Correction to: Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

The authors note that there is a discrepancy between the text of the paper and Table 2 regarding physician subspecialty certification requirements in neurocritical care for Level II centers.

Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

Neurocritical care is a distinct subspecialty focusing on the optimal management of acutely ill patients with life-threatening neurologic and neurosurgical disease or with life-threatening neurologic manifestations of systemic disease. Care by expert healthcare providers to optimize neurologic recovery is necessary. Given the lack of an organizational framework and criteria for the development and maintenance of neurological critical care units (NCCUs), this document is put forth by the Neurocritical Care Society (NCS). Recommended organizational structure, personnel and processes necessary to develop a successful neurocritical care program are outlined. Methods: Under the direction of NCS Executive Leadership, a multidisciplinary writing group of NCS members was formed. After an iterative process, a framework was proposed and approved by members of the writing group. A draft was then written, which was reviewed by the NCS Quality Committee and NCS Guidelines Committee, members at large, and posted for public comment. Feedback was formally collated, reviewed and incorporated into the final document which was subsequently approved by the NCS Board of Directors.

Optimizing Outcomes for Mechanically Ventilated Patients in an Era of Endovascular Acute Ischemic Stroke Therapy.

Endovascular mechanical thrombectomy is a new standard of care for acute ischemic stroke (AIS). The majority of these patients receive mechanical ventilation (MV), which has been associated with poor outcomes. The implication of this is significant, as most neurointerventionalists prefer general compared to local anesthesia during the procedure. Consequences of hemodynamic and respiratory perturbations during general anesthesia and MV are thought to contribute significantly to the poor outcomes that are encountered. In this review, we first describe the unique risks associated with MV in the specific context of AIS and then discuss evidence of brain goal-directed approaches that may mitigate these risks. These strategies include an individualized approach to hemodynamic parameters (eg, adherence to a minimum blood pressure goal and adequate volume resuscitation), respiratory parameters (eg, arterial carbon dioxide optimization), and the use of ventilator settings that optimize neurological outcomes (eg, arterial oxygen optimization).

Systematic Quality Assessment of Published Antishivering Protocols.

Shivering is a common side effect of targeted temperature modulation and general anesthesia. Antishivering strategies often employ a stepwise approach involving both pharmacological and physical interventions. However, approaches to treat shivering are often empiric and vary widely across care environments. We evaluated the quality of published antishivering protocols and guidelines with respect to methodological rigor, reliability, and consistency of recommendations.Using 4 medical databases, we identified 4027 publications that addressed shivering therapy, and excluded 3354 due to lack of relevance. After applying predefined eligibility criteria with respect to minimal protocol standards, 18 protocols/guidelines remained. Each was assessed using a modified Appraisal of Guidelines for Research and Evaluation II (mAGREE II) instrument containing 23 quality items within 6 domains (maximal score 23). Among 18 protocols/guidelines, only 3 incorporated systematically reviewed recommendations, whereas 15 merely targeted practice standardization. Fifteen of 18 protocols/guidelines addressed shivering during therapeutic cooling in which skin counterwarming and meperidine were most commonly cited. However, their mAGREE II scores were within the lowest tertile (1 to 7 points) and the median for all 18 protocols was 5. The quality domains most commonly absent were stakeholder involvement, rigor of development, and editorial independence. Three of 18 protocols/guidelines addressed postanesthetic antishivering. Of these, the American Society of Anesthesiologists guidelines recommending forced-air warming and meperidine received the highest mAGREE II score (14 points), whereas the remaining 2 recommendations had low scores (<5 points).Current published antishivering protocols/guidelines lack methodological rigor, reliability, and strength, and even the highest scoring of the 18 protocols/guidelines fulfilled only 60% of quality items. To be consistent with evidence-based protocol/guideline development processes, future antishivering treatment algorithms should increase methodological rigor and transparency.

Transcranial Doppler Changes in Patients Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND: Transcranial Doppler (TCD) has significant implications for neurovascular assessment in patients being treated with venoarterial-extracorporeal membrane oxygenation (VA-ECMO). However, there have been no studies demonstrating the changes in pulsatility indices (PIs) seen in these patients. Nonpulsatile waveforms are seen during on-pump coronary artery bypass graft, but low or low-normal PIs have never been reported. It is important to be aware of these changes, as they can be misinterpreted as cerebral vasodilation, vasoconstriction, increased intracranial pressures (ICPs), or cerebral circulatory arrest. METHODS: Data from 11 TCDs from 8 patients on VA-ECMO in the Cedars Sinai Medical Center Cardiac Surgical Intensive Care Unit were reviewed. Mean pulsatility indices were calculated for each patient using Gosling's PI formula. The values obtained were correlated with ejection fraction (EF) values obtained from a transthoracic or transesophageal echocardiogram. RESULTS: PIs were globally low or absent in all 11 TCDs. In 3 patients, TCDs were performed at the initiation and conclusion of the VA-ECMO cannulation. The PI values for these TCDs correlated directly with changes in EFs. Also, an abrupt rise in PI to normal value was seen with the placement of a total artificial heart and the return of pulsatile circulation. CONCLUSIONS: We demonstrate that PIs on TCDs in patients treated with VA-ECMO are either low or cannot be calculated depending on the severity of myocardial suppression, and should not be mistaken for cerebral vasodilation or cerebral circulatory arrest. Moreover, rising PIs in these patients can represent improving cardiac function and should not be confused with elevated ICPs.

Hospital Readmission Rates Among Mechanically Ventilated Patients With Stroke.

BACKGROUND AND PURPOSE: Tracheostomy is frequently performed in patients with severe ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Little is known about readmission rates among stroke patients who undergo mechanical ventilation. METHODS: We used previously validated International Classification of Diseases, Ninth Edition-Clinical Modification codes and data on all discharges from nonfederal acute care hospitals in 3 states. We compared readmission rates among mechanically ventilated patients with stroke who were discharged with or without a tracheostomy. RESULTS: Among 39,881 patients who underwent mechanical ventilation during the index stroke hospitalization and survived to discharge, 10,690 (26.8%; 95% confidence interval, 26.4%-27.2%) underwent tracheostomy. During a mean follow-up period of 3.4 (±2.0) years, the overall incidence rate of readmissions was 4.25 (95% confidence interval, 4.22-4.28) per 100 patients per 30 days. The rate of any readmissions within 30 days was 26.9% among patients with tracheostomy compared with 22.5% among those without a tracheostomy (absolute risk difference, 4.4%; 95% confidence interval, 3.5%-5.4%; P<0.001). After adjustment for potentially confounding variables, tracheostomy was associated with a slightly increased readmission rate (incidence rate ratio, 1.07; 95% confidence interval, 1.03-1.11). CONCLUSIONS: Approximately one quarter of mechanically ventilated patients with stroke who survive to discharge are readmitted to the hospital within 30 days. Readmission rates are significantly higher in patients with stroke who undergo tracheostomy, but the difference is not clinically meaningful. Thirty-day readmission rates among mechanically ventilated patients with stroke are similar to Medicare beneficiaries hospitalized with major medical diseases such as pneumonia.

Efficacy of Nonpharmacological Antishivering Interventions: A Systematic Analysis.

OBJECTIVE: We performed a systematic review of the published evidence regarding nonpharmacologic antishivering interventions in various clinical settings. DATA SOURCES: Studies through November 2014 were identified using predefined search terms in electronic databases, including PubMed, the Cochrane Library, EMBASE: Excerpta Medica (Ovid), and Web of Science. STUDY SELECTION: All identified articles were critically analyzed by applying prespecified criteria. We included experimental trials with comparable baseline data investigating the antishivering efficacy of nonpharmacological interventions in subjects without underlying thermoregulatory dysfunction. DATA EXTRACTION: Sixty-five publications (3,361 subjects) were analyzed by the type of clinical setting, intervention, comparison, and study design. In addition, each study underwent a standardized study quality assessment. DATA SYNTHESIS: Nonpharmacological interventions consisted of active cutaneous warming (forced-air warming, electric heating pad/blanket, radiant heating, and water-circulating mattress), body core warming (fluid or gas warming system), passive cutaneous warming (space blankets or towels), and electroacupuncture. Identified clinical settings included perioperative settings without induced hypothermia (60 of 77 comparisons), perioperative settings with induced hypothermia (8 of 77), and induced hypothermia without anesthesia (9 of 77). Active cutaneous warming was the most commonly studied intervention, and it was associated with the highest prevalence of positive results when compared with controls in all three clinical settings. In contrast, passive cutaneous warming and body core warming showed conflicting efficacy. Comparison evaluations among different antishivering interventions were limited due to the paucity and heterogeneity of studies directly comparing different interventions against one another. CONCLUSION: This systematic review of the effectiveness of nonpharmacological antishivering methods delineates active cutaneous warming as the most effective nonpharmacologic antishivering intervention in the perioperative and induced hypothermia settings.

Mechanical Ventilation for Acute Stroke: A Multi-state Population-Based Study.

BACKGROUND: Mechanical ventilation is frequently performed in patients with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). In this study, we used statewide administrative claims data to examine the rates of use, associated conditions, and in-hospital mortality rates for mechanically ventilated stroke patients. METHODS: We used statewide administrative claims data from three states and ICD-9-CM codes to identify patients admitted with stroke and those who received mechanical ventilation and tracheostomy. Descriptive statistics and exact 95 % confidence intervals were used to report rates of mechanical ventilation, tracheostomy, and in-hospital mortality. Logistic regression analysis was performed to identify conditions associated with mechanical ventilation based on previously described risk factors. RESULTS: 798,255 hospital admissions for stroke were identified. 12.5 % of these patients underwent mechanical ventilation. This rate varied by stroke type: 7.9 % for IS, 29.9 % for ICH, and 38.5 % for SAH. Increased age was associated with a decreased risk of receiving mechanical ventilation (RR per decade, 0.91). Of stroke patients who underwent mechanical ventilation, 16.3 % received a tracheostomy. Mechanical ventilation was more likely to occur in association with status epilepticus (RR, 5.1), pneumonia (RR, 4.9), sepsis (RR, 3.6), and hydrocephalus (RR, 3.3). In-hospital mortality rate for mechanically ventilated stroke patients was 52.7 % (46.8 % for IS, 61.0 % for ICH, and 54.6 % for SAH). CONCLUSIONS: In this large population-based sample, over half of mechanically ventilated stroke patients died in the hospital despite the fact that younger patients were more likely to receive mechanical ventilation. Future studies are indicated to elucidate mechanical ventilation strategies to optimize long-term outcomes after severe stroke.

Hemicraniectomy and durotomy upon deterioration from infarction-related swelling trial: randomized pilot clinical trial.

BACKGROUND AND PURPOSE: Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. METHODS: All patients with stroke were screened for eligibility (age 18-75 years, National Institutes of Health Stroke Scale≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. RESULTS: Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. CONCLUSIONS: HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. CLINICAL TRIAL REGISTRATION: This trial was not registered because enrollment began before July 1, 2005.

A 59-year-old man with acute onset of paralysis.

Botulism is a neuroparalytic illness resulting from the action of a potent toxin produced by the organism Clostridium botulinum. It can present with a classic triad of clear mentation, bulbar palsy and symmetric descending paralysis. Treatment is symptomatic and includes a botulinum antitoxin.

A young man with altered mental status and new-onset seizures.

Signs and symptoms of a subacute, progressive, imaging-negative encephalopathy can be misdiagnosed as a neuropsychiatric or progressive neurodegenerative disorder. However, encephalopathies often can be reversed if the autoimmune component is recognized early through a careful history and diagnostic testing, including cerebrospinal fluid analysis for antibodies.

Efficacy spectrum of antishivering medications: meta-analysis of randomized controlled trials.

OBJECTIVES: Shivering after anesthesia or in the critical care setting is frequent, can be prolonged, and has the potential for serious adverse events and worsening outcomes. Furthermore, there are conflicting published data and clinical protocols on how to best treat shivering. In this study, we aimed to critically analyze the published evidence of antishivering medications. DATA SOURCES: We systematically reviewed, categorized, and analyzed all literature on antishivering medications published in English. Target key words and study types were determined and major scientific databases (PubMed, EMBASE, the Cochrane Controlled Trials Register, Ovid-Medline, and JAMA Evidence) and individual target journals were systematically searched up to August 1, 2011. STUDY SELECTION: Publications were categorized by the pharmacological intervention used, regardless of whether the subjects were ventilated, underwent surgery, received anesthesia, or received additional medications. Randomized, double-blinded, placebo-controlled trials investigating antishivering treatment were extracted and evaluated for clinical and statistical homogeneity and, if suitable, included in a subsequent meta-analysis using linear comparisons calculating shivering risk-reduction ratios. DATA EXTRACTION: A total of 41 individual and eight combination antishivering medications were tested in 124 publications containing 208 substudies and recruiting a total of 9,668 subjects. Among those, 80 publications containing 119 substudies were identified as randomized, double-blinded, placebo-controlled of which 94 substudies were subjected to linear comparison analysis. DATA SYNTHESIS: Study drug frequencies, calculated pooled risk benefits, and pooled numbers needed to treat of the five most frequently studied and efficacious medications were clonidine (22 studies; risk ratio: 1.6, numbers needed to treat: 4), meperidine (16; 2.2, 2), tramadol (8; 2.2, 2), nefopam (7; 2.1, 2), and ketamine (7; 1.8, 3). CONCLUSIONS: There is significant heterogeneity in the literature with respect to study methods and efficacy testing of antishivering treatments. Clonidine, meperidine, tramadol, nefopam, and ketamine were the most frequently reported pharmacological interventions and showed a variable degree of efficacy in randomized, double-blinded, placebo-controlled trials.

Using CT perfusion during the early baseline period in aneurysmal subarachnoid hemorrhage to assess for development of vasospasm.

INTRODUCTION: The aim of this study is to evaluate computed tomography perfusion (CTP) during admission baseline period (days 0-3) in aneurysmal subarachnoid hemorrhage (A-SAH) for development of vasospasm. METHODS: Retrospective analysis was performed on A-SAH patients from Dec 2004 to Feb 2007 with CTP on days 0-3. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were analyzed for qualitative perfusion deficits. Quantitative analysis was performed using region-of-interest placement to obtain mean CTP values. Development of vasospasm was determined by a multistage hierarchical reference standard incorporating both imaging and clinical criteria. Student's t test and threshold analysis were performed. RESULTS: Seventy-five patients were included, 37% (28/75) were classified as vasospasm. Mean CTP values in vasospasm compared to no vasospasm groups were: CBF 31.90 ml/100 g/min vs. 39.88 ml/100 g/min (P < 0.05), MTT 7.12 s vs. 5.03 s (P < 0.01), and CBV 1.86 ml/100 g vs. 2.02 ml/100 g (P = 0.058). Fifteen patients had qualitative perfusion deficits with 73% (11/15) developed vasospasm. Optimal threshold for CBF is 24-25 mL/100 g/min with 91% specificity and 50% sensitivity, MTT is 5.5 s with 70% specificity and 61% sensitivity and CBV is 1.7 mL/100 g with 89% specificity and 36% sensitivity. CONCLUSION: These initial results support our hypothesis that A-SAH patients who develop vasospasm may demonstrate early alterations in cerebral perfusion, with statistically significant CBF reduction and MTT prolongation. Overall, CTP has high specificity for development of vasospasm. Future clinical implications include using CTP during the baseline period for early identification of A-SAH patients at high risk for vasospasm to prompt robust preventative measures and treatment.

P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine.

INTRODUCTION: Dual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors. METHODS: Assessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices. RESULTS: Both geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy. CONCLUSIONS: The latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Simple intravenous fluid regimens to control fever in hospitalized stroke patients: a theoretical evaluation.

Fever is an independent predictor of worse outcome in stroke patients. We hypothesized that a peripheral infusion of saline in chilled or ice slurry form can be a practical adjuvant therapy to maintain euthermia. We developed a theoretical model simulating systemic body cooling in response to 0 degrees C saline and 50% ice slurry. Temperature elevations up to 39 degrees C were studied with respect to the time needed to reach a core temperature of 37 degrees C. Mathematical modeling identified a cooling rate of 0.48 degrees C/hr and 0.24 degrees C/hr using a 450 mL/hr infusion of 50% ice slurry and chilled saline. A reduction of the infusion rate to 150 mL/hr decreased euthermia time by a factor of 3; however, the total amount of coolant remained constant. Thus, based on mathematical modeling, peripheral infusions of saline in chilled or ice slurry form can be used as an adjunct therapy to achieve euthermia and control fever. Using intravenous coolants in an on-demand, temperature-guided and supervised treatment setting seems most reasonable to avoid potentially unsafe use of extended fluid volumes and infusion times.

Locked-in syndrome from rostro-caudal herniation.

Locked-in syndrome (LIS) is often caused by ventral pontine injury involving the perforating pontine vessels of the basilar artery and recovery is rarely reported. We report a patient who developed LIS acutely after aneurysmal subarachnoid haemorrhage and rostro-caudal herniation from hydrocephalus. The patient's clinical course and diagnostic studies suggest that the likely mechanism of this patient's LIS is mechanical compression of the ventral pons anteriorly against the clivus. The patient's slow but full recovery allowed us to further differentiate this clinical entity from the more common LIS due to ischaemic mechanisms.

Improvement of in vitro thrombolysis employing magnetically-guided microspheres.

Significant shortcomings in clinical thrombolysis efficiencies and arterial recanalization rates still exist to date necessitating the development of additional thrombolysis-enhancing technologies. For example, to improve tPA-induced systemic clot lysis several supplementary treatment methods have been proposed, among them ultrasound-enhanced tissue plasminogen activator (tPA) thrombolysis which has already found some clinical applicability. The rationale of this study was to investigate whether biodegradable, magnetic spheres can be a useful adjuvant to currently existing tPA-induced thrombolysis and further enhance clot lysis results. Based on an envisioned, novel thrombolysis technology--magnetically-guided, tPA-loaded nanocarriers with triggered release of the shielded drug at an intravascular target site--we evaluated the lysis efficiencies of magnetically-guided, non-medicated magnetic spheres in various combinations with tPA and ultrasound. When tPA was used in conjunction with magnetic spheres and a magnetic field, the lysis efficiency under static, no-flow conditions improved by 1.7 and 2.7 fold for red and white clots, respectively. In dynamic lysis studies, the addition of ultrasound and magnetically-guided spheres to lytic tPA dosages resulted in both maximum clot lysis efficiency and shortest reperfusion time corresponding to a 2-fold increase in lysis and 7-fold reduction in recanalization time, respectively. Serial microscopic evaluations on histochemical sections reconfirmed that tPA penetration into and fragmentation of the clot increased with escalating exposure time to tPA and magnetic spheres/field. These results delineate the effectiveness of magnetic spheres as an adjuvant to tPA therapy accelerating in vitro lysis efficiencies beyond values found for tPA with and without ultrasound. We demonstrated that the supplementary use of magnetically-guided, non-medicated magnetic spheres significantly enhances in vitro static and dynamic lysis of red and white blood clots.

Brainstem ischemia in acute herniation syndrome.

Brain herniation from hemispheric mass lesions injures mainly the upper brainstem around the tentorial incisura. While mechanical tissue compression is usually the process of deterioration and injury, the primary injury mechanism in some patients is early brainstem ischemia from arterial compromise as demonstrated by this patient's magnetic resonance imaging (MRI) and pathology.