Surgical Versus Dilational Tracheostomy in Patients with Severe Stroke: A SETPOINT2 Post hoc Analysis.

BACKGROUND: Tracheostomy in mechanically ventilated patients with severe stroke can be performed surgically or dilationally. Prospective data comparing both methods in patients with stroke are scarce. The randomized Stroke-Related Early Tracheostomy vs Prolonged Orotracheal Intubation in Neurocritical Care Trial2 (SETPOINT2) assigned 382 mechanically ventilated patients with stroke to early tracheostomy versus extubation or standard tracheostomy. Surgical tracheostomy (ST) was performed in 41 of 307 SETPOINT2 patients, and the majority received dilational tracheostomy (DT). We aimed to compare ST and DT in these patients with patients. METHODS: All SETPOINT2 patients with ST were compared with a control group of patients with stroke undergoing DT (1:2), selected by propensity score matching that included the factors stroke type, SETPOINT2 randomization group, Stroke Early Tracheostomy score, patient age, and premorbid functional status. Successful decannulation was the primary outcome, and secondary outcome parameters included functional outcome at 6 months and adverse events attributable to tracheostomy. Potential predictors of decannulation were evaluated by regression analysis. RESULTS: Baseline characteristics were comparable in the two groups of patients with stroke undergoing ST (n = 41) and matched patients with stroke undergoing DT (n = 82). Tracheostomy was performed significantly later in the ST group than in the DT group (median 9 [interquartile range {IQR} 5-12] vs. 9 [IQR 4-11] days after intubation, p = 0.025). Patients with ST were mechanically ventilated longer (median 19 [IQR 17-24] vs.14 [IQR 11-19] days, p = 0.008) and stayed in the intensive care unit longer (median 23 [IQR 16-27] vs. 17 [IQR 13-24] days, p = 0.047), compared with patients with DT. The intrahospital infection rate was significantly higher in the ST group compared to the DT group (14.6% vs. 1.2%, p = 0.002). At 6 months, decannulation rates (56% vs. 61%), functional outcomes, and mortality were not different. However, decannulation was performed later in the ST group compared to the DT group (median 81 [IQR 66-149] vs. 58 [IQR 32-77] days, p = 0.004). Higher baseline Stroke Early Tracheostomy score negatively predicted decannulation. CONCLUSIONS: In ventilated patients with severe stroke in need of tracheostomy, surgical and dilational methods are associated with comparable decannulation rate and functional outcome at 6 months. However, ST was associated with longer time to decannulation and higher rates of early infections, supporting the dilational approach to tracheostomy in ventilated patients with stroke.

Fit for Service: Preparing Residents for Neurointensive Care with Entrustable Professional Activities: A Delphi Study.

BACKGROUND: Although the relevance of neurointensive medicine and high-quality training of corresponding physicians is increasingly recognized, there is high heterogeneity in the nature, duration, and quality of neurointensive care curricula around the world. Thus, we aimed to identify, define, and establish validity evidence for entrustable professional activities (EPAs) for postgraduate training in neurointensive care to determine trainees' readiness for being on-call. METHODS: After defining EPAs through an iterative process by an expert group, we used a modified Delphi approach with a single-center development process followed by a national consensus and a single-center validation step. EPAs were evaluated by using the EQual rubric (Queen's EPA Quality Rubric). Interrater reliability was measured with Krippendorff's α. RESULTS: The expert group defined seven preliminary EPAs for neurointensive care. In two consecutive Delphi rounds, EPAs were adapted, and consensus was reached for level of entrustment and time of expiration. Ultimately, EPAs reached a high EQual score of 4.5 of 5 and above. Interrater reliability for the EQual scoring was 0.8. CONCLUSIONS: Using a multistep Delphi process, we defined and established validity evidence for seven EPAs for neurointensive medicine with a high degree of consensus to objectively describe readiness for on-call duty in neurointensive care. This operationalization of pivotal clinical tasks may help to better train clinical residents in neurointensive care across sites and health care systems and has the potential to serve as a blueprint for training in general intensive care medicine. It also represents a starting point for further research and development of medical curricula.

Liberation from Mechanical Ventilation and Tracheostomy Practice in Traumatic Brain Injury.

Liberating patients with severe traumatic brain injury (TBI) from mechanical ventilation is often a challenging task. These patients frequently require prolonged ventilation and have persistent alterations in the level and content of consciousness. Questions about their ability to protect their airway are common. Pulmonary complications and copious respiratory secretions are also very prevalent. Thus, it is hardly surprising that rates of extubation failure are high. This is a major problem because extubation failure is associated with a host of poor outcome measures. When the safety of an extubation attempt is uncertain, direct tracheostomy is favored by some, but there is no evidence that this practice leads to better outcomes. Current knowledge is insufficient to reliably predict extubation outcomes in TBI, and practices vary substantially across trauma centers. Yet observational studies provide relevant information that must be weighted when considering the decision to attempt extubation in patients with head injury. This review discusses available evidence on liberation from mechanical ventilation in TBI, proposes priorities for future research, and offers practical advice to guide decisions at the bedside.

[Neurointensive care medicine and COVID-19]. / Neurointensivmedizin und COVID-19.

This review article summarizes important findings on the interfaces between the coronavirus disease 2019 (COVID-19) pandemic and neurology with an emphasis of the implications for neurointensive care medicine. More specifically, the prevalence, pathomechanisms and impact of neurological manifestations are reported. The most common neurological manifestations of critically ill COVID-19 patients are cerebrovascular complications, encephalopathies and intensive care unit-acquired weakness (ICUAW). A relevant direct pathophysiological effect by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) itself has not yet been established with certainty. In fact, indirect systemic inflammatory processes triggered by the viral infection and side effects of intensive care treatment are much more likely to cause the reported sequelae. The impact of the pandemic on patients with neurological disorders and neurointensive care medicine is far-reaching but not yet sufficiently studied.

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis-A Multicenter Analysis.

BACKGROUND: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. METHODS: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. RESULTS: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). CONCLUSION: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.

Automated Pupillometry for Assessment of Treatment Success in Nonconvulsive Status Epilepticus.

BACKGROUND: Altered pupillary function may reflect nonconvulsive status epilepticus (NCSE). Neurological pupil index (NPi) assessed by automated pupillometry is a surrogate marker of global pupillary function. We aimed to assess NPi changes in relation to NCSE treatment response. METHODS: In this prospective observational study, serial automated pupillometry was performed in 68 NCSE episodes. In accordance with local standards, patients were treated with clonazepam (1-2 mg), levetiracetam (40 mg/kg), and lacosamide (5 mg/kg) in a stepwise approach under continuous electroencephalography monitoring until NCSE was terminated. Patients with refractory NCSE received individualized regimens. NPi was assessed bilaterally before and after each treatment step. For statistical analysis, the lower NPi of both sides (minNPi) was used. Nonparametric testing for matched samples and Cohen's d to estimate effect size were performed. Principal component analysis was applied to assess the contribution of baseline minNPi, age, sex, and NCSE duration to treatment outcome. RESULTS: In 97.1% of 68 episodes, NCSE could be terminated; in 16.2%, NCSE was refractory. In 85.3% of episodes, an abnormal baseline minNPi ≤ 4.0 was obtained. After NCSE termination, minNPi increased significantly (p < 0.001). Cohen's d showed a strong effect size of 1.24 (95% confidence interval 0.88-1.61). Baseline minNPi was higher in clonazepam nonresponders vs. responders (p = 0.008), minNPi increased in responders (p < 0.001) but not in nonresponders. NCSE refractivity was associated with normal baseline minNPi (principal component analysis, component 1, 32.6% of variance, r = 0.78), male sex, and longer NCSE duration (component 2, 27.1% of variance, r = 0.62 and r = 0.78, respectively). CONCLUSIONS: Automated pupillometry may be a helpful noninvasive neuromonitoring tool for the assessment of patients with NCSE and response to treatment.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

Dying in the Neurointensive Care Unit After Withdrawal of Life-Sustaining Therapy: Associations of Advance Directives and Health-Care Proxies With Timing and Treatment Intensity.

BACKGROUND AND PURPOSE: Critically ill patients require a careful approach for prognosis and decision-making. The German health legislation aims to strengthen the role of advance directives (ADs) and health-care proxies (HCPs). Their impact within a dedicated neurocritical care setting is unknown. This study aimed to assess the practice of withdrawal or withholding of life-sustaining therapy (WOLST) in a German neurointensive care unit (NICU) focusing on whether AD or HCP is associated with timing and treatment intensity. METHODS: Data on patients who died after WOLST at a dedicated NICU of a German university hospital, from 2010 to 2013, were retrospectively analyzed. RESULTS: Of 400 deceased patients, 310 (77.5%) died after initiation of WOLST. Among them, 68 (21.9%) were identified to have AD or HCP or both (AD + HCP). WOLST patients with AD, HCP, or AD + HCP were older than those without (median age: 77 vs 72 years, P < .001) but did not show any other distinct baseline features. There was no difference in the specific neurocritical care measures between the groups. Poisson regression analysis showed no significant difference in the probability of time-dependent WOLST initiation between those with and without AD/HCP, after adjusting for age and sex (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.94-1.28; P = .244). CONCLUSIONS: In this single-center study of mainly cerebrovascular NICU patients, AD or HCP was neither associated with an earlier WOLST nor associated with a difference in treatment intensity before WOLST. Further prospective studies should assess the emerging concept of advance care planning in neurocritical care.

Quantitative Infrared Pupillometry in Nonconvulsive Status Epilepticus.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a frequent disorder in neurocritical care and diagnosing it can be challenging. NCSE patients often show altered pupil function, but nature and extent may vary. Infrared pupillometry allows detection of subtle changes of pupil function. The neurological pupil index (NPi) is considered a surrogate marker of global pupil function which is supposed to be independent of absolute parameters such as the pupil diameter. OBJECTIVE: Cross-sectional observational study to assess whether NPi is altered in NCSE. METHODS: 128 consecutive adult emergency patients who had experienced a suspected seizure, have not reached their prior functional level regarding level of consciousness, mental status or focal deficits, had no obvious clinical signs of status epilepticus and had an EEG indication as determined by the treating clinician for exclusion of NCSE were examined by routine EEG and pupillometry. Exclusion criteria were ocular comorbidity (n = 21) and poor EEG quality (n = 4). Pupillometry was performed once directly before the beginning of EEG recording. NCSE diagnosis (no NCSE, possible NCSE and confirmed NCSE) was established according to Salzburg consensus criteria blinded to pupillometry results. Group comparison was performed for right NPi, left NPi, lowest NPi of both sides (minNPi) and the absolute difference of both sides (diffNPi) applying non-parametric testing. In post-hoc analysis, receiver operating characteristics (ROC) of NCSE diagnosis (combined confirmed NCSE and possible NCSE) were performed for minNPi and diffNPi. RESULTS: From 103 patients included in the final analysis, 5 (4.9%) had confirmed NCSE, 7 (6.8%) had possible NCSE. Right NPi (p = 0.002), left NPi (p < 0.001) and minNPi (p < 0.001) were significantly lower in "confirmed NCSE" and "possible NCSE" compared to "no NCSE"; diffNPi was significantly higher in "confirmed NCSE" and "possible NCSE" compared to "no NCSE" (p < 0.001). There was no significant difference of minNPi and diffNPi between "confirmed NCSE" and "possible NCSE". ROC analysis showed an optimal cut-off of minNPi for NCSE diagnosis of 4.0 (AUC = 0.93, 95% CI 0.86-0.99). Optimal ROC analysis cut-off of diffNPi for NCSE diagnosis was 0.2 (AUC = 0.89, 95% CI 0.80-0.99). CONCLUSIONS: NPi was significantly reduced and the difference between left and right NPi was significantly higher in confirmed NCSE. An NPi < 4.0 on either side as well as an NPi difference of both sides > 0.2 may be potential indicators of NCSE. Infrared pupillometry may be a helpful diagnostic tool in the assessment of NCSE and should be studied further in larger populations.

Hemodynamic Status During Endovascular Stroke Treatment: Association of Blood Pressure with Functional Outcome.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment in patients with large-vessel occlusion is not well established. We aimed to investigate associations of BP during different phases of endovascular therapy with reperfusion and functional outcome. METHODS: We performed a post hoc analysis of a single-center prospective study that evaluated a new simplified procedural sedation standard during endovascular therapy (Keep Evaluating Protocol Simplification in Managing Periinterventional Light Sedation for Endovascular Stroke Treatment). BP during endovascular therapy in patients was managed according to protocol. Data from four different phases (baseline, pre-recanalization, post recanalization, and post intervention) were obtained, and mean BP values, as well as changes in BP between different phases and reductions in systolic BP (SBP) and mean arterial pressure (MAP) from baseline to pre-recanalization, were used as exposure variables. The main outcome was a modified Rankin Scale score of 0-2 three months after admission. Secondary outcomes were successful reperfusion and change in the National Institutes of Health Stroke Scale score after 24 h. Multivariable linear and logistic regression models were used for statistical analysis. RESULTS: Functional outcomes were analyzed in 139 patients with successful reperfusion (defined as thrombolysis in cerebral infarction grade 2b-3). The mean (standard deviation) age was 76 (10.9) years, the mean (standard deviation) National Institutes of Health Stroke Scale score was 14.3 (7.5), and 70 (43.5%) patients had a left-sided vessel occlusion. Favorable functional outcome (modified Rankin Scale score 0-2) was less likely with every 10-mm Hg increase in baseline (odds ratio [OR] 0.76, P = 0.04) and pre-recanalization (OR 0.65, P = 0.011) SBP. This was also found for baseline (OR 0.76, P = 0.05) and pre-recanalization MAP (OR 0.66, P = 0.03). The maximum Youden index in a receiver operating characteristics analysis revealed an SBP of 163 mm Hg and MAP of 117 mm Hg as discriminatory thresholds during the pre-recanalization phase to predict functional outcome. CONCLUSIONS: In our protocol-based setting, intraprocedural pre-recanalization BP reductions during endovascular therapy were not associated with functional outcome. However, higher intraprocedural pre-recanalization SBP and MAP were associated with worse functional outcome. Prospective randomized controlled studies are needed to determine whether BP is a feasible treatment target for the modification of outcomes.

Isoflurane in (Super-) Refractory Status Epilepticus: A Multicenter Evaluation.

BACKGROUND: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs). METHODS: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011-2018. RESULTS: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy. CONCLUSIONS: Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.

The KEEP SIMPLEST Study: Improving In-House Delays and Periinterventional Management in Stroke Thrombectomy-A Matched Pair Analysis.

BACKGROUND AND PURPOSE: Although the treatment window for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) has been extended in recent years, it has been proven that recanalizing treatment must be administered as soon as possible. We present a new standard operating procedure (SOP) to reduce in-house delay, standardize periinterventional management and improve patient safety during MT. METHODS: KEep Evaluating Protocol Simplification In Managing Periinterventional Light Sedation for Endovascular Stroke Treatment (KEEP SIMPLEST) was a prospective, single-center observational study aimed to compare aspects of periinterventional management in AIS patients treated according to our new SOP using a combination of esketamine and propofol with patients having been randomized into conscious sedation (CS) in the Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial. Primary outcome was early neurological improvement at 24h using the National Institutes of Health Stroke Scale, and secondary outcomes were door-to-recanalization, recanalization grade, conversion rate and modified Rankin Scale (mRS) at 3 months. RESULTS: Door-to-recanalization time (128.6 ± 69.47 min vs. 156.8 ± 75.91 min; p = 0.02), mean duration of MT (92.01 ± 52 min vs. 131.9 ± 64.03 min; p < 0.001), door-to-first angiographic image (51.61 ± 31.7 min vs. 64.23 ± 21.53 min; p = 0.003) and computed tomography-to-first angiographic image time (31.61 ± 20.6 min vs. 44.61 ± 19.3 min; p < 0.001) were significantly shorter in the group treated under the new SOP. There were no differences in early neurological improvement, mRS at 3 months or other secondary outcomes between the groups. Conversion rates of CS to general anesthesia were similar in both groups. CONCLUSION: An SOP using a novel sedation regimen and optimization of equipment and procedures directed at a leaner, more integrative and compact periinterventional management can reduce in-house treatment delays significantly in stroke patients receiving thrombectomy in light sedation and demonstrated the safety and feasibility of our improved approach.

Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis.

IMPORTANCE: General anesthesia during thrombectomy for acute ischemic stroke has been associated with poor neurological outcome in nonrandomized studies. Three single-center randomized trials reported no significantly different or improved outcomes for patients who received general anesthesia compared with procedural sedation. OBJECTIVE: To detect differences in functional outcome at 3 months between patients who received general anesthesia vs procedural sedation during thrombectomy for anterior circulation acute ischemic stroke. DATA SOURCE: MEDLINE search for English-language articles published from January 1, 1980, to July 31, 2019. STUDY SELECTION: Randomized clinical trials of adults with a National Institutes of Health Stroke Scale score of at least 10 and anterior circulation acute ischemic stroke assigned to receive general anesthesia or procedural sedation during thrombectomy. DATA EXTRACTION AND SYNTHESIS: Individual patient data were obtained from 3 single-center, randomized, parallel-group, open-label treatment trials with blinded end point evaluation that met inclusion criteria and were analyzed using fixed-effects meta-analysis. MAIN OUTCOMES AND MEASURES: Degree of disability, measured via the modified Rankin Scale (mRS) score (range 0-6; lower scores indicate less disability), analyzed with the common odds ratio (cOR) to detect the ordinal shift in the distribution of disability over the range of mRS scores. RESULTS: A total of 368 patients (mean [SD] age, 71.5 [12.9] years; 163 [44.3%] women; median [interquartile range] National Institutes of Health Stroke Scale score, 17 [14-21]) were included in the analysis, including 183 (49.7%) who received general anesthesia and 185 (50.3%) who received procedural sedation. The mean 3-month mRS score was 2.8 (95% CI, 2.5-3.1) in the general anesthesia group vs 3.2 (95% CI, 3.0-3.5) in the procedural sedation group (difference, 0.43 [95% CI, 0.03-0.83]; cOR, 1.58 [95% CI, 1.09-2.29]; P = .02). Among prespecified adverse events, only hypotension (decline in systolic blood pressure of more than 20% from baseline) (80.8% vs 53.1%; OR, 4.26 [95% CI, 2.55-7.09]; P < .001) and blood pressure variability (systolic blood pressure >180 mm Hg or <120 mm Hg) (79.7 vs 62.3%; OR, 2.42 [95% CI, 1.49-3.93]; P < .001) were significantly more common in the general anesthesia group. CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke involving the anterior circulation undergoing thrombectomy, the use of protocol-based general anesthesia, compared with procedural sedation, was significantly associated with less disability at 3 months. These findings should be interpreted tentatively, given that the individual trials examined were single-center trials and disability was the primary outcome in only 1 trial.

[Levetiracetam for treatment of status epilepticus - an update]. / Levetiracetam in der Behandlung des Status epilepticus ­ ein update.

Since 2004 several reports on the treatment of status epilepticus with levetiracetam have been published. In this review, the results of a PubMed-based search of publications December 12, 2011 - July 6, 2018 are summarized and compared to those of earlier publications. In total, 28 treatment episodes in case reports, each on one or two cases of treatment episodes, and 412 treatment episodes in case series and prospective studies were analyzed. Case series and prospective studies reported an average success rate for termination of status probably of 55,0 %-59,4 %. Since preclinical data suggest a delayed effect of levetiracetam, its use in the treatment of generalized convulsive status epilepticus appears still questionable. A loading dose of 30 mg / kg seems to be reasonable.

Association of Blood Pressure With Short- and Long-Term Functional Outcome After Stroke Thrombectomy: Post Hoc Analysis of the SIESTA Trial.

BACKGROUND AND PURPOSE: Outcome after mechanical thrombectomy for ischemic stroke may be influenced by blood pressure (BP). This study aims to assess the association of BP changes during general anesthesia versus conscious sedation with functional outcome after mechanical thrombectomy. METHODS: SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment) was a monocentric randomized trial of general anesthesia versus conscious sedation during mechanical thrombectomy involving BP target protocols. In this post hoc analysis, BP measurements were divided into 4 phases: preintervention, prerecanalization, postrecanalization, and postintervention. We examined the association between BP and functional outcomes (defined by improvement of 24-hour National Institutes of Health Stroke Scale [NIHSS] and 3-month modified Rankin Scale). RESULTS: We found no association between the difference in systolic BP, diastolic BP, and mean arterial pressure from baseline to the different phases of intervention and NIHSS change after 24 hours. Only baseline diastolic BP was associated with a reduced improvement in NIHSS (ß=0.17, P<0.01). There was no association of BP drops with a change in modified Rankin Scale at 3 months. About sedation, only baseline mean arterial pressure preintervention revealed significant associations (ß=0.16, P<0.01) with less change in 24-hour NIHSS in conscious sedation group. Otherwise, there was no association for differences of any of the BP measurements with a change in 24-hour NIHSS and long-term functional outcome either in general anesthesia or the conscious sedation group when analyzed separately, consistent with our findings in the entire cohort. Doses of propofol (ß=0.84, P=0.04) and norepinephrine (ß=1.87, P=0.01) administered during intervention before recanalization were associated with reduced improvement of NIHSS at 24 hours. CONCLUSIONS: In a setting, where both sedation regimes general anesthesia and conscious sedation were performed according to strict protocols directed at avoiding BP extremes, our findings suggest that peri-interventional BP drops were not associated with either early neurological improvement or long-term functional outcome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02126085.

Effect of General Anesthesia versus Conscious Sedation for Stroke Thrombectomy on Angiographic Workflow in a Randomized Trial: A Post Hoc Analysis of the SIESTA Trial.

Purpose To investigate whether the sedation mode (ie, conscious sedation [CS] vs general anesthesia [GA]) affects the angiographic workflow applied for treatment of endovascular stroke in a post hoc analysis of a recent randomized controlled trial, Sedation versus Intubation for Endovascular Stroke Treatment (SIESTA). Materials and Methods SIESTA was an institutional review board-approved, single-center, prospective, randomized, parallel-group, open-label treatment trial with a blinded end-point evaluation to compare GA with CS for treatment of endovascular stroke in 73 and 77 patients, respectively. By using descriptive data from SIESTA, the influence of the mode of sedation on angiographic workflow during treatment for endovascular stroke (eg, procedure times) and other radiologic outcome parameters (eg, radiation exposure) were analyzed. The time between angiographic key steps for patients who underwent GA and CS was evaluated with t tests. P values were corrected for false discovery rate. Results The median time from groin puncture to first intracranial flow restoration with CS was 47 minutes (interquartile range [IQR], 29-70 minutes), and for GA, it was 41 minutes (IQR, 28-60 minutes) (P = .546). The median time to the end of angiography with CS was 104 minutes (IQR, 75-150 minutes), and with GA, it was 73 minutes (IQR, 53-125 minutes) (P = .052). Fluoroscopy time with CS was 49 minutes (IQR, 25-85 minutes), and with GA, it was 35 minutes (IQR, 20-74 minutes) (P = .098). The times were comparable in both groups for these measures. The time from groin puncture to the final angiographic result with GA, at 72 minutes (IQR, 45-109 minutes) was shorter than that with CS, at 98 minutes (IQR, 64-135 minutes) (P = .048). Conclusion This post hoc analysis of the single-center SIESTA trial revealed that time from groin puncture to final angiographic result was shorter with patients under GA than that with patients under CS. © RSNA, 2017 Online supplemental material is available for this article.

[Modern principles of neurocritical care]. / Moderne Prinzipien der neurologischen Intensivmedizin.

Neurological diseases frequently demanding admittance to a dedicated neurological intensive care unit (neurocritical care) comprise space-occupying ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, status epilepticus, bacterial meningitis, myasthenic crisis and Guillain-Barré syndrome. Due to often necessary analgesia, sedation and mechanical ventilation, neuromonitoring should ideally be employed. This consists of bedside invasive and non-invasive methods for monitoring cerebral perfusion, oxygenation, metabolism and neurophysiology. Modern treatment principles in neurocritical care mainly aim at avoiding or attenuating secondary neurological brain damage, in particular directed at sufficient perfusion and oxygenation. These include measures such as neuroprotective ventilation, stabilization of the circulation, decreasing intracranial pressure in brain edema and space-occupying processes, anticonvulsive treatment, temperature management and targeted disease-specific treatment.

Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke.

BACKGROUND: Early decompressive hemicraniectomy reduces mortality without increasing the risk of very severe disability among patients 60 years of age or younger with complete or subtotal space-occupying middle-cerebral-artery infarction. Its benefit in older patients is uncertain. METHODS: We randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization. RESULTS: Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group. CONCLUSIONS: Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.).