Fragility Index Meta-Analysis of Randomized Controlled Trials Shows Highly Robust Evidential Strength for Benefit of <3 Hour Intravenous Alteplase.

BACKGROUND: Cumulative fragility index (FI) analysis enables quantification of the evidential strength of intravenous alteplase's core indication-treatment of disabling acute ischemic stroke within 3 hours of onset. METHODS: Meta-analyses were performed (study level) or identified (individual participant level) for freedom-from-disability (modified Rankin Scale [mRS] score 0-1, primary efficacy), functional independence (mRS score 0-2, secondary efficacy), and mortality outcomes. Individual trial and cumulative FI analyses were serially conducted after each successive randomized controlled trial (RCT). FI scores were classified as follows: not robust (FI 0-4), somewhat robust (FI 5-12), robust (FI 13-33), and highly robust (FI >33). RESULTS: Nine randomized controlled trials were identified from 1995 to 2021 of within-3-hour intravenous alteplase for acute ischemic stroke. In study-level meta-analyses, alteplase increased freedom-from-disability outcome (mRS score 0-1), 31.0% versus 22.3%, relative risk, 1.39 (95% CI, 1.20-1.61); P<0.00001; increased functional independence (mRS score 0-2), 39.7% versus 31.2%, relative risk, 1.29 (95% CI, 1.14-1.45), P<0.000; and did not alter mortality, 24.1% versus 26.1%; P=0.23. Overall FIs for study-level meta-analyses were both highly robust at 42 and 40 for mRS score 0-1 and mRS score 0-2, respectively. Serial FI analyses showed robust evidential strength for intravenous alteplase superiority with publication of the 2 NINDS-tPA trials (National Institute of Neurological Disorders and Stroke-tissue-type plasminogen activator) in 1995, increased to highly robust in 2012, and remains highly robust in 2021. CONCLUSIONS: Within-3-hour intravenous alteplase for acute ischemic stroke is one of the most robustly proven therapies in medicine. The initial concurrent trials 25 years ago showed robust evidence for benefit and, after additional studies, advanced to highly robust.

The Present State of Neurointensivist Training in the United States: A Comparison to Other Critical Care Training Programs.

OBJECTIVE: This manuscript describes the state of neurocritical care fellowship training, compares its written standards to those of other critical care fellowship programs, and discusses how programmatic oversight by the United Council for Neurological Subspecialties should evolve to meet American College of Graduate Medical Education standards. This review is a work product of the Society of Critical Care Medicine Neuroscience section and was reviewed and approved by the Council of the Society of Critical Care Medicine. DATA SOURCES: We evaluated the published training criteria and requirements of American College of Graduate Medical Education Critical Care subspecialty fellowships programs of Internal Medicine, Surgery, and Anesthesia and compared them with the training criteria and required competencies for neurocritical care. STUDY SELECTION: We have reviewed the published training standards from American College of Graduate Medical Education as well as the United Council for Neurologic Subspecialties subspecialty training documents and clarified the definition and responsibilities of an intensivist with reference to the Leapfrog Group, the National Quality Forum, and the Joint Commission. DATA EXTRACTION: No data at present exist to test the concept of similarity across specialty fellowship critical care training programs. DATA SYNTHESIS: Neurocritical care training differs in its exposure to clinical entities that are directly associated to other critical care subspecialties. However, the core critical care knowledge, procedural skills, and competencies standards for neurocritical care appears to be similar with some important differences compared with American College of Graduate Medical Education critical care training programs. CONCLUSIONS: The United Council for Neurologic Subspecialties has developed a directed program development strategy to emulate American College of Graduate Medical Education standards with the goal to have standards that are similar or identical to American College of Graduate Medical Education standards.

The degree of bandemia in septic ED patients does not predict inpatient mortality.

BACKGROUND: A delay in diagnosis of sepsis and appropriate treatment increases subsequent mortality. An association with the degree of bandemia, or the presence of immature neutrophils in the white blood cell count, has not been explored in septic patients presenting to the emergency department (ED). We hypothesized that the presenting band levels would be higher in septic patients who die in hospital compared with survivors. METHODS: This study reviewed charts of ED patients presenting with sepsis to a single urban, academic, tertiary care ED with an annual census of 80,000 visits. Patients were included if they had bandemia assessed and were eligible for early goal-directed therapy. Reviewers blinded to the study purpose abstracted data using predetermined definitions. The band level was compared between patients who died and those who survived to discharge using the Mann-Whitney U test. Logistic regression was used to estimate the effect of bandemia levels on the odds of death. RESULTS: Ninety-six patients meeting inclusion criteria were enrolled; 2 were excluded with incomplete data. Mean age was 59 years, 53% were white, and 51% were male. Thirty-two patients (34%) died during admission. The median band levels in patients who died was 17% (range, 0%-67%); and in patients surviving to discharge, the median band level was 9% (range, 0%-77%) (difference in medians, 8%; CI(95), -27.04 to 11.04; P = .222). CONCLUSIONS: The band level on presentation was not found to be associated with inpatient mortality in ED patients with sepsis who are eligible for early goal-directed therapy.

Withdrawal of antithrombotic agents and its impact on ischemic stroke occurrence.

BACKGROUND AND PURPOSE: Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication. METHODS: Patient records from the population-based Greater Cincinnati/Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review. RESULTS: In 2005, 2197 cases of ischemic stroke among residents of the region were identified through hospital discharge records. Of the 2197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal, 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes after withdrawal, 71 (62.3%) were first-ever and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period. CONCLUSIONS: The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision-making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance.

Inadequate provision of postintubation anxiolysis and analgesia in the ED.

INTRODUCTION: Patients intubated in the emergency department (ED) often have extended ED stays. We hypothesize that ED intubated patients receive inadequate postintubation anxiolysis and analgesia after rapid sequence induction (RSI). METHODS: This was a retrospective cohort study of every adult intubated in a tertiary-care ED (July 2003-June 2004). Patients were included if they underwent RSI, remained in the ED for more than 30 minutes post intubation, and survived to admission. Presuming a mean patient weight of 70 kg, we defined adequacy of anxiolysis and analgesia on the provision postintubation of weight-based doses of lorazepam (0.77 mg/h) or midazolam (4.2 mg/h) and fentanyl (35 microg/h), referenced from pharmaceutical texts. Demographic data, time in ED, and dosage of each medication given were abstracted. The proportion, with 95% confidence intervals (CIs), of patients receiving inadequate anxiolysis and analgesia were computed. RESULTS: One hundred seventeen patients met the inclusion criteria. Mean time in the ED was 4.2 hours (SD +/- 3.1 hours). Thirty-nine patients received no anxiolytic (33%, CI 25%-43%), and 62 received no analgesic (53%, CI 44%-62%). Twenty-three patients received neither anxiolytic nor analgesic (20%, CI 13%-28%). Of 70 patients given postintubation vecuronium, 67 received either no or inadequate anxiolysis or analgesia (96%, CI 87%-99%). Overall, 87 of 117 patients received no or inadequate anxiolysis (74%, CI 65%-82%); and 88 of 117 received no or inadequate analgesia (75%, CI 66%-83%). CONCLUSION: Patients undergoing RSI in the ED frequently receive inadequate postintubation anxiolysis and analgesia.

The incidence of seizures in patients undergoing therapeutic hypothermia after resuscitation from cardiac arrest.

STUDY OBJECTIVE: Non-convulsive seizures/status epilepticus occur in approximately 20% of comatose, non-cardiac arrest intensive care unit (ICU) patients, and are associated with increased mortality. The prevalence and clinical significance of seizures in comatose survivors of cardiac arrest undergoing therapeutic hypothermia is not well described. METHODS: At this urban level I trauma center, every patient undergoing therapeutic hypothermia is monitored with continuous video encephalography (cvEEG). We abstracted medical records for all cardiac arrest patients treated with therapeutic hypothermia during 2010. Clinical data were extracted in duplicate. cvEEGs were independently reviewed for seizures by two board-certified epileptologists. RESULTS: There were 33 patients treated with therapeutic hypothermia after cardiac arrest in 2010 who met inclusion criteria for this study. Median age was 58 (range 28-86 years), 63% were white, 55% were male, and 9% had a history of seizures or epilepsy. During cooling, seizures occurred in 5/33 patients (15%, 95%CI 6%-33%). 11/33 patients (33%, 95% CI 19%-52%) had seizures at some time during hospitalization. 13/33 (39%) survived to discharge and of these, 7/13 (54%) survived to 30 days. 9/11 patients with seizures died during hospitalization, compared with 11/22 patients without seizures (82% vs. 50%; difference 32%, CI 951%-63%). No patient with seizures was alive at 30 days. CONCLUSIONS: Seizures are common in comatose patients treated with therapeutic hypothermia after cardiac arrest. All patients with seizures were deceased within 30 days of discharge. Routine use of EEG monitoring could assist in early detection of seizures in this patient population, providing an opportunity for intervention to potentially improve outcomes.

Neurogenic stunned myocardium associated with acute spinal cord infarction: a case report.

Introduction. Neurogenic stunned myocardium (NSM) is a reversible cardiomyopathy resulting in transient left ventricular apical ballooning presumed to result from catecholamine surge occurring under physiologic stress. Acute spinal cord ischemia is a rare ischemic vascular lesion. We report a case of neurogenic stunned myocardium occurring in the setting of acute spinal cord infarction. Methods. Singe case report was used. Results. We present the case of a 63-year-old female with a history of prior lacunar stroke, hypertension, chronic back pain, and hypothyroidism who presented with a brief episode of diffuse abdominal and bilateral lower extremity pain which progressed within minutes to bilateral lower extremity flaccid paralysis. MRI of the spinal cord revealed central signal hyperintensity of T2-weighted imaging from conus to T8 region, concerning for acute spinal cord ischemia. Transthoracic echocardiogram was performed to determine if a cardiac embolic phenomenon may have precipitated this ischemic event and showed left ventricular apical hypokinesis and ballooning concerning for NSM. Conclusion. Neurogenic stunned myocardium is a reversible cardiomyopathy which has been described in patients with physiologic stress resulting in ventricular apical ballooning. Our case suggests that it is possible for neurogenic stunned myocardium to occur in the setting of acute spinal cord ischemia.

Cost-effectiveness of diagnostic strategies for evaluation of suspected subarachnoid hemorrhage in the emergency department.

OBJECTIVES: Diagnosing subarachnoid hemorrhage (SAH) in emergency department (ED) patients is challenging. Potential diagnostic strategies include computed tomography (CT) only, CT followed by lumbar puncture (CT/LP), CT followed by magnetic resonance imaging and angiography (CT/MRA), and CT followed by CT angiography (CT/CTA). The objective was to determine the relative cost-effectiveness of diagnostic strategies for SAH. METHODS: The authors created a decision model to evaluate the cost-effectiveness of SAH diagnostic strategies in ED patients with suspected SAH. Clinical probabilities were obtained from published data; sensitivity analyses were conducted across plausible ranges. RESULTS: In the base-case scenario, CT-only had a cost of $10,339 and effectiveness of 20.25 quality-adjusted life-years (QALYs), and CT/LP had a cost of $15,120 and effectiveness of 20.366 QALYs. Among the alternative strategies, CT/CTA had a cost of $12,840 and effectiveness of 20.24 QALYs, and CT/MRA had a cost of $16,207 and effectiveness of 20.27 QALYs. In sensitivity analyses, probability of severe disability from SAH, sensitivity of noncontrast CT, and specificity of LP and MRA were key drivers of the model, and CT-only and CT/LP were preferable. CONCLUSIONS: In the base-case scenario, CT-only was preferable to the CT/CTA and CT/MRA strategies. When considering sensitivity analyses and the current medicolegal environment, there are no overwhelming differences between the cost-effectiveness of CT/LP and the alternative strategies to suggest that clinicians should abandon the standard CT/LP approach.