Temperature Control Parameters Are Important: Earlier Preinduction Is Associated With Improved Outcomes Following Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes. METHODS: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding. RESULTS: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively. CONCLUSION: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials.

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Cerebral Edema Monitoring and Management Strategies: Results from an International Practice Survey.

BACKGROUND: Cerebral edema is a common, potentially life-threatening complication in critically ill patients with acute brain injury. However, uncertainty remains regarding best monitoring and treatment strategies, which may result in wide practice variations. METHODS: A 20-question digital survey on monitoring and management practices was disseminated between July 2022 and May 2023 to clinicians who manage cerebral edema. The survey was promoted through email, social media, medical conferences, and the Neurocritical Care Society Web site. We used the χ2 test, Fisher's exact test, analysis of variance, and logistic regression to report factors associated with practice variation, diagnostic monitoring methods, and therapeutic triggers based on practitioner and institutional characteristics. RESULTS: Of 321 participants from 160 institutions in 30 countries, 65% were from university-affiliated centers, 74% were attending physicians, 38% were woman, 38% had neurology training, and 55% were US-based. Eighty-four percent observed practice variations at their institutions, with "provider preference" being cited most (87%). Factors linked to variation included gender, experience, university affiliation, and practicing outside the United States. University affiliates tended to use more tests (median 3.87 vs. 3.43, p = 0.01) to monitor cerebral edema. Regarding management practices, 20% of respondents' preferred timing for decompressive hemicraniectomy was after 48 h, and 37% stated that radiographic findings only would be sufficient to trigger surgery. Fifty percent of respondents reported initiating osmotic therapy based on radiographic indications or prophylactically. There were no significant associations between management strategies and respondent or center characteristics. Twenty-seven percent of respondents indicated that they acquired neuroimaging at intervals of 24 h or less. Within this group, attending physicians were more likely to follow this practice (65.5% vs. 34.5%, p = 0.04). CONCLUSIONS: Cerebral edema monitoring and management strategies vary. Features associated with practice variations include both practitioner and institutional characteristics. We provide a foundation for understanding practice patterns that is crucial for informing educational initiatives, standardizing guidelines, and conducting future trials.

Impact of Therapeutic Interventions on Cerebral Autoregulatory Function Following Severe Traumatic Brain Injury: A Secondary Analysis of the BOOST-II Study.

BACKGROUND: The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II randomized controlled trial used a tier-based management protocol based on brain tissue oxygen (PbtO2) and intracranial pressure (ICP) monitoring to reduce brain tissue hypoxia after severe traumatic brain injury. We performed a secondary analysis to explore the relationship between brain tissue hypoxia, blood pressure (BP), and interventions to improve cerebral perfusion pressure (CPP). We hypothesized that BP management below the lower limit of autoregulation would lead to cerebral hypoperfusion and brain tissue hypoxia that could be improved with hemodynamic augmentation. METHODS: Of the 119 patients enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase II trial, 55 patients had simultaneous recordings of arterial BP, ICP, and PbtO2. Autoregulatory function was measured by interrogating changes in ICP and PbtO2 in response to fluctuations in CPP using time-correlation analysis. The resulting autoregulatory indices (pressure reactivity index and oxygen reactivity index) were used to identify the "optimal" CPP and limits of autoregulation for each patient. Autoregulatory function and percent time with CPP outside personalized limits of autoregulation were calculated before, during, and after all interventions directed to optimize CPP. RESULTS: Individualized limits of autoregulation were computed in 55 patients (mean age 38 years, mean monitoring time 92 h). We identified 35 episodes of brain tissue hypoxia (PbtO2 < 20 mm Hg) treated with CPP augmentation. Following each intervention, mean CPP increased from 73 ± 14 mm Hg to 79 ± 17 mm Hg (p = 0.15), and mean PbtO2 improved from 18.4 ± 5.6 mm Hg to 21.9 ± 5.6 mm Hg (p = 0.01), whereas autoregulatory function trended toward improvement (oxygen reactivity index 0.42 vs. 0.37, p = 0.14; pressure reactivity index 0.25 vs. 0.21, p = 0.2). Although optimal CPP and limits remained relatively unchanged, there was a significant decrease in the percent time with CPP below the lower limit of autoregulation in the 60 min after compared with before an intervention (11% vs. 23%, p = 0.05). CONCLUSIONS: Our analysis suggests that brain tissue hypoxia is associated with cerebral hypoperfusion characterized by increased time with CPP below the lower limit of autoregulation. Interventions to increase CPP appear to improve autoregulation. Further studies are needed to validate the importance of autoregulation as a modifiable variable with the potential to improve outcomes.

Comparison of induction agents for rapid sequence intubation in refractory status epilepticus: A single-center retrospective analysis.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

Later Midline Shift Is Associated with Better Outcomes after Large Middle Cerebral Artery Stroke.

Background/Objective: Space occupying cerebral edema is the most feared early complication after large ischemic stroke, occurring in up to 30% of patients with middle cerebral artery (MCA) occlusion, and is reported to peak 2-4 days after injury. Little is known about the factors and outcomes associated with peak edema timing, especially when it occurs after 96 hours. We aimed to characterize differences between patients who experienced maximum midline shift (MLS) or decompressive hemicraniectomy (DHC) in the acute (<48 hours), average (48-96 hours), and subacute (>96 hours) groups and determine whether patients with subacute peak edema timing have improved discharge dispositions. Methods: We performed a two-center, retrospective study of patients with ≥1/2 MCA territory infarct and MLS. We constructed a multivariable model to test the association of subacute peak edema and favorable discharge disposition, adjusting for age, admission Alberta Stroke Program Early CT Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS), acute thrombolytic intervention, cerebral atrophy, maximum MLS, parenchymal hemorrhagic transformation, DHC, and osmotic therapy receipt. Results: Of 321 eligible patients with MLS, 32%, 36%, and 32% experienced acute, average, and subacute peak edema. Subacute peak edema was significantly associated with higher odds of favorable discharge than non-subacute swelling, adjusting for confounders (aOR, 1.85; 95% CI, 1.05-3.31). Conclusions: Subacute peak edema after large MCA stroke is associated with better discharge disposition compared to earlier peak edema courses. Understanding how the timing of cerebral edema affects risk of unfavorable discharge has important implications for treatment decisions and prognostication.

Characterization of CSF inflammatory markers after hemorrhagic stroke and their relationship to disease severity.

Background: The inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity. Methods: Biological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected. Results: Plasma and/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p<0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p<0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only. Conclusions: Within 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.