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Background: Pathologically low brain glucose levels, referred to as neuroglucopenia, are associated with unfavorable outcomes in neurocritical care patients. We sought to investigate whether an increase in serum glucose levels would be associated with a reduction of neuroglucopenia., Methods: In this retrospective analysis of prospectively collected data, we included 55 consecutive patients with spontaneous subarachnoid hemorrhage who underwent cerebral microdialysis (CMD) monitoring. Neuroglucopenia was defined as CMD-glucose levels < 0.7 mmol/l. We identified systemic glucose liberalization events, defined as a day with median serum glucose levels < 150 mg/dl, followed by a day with median serum glucose levels > 150 mg/dl, and compared concentrations of cerebral metabolites between these days. Unfavorable outcome was defined as modified Rankin Scale score ≥ 3 at 3 months after the bleeding., Results: Episodes of neuroglucopenia were more frequent in patients with unfavorable outcome (19.8% [19.3-20.3%] vs. 10.9% [10.4-11.5%], p = 0.007). Sixty-nine systemic glucose liberalization events were identified in 40 patients. Blood glucose levels increased from 141.2 (138.7-143.6) mg/dl to 159.5 (157.0-162.2) mg/dl (p < 0.001), CMD-glucose levels increased from 1.44 (1.39-1.50) mmol/l to 1.68 (1.62-1.75) mmol/l (p = 0.001), and the frequency of neuroglucopenia decreased from 24.7% (22.9-26.5%) to 20.2% (18.7-21.8%) (p = 0.002) during these events. Liberalization was not associated with changes in CMD-lactate, CMD-pyruvate, CMD-lactate-to-pyruvate ratio, CMD-glutamate, or CMD-glycerol., Conclusions: In conclusion, the liberalization of serum glucose concentrations to levels between 150 and 180 mg/dl was associated with a significant reduction of neuroglucopenia., (© 2024. The Author(s).)

Background: Cardiac point-of-care ultrasound (cPOCUS) can aid in the diagnosis and treatment of cardiac disorders. Such disorders can arise as complications of acute brain injury, but most neurologic intensive care unit (NICU) providers do not receive formal training in cPOCUS. Caption artificial intelligence (AI) uses a novel deep learning (DL) algorithm to guide novice cPOCUS users in obtaining diagnostic-quality cardiac images. The primary objective of this study was to determine how often NICU providers with minimal cPOCUS experience capture quality images using DL-guided cPOCUS as well as the association between DL-guided cPOCUS and change in management and time to formal echocardiograms in the NICU., Methods: From September 2020 to November 2021, neurology-trained physician assistants, residents, and fellows used DL software to perform clinically indicated cPOCUS scans in an academic tertiary NICU. Certified echocardiographers evaluated each scan independently to assess the quality of images and global interpretability of left ventricular function, right ventricular function, inferior vena cava size, and presence of pericardial effusion. Descriptive statistics with exact confidence intervals were used to calculate proportions of obtained images that were of adequate quality and that changed management. Time to first adequate cardiac images (either cPOCUS or formal echocardiography) was compared using a similar population from 2018., Results: In 153 patients, 184 scans were performed for a total of 943 image views. Three certified echocardiographers deemed 63.4% of scans as interpretable for a qualitative assessment of left ventricular size and function, 52.6% of scans as interpretable for right ventricular size and function, 34.8% of scans as interpretable for inferior vena cava size and variability, and 47.2% of scans as interpretable for the presence of pericardial effusion. Thirty-seven percent of screening scans changed management, most commonly adjusting fluid goals (81.2%). Time to first adequate cardiac images decreased significantly from 3.1 to 1.7 days (p < 0.001)., Conclusions: With DL guidance, neurology providers with minimal to no cPOCUS training were often able to obtain diagnostic-quality cardiac images, which informed management changes and significantly decreased time to cardiac imaging., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP)., Methods: In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO 2 ), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed., Results: We included 19 patients with a median age of 61 years (range 46-78 years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2 mm Hg), PBrO 2 (31.0 ± 13.2 vs. 32.2 ± 12.4 mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9 mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6 µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8 mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6 mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support., Conclusions: Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: The purpose of this study was to assess the prevalence of coma among patients in critical care units in Chile. We also aimed to provide insight into the demographic characteristics, etiologies, and complications associated with coma., Methods: A single day cross-sectional study was conducted through a national survey of public and private hospitals with critical and intensive cardiac care units across Chile. Data were collected using an online questionnaire that contained questions regarding critically ill patients' information, demographic characteristics, etiology and duration of coma, medical complications, and support requirements., Results: A total of 84% of all health facilities answered, accounting for a total of 2,708 patients. The overall coma prevalence was 2.9%. The median age of the comatose patients was 61 years (interquartile range 50-72) and 66.2% were male. The median coma duration was five days (interquartile range 2-9). Cerebral hemorrhage was the most common etiology, followed by severe hypoxic-ischemic encephalopathy, acute ischemic stroke, and traumatic brain injury. A total of 48.1% of coma patients experienced acute and ongoing treatment complications, with pneumonia being the most common complication, and 97.4% required support during comatose management., Conclusions: This study provides an overview of the prevalence of coma in Chilean critical and cardiac care units. Coma is a common condition. Comatose patients frequently experience medical complications during their hospitalization., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Intracranial compliance refers to the relationship between changes in volume and the resultant changes in intracranial pressure (ICP). This study aimed to assess the agreement of a noninvasive ICP waveform device for the estimation of compliance compared with invasive ICP monitoring employing three distinct methods., Methods: We conducted a retrospective analysis of ICP waveform morphology recorded through both invasive (external ventricular drain) and noninvasive (mechanical extensometer) methods in adult patients with acute brain injury admitted to a neurointensive care unit between August 2021 and August 2022. Compliance was calculated as the amplitude of the fundamental component of cerebral arterial blood volume (estimated with concurrent Transcranial Doppler [TCD] recordings), divided by the amplitude of the fundamental component of the invasive and noninvasive ICP waveforms. Subsequently, we assessed the agreement between invasive and noninvasive intracranial compliance by repeated measures correlation coefficient analysis using three methods: TCD-derived, P2/P1 ratio, and time-to-peak (TTP). A linear mixed-effects model was used to compute the concordance correlation coefficient, total deviation index, and coefficient of individual agreement. Coverage probability plot was calculated to estimate the percent of observations within different cut points for each of the three methods., Results: A total of 21 patients were identified for this study. Repeated measures correlation analysis showed a strong correlation (R = 0.982, 95% confidence interval [0.980-0.984], p < 0.0001) between log-transformed noninvasive and invasive compliance. Agreement statistics for TCD, P2/P1 ratio, and TTP indicated that although the concordance correlation coefficient was highest for log(TCD) values, TTP and P2:P1 ratio measures had better agreement with total deviation index and coverage probability plot analyses., Conclusions: Repeated measures correlations suggest that ICP waveform analyses may offer a more accurate estimate of compliance than TCD-derived methods for noninvasive ICP monitoring. Further validations studies are warranted to confidently establish this method as an indicator of intracranial compliance., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Interventions to reduce intracranial pressure (ICP) in patients with traumatic brain injury (TBI) are multimodal but variable, including sedation-dosing strategies. This article quantifies the different sedation intensities administered in patients with moderate to severe TBI (msTBI) using the therapy intensity level (TIL) across different intensive care units (ICUs), including the use of additional ICP-lowering therapies., Methods: Within the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, we performed a retrospective analysis of adult patients with msTBI admitted to an ICU for a least 5 days from seven US level 1 trauma centers who received invasive ICP monitoring and intravenous sedation. Sedation intensity was classified prospectively as one of three ordinal levels as part of the validated TIL score, which were collected at least once a day., Results: A total of 127 patients met inclusion criteria (mean age 41.6 ± 17.7 years; 20% female). The median Injury Severity Score was 27 (interquartile range 17-33), with a median admission Glasgow Coma Score of 3 (interquartile range 3-7); 104 patients had severe TBI (82%), and 23 patients had moderate TBI (18%). The sedation intensity score was highest on the first ICU day (2.69 ± 1.78), independent of patient severity. Time to reaching each sedation intensity level varied by site. Sedation level I was reached within 24 h for all sites, but sedation levels II and III were reached variably between days 1 and 3. Sedation level III was never reached by two of seven sites. The total TIL score was highest on the first ICU day, with a modest decrease for each subsequent ICU day, but there was high site-specific practice-pattern variation., Conclusions: Intensity of sedation and other therapies for elevated ICP for patients with msTBI demonstrate large practice-pattern variation across level 1 trauma centers within the TRACK-TBI cohort study, independent of patient severity. Optimizing sedation strategies using patient-specific physiologic and pathoanatomic information may optimize patient outcomes., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids., Methods: Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium., Results: Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium., Conclusions: Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures., (© 2024. The Author(s).)

The term "urban-rural divide" encompasses several dimensions and has remained an important concern for any country. The economic disparity; lack of infrastructure; dearth of medical specialists; limited opportunities to education, training, and health care; lower level of sanitation; and isolating effect of geographical location deepens this gap, especially in low-income and middle-income countries (LMICs). This article gives an overview of the rural-urban differences in terms of facilities related to neurocritical care (NCC) in LMICs. Issues related to common clinical conditions such as stroke, traumatic brain injury, myasthenia gravis, epilepsy, tubercular meningitis, and tracheostomy are also discussed. To facilitate delivery of NCC in resource-limited settings, proposed strategies include strengthening preventive measures, focusing on basics, having a multidisciplinary approach, promoting training and education, and conducting cost-effective research and collaborative efforts. The rural areas of LMICs bear the maximum impact because of their limited access to preventive health services, high incidence of acquired brain injury, inability to have timely management of neurological emergencies, and scarcity of specialist services in a resource-deprived health center. An increase in the health budget allocation for rural areas, NCC education and training of the workforce, and provision of telemedicine services for rapid diagnosis, management, and neurorehabilitation are some of the steps that can be quite helpful., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Health disparities continue to plague racial and ethnic underserved patients in the United States. Disparities extend to the most critically ill patients, including those experiencing neurologic injury and patients at the end of life. Achieving health equity in palliative care in the neurointensive care unit requires clinicians to acknowledge and address structural racism and the social determinants of health. This article highlights racial and ethnic disparities in neurocritical care and palliative care and offers recommendations for an anti-racist approach to palliative care in the neurointensive care unit for clinicians., (© 2024. The Author(s).)

Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke, and it is associated with high morbidity and mortality. Patients with a spontaneous ICH are routinely admitted to an intensive care unit (ICU). However, an ICU is a valuable and limited resource, and not all patients may require this level of care. The authors conducted a systematic review and meta-analysis evaluating the safety and outcome of admission to a step-down level of care or stroke unit (SU) compared to intensive care in adult patients with low-risk spontaneous ICH. PubMed, Embase, and the Cochrane Library were searched for randomized clinical trials and observational cohort studies. The Mantel-Haenszel method or inverse variance, as applicable, was applied to calculate an overall effect estimate for each outcome by combining the specific risk ratio (RR) or standardized mean difference. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (CRD42023481915). The primary outcome examined was in-hospital mortality. Secondary outcomes were unfavorable short-term outcome, length of hospital stay, and (re)admission to the ICU. Five retrospective cohort studies involving 1347 patients were included in the qualitative analysis. Two of the studies had severity-matched groups. The definition of low-risk ICH was heterogeneous among the studies. Admission to an SU was associated with a similar rate of mortality compared to admission to an ICU (1.4% vs. 0.6%; RR 1.66; 95% confidence interval [CI] 0.24-11.41; P = 0.61), a similar rate of unfavorable short-term outcome (14.6% vs. 19.2%; RR 0.77; 95% CI 0.43-1.36; P = 0.36), and a significantly shorter mean length of stay (standardized mean difference - 0.87 days; 95% CI - 1.15 to - 0.60; P < 0.01). Risk of bias was low to moderate for each outcome. The available literature suggests that a select subgroup of patients with ICH may be safely admitted to the SU without affecting short-term outcome, potentially saving in-hospital resources and reducing length of stay. Further studies are needed to identify specific and reliable characteristics of this subgroup of patients., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Data on the efficacy of perampanel in refractory status epilepticus (RSE) and postanoxic encephalopathy (PAE) are limited; its use in such conditions is currently off-label., Methods: We conducted a retrospective cohort study of consecutive adult patients with RSE, including PAE, exhibiting electroencephalographic patterns indicative of status epilepticus who were treated at our center (January 2018 to December 2022) with assessment of clinical and electroencephalographic outcomes., Results: Thirty-six patients were included in the study, of whom 29 had nonanoxic RSE and 7 had PAE. Within the nonanoxic RSE subgroup, 45% (13 of 29; 95% confidence interval [CI] 27-63%) of study participants were responders, 34% (10 of 29; 95% CI 17-52%) were partial responders, and 21% (6 of 29; 95% CI 6-35%) were nonresponders. In the PAE subgroup (n = 7), no patients fully responded to perampanel; 43% (3 of 7; 95% CI 6-80%) were partial responders, and 57% (4 of 7; 95% CI 20-95%) were nonresponders. Responder and nonresponder study participants exhibited overlapping baseline characteristics. No significant differences in duration of hospitalization were observed between responders and nonresponders in both subgroups. Responders in the RSE subgroup had a median discharge modified Rankin Scale score of 3 (interquartile range 3-4), and nonresponders had a median discharge modified Rankin Scale score of 5 (interquartile range 5-6)., Conclusions: Despite limitations from the retrospective design and the small population size, this study suggests that perampanel use in nonanoxic RSE appears to yield promising results at moderate doses, including a tendency toward a better functional outcome at discharge, without significant adverse effects. However, in patients with PAE, the drug seems to show suboptimal performance. Perampanel appears to have promising efficacy as an add-on therapy in nonanoxic RSE. However, in patients with PAE, its efficacy seems to be lower. Further studies are warranted to confirm these observations., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Remote ischemic lesions on diffusion-weighted imaging (DWI) occur in one third of patients with intracerebral hemorrhage (ICH) and are associated with worse outcomes. The etiology is unclear and not solely due to blood pressure reduction. We hypothesized that impaired cerebrovascular autoregulation and hypoperfusion below individualized lower limits of autoregulation are associated with the presence of DWI lesions., Methods: This was a retrospective, single-center study of all primary ICH with intraparenchymal pressure monitoring within 10 days from onset and subsequent magnetic resonance imaging. Pressure reactivity index was calculated as the correlation coefficient between mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure (CPPopt) is the cerebral perfusion pressure (CPP) with the lowest corresponding pressure reactivity index. The difference between CPP and CPPopt, time spent below the lower limit of autoregulation (LLA), and time spent above the upper limit of autoregulation (ULA) were calculated by using mean hourly physiologic data. Univariate associations between physiologic parameters and DWI lesions were analyzed by using binary logistic regression., Results: A total of 505 h of artifact-free data from seven patients without DWI lesions and 479 h from six patients with DWI lesions were analyzed. Patients with DWI lesions had higher intracranial pressure (17.50 vs. 10.92 mm Hg; odds ratio 1.14, confidence interval 1.01-1.29) but no difference in mean arterial pressure or CPP compared with patients without DWI lesions. The presence of DWI lesions was significantly associated with a greater percentage of time spent below the LLA (49.85% vs. 14.70%, odds ratio 5.77, confidence interval 1.88-17.75). No significant association was demonstrated between CPPopt, the difference between CPP and CPPopt, ULA, LLA, or time spent above the ULA between groups., Conclusions: Blood pressure reduction below the LLA is associated with ischemia after acute ICH. Individualized, autoregulation-informed targets for blood pressure reduction may provide a novel paradigm in acute management of ICH and require further study., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates., Methods: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios., Results: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information., Conclusions: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management., (© 2024. The Author(s).)

Background: Partial pressure of carbon dioxide (PaCO 2 ) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO 2 levels and clinical outcomes at high altitudes., Methods: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up., Results: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO 2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO 2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO 2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome., Conclusions: Higher PaCO 2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO 2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes., (© 2024. The Author(s).)

Background: Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH)., Methods: A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included., Results: Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH., Conclusions: In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers., Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted., Results: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis., Conclusions: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication., (© 2024. The Author(s).)

Background: Burnout is a growing problem among medical professionals, reaching a crisis proportion. It is defined by emotional exhaustion, cynicism, and career dissatisfaction and is triggered by a mismatch between the values of the person and the demands of the workplace. Burnout has not previously been examined thoroughly in the Neurocritical Care Society (NCS). The purpose of this study is to assess the prevalence, contributing factors, and potential interventions to reduce burnout within the NCS., Methods: A cross-sectional study of burnout was conducted using a survey distributed to members of the NCS. The electronic survey included personal and professional characteristic questions and the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI). This validated measure assesses for emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). These subscales are scored as high, moderate, or low. Burnout (MBI) was defined as a high score in either EE or DP or a low score in PA. A Likert scale (0-6) was added to the MBI (which contained 22 questions) to provide summary data for the frequencies of each particular feeling. Categorical variables were compared using χ 2 tests, and continuous variables were compared using t-tests., Results: A total of 82% (204 of 248) of participants completed the entire questionnaire; 61% (124 of 204) were burned out by MBI criteria. A high score in EE was present in 46% (94 of 204), a high score in DP was present in 42% (85 of 204), and a low score in PA was present in 29% (60 of 204). The variables feeling burned out now, feeling burned out in the past, not having an effective/responsive supervisor, thinking about leaving one's job due to burnout, and leaving one's job due to burnout were significantly associated with burnout (MBI) (p < 0.05). Burnout (MBI) was also higher among respondents early in practice (currently training/post training 0-5 years) than among respondents post training 21 or more years. In addition, insufficient support staff contributed to burnout, whereas improved workplace autonomy was the most protective factor., Conclusions: Our study is the first to characterize burnout among a cross-section of physicians, pharmacists, nurses, and other practitioners in the NCS. A call to action and a genuine commitment by the hospital, organizational, local, and federal governmental leaders and society as a whole is essential to advocate for interventions to ameliorate burnout and care for our health care professionals., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide and many patients with TBI require intensive care unit (ICU) management. When facing a life-threatening illness, such as TBI, a palliative care approach that focuses on noncurative aspects of care should always be considered in the ICU. Research shows that neurosurgical patients in the ICU receive palliative care less frequently than the medical patients in the ICU, which is a missed opportunity for these patients. However, providing appropriate palliative care to neurotrauma patients in an ICU can be difficult, particularly for young adult patients. The patients' prognoses are often unclear, the likelihood of advance directives is small, and the bereaved families must act as decision-makers. This article highlights the different aspects of the palliative care approach as well as barriers and challenges that accompany the TBI patient population, with a particular focus on young adult patients with TBI and the role of their family members. The article concludes with recommendations for physicians for effective and adequate communication to successfully implement the palliative care approach into standard ICU care and to improve quality of care for patients with TBI and their families., (© 2023. The Author(s).)

Background: Intensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury., Methods: This is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals., Results: The analysis comprised 110 patients with a median Hunt & Hess score of 4 (interquartile range 3-5). Median age was 61 (50-70) years, 73 patients (66%) were women. Baseline temporal muscle volume was 18.5 ± 0.78 cm 3 and significantly decreased over time (p < 0.001) by a mean of 7.9% per week. Higher disease severity (p = 0.002), hydrocephalus (p = 0.020), pneumonia (p = 0.032), and bloodstream infection (p = 0.015) were associated with more pronounced muscle volume loss. Patients with poor functional outcome had smaller muscle volumes 2 and 3 weeks after subarachnoid hemorrhage compared with those with good outcome (p = 0.025). The maximum muscle volume loss during ICU stay was greater in patients with poor functional outcome (- 32.2% ± 2.5% vs. - 22.7% ± 2.5%, p = 0.008). The hazard ratio for poor functional outcome was 1.027 (95% confidence interval 1.003-1.051) per percent of maximum muscle volume loss., Conclusions: Temporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication., (© 2023. The Author(s).)

Background: Teleneurocritical care (TNCC) provides 24/7 virtual treatment of patients with neurological disease in the emergency department or intensive care unit. However, it is not known if TNCC is safe, effective, or associated with similar outcomes compared with in-person neurocritical care. We aim to determine the effect of daily inpatient consults from TNCC on the outcomes of patients with large vessel occlusive acute ischemic stroke treated by thrombectomy., Methods: A multicenter, retrospective cohort of consecutive patients ≥ 18 years old with acute ischemic stroke from a large vessel occlusion treated by thrombectomy were identified from 2018 to 2021 within a telehealth network of an integrated not-for-profit health care system in the United States. The primary end point was good functional outcome, i.e., modified Rankin Scale 0-3, at the time of hospital discharge in patients receiving in-person neurocritical care versus TNCC., Results: A total of 437 patients met inclusion criteria, 226 at the in-person hospital (median age 67, 53% women) and 211 at the two TNCC hospitals (median age 74, 49% women). The rate of successful endovascular therapy (modified Thrombolysis in Cerebral Infarction score 2b-3) was not different among hospitals. Good functional outcome at discharge was similar between in-person neurocritical care and TNCC (in-person 31.4% vs. TNCC 33.5%, odds ratio 0.88, 95% confidence interval 0.6-1.3; p = 0.64). Only National Institutes of Health stroke scale and age were multivariable predictors of outcome. There were no differences in mortality (9.3% vs. 13.2%, p = 0.19), intensive care unit length of stay (2.1 vs. 1.9 days, p = 0.39), or rate of symptomatic intracerebral hemorrhage (6.8% vs. 6.6%, p = 0.47) between in-person neurocritical care and TNCC., Conclusions: Teleneurocritical care allows for equivalent favorable functional outcomes compared with in-person neurocritical care for patients with acute large vessel ischemic stroke receiving thrombectomy. The standardized protocols used by TNCC in this study, specifically the comprehensive 24/7 treatment of patients in the intensive care unit for the length of their stay, may be relevant for other health systems with limited in-person resources; however, additional study is required., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: COVID-19 surges led to significant challenges in ensuring critical care capacity. In response, some centers leveraged neurocritical care (NCC) capacity as part of the surge response, with neurointensivists providing general critical care for patients with COVID-19 without neurologic illness. The relative outcomes of NCC critical care management of patients with COVID-19 remain unclear and may help guide further surge planning and provide broader insights into general critical care provided in NCC units., Methods: We performed an observational cohort study of all patients requiring critical care for COVID-19 across four hospitals within the Emory Healthcare system during the first three surges. Patients were categorized on the basis of admission to intensive care units (ICUs) staffed by general intensivists or neurointensivists. Patients with primary neurological diagnoses were excluded. Baseline demographics, clinical complications, and outcomes were compared between groups using univariable and propensity score matching statistics., Results: A total of 1141 patients with a primary diagnosis of COVID-19 required ICU admission. ICUs were staffed by general intensivists (n = 1071) or neurointensivists (n = 70). Baseline demographics and presentation characteristics were similar between groups, except for patients admitted to neurointensivist-staffed ICUs being younger (59 vs. 65, p = 0.027) and having a higher PaO 2 /FiO 2 ratio (153 vs. 120, p = 0.002). After propensity score matching, there was no correlation between ICU staffing and the use of mechanical ventilation, renal replacement therapy, and vasopressors. The rates of in-hospital mortality and hospice disposition were similar in neurointensivist-staffed COVID-19 units (odds ratio 0.9, 95% confidence interval 0.31-2.64, p = 0.842)., Conclusions: COVID-19 surges precipitated a natural experiment in which neurology-trained neurointensivists provided critical care in a comparable context to general intensivists treating the same disease. Neurology-trained neurointensivists delivered comparable outcomes to those of general ICUs during COVID-19 surges. These results further support the role of NCC in meeting general critical care needs of neurocritically ill patients and as a viable surge resource in general critical care., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Patients with critical neurological illness are diverse. As a result of the heterogeneity of this patient population, standardized approaches to patient management might not confer benefit. A precision medicine approach to neurocritical care is therefore urgently needed to improve our understanding of neurocritical illness and the care provided to this vulnerable cohort. Research designs and approaches based on Bayesian models have the potential to meet this need, as they are specifically designed to evolve with emerging evidence. This adaptability provides a benefit over the popular frequentist statistical approach, as it provides a way of adjusting hypotheses and trial procedures to maximize efficacy. This review summarizes the current state of knowledge on Bayes' theorem, and its potential applications to the field of neurocritical care. We review the basic principles underlying Bayes' theorem, compare the use of Bayesian versus frequentist statistics in medicine, and discuss the relevance of Bayesian statistics to the field of neuroscience and to clinical research. Finally, we explore the potential benefits of employing Bayesian methods within the field of neurocritical care as a steppingstone toward implementing precision medicine approaches to improve patient outcomes for complex, heterogeneous disorders., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

This proceedings article presents the scope of pediatric coma and disorders of consciousness based on presentations and discussions at the First Pediatric Disorders of Consciousness Care and Research symposium held on September 14th, 2021. Herein we review the current state of pediatric coma care and research opportunities as well as shared experiences from seasoned researchers and clinicians. Salient current challenges and opportunities in pediatric and neonatal coma care and research were identified through the contributions of the presenters, who were Jose I. Suarez, MD, Nina F. Schor, MD, PhD, Beth S. Slomine, PhD Erika Molteni, PhD, and Jan-Marino Ramirez, PhD, and moderated by Varina L. Boerwinkle, MD, with overview by Mark Wainwright, MD, and subsequent audience discussion. The program, executively planned by Varina L. Boerwinkle, MD, Mark Wainwright, MD, and Michelle Elena Schober, MD, drove the identification and development of priorities for the pediatric neurocritical care community., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: When using an external ventricular drain (EVD) to monitor intracranial pressure (ICP), nurses need to know how long to wait after each manipulation of the transducer before the displayed ICP value represents an accurate signal. This study explores ICP signal equilibration time (EqT) under clinical conditions., Methods: This was a prospective ex vivo study using a simulated skull, standard EVD tubing, and a strain gauge transducer. All 270 trials simulating 90 combinations of different pressures and common clinical conditions were completed in August 2021. Each trial was recorded on video. Videos were scored using video editing software to obtain the exact start and stop time for each trial., Results: The mean EqT was 44.90 (18.77) seconds. One hundred fifty (55.56%) observations did not reach their expected value within 60 s. The longest mean EqTs were noted when blood was present in the EVD tubing (57.67 [8.91] seconds), when air bubbles were in the tubing (57.41 [8.73] seconds), and when EVD tubing was not flat (level) (50.77 [15.43] seconds). An omnibus test comparing mean EqT for conditions with no variables manipulated (30.08 [16.07] seconds) against mean EqT for all others (47.18 [18.13] seconds) found that mean EqTs were significantly different (P < 0.001)., Conclusions: Even when no additional variables were introduced, the mean EqTs were ~ 30 s. Common clinical variables increase the length of time before a transducer connected to an EVD will provide an accurate reading. Nurses should wait at least 30 s after turning the EVD stopcock before assuming ICP value reflects accurate ICP., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Delirium occurs frequently in patients with stroke and neurocritical illness but is often underrecognized. We developed a novel delirium screening tool designed specifically for neurocritical care patients called the fluctuating mental status evaluation (FMSE) and aimed to test its usability and accuracy in a representative cohort of patients with intracerebral hemorrhage (ICH)., Methods: We performed a single-center prospective study in a pilot cohort of patients with ICH who had daily delirium assessments throughout their admission. Reference-standard expert ratings were performed each afternoon using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and were derived from bedside assessments and clinical data from the preceding 24 h. Paired FMSE assessments were performed by patients' clinical nurses after receiving brief one-on-one training from research staff. Nursing assessments were aggregated over 24-h periods (including day and night shifts), and accuracy of the FMSE was analyzed in patients who were not comatose to determine optimal scoring thresholds., Results: We enrolled 40 patients with ICH (mean age 71.1 ± 12.2, 55% male, median National Institutes of Health Stroke Scale score 16.5 [interquartile range 12-20]), of whom 85% (n = 34) experienced delirium during their hospitalization. Of 308 total coma-free days with paired assessments, 208 (68%) were rated by experts as days with delirium. Compared with expert ratings, FMSE scores ≥ 1 had 86% sensitivity and 73% specificity on a per-day basis, whereas FMSE scores ≥ 2 had 68% sensitivity and 82% specificity. Accuracy remained high in patients with aphasia (FMSE scores ≥ 1: 83% sensitivity, 77% specificity; FMSE scores ≥ 2: 68% sensitivity, 85% specificity) and decreased arousal (FMSE scores ≥ 1: 80% sensitivity, 100% specificity; FMSE scores ≥ 2: 73% sensitivity, 100% specificity)., Conclusions: In this pilot study, the FMSE achieved a high sensitivity and specificity in detecting delirium. Follow-up validation studies in a larger more diverse cohort of neurocritical care patients will use score cutoffs of ≥ 1 as "possible" delirium and ≥ 2 as "probable" delirium., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Hypoxic brain injury is the leading cause of death in comatose patients following resuscitation from cardiac arrest. Neurological outcome can be difficult to prognosticate following resuscitation, and goals of care discussions are often informed by multiple prognostic tools. One tool that has shown promise is the SLANT score, which encompasses five metrics including initial nonshockable rhythm, leukocyte count after targeted temperature management, total adrenaline dose during resuscitation, lack of bystander cardiopulmonary resuscitation, and time to return of spontaneous circulation. This cohort study aimed to provide an external validation of this score by using a database of comatose cardiac arrest survivors from our institution., Methods: We retrospectively queried our database of cardiac arrest survivors, selecting for patients with coma, sustained return of spontaneous circulation, and use of targeted temperature management to have a comparable sample to the index study. We calculated SLANT scores for each patient and separated them into risk levels, both according to the original study and according to a Youden index analysis. The primary outcome was poor neurologic outcome (defined by a cerebral performance category score of 3 or greater at discharge), and the secondary outcome was in-hospital mortality. Univariable and multivariable analyses, as well as a receiver operator characteristic curve, were used to assess the SLANT score for independent predictability and diagnostic accuracy for poor outcomes., Results: We demonstrate significant association between a SLANT group with increased risk and poor neurologic outcome on univariable (p = 0.005) and multivariable analysis (odds ratio 1.162, 95% confidence interval 1.003-1.346, p = 0.046). A receiver operating characteristic analysis indicates that SLANT scoring is a fair prognostic test for poor neurologic outcome (area under the curve 0.708, 95% confidence interval 0.536-0.879, p = 0.024). Among this cohort, the most frequent SLANT elements were initial nonshockable rhythm (84.5%) and total adrenaline dose ≥ 5 mg (63.9%). There was no significant association between SLANT score and in-hospital mortality (p = 0.064)., Conclusions: The SLANT score may independently predict poor neurologic outcome but not in-hospital mortality. Including the SLANT score as part of a multimodal approach may improve our ability to accurately prognosticate comatose survivors of cardiac arrest., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Continuous monitoring of cerebral oxygenation is one of the diagnostic tools used in patients with brain injury. Direct and invasive measurement of cerebral oxygenation with a partial brain oxygen pressure (PbtO 2 ) probe is promising but invasive. Noninvasive assessment of regional transcranial oxygen saturation using near-infrared spectroscopy (NIRS) may be feasible. The aim of this study was to evaluate the interchangeability between PbtO 2 and NIRS over time in patients with nontraumatic subarachnoid hemorrhage., Methods: This retrospective study was performed in a neurocritical care unit. Study participants underwent hourly PbtO 2 and NIRS measurements over 72 h. Temporal agreement between markers was described by their pointwise correlation. A secondary analysis assessed the structure of covariation between marker trajectories using a bivariate linear mixed model., Results: Fifty-one patients with subarachnoid hemorrhage were included. A total of 3362 simultaneous NIRS and PbtO 2 measurements were obtained. The correlation at each measurement time ranged from - 0.25 to 0.25. The global correlation over time was - 0.026 (p = 0.130). The bivariate linear mixed model confirmed the lack of significant correlation between the PbtO 2 and NIRS measurements at follow-up. NIRS was unable to detect PbtO 2 values below 20 mm Hg (area under the receiver operating characteristic curve 0.539 [95% confidence interval 0.536-0.542]; p = 0.928), and percentage changes in NIRS were unable to detect a decrease in PbtO 2  ≥ 10% (area under the receiver operating characteristic curve 0.615 [95% confidence interval 0.614-0.616]; p < 0.001)., Conclusions: PbtO 2 and NIRS measurements were not correlated. There is no evidence that NIRS could be a substitute for PbtO 2 monitoring in patients with nontraumatic subarachnoid hemorrhage., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Unplanned readmission to the neurological intensive care unit (ICU) is an underinvestigated topic in patients admitted after spontaneous intracerebral hemorrhage (ICH). The purpose of this study is to investigate the frequency, clinical risk factors, and outcome of bounce back to the neurological ICU in a cohort of patients admitted after ICH., Methods: This is a retrospective observational study inspecting bounce back to the neurological ICU in patients admitted with spontaneous ICH over an 8-year period. For each patient, demographics, medical history, clinical presentation, length of ICU stay, unplanned readmission to neurological ICU, cause of readmission, and mortality were reviewed. Bounce back to the neurological ICU was defined as an unplanned readmission to the neurological ICU from a general floor service during the same hospitalization. A multivariable analysis was used to define independent variables associated with bounce back to the neurological ICU as well as association between bounce back to the neurological ICU and mortality. The significance level was set at p < 0.05., Results: A total of 221 patients were included. Among those, 20 (9%) had a bounce back to the neurological ICU. Respiratory complications (n = 11) was the most common reason for bounce back to the neurological ICU, followed by neurological (n = 5) and cardiological (n = 4) complications. In a multivariable logistic regression, location of hemorrhage in the basal ganglia (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0-8.9, p = 0.03) and dysphagia at the time of transfer (OR: 3.9, 95% CI: 1.0-15.4, p = 0.04) were significantly associated with bounce back to the neurological ICU. After we controlled for ICH score, readmission to the ICU was also independently associated with higher mortality (OR: 14.1, 95% CI: 2.8-71.7, p < 0.01)., Conclusions: Bounce back to the neurological ICU is not an infrequent complication in patients with spontaneous ICH and is associated with higher hospital length of stay and mortality. We identified relevant and potentially modifiable risk factors associated with bounce back to the neurological ICU. Future prospective studies are necessary to develop patient-centered strategies that may improve transition from the neurological ICU to the general floor., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Predictions of functional outcome in neurocritical care (NCC) patients impact care decisions. This study compared the predictive values (PVs) of good and poor functional outcome among health care providers with and without NCC training., Methods: Consecutive patients who were intubated for  ≥ 72 h with primary neurological illness or neurological complications were prospectively enrolled and followed for 6-month functional outcome. Medical intensive care unit (MICU) attendings, NCC attendings, residents (RES), and nurses (RN) predicted 6-month functional outcome on the modified Rankin scale (mRS). The primary objective was to compare these four groups' PVs of a good (mRS score 0-3) and a poor (mRS score 4-6) outcome prediction., Results: Two hundred eighty-nine patients were enrolled. One hundred seventy-six had mRS scores predicted by a provider from each group and were included in the primary outcome analysis. At 6 months, 54 (31%) patients had good outcome and 122 (69%) had poor outcome. Compared with other providers, NCC attendings expected better outcomes (p < 0.001). Consequently, the PV of a poor outcome prediction by NCC attendings was higher (96% [95% confidence interval [CI] 89-99%]) than that by MICU attendings (88% [95% CI 80-93%]), RES (82% [95% CI 74-88%]), and RN (85% [95% CI 77-91%]) (p = 0.047, 0.002, and 0.012, respectively). When patients who had withdrawal of life-sustaining therapy (n = 67) were excluded, NCC attendings remained better at predicting poor outcome (NCC 90% [95% CI 75-97%] vs. MICU 73% [95% CI 59-84%], p = 0.064). The PV of a good outcome prediction was similar among groups (MICU 65% [95% CI 52-76%], NCC 63% [95% CI 51-73%], RES 71% [95% CI 55-84%], and RN 64% [95% CI 50-76%])., Conclusions: Neurointensivists expected better outcomes than other providers and were better at predicting poor functional outcomes. The PV of a good outcome prediction was modest among all providers., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Effective shared decision-making relies on some degree of alignment between families and the medical team regarding a patient's likelihood of recovery. Patients with severe acute brain injury (SABI) are often unable to participate in decisions, and therefore family members make decisions on their behalf. The goal of this study was to evaluate agreement between prognostic predictions by families, physicians, and nurses of patients with SABI regarding their likelihood of regaining independence and to measure each group's prediction accuracy., Methods: This observational cohort study, conducted from 01/2018 to 07/2020, was based in the neuroscience and medical/cardiac intensive care units of a single center. Patient eligibility included a diagnosis of SABI-specifically stroke, traumatic brain injury, or hypoxic ischemic encephalopathy-and a Glasgow Coma Scale ≤ 12 after hospital day 2. At enrollment, families, physicians, and nurses were asked separately to predict a patient's likelihood of recovering to independence within 6 months on a 0-100 scale, regardless of whether a formal family meeting had occurred. True outcome was based on modified Rankin Scale assessment through a family report or medical chart review. Prognostic agreement was measured by (1) intraclass correlation coefficient; (2) mean group prediction comparisons using paired Student's t-tests; and (3) prevalence of concordance, defined as an absolute difference of less than 20 percentage points between predictions. Accuracy for each group was measured by calculating the area under a receiver operating characteristic curve (C statistic) and compared by using DeLong's test., Results: Data were collected from 222 patients and families, 45 physicians, and 103 nurses. Complete data on agreement and accuracy were available for 187 and 177 patients, respectively. The intraclass correlation coefficient, in which 1 indicates perfect correlation and 0 indicates no correlation, was 0.49 for physician-family pairs, 0.40 for family-nurse pairs, and 0.66 for physician-nurse pairs. The difference in mean predictions between families and physicians was 23.5 percentage points (p < 0.001), 25.4 between families and nurses (p < 0.001), and 1.9 between physicians and nurses (p = 0.38). Prevalence of concordance was 39.6% for family-physician pairs, 30.0% for family-nurse pairs, and 56.2% for physician-nurse pairs. The C statistic for prediction accuracy was 0.65 for families, 0.82 for physicians, and 0.76 for nurses. The p values for differences in C statistics were < 0.05 for family-physician and family-nurse groups and 0.18 for physician-nurse groups., Conclusions: For patients with SABI, agreement in predictions between families, physicians, and nurses regarding likelihood of recovery is poor. Accuracy appears higher for physicians and nurses compared with families, with no significant difference between physicians and nurses., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures., Methods: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect., Results: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours., Conclusions: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Dysfunctional cerebral autoregulation often precedes delayed cerebral ischemia (DCI). Currently, there are no data-driven techniques that leverage this information to predict DCI in real time. Our hypothesis is that information using continuous updated analyses of multimodal neuromonitoring and cerebral autoregulation can be deployed to predict DCI., Methods: Time series values of intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure (CPP), optimal CPP (CPPOpt), ΔCPP (CPP - CPPOpt), mean arterial pressure, and pressure reactivity index were combined and summarized as vectors. A validated temporal signal angle measurement was modified into a classification algorithm that incorporates hourly data. The time-varying temporal signal angle measurement (TTSAM) algorithm classifies DCI at varying time points by vectorizing and computing the angle between the test and reference time signals. The patient is classified as DCI+ if the error between the time-varying test vector and DCI+ reference vector is smaller than that between the time-varying test vector and DCI- reference vector. Finally, prediction at time point t is calculated as the majority voting over all the available signals. The leave-one-patient-out cross-validation technique was used to train and report the performance of the algorithms. The TTSAM and classifier performance was determined by balanced accuracy, F1 score, true positive, true negative, false positive, and false negative over time., Results: One hundred thirty-one patients with aneurysmal subarachnoid hemorrhage who underwent multimodal neuromonitoring were identified from two centers (Columbia University: 52 [39.7%], Aachen University: 79 [60.3%]) and included in the analysis. Sixty-four (48.5%) patients had DCI, and DCI was diagnosed 7.2 ± 3.3 days after hemorrhage. The TTSAM algorithm achieved a balanced accuracy of 67.3% and an F1 score of 0.68 at 165 h (6.9 days) from bleed day with a true positive of 0.83, false positive of 0.16, true negative of 0.51, and false negative of 0.49., Conclusions: A TTSAM algorithm using multimodal neuromonitoring and cerebral autoregulation calculations shows promise to classify DCI in real time., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Helicopter medical transportation (HMT) is a valuable resource that can expedite medical care by shortening transferring times. However, there is conflicting evidence regarding its cost and efficacy. No specific studies have addressed its use in patients transferred to the neuroscience intensive care unit (NSICU)., Methods: This was a retrospective study performed at a university hospital in the coastal southeastern USA. The flight logs for the air ambulance company were reviewed, and all patients undergoing HMT to the NSICU during a 1-year period were identified. Flight logs and medical records were reviewed to obtain basic demographics, diagnosis, mortality, transportation distance, and performance of time-sensitive interventions (TSIs) to include ventriculostomy placement, emergency craniotomy, emergency craniectomy, emergency aneurysm obliteration, emergency spine surgery, emergent endovascular procedures, subdural drain placement, emergent shunt revision, and continuous electroencephalography (EEG) performed within 4 h of admission. We analyzed the cost of HMT and correlated the clinical variables with the performance of TSIs., Results: A total of 101 patients underwent HMT during a 12-month period; 26 underwent 30 TSIs (4 underwent 2 TSIs) and an additional 4 were transported for EEG monitoring. The only clinical variable associated with a TSI was subarachnoid hemorrhage with ventriculostomy placement. Continuous EEG monitoring performed in four patients with suspected status epilepticus did not show status epilepticus in any of them (one was performed after 4 h). Transportation distance was less than 60 miles in four patients who underwent TSIs. The total cost of HMT was $3,360,573: $842,672 for those who underwent TSIs and $2,517,901 for those who did not. When compared with ground transportation, an excess cost of $3,129,415.25 was incurred by using HMT. There was no difference in the median cost of transportation between patients who underwent TSIs and those who did not ($30,210 vs. $30,211). The median cost transportation difference between HMT and ground transportation was significantly different (p < 0.001), with a median excess cost of $28,023 (range $15,553-76,155) per patient., Conclusions: The majority of patients who were transferred via HMT did not undergo TSIs, and among those who underwent TSIs, approximately one in six was transported from a hospital located less than 60 miles away from the NSICU; the distances of ground and air transportation are equivalent. Helicopter transfers may play a role in subarachnoid hemorrhage management. A significant expense was incurred by using HMT for the majority of patients (75%) who did not undergo TSIs., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Intravenous propacetamol is commonly used to control fever and pain in neurocritically ill patients in whom oral administration is often difficult. However, several studies reported that intravenous propacetamol may cause blood pressure drop. Thus, we aimed to investigate the occurrence and risk factors for intravenous propacetamol-induced blood pressure drop in neurocritically ill patients., Methods: This retrospective study included consecutive patients who were administered intravenous propacetamol in a neurointensive care unit at a single tertiary academic hospital between April 2013 and June 2020. The exact timing of intravenous propacetamol administration was collected from a database of the electronic barcode medication administration system. Blood pressure drop was defined as a systolic blood pressure below 90 mm Hg or a decrease by 30 mm Hg or more. Blood pressure, pulse rate, and body temperature were collected at baseline and within 2 h after intravenous propacetamol administration. The incidence of blood pressure drop was evaluated, and multivariable logistic regression analysis was performed to identify risk factors for blood pressure drop events., Results: A total of 16,586 instances of intravenous propacetamol administration in 4916 patients were eligible for this study. Intravenous propacetamol resulted in a significant decrease in systolic blood pressure (baseline 131.1 ± 17.8 mm Hg; within 1 h 124.6 ± 17.3 mm Hg; between 1 and 2 h 123.4 ± 17.4 mm Hg; P < 0.01). The incidence of blood pressure drop events was 13.5% within 2 h after intravenous propacetamol. Older age, lower or higher baseline systolic blood pressure, fever, higher Acute Physiology and Chronic Health Evaluation II score, and concomitant administration of vasopressors/inotropes or analgesics/sedatives were significant factors associated with the occurrence of blood pressure drop events after intravenous propacetamol administration., Conclusions: Intravenous propacetamol can induce hemodynamic changes and blood pressure drop events in neurocritically ill patients. This study identified the risk factors for blood pressure drop events. On the basis of our results, judicious use of intravenous propacetamol is warranted for neurocritically ill patients with risk factors that make them more susceptible to hemodynamic changes., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Cortical spreading depolarizations (CSDs) are associated with worse outcomes in many forms of acute brain injury, including traumatic brain injury (TBI). Animal models could be helpful in developing new therapies or biomarkers to improve outcomes in survivors of TBI. Recently, investigators have observed CSDs in murine models of mild closed head injury (CHI). We designed the currently study to determine additional experimental conditions under which CSDs can be observed, from mild to relatively more severe TBI., Methods: Adult male C57Bl/6J mice (8-14 weeks old) were anesthetized with isoflurane and subjected to CHI with an 81-g weight drop from 152 or 183 cm. CSDs were detected with minimally invasive visible light optical intrinsic signal imaging. Cerebral blood flow index (CBFi) was measured in the 152-cm drop height cohort using diffuse correlation spectroscopy at baseline before and 4 min after CHI. Cognitive outcomes were assessed at 152- and 183-cm drop heights for the Morris water maze hidden platform, probe, and visible platform tests., Results: CSDs occurred in 43% (n = 12 of 28) of 152-cm and 58% (n = 15 of 26) of 183-cm drop height CHI mice (p = 0.28). A lower baseline preinjury CBFi was associated with development of CSDs in CHI mice (1.50 ± 0.07 × 10 -7 CHI without CSD [CSD-] vs. 1.17 ± 0.04 × 10 -7 CHI with CSD [CSD+], p = 0.0001). Furthermore, in CHI mice that developed CSDs, the ratio of post-CHI to pre-CHI CBFi was lower in the hemisphere ipsilateral to a CSD compared with non-CSD hemispheres (0.19 ± 0.07 less in the CSD hemisphere, p = 0.028). At a 152-cm drop height, there were no detectable differences between sham injured (n = 10), CHI CSD+ (n = 12), and CHI CSD- (n = 16) mice on Morris water maze testing at 4 weeks. At a 183-cm drop height, CHI CSD+ mice had worse performance on the hidden platform test at 1-2 weeks versus sham mice (n = 15 CHI CSD+, n = 9 sham, p = 0.045), but there was no appreciable differences compared with CHI CSD- mice (n = 11 CHI CSD-)., Conclusions: The data suggest that a lower baseline cerebral blood flow prior to injury may contribute to the occurrence of a CSD. Furthermore, a CSD at the time of injury can be associated with worse cognitive outcome under the appropriate experimental conditions in a mouse CHI model of TBI., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Cortical spreading depolarizations (CSDs) are associated with worse outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). Animal models are required to assess whether CSDs can worsen outcomes or are an epiphenomenon; however, little is known about the presence of CSDs in existing animal models. Therefore, we designed a study to determine whether CSDs occur in a mouse model of SAH., Methods: A total of 36 mice were included in the study. We used the anterior prechiasmatic injection model of SAH under isoflurane anesthesia. A needle was inserted through the mouse olfactory bulb with the point terminating at the base of the skull, and arterial blood or saline (100 µl) was injected over 10 s. Changes in cerebral blood volume over the entire dorsal cortical surface were assessed with optical intrinsic signal imaging for 5 min following needle insertion., Results: CSDs occurred in 100% of mice in the hemisphere ipsilateral to olfactory bulb needle insertion (CSD1). Saline-injected mice had 100% survival (n = 10). Blood-injected mice had 88% survival (n = 23 of 26). A second, delayed, CSD ipsilateral to CSD1 occurred in 31% of blood-injected mice. An increase in the time interval between CSD1 and blood injection was associated with the occurrence of a second CSD in blood-injected mice (mean intervals 26.4 vs. 72.7 s, p < 0.0001, n = 18 and 8). We observed one blood-injected animal with a second CSD in the contralateral hemisphere and observed terminal CSDs in mice that died following SAH injection., Conclusions: The prechiasmatic injection model of SAH includes CSDs that occur at the time of needle insertion. The occurrence of subsequent CSDs depends on the timing between CSD1 and blood injection. The mouse prechiasmatic injection model could be considered an SAH plus CSD model of the disease. Further work is needed to determine the effect of multiple CSDs on outcomes following SAH., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Patients who require readmission to an intensive care unit (ICU) after transfer to a lower level of care ("bounceback") suffer from increased mortality and longer hospital stays. We aimed to create a multifaceted standardized transfer process for patients moving from the neurointensive care unit (neuro-ICU) to a lower level of care. We hypothesized that this process would lead to improvement in provider-rated safety and a decreased rate of bouncebacks to the neuro-ICU after transfer., Methods: The study took place at the Hospital of the University of Pennsylvania from October 2018 to October 2020. A standardized five-step transfer process was created and implemented for transferring patients from the neuro-ICU to a lower level of care. Patient care providers completed a survey before and after implementation of the protocol to assess a variety of components related to safety concerns when transferring patients. The rate of bouncebacks pre and post intervention was calculated by using a two-sample Wilcoxon rank-sum test, and disposition at discharge was calculated by using Fisher's exact test., Results: Of the 1176 total patient transfers out of the neuro-ICU, 29 patients bounced back within 48 h. The average age of patients who bounced back was 63.3 years old, with a similar distribution among men and women. The most common reason for bounceback was respiratory distress, followed by cardiac arrhythmia, stroke, and sepsis. Implementation of the standardized process led to a decrease in provider-rated concern of overall safety (5 to 3, p = 0.008). There was improvement in transfer delays due to bed availability (3 to 4.5, p = 0.020), identification of high-risk patients (5 to 6, p = 0.021), patient assignment to the appropriate level of care (5 to 6, p = 0.019), and use of the electronic medical record handoff indicator (5 to 6, p = 0.003). There was no statistically significant difference in terms of patient bounceback rate after implementation of the process (2.4% vs. 2.5%, p = 1.00) or patient disposition at discharge (p = 0.553)., Conclusions: Patients who bounceback to the neuro-ICU within 48 h had an increased length of hospital stay, had an increased length of ICU stay, and were more likely to be intubated for more than 96 h. Implementation of a standardized five-step transfer process from the neuro-ICU to a lower level of care resulted in improvement in multiple provider-rated safety outcomes and identification of high-risk patients but led to no difference in the patient bounceback rate or patient disposition at discharge., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Delirium screening instruments (DSIs) should be used to detect delirium, but they only show moderate sensitivity in patients with neurocritical illness. We explored whether, for these patients, DSI validity is impacted by patient-specific covariates., Methods: Data were prospectively collected in a single-center quality improvement project. Patients were screened for delirium once daily using the Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference was the daily assessment using criteria from the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR). In a two-step receiver operating characteristics regression analysis adjusting for repeated measurements, the impact of acute diagnosis of stroke or transient ischemic attack (TIA), neurosurgical intervention, Richmond Agitation Sedation Scale, and ventilation status on test validity was determined., Results: Of 181 patients screened, 101 went into final analysis. Delirium incidence according to DSM-IV-TR was 29.7%. For the first complete assessment series (CAM-ICU, ICDSC, and DSM-IV-TR), sensitivity for the CAM-ICU and the ICDSC was 73.3% and 66.7%, and specificity was 91.8% and 94.1%, respectively. Consideration of daily repeated measurements increased sensitivity for the CAM-ICU and ICDSC to 75.7% and 73.4%, and specificity to 97.3% and 98.9%, respectively. Receiver operating characteristics regression revealed that lower Richmond Agitation Sedation Scale levels significantly impaired validity of the ICDSC (p = 0.029) and the CAM-ICU in its severity scale version (p = 0.004). Neither acute diagnosis of stroke or TIA nor neurosurgical intervention or mechanical ventilation significantly influenced DSI validity., Conclusions: The CAM-ICU and ICDSC perform well in patients requiring neurocritical care, regardless of the presence of acute stroke, TIA, or neurosurgical interventions. Yet, even very light or moderate sedation can significantly impair DSI performance., (© 2021. The Author(s).)

Background: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate., Methods: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications., Results: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission., Conclusions: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Analysis of intracranial multimodality monitoring data is challenging, and quantitative methods may help identify unique physiological signatures that inform therapeutic strategies and outcome prediction. The aim of this study was to test the hypothesis that data-driven approaches can identify distinct physiological states from intracranial multimodality monitoring data., Methods: This was a single-center retrospective observational study of patients with either severe traumatic brain injury or high-grade subarachnoid hemorrhage who underwent invasive multimodality neuromonitoring. We used hierarchical cluster analysis to group hourly values for heart rate, mean arterial pressure, intracranial pressure, brain tissue oxygen, and cerebral microdialysis across all included patients into distinct groups. Average values for measured physiological variables were compared across the identified clusters, and physiological profiles from identified clusters were mapped onto physiological states known to occur after acute brain injury. The distribution of clusters was compared between patients with favorable outcome (discharged to home or acute rehab) and unfavorable outcome (in-hospital death or discharged to chronic nursing facility)., Results: A total of 1704 observations from 20 patients were included. Even though the difference in mean values for measured variables between patients with favorable and unfavorable outcome were small, we identified four distinct clusters within our data: (1) events with low brain tissue oxygen and high lactate-to-pyruvate ratio-values (consistent with cerebral ischemia), (2) events with higher intracranial pressure values without evidence for ischemia (3) events which appeared to be physiologically "normal," and (4) events with high cerebral lactate without brain hypoxia (consistent with cerebral hyperglycolysis). Patients with a favorable outcome had a greater proportion of cluster 3 (normal) events, whereas patients with an unfavorable outcome had a greater proportion of cluster 1 (ischemia) and cluster 4 (hyperglycolysis) events (p < 0.0001, Fisher-Freeman-Halton test)., Conclusions: A data-driven approach can identify distinct groupings from invasive multimodality neuromonitoring data that may have implications for therapeutic strategies and outcome predictions. These groupings could be used as classifiers to train machine learning models that can aid in the treatment of patients with acute brain injury. Further work is needed to replicate the findings of this exploratory study in larger data sets., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis., Methods: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported., Results: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert., Conclusions: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: Seizures and abnormal periodic or rhythmic patterns are observed on continuous electroencephalography monitoring (cEEG) in up to half of patients hospitalized with moderate to severe traumatic brain injury (TBI). We aimed to determine the impact of seizures and abnormal periodic or rhythmic patterns on cognitive outcome 3 months following moderate to severe TBI., Methods: This was a post hoc analysis of the multicenter randomized controlled phase 2 INTREPID 2566 clinical trial conducted from 2010 to 2016 across 20 United States Level I trauma centers. Patients with nonpenetrating TBI and postresuscitation Glasgow Coma Scale scores 4-12 were included. Bedside cEEG was initiated per protocol on admission to intensive care, and the burden of ictal-interictal continuum (IIC) patterns, including seizures, was quantified. A summary global cognition score at 3 months following injury was used as the primary outcome., Results: 142 patients (age mean + / - standard deviation 32 + / - 13 years; 131 [92%] men) survived with a mean global cognition score of 81 + / - 15; nearly one third were considered to have poor functional outcome. 89 of 142 (63%) patients underwent cEEG, of whom 13 of 89 (15%) had severe IIC patterns. The quantitative burden of IIC patterns correlated inversely with the global cognition score (r =  - 0.57; p = 0.04). In multiple variable analysis, the log-transformed burden of severe IIC patterns was independently associated with the global cognition score after controlling for demographics, premorbid estimated intelligence, injury severity, sedatives, and antiepileptic drugs (odds ratio 0.73, 95% confidence interval 0.60-0.88; p = 0.002)., Conclusions: The burden of seizures and abnormal periodic or rhythmic patterns was independently associated with worse cognition at 3 months following TBI. Their impact on longer-term cognitive endpoints and the potential benefits of seizure detection and treatment in this population warrant prospective study., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: The amount of intracranial blood is a strong predictor of poor outcome after subarachnoid hemorrhage (SAH). Here, we aimed to measure iron concentrations in the cerebral white matter, using the cerebral microdialysis (CMD) technique, and to associate iron levels with the local metabolic profile, complications, and functional outcome., Methods: For the observational cohort study, 36 patients with consecutive poor grade SAH (Hunt & Hess grade of 4 or 5, Glasgow Coma Scale Score ≤ 8) undergoing multimodal neuromonitoring were analyzed for brain metabolic changes, including CMD iron levels quantified by graphite furnace atomic absorption spectrometry. The study time encompassed 14 days after admission. Statistical analysis was performed using generalized estimating equations., Results: Patients were admitted in a poor clinical grade (n = 26, 72%) or deteriorated within 24 h (n = 10, 28%). The median blood volume in the subarachnoid space was high (SAH sum score = 26, interquartile range 20-28). Initial CMD iron was 44 µg/L (25-65 µg/L), which significantly decreased to a level of 25 µg/L (14-30 µg/L) at day 4 and then constantly increased over the remaining neuromonitoring days (p < 0.01). A higher intraventricular hemorrhage sum score (≥ 5) was associated with higher CMD iron levels (Wald-statistic = 4.1, df  = 1, p = 0.04) but not with the hemorrhage load in the subarachnoid space (p = 0.8). In patients developing vasospasm, the CMD iron load was higher, compared with patients without vasospasm (Wald-statistic = 4.1, degree of freedom = 1, p = 0.04), which was not true for delayed cerebral infarction (p = 0.4). Higher iron concentrations in the brain extracellular fluid (34 µg/L, 36-56 µg/L vs. 23 µg/L, 15-37 µg/L) were associated with mitochondrial dysfunction (CMD lactate to pyruvate ratio > 30 and CMD-pyruvate > 70 µM/L, p < 0.001). Brain extracellular iron load was not associated with functional outcome after 3 months (p > 0.5)., Conclusions: This study suggests that iron accumulates in the cerebral white matter in patients with poor grade SAH. These findings may support trials aiming to scavenger brain extracellular iron based on the hypothesis that iron-mediated neurotoxicity may contribute to acute and secondary brain injury following SAH., (© 2021. The Author(s).)

Background: Transcranial color-coded duplex Doppler (TCCD) is commonly used to detect and monitor vasospasm in subarachnoid aneurysmal hemorrhage (aSAH). However, contrast enhanced TCCD (CE-TCCD) may be more effective. The objective of this study was to compare the accuracy of TCCD and CE-TCCD in the detection of vasospasm., Methods: This study was a prospective comparison of TCCD and CE-TCCD for the detection of vasospasm, using computed tomography angiography (CT Angio) as a reference examination. The setting was the Department of Anesthesiology and Intensive Care at the Bicêtre University Hospital in Le Kremlin Bicêtre, France. TCCD and CE-TCCD were performed in 47 patients admitted to the intensive care unit (ICU) following aSAH over a 7-month period. TCCD and CE-TCCD were performed at ICU admission and between days 7 and 10. We aimed to visualize the seven intracranial arteries of the circle of Willis. Vasospasm diagnosis was assessed by CT Angio  and graded as moderate when the percentage change in arterial diameter since admission was between 25 and 50% or as severe when the percentage change was greater than 50%., Results: On ICU admission, TCCD allowed visualization of all intracranial arteries in 16 (34%) of 47 patients, whereas CE-TCCD allowed visualization of all vessels in 37 (79%) of 47 patients (p < 0.001). These results were consistent between days 7 and 10. The proportions of middle cerebral arteries (MCAs), anterior cerebral arteries (ACAs) and posterior cerebral arteries (PCAs) visualized were greater with CE-TCCD. There was no difference in the visualization of basilar arteries (BAs). We performed vasospasm analysis on 67 of 94 MCAs in 47 patients. Area under the curve (AUC) of mean flow velocity to detect MCA vasospasm (moderate and severe) was 0.86 (0.58-1.00) for TCCD and 0.90 (0.77-1.00) for CE-TCCD. AUC of mean velocity to detect severe MCA vasospasm was 0.86 (0.58-1.00) for TCCD and 0.90 (0.77-1.00) for CE-TCCD, without any significant difference between the two techniques. For other arteries, the accuracy of TCCD and CE-TCCD to diagnose vasospasm was poor., Conclusions: CE-TCCD allows better visualization of intracranial arteries in patients with aSAH. The accuracy of CE-TCCD to screen severe MCA vasospasm is similar to that of TCCD. CE-TCCD is an alternative tool for monitoring patients with aSAH without a temporal bone window for an ultrasound., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: Evidence suggests that early physical activity can be accomplished safely in the neurocritical care unit (NCCU); however, many NCCU patients are often maintained in a state of inactivity due to impaired consciousness, sensorimotor deficits, and concerns for intracranial pressure elevation or cerebral hypoperfusion in the setting of autoregulatory failure. Structured in-bed mobility interventions have been proposed to prevent sequelae of complete immobility in such patients, yet the feasibility and safety of these interventions is unknown. We studied neurological and hemodynamic changes before and after cycle ergometry (CE) in a subset of NCCU patients with external ventricular drains (EVDs)., Methods: Patients admitted to the NCCU who had an EVD placed for cerebrospinal fluid drainage and intracranial pressure (ICP) monitoring underwent supine CE therapy with passive and active cycling settings. Neurologic status, ICP and hemodynamic parameters were monitored before and after each CE session., Results: Twenty-seven patients successfully underwent in-bed CE in the NCCU. No clinically significant changes were recorded in neurologic or in physiological parameters before or after CE. There were no device dislodgements or other adverse effects requiring cessation of a CE session., Conclusion: These data suggest that supine CE in a heterogeneous cohort of neurocritical care patients with EVDs is safe and tolerable. Larger prospective studies are needed to determine the efficacy and optimal dose and timing of supine CE in neurocritical care patients., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)