an adequate sedation depth despite high doses of common intravenous sedatives. Balanced sedation protocols incorporating low-dose volatile isoflurane administration might improve insufficient sedation depth in these patients. We retrospectively analyzed ICU patients with severe aneurysmal SAH who received isoflurane in addition to intravenous anesthetics in order to improve insufficient sedation depth. Routinely recorded data from neuromonitoring, laboratory and hemodynamic parameters were compared before and up to 6 days after initiation of isoflurane. Sedation depth measured using the bispectral index improved in thirty-six SAH patients (-15.16; p = 0.005) who received additional isoflurane for a mean period of 9.73 ± 7.56 days. Initiation of isoflurane sedation caused a decline in mean arterial pressure (-4.67 mmHg; p = 0.014) and cerebral perfusion pressure (-4.21 mmHg; p = 0.013) which had to be balanced by increased doses of vasopressors. Patients required increased minute ventilation in order to adjust for the increase in PaCO2 (+2.90 mmHg; p < 0.001). We did not detect significant increases in mean intracranial pressure. However, isoflurane therapy had to be terminated prematurely in 25% of the patients after a median of 30 h due to episodes of intracranial hypertension or refractory hypercapnia. A balanced sedation protocol including isoflurane is feasible for SAH patients experiencing inadequately shallow sedation. However, therapy should be restricted to patients without impaired lung function, hemodynamic instability and impending intracranial hypertension.

Impact of early percutaneous dilatative tracheostomy in patients with subarachnoid hemorrhage on main cerebral, hemodynamic, and respiratory variables: A prospective observational study.

Patients with poor-grade subarachnoid hemorrhage (SAH) admitted to the intensive care unit (ICU) often require prolonged invasive mechanical ventilation due to prolonged time to obtain neurological recovery. Impairment of consciousness and airway protective mechanisms usually require tracheostomy during the ICU stay to facilitate weaning from sedation, promote neurological assessment, and reduce mechanical ventilation (MV) duration and associated complications. Percutaneous dilatational tracheostomy (PDT) is the technique of choice for performing a tracheostomy. However, it could be associated with particular risks in neurocritical care patients, potentially increasing the risk of secondary brain damage. We conducted a single-center, prospective, observational study aimed to assess PDT-associated variations in main cerebral, hemodynamic, and respiratory variables, the occurrence of tracheostomy-related complications, and their relationship with outcomes in adult patients with SAH admitted to the ICU of a neurosurgery/neurocritical care hub center after aneurysm control through clipping or coiling and undergoing early PDT. We observed a temporary increase in ICP during early PDT; this increase was statistically significant in patients presenting with higher therapy intensity level (TIL) at the time of the procedural. The episodes of intracranial hypertension were brief, and appeared mainly due to the activation of cerebral autoregulatory mechanisms in patients with impaired compensatory mechanisms and compliance. The low number of observed complications might be related to our organizational strategy, all based on a dedicated "tracheo-team" implementing both PDT following a strictly defined protocol and accurate follow-up.

Development and External Validation of a Machine Learning Model for the Early Prediction of Doses of Harmful Intracranial Pressure in Patients with Severe Traumatic Brain Injury.

Treatment and prevention of elevated intracranial pressure (ICP) is crucial in patients with severe traumatic brain injury (TBI). Elevated ICP is associated with secondary brain injury, and both intensity and duration of an episode of intracranial hypertension, often referred to as "ICP dose," are associated with worse outcomes. Prediction of such harmful episodes of ICP dose could allow for a more proactive and preventive management of TBI, with potential implications on patients' outcomes. The goal of this study was to develop and validate a machine-learning (ML) model to predict potentially harmful ICP doses in patients with severe TBI. The prediction target was defined based on previous studies and included a broad range of doses of elevated ICP that have been associated with poor long-term neurological outcomes. The ML models were used, with minute-by-minute ICP and mean arterial blood pressure signals as inputs. Harmful ICP episodes were predicted with a 30 min forewarning. Models were developed in a multi-center dataset of 290 adult patients with severe TBI and externally validated on 264 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset. The external validation of the prediction model on the CENTER-TBI dataset demonstrated good discrimination and calibration (area under the curve: 0.94, accuracy: 0.89, precision: 0.87, sensitivity: 0.78, specificity: 0.94, calibration-in-the-large: 0.03, calibration slope: 0.93). The proposed prediction model provides accurate and timely predictions of harmful doses of ICP on the development and external validation dataset. A future interventional study is needed to assess whether early intervention on the basis of ICP dose predictions will result in improved outcomes.

Impact of Intracranial Hypertension on Outcome of Severe Traumatic Brain Injury Pediatric Patients: A 15-Year Single Center Experience.

Background: Intracranial hypertension (IC-HTN) is significantly associated with higher risk for an unfavorable outcome in pediatric trauma. Intracranial pressure (ICP) monitoring is widely becoming a standard of neurocritical care for children. Methods: The present study was designed to evaluate influences of IC-HTN on clinical outcomes of pediatric TBI patients. Demographic, injury severity, radiologic characteristics were used as possible predictors of IC-HTN or of functional outcome. Results: A total of 118 pediatric intensive care unit (PICU) patients with severe TBI (sTBI) were included. Among sTBI cases, patients with GCS < 5 had significantly higher risk for IC-HTN and for mortality. Moreover, there was a statistically significant positive correlation between IC-HTN and severity scoring systems. Kaplan–Meier analysis determined a significant difference for good recovery among patients who had no ICP elevations, compared to those who had at least one episode of IC-HTN (log-rank chi-square = 11.16, p = 0.001). A multivariable predictive logistic regression analysis distinguished the ICP-monitored patients at risk for developing IC-HTN. The model finally revealed that higher ISS and Helsinki CT score increased the odds for developing IC-HTN (p < 0.05). Conclusion: The present study highlights the importance of ICP-guided clinical practices, which may lead to increasing percentages of good recovery for children.

Invasive brain tissue oxygen and intracranial pressure (ICP) monitoring versus ICP-only monitoring in pediatric severe traumatic brain injury.

Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population. While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes. The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have better outcomes than those who underwent ICP-only monitoring and treatment. Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children's hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay (LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow Outcome Score-Extended (GOS-E) scale at 6 months postinjury. Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak negative association between ICP and PbtO2 (β = -0.04). Conversely, there was a strong positive correlation between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (β = 0.30 and β = 0.29, p < 0.001, respectively). An increased number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p = 0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation (p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively). An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p = 0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E score difference between groups (p = 0.733). An increased number of cerebral hypoxic episodes and an increased number of intracranial hypertension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance of multimodal invasive neuromonitoring in pediatric severe TBI.

Intracranial Pressure Monitoring in Patients With Spontaneous Intracerebral Hemorrhage: Insights From the SYNAPSE-ICU Study.

Uncertainties exist regarding the indications, management, and effect of intracranial pressure (ICP) monitoring and treatment on outcome in patients with spontaneous intracranial hemorrhage (ICH). We performed an analysis of patients with spontaneous ICH enrolled in the SYNAPSE-ICU study, an international prospective observational study on the use of ICP monitoring. This study aimed to describe, in a large cohort of patients with spontaneous ICH admitted to the intensive care unit (ICU), the clinical practice of ICP monitoring, the occurrence of intracranial hypertension, and its therapeutic management. We assessed in-hospital mortality and the association between ICP monitoring and 6-month mortality and outcome by a propensity score approach with inverse probability weighting. A total of 587 patients with ICH were included in this study; 281 (47.9%) received ICP monitoring. ICP-monitored patients, compared with nonmonitored patients, were younger (61 vs 67 years; p < 0.001), presented more frequently with both reactive pupils (67.2% vs 55.2%; p = 0.008), with better neurologic status at admission (Glasgow Coma Scale ≤8, 82.3% vs 88.8%; p = 0.038), and received higher therapy intensity level during the ICU stay. In 70.5% (170 out of 241) of ICP-monitored patients, the ICH score was equal to 3 or 4. Nearly half of monitored patients (46.6%) had at least one episode of ICP ≥20 mm Hg during the first week. An intraventricular catheter (53.6%) was the most frequently used device and was associated with fewer episodes of intracranial hypertension compared with the other monitoring devices (43.7% vs 64.9%, respectively). At weighted Cox regression model, ICP monitoring was associated with a significant reduction of 6-month mortality (hazard ratio 0.49 [95% CI 0.35-0.71; p = 0.001), but not with neurologic outcome (odds ratio 0.83 [95% CI 0.41-1.68]; p = 0.6077). ICP monitoring in ICH was utilized mainly in moderately severe cases. ICP monitoring was associated with a reduction of in-hospital and 6-month mortality but did not improve 6-month functional outcomes. Further research and randomized controlled trials to generate higher-level medical evidence to support guidelines regarding ICP use and treatment in patients with ICH are needed. SYNAPSE-ICU: ClinicalTrials.gov NCT03257904.

Primary Small Bowel Melanoma or Small Bowel Metastasis with Vanishing Primary Cutaneous Lesion

The small bowel represents one of the main sites for cutaneous melanoma metastasis; however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.

Intracranial Pressure Monitoring in Poor-Grade Patients with Aneurysmal Subarachnoid Hemorrhage Treated by Coiling

The main objective of the present study was to analyze the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) changes during coiling. We also evaluated the prevalence of rebleeding and outcomes for patients monitored before and after coiling. Ninety-nine consecutive poor-grade patients with aneurysmal subarachnoid hemorrhage (aSAH; World Federation of Neurological Surgeons grade IV and V) were enrolled in our prospective observational study. For 31 patients, ICP and CPP monitoring was started immediately after the diagnosis of aSAH, and the values were recorded every 15 minutes during coiling (early ICP group). For 68 patients, ICP and CPP monitoring began after coiling (late ICP group). The outcomes were evaluated at 90 days using the modified Rankin scale. At the beginning of coiling, the ICP was >20 mm Hg in 10 patients (35.7%). The median ICP was 18 mm Hg (range, 5-60 mm Hg). The CPP was <60 mm Hg in 6 patients (24%). The median CPP was 70 mm Hg (range, 30-101 mm Hg). Despite medical treatment and/or cerebrospinal fluid drainage, 51.6% of the patients monitored during coiling had at least one episode of intracranial hypertension (defined as ICP >20 mm Hg), and 51.6% had at least one episode of reduced CPP (defined as CPP <60 mm Hg). Early monitoring (before aneurysm repair) was not associated with rebleeding. At 90 days, the functional recovery was better in the early ICP group (P= 0.004). During coiling, patients with poor-grade aSAH can experience episodes of intracranial hypertension and reduced CPP. Early and appropriate treatment of elevated ICP was not associated with rebleeding and might have improved the outcomes.

Association of Dose of Intracranial Hypertension with Outcome in Subarachnoid Hemorrhage.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) the burden of intracranial pressure (ICP) and its contribution to outcomes remains unclear. In this multicenter study, the independent association between intensity and duration, or "dose," of episodes of intracranial hypertension and 12-month neurological outcomes was investigated. This was a retrospective analysis of multicenter prospectively collected data of 98 adult patients with aSAH amendable to treatment. Patients were admitted to the intensive care unit of two European centers (Medical University of Innsbruck [Austria] and San Gerardo University Hospital of Monza [Italy]) from 2009 to 2013. The dose of intracranial hypertension was visualized. The obtained visualizations allowed us to investigate the association between intensity and duration of episodes of intracranial hypertension and the 12-month neurological outcomes of the patients, assessed with the Glasgow Outcome Score. The independent association between the cumulative dose of intracranial hypertension and outcome for each patient was investigated by using multivariable logistic regression models corrected for age, occurrence of delayed cerebral ischemia, and the Glasgow Coma Scale score at admission. The combination of duration and intensity defined the tolerance to intracranial hypertension for the two cohorts of patients. A semiexponential transition divided ICP doses that were associated with better outcomes (in blue) with ICP doses associated with worse outcomes (in red). In addition, in both cohorts, an independent association was found between the cumulative time that the patient experienced ICP doses in the red area and long-term neurological outcomes. The ICP pressure-time burden was a stronger predictor of outcomes than the cumulative time spent by the patients with an ICP greater than 20mmHg. In two cohorts of patients with aSAH, an association between duration and intensity of episodes of elevated ICP and 12-month neurological outcomes could be demonstrated and was visualized in a color-coded plot.

G-computation and machine learning for estimating the causal effects of binary exposure statuses on binary outcomes

In clinical research, there is a growing interest in the use of propensity score-based methods to estimate causal effects. G-computation is an alternative because of its high statistical power. Machine learning is also increasingly used because of its possible robustness to model misspecification. In this paper, we aimed to propose an approach that combines machine learning and G-computation when both the outcome and the exposure status are binary and is able to deal with small samples. We evaluated the performances of several methods, including penalized logistic regressions, a neural network, a support vector machine, boosted classification and regression trees, and a super learner through simulations. We proposed six different scenarios characterised by various sample sizes, numbers of covariates and relationships between covariates, exposure statuses, and outcomes. We have also illustrated the application of these methods, in which they were used to estimate the efficacy of barbiturates prescribed during the first 24 h of an episode of intracranial hypertension. In the context of GC, for estimating the individual outcome probabilities in two counterfactual worlds, we reported that the super learner tended to outperform the other approaches in terms of both bias and variance, especially for small sample sizes. The support vector machine performed well, but its mean bias was slightly higher than that of the super learner. In the investigated scenarios, G-computation associated with the super learner was a performant method for drawing causal inferences, even from small sample sizes.

Equimolar doses of hypertonic agents (saline or mannitol) in the treatment of intracranial hypertension after severe traumatic brain injury.

Background:Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP has not been evaluated rigorously.Objective:To evaluate the efficacy of repeated bolus dosing of HTS and mannitol in similar osmotic burdens to treat intracranial hypertension (ICH) in patients with severe TBI.Methods:The authors used an alternating treatment protocol to evaluate the efficacy of HTS with that of mannitol given for ICH episodes in patients treated for severe TBI at their hospital during 2017 to 2019. Doses of similar osmotic burdens (20% mannitol, 2 ml/kg, or 10% HTS, 0.63 ml/kg, administered as a bolus via a central venous catheter, infused over 15 minutes) were given alternately to the individual patient with severe TBI during ICH episodes. The choice of osmotic agents for the treatment of the initial ICH episode was determined on a randomized basis; osmotic agents were alternated for every subsequent ICH episode in each individual patient. intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were continuously monitored between the beginning of each osmotherapy and the return of ICP to 20 mm Hg. The duration of the effect of ICP reduction (between the beginning of osmotherapy and the return of ICP to 20 mm Hg), the maximum reduction of ICP and its time was recorded after each dose. Serum sodium and plasma osmolality were measured before, 0.5 hours and 3 hours after each dose. Adverse effects such as central pontine myelinolysis (CPM), severe fluctuations of serum sodium and plasma osmolality were assessed to evaluate the safety of repeated dosing of HTS and mannitol.Results:Eighty three patients with severe TBI were assessed, including 437 ICH episodes, receiving 236 doses of HTS and 221 doses of mannitol totally. There was no significant difference between equimolar HTS and mannitol boluses on the magnitude of ICP reduction, the duration of effect, and the time to lowest ICP achieved (P > .05). The proportion of efficacious boluses was higher for HTS than for mannitol, although which showed a slight difference (p = 0.207), as was the increase in serum sodium (P = .038). The serum osmolality increased immediately after osmotherapy with a significant difference (P = .017). No cases of CPM were detected.Conclusion:Repeat bolus dosing of 10% HTS and 20% mannitol appears to be significantly and similarly effective for treating ICH in patients with severe TBI. The proportion of efficacious doses of HTS on ICP reduction may be slightly higher than mannitol.

Cortical Thickness in Crouzon-Pfeiffer Syndrome: Findings in Relation to Primary Cranial Vault Expansion.

Background:Episodes of intracranial hypertension are associated with reductions in cerebral cortical thickness (CT) in syndromic craniosynostosis. Here we focus on Crouzon–Pfeiffer syndrome patients to measure CT and evaluate associations with type of primary cranial vault expansion and synostosis pattern.Methods:Records from 34 Crouzon–Pfeiffer patients were reviewed along with MRI data on CT and intracranial volume to examine associations. Patients were grouped according to initial cranial vault expansion (frontal/occipital). Data were analyzed by multiple linear regression controlled for age and brain volume to determine an association between global/lobar CT and vault expansion type. Synostosis pattern effect sizes on global/lobar CT were calculated as secondary outcomes.Results:Occipital expansion patients demonstrated 0.02 mm thicker cortex globally (P = 0.81) with regional findings, including: thicker cortex in frontal (0.02 mm, P = 0.77), parietal (0.06 mm, P = 0.44) and occipital (0.04 mm, P = 0.54) regions; and thinner cortex in temporal (−0.03 mm, P = 0.69), cingulate (−0.04 mm, P = 0.785), and, insula (−0.09 mm, P = 0.51) regions. Greatest effect sizes were observed between left lambdoid synostosis and the right cingulate (d = −1.00) and right lambdoid synostosis and the left cingulate (d = −1.23). Left and right coronal synostosis yielded effect sizes of d = −0.56 and d = −0.42 on respective frontal lobes.Conclusions:Both frontal and occipital primary cranial vault expansions correlate to similar regional CT in Crouzon–Pfeiffer patients. Lambdoid synostosis appears to be associated with cortical thinning, particularly in the cingulate gyri.

Turning and suctioning traumatic brain injury patients lead to predictable and sustained episodes of intracranial hypertension

Turning and suctioning traumatic brain injury patients lead to predictable and sustained episodes of intracranial hypertension

A Modified Translaryngeal Tracheostomy Technique in the Neurointensive Care Unit. Rationale and Single-center Experience on 199 Acute Brain-damaged Patients.

Brain-injured patients frequently require tracheostomy, but no technique has been shown to be the gold standard for these patients. We developed and introduced into standard clinical practice an innovative bedside translaryngeal tracheostomy (TLT) technique aided by suspension laryngoscopy (modified TLT). During this procedure, the endotracheal tube is left in place until the airway is secured with the new tracheostomy. This study assessed the clinical impact of this technique in brain-injured patients. This is a retrospective analysis of prospectively collected data from adult brain-injured patients who had undergone modified TLT during the period spanning from January 2010 to December 2016 at the Neurointensive care unit, San Gerardo Hospital (Monza, Italy). The incidence of intraprocedural complications, including episodes of intracranial hypertension (intracranial pressure [ICP] >20 mm Hg), was documented. Neurological, ventilatory, and hemodynamic parameters were retrieved before, during, and after the procedure. Risk factors for complications and intracranial hypertension were assessed by univariate logistic analysis. Data are presented as n (%) and median (interquartile range) for categorical and continuous variables, respectively. A total of 199 consecutive brain-injured patients receiving modified TLT were included. An overall 52% male individuals who were 66 (54 to 74) years old and who had an admission Glasgow Coma Scale of 7 (6 to 10) were included in the cohort. Intracerebral hemorrhage (30%) was the most frequent diagnosis. Neurointensivists performed 130 (65%) of the procedures. Patients underwent tracheostomy 10 (7 to 13) days after intensive care unit admission. Short (ie, <2 min) and clinically uneventful increases in ICP>20 mm Hg were observed in 11 cases. Overall, the procedure was associated with an increase in ICP from 7 (4 to 10) to 12 (7 to 18) mm Hg (P<0.001). Compared with baseline, cerebral perfusion pressure (CPP), respiratory variables, and hemodynamics were unchanged during the procedure (P-value, not significant). Higher baseline ICP and core temperature were associated with an increased risk of complications and intracranial hypertension. Complication rates were low: 1 procedure had to be converted to a surgical tracheostomy, and 1 (0.5%) episode of minor bleeding and 5 (2.5%) of minor non-neurological complications were recorded. Procedures performed by intensivists did not have a higher risk of complications compared with those performed by ear, nose, and throat specialists. A modified TLT (by means of suspension laryngoscopy) performed by neurointensivists is feasible in brain-injured patients and does not adversely impact ICP and CPP.

Secondary (Duret) brainstem haemorrhage may not always represent a fatal event

Background. Secondary brainstem haemorrhage (eponymously called Duret haemorrhage) is a well-known complication of transtentorial brain herniation or of rapid decompression of intracranial space. It is considered to be a consequence of arterial rupture, venous infarction or ischemia-reperfusion injury and it is regarded as a harbinger of an unfavourable outcome for the patient. Despite this, several case reports describing good outcome after Duret haemorrhage preceded by evacuation of an expansive traumatic intracranial mass lesion, an episode of intracranial hypotension or lumbar drainage have been published.Case description. We present four cases of patients with secondary brainstem haemorrhage linked to an episode of intracranial hypertension due to various reasons who were treated at our clinic. The first patient suffered a small brainstem haemorrhage that was described on his initial CT scan presumably as a result of massive intracranial expansion caused by an acute subdural haematoma and this Duret haemorrhage markedly expanded after the subdural haematoma was evacuated by means of a decompressive craniectomy. The next two patients developed Duret haemorrhage after the evacuation of intracranial haematomas. The fourth patient presented with posttraumatic cerebral oedema complicated by a subtle Duret haemorrhage displayed on his initial CT scan and this bleeding remained stable even after a bilateral decompressive craniectomy. One patient passed away, one remained in a persistent coma and two survived with a light neurological deficit.Conclusions. However ominous a newly discovered Duret haemorrhage may be, it alone should not discourage us from the further intensive treatment of our patients as their outcome may considerably vary. The extent of this bleeding, type and severity of underlying brain injury and complete clinical status and history of our patients should all be taken into account when deciding about patients’ prognosis.