Jeanne Teitelbaum

Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial

Background— The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. Methods and Results— Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% (P=0.006). Symptom onset-to-imaging time was not associated with outcome (P>0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). Conclusions— Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

The ketamine effect on intracranial pressure in nontraumatic neurological illness

PURPOSE The purpose of the study was to perform a systematic review of the literature on the use of ketamine in nontraumatic neurological illness and its effects on intracranial pressure (ICP). MATERIALS AND METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to January 2014), and gray literature were searched. Two reviewers identified manuscripts on the administration of ketamine in nontraumatic neurological illness that recorded effects on ICP. The strength of evidence was adjudicated using the Oxford and Grading of Recommendation Assessment Development and Education (GRADE) methodology. RESULTS Our search produced a total of 179 citations. Sixteen articles, 15 manuscripts, and 1 meeting proceeding were included in the review. Across all studies, there were 127 adult and 87 pediatric patients described. Intracranial pressure did not increase in any of the adult studies reporting premedication during ketamine administration, with 2 studies reporting a decrease in ICP. No significant non-ICP-related adverse events from ketamine were recorded in any of the studies. CONCLUSIONS There exists Oxford level 2b, GRADE C evidence in adults and level 4, GRADE C in pediatrics to support that ketamine does not increase ICP in nontraumatic neurological illness when patients are sedated and ventilated, and in fact may lower it in selected cases.

Time to loss of brain function and activity during circulatory arrest

PURPOSE Brain function during the dying process and around the time of cardiac arrest is poorly understood. To better inform the clinical physiology of the dying process and organ donation practices, we performed a scoping review of the literature to assess time to loss of brain function and activity after circulatory arrest. MATERIALS AND METHODS Medline and Embase databases were searched from inception to June 2014 for articles reporting the time interval to loss of brain function or activity after loss of systemic circulation. RESULTS Thirty-nine studies met selection criteria. Seven human studies and 10 animal studies reported that electroencephalography (EEG) activity is lost less than 30seconds after abrupt circulatory arrest. In the setting of existing brain injury, with progressive loss of oxygenated circulation, loss of EEG may occur before circulatory arrest. Cortical evoked potentials may persist for several minutes after loss of circulation. CONCLUSION The time required to lose brain function varied according to clinical context and method by which this function is measured. Most studies show that clinical loss of consciousness and loss of EEG activity occur within 30seconds after abrupt circulatory arrest and may occur before circulatory arrest after progressive hypoxia-ischemia. Prospective clinical studies are required to confirm these observations.

VNS for refractory status epilepticus.

BACKGROUND Our goal was to perform a systematic review of the literature on the insertion of vagal nerve stimulators (VNS) for refractory status epilepticus (RSE) and its impact on the control of RSE. METHODS All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2014), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers (FZ and MW). RESULTS Overall, 17 studies were identified, with 7 manuscripts and 10 meeting abstracts. A total of 28 patients were treated. In those with generalized RSE, 76% displayed cessation of RSE with VNS insertion. In cases of focal RSE, 25% responded to VNS insertion. Few adverse effects related to VNS insertion were described. CONCLUSIONS We currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D evidence exists to suggest improvement in seizure control with the use of urgent VNS in generalized RSE. No comments can be made on the utility of VNS in focal RSE. Further prospective study is warranted.

A Critical Appraisal of Sedation, Analgesia and Delirium in Neurocritical Care

Administering analgesics, sedatives and antipsychotics is challenging in the Neurological Intensive Care Unit (NICU). We reviewed this literature and our current practice to better inform the critical care practitioner and to identify gaps for future research. We electronically searched observational, intervention and outcome studies addressing sedation, analgesia and delirium in the NICU, and their bibliographies. Practice patterns were assessed in three critical care units with specialized neurological care in Montreal. Bedside pain assessment tools are psychometrically validated in the neuro-critically ill but sedation and delirium tools are not. Rigorous pain and sedation assessments appear feasible; delirium screening has not been tested. Publications addressing outcomes and responses to pharmacologic treatment lack consistency, rigor or both. In daily practice, pharmacologic management varies greatly. Clearly, little information exists on analgesia, sedation and delirium in the NICU. Systematic evaluation of pain improves outcome. No evidence-based therapeutic recommendations can be proffered.

Modern inhalational anesthetics for refractory status epilepticus.

BACKGROUND Our goal was to perform a systematic review of the literature on the use of modern inhalational anesthetic agents for refractory status epilepticus and their impact on seizure control. METHODS All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to March 2014), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendation Assessment Development and Education methodology by two independent reviewers. RESULTS Overall, 19 studies were identified, with 16 manuscripts and 3 meeting abstracts. A total of 46 patients were treated. Adult (n=28) and pediatric patients (n=18) displayed 92.9% and 94.4% seizure control with treatment, respectively. Isoflurane was used in the majority of cases. Hypotension was the only complication described. CONCLUSIONS Oxford level 4, Grading of Recommendation Assessment Development and Education D evidence exists to support the use of isoflurane in refractory status epilepticus to obtain burst suppression. Insufficient data exist to comment on the efficacy of desflurane and xenon at this time.

THAM for control of ICP.

Our goal was to perform a systematic review of the literature on the use of tromethamine (THAM) and its effects on intracranial pressure (ICP) in patients with neurological illness. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to February 2014), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts pertaining to the administration of THAM in human patients that recorded effects on ICP. Secondary outcomes of effect on cerebral perfusion pressure, mean arterial pressure, patient outcome, and adverse effects were recorded. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total 2,268 citations. Twelve articles, 9 manuscripts, and 3 meeting proceedings were considered for the review with all utilizing THAM while documenting ICP in neurosurgical patients. All studies were prospective. Across all studies, there were a total of 488 patients studied, with 263 receiving THAM and 225 serving as controls in a variety of heterogeneous studies. All but one study documented a decrease in ICP with THAM administration, with both bolus and continuous infusions. One study documented a reduction in cerebral perfusion pressure. No significant renal dysfunction, hepatocellular injury, or hypoglycemia were reported. Three prospective randomized control trials displayed trends to improved outcome in severe traumatic brain injury (TBI) patients with THAM administration. There currently exists Oxford level 2b, GRADE B evidence to support that THAM reduces ICP in the TBI and malignant ischemic infarct population, with minimal side effects. The literature suggests THAM may be useful for ICP reduction in certain cases, though the safety of the compound in these circumstances is still unclear. Further prospective study is warranted.

Electroconvulsive therapy for refractory status epilepticus: A systematic review

BACKGROUND Our goal was to perform an extensive systematic review of the literature on the use of electroconvulsive therapy (ECT) for refractory status epilepticus (RSE). METHODS Articles from MEDLINE, BIOSIS, EMBASE, Healthstar, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS We identified 14 original articles with a total of 19 patients receiving ECT for RSE. Of the 19 patients, 15 were adult, and 4 were pediatric. All studies were retrospective in nature. Seizure reduction/control with the application of ECT occurred in 11 of the 19 patients (57.9%), with 4 (21.0%) and 7 (36.8%) displaying partial and complete responses respectively. Seizures control lasted for variable duration, with the most commonly quoted duration ranging from 2 weeks to 3 months. Data on patient functional outcome was available in 13 patients, with 10 patients falling into the categories of dead or severely disabled. All studies were an Oxford level 4, GRADE D level of evidence. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest an improvement in seizure control with ECT application for RSE. Routine use of ECT cannot be recommended at this time. Further prospective study of this therapy is required in order to determine its efficacy in this setting.

The Cerebrovascular Response to Ketamine: A Systematic Review of the Animal and Human Literature.

Background: The aim of the study was to perform a systematic review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of ketamine in both animal and human subjects. Materials and Methods: We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2014. Two reviewers independently identified all manuscripts pertaining to the administration of ketamine in both human and animal subjects in which the impact on CBF/cerebral vasculature was recorded by means of functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, xenon computed tomography, transcranial Doppler velocities, arteriovenous difference in N2O method of CBF measurement, cerebral digital subtraction angiography, or any other objective means of CBF determination. Results: We identified 38 animal studies with various animal models studied. Overall there was a trend to a direct vasodilatory effect of ketamine on the cerebral vasculature, with a trend in most studies to an increase or regional CBF (rCBF) or global CBF. Twenty human studies were identified. The majority displayed an increase in rCBF and global CBF on imaging in patients without neurological illness. Conclusions: Animal models indicate an increase in global CBF and rCBF with ketamine administration, with a trend to vasodilation of medium-sized intracranial vessels through a calcium-dependent mechanism. Human studies display an Oxford 2b, Grading of Recommendation Assessment Development and Education C, level of evidence to support a trend to increased global CBF and rCBF with ketamine administration in both healthy volunteers and elective surgical patients without neurological illness.

Lidocaine for status epilepticus in adults

INTRODUCTION Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. METHODS All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Overall, 13 studies were identified, with 11 manuscripts and 2 meeting abstracts. Seventy-six adult patients were treated for 82 episodes of SE/RSE. Patients had varying numbers of anti-epileptic drugs (AEDs), 1-12, on board prior to lidocaine therapy. During 69 of the 82 (84.1%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some utilizing bolus dosing alone; others utilizing a combination of bolus and infusion therapy. Overall, 70.7% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 64.1% and 6.1% respectively. Patient outcomes were sparingly reported. CONCLUSIONS There currently exists level 4, GRADE C evidence to support the consideration of lidocaine for SE and RSE in the adult population. Thus there is currently weak evidence to support the use of lidocaine in this context. Further prospective studies of lidocaine administration in this setting are warranted.