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.

Impella in Transport: Physiology, Mechanics, Complications, and Transport Considerations.

Cardiogenic shock (CS) represents a spectrum of hemodynamic deficits in which the cardiac output is insufficient to provide adequate tissue perfusion. The Impella (Abiomed Inc, Danvers, MA) device, a contemporary percutaneous ventricular support, is most often indicated for classic, deteriorating, and extremis Society for Coronary Angiography and Intervention stages of CS, which describe CS that is not responsive to optimal medical management and conventional treatment measures. Impella devices are an evolving field of mechanical support that is used with increasing frequency. Critical care transport medicine crews are required to transport patient support by the Impella device with increasing frequency. It is important that critical care transport medicine crews are familiar with the Impella device and are able to troubleshoot complications that may arise in the transport environment. This article reviews many aspects of the Impella device critical to the transport of this complex patient population.

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.

Intersection of prognosis and palliation in neurocritical care.

PURPOSE OF REVIEW: Difficult discussions regarding end-of-life care are common in neurocritical care. Because of a patient's neurological impairment, decisions regarding continuing or limiting aggressive care must often be made by patients' families in conjunction with medical providers. This review provides perspective on three major aspects of this circumstance: prognostication, family-physician discussions, and determination of death (specifically as it impacts on organ donation). RECENT FINDINGS: Numerous studies have now demonstrated that prediction models developed from populations of brain-injured patients may be misleading when applied to individual patients. Early care limitations may lead to the self-fulfilling prophecy of poor outcomes because of care decisions rather than disease course. A shared decision-making approach that emphasizes transmission of information and trust between families and medical providers is ethically appropriate in severely brain-injured patients and as part of the transition to end-of-life palliative care. Standard definitions of death by neurological criteria exist, although worldwide variation and the relationship to organ donation make this complex. SUMMARY: End-of-life care in patients with severe brain injuries is common and represents a complex intersection of prognostication, family communication, and decision-making. Skills to optimize this should be emphasized in neurocritical care providers.

Factors associated with adverse outcomes in patients with traumatic intracranial hemorrhage and Glasgow Coma Scale of 15.

Patients with mild traumatic brain injury (mTBI) with associated intracranial injury, or complicated mTBI, are at risk of deterioration. Clinical management differs within and between institutions. We conducted an exploratory analysis to determine which of these patients are unlikely to have an adverse outcome and may be future targets for less resource intensive care. This single center retrospective cohort study included patients presenting to the ED with blunt complicated mTBI between January 2001 and December 2010. Patients with a Glasgow coma score (GCS) of 15, an initial head CT with a traumatic abnormality, and a repeat head CT within 24h were eligible. We defined the composite adverse outcome as death within two weeks, neurosurgical procedure within two weeks, hospitalization >48h, and worsened second head CT. Classification and Regression Tree methodology was used to identify factors associated with adverse outcomes. Of 1011 patients with two head CTs performed in a 24-h period, 240 (24%) had complicated mTBI and GCS 15. Of these, 56 (23%) experienced the composite adverse outcome defined above. Age, headache, and subarachnoid hemorrhage, correctly classified 93% of patients with an adverse outcome. No instance of death or neurosurgical procedure was missed. Our analysis highlighted three factors associated with adverse outcomes in persons who have complicated mTBI but a GCS of 15. Absence of these risk factors suggests low risk of adverse outcomes, and may suggest that a patient is safe for discharge home. Additional research is required before utilizing these findings in clinical practice.

Recommendations for the Critical Care Management of Devastating Brain Injury: Prognostication, Psychosocial, and Ethical Management : A Position Statement for Healthcare Professionals from the Neurocritical Care Society.

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

The Code of Professional Conduct for the Neurocritical Care Society.

Part of the responsibility of a professional society is to establish the expectations for appropriate behavior for its members. Some codes are so essential to a society that the code itself becomes the central document defining the organization and its tenets, as we see with the Hippocratic Oath. In that tradition, we have revised the code of professional conduct for the Neurocritical Care Society into its current version, which emphasizes guidelines for personal behavior, relationships with fellow members, relationships with patients, and our interactions with society as a whole. This will be a living document and updated as the needs of our society change in time.Available online: http://www.neurocriticalcare.org/about-us/bylaws-procedures-and-code-professional-conduct (1) Code of professional conduct (this document) (2) Leadership code of conduct (3) Disciplinary policy.

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.

Eligibility of out-of-hospital cardiac arrest patients for extracorporeal cardiopulmonary resuscitation in the United States: A geographic information system model.

BACKGROUND: Recent evidence suggest that extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers. METHODS: We constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. The combined model was used to estimate the total number of ECPR candidates. RESULTS: There were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were deemed eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model. CONCLUSIONS: Less than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.

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.

NeuroEthics and End of Life Care.

The emergency department is where the patient and potential ethical challenges are first encountered. Patients with acute neurologic illness introduce a unique set of dilemmas related to the pressure for ultra-early prognosis in the wake of rapidly advancing treatments. Many with neurologic injury are unable to provide autonomous consent, further complicating the picture, potentially asking uncertain surrogates to make quick decisions that may result in significant disability. The emergency department physician must take these ethical quandaries into account to provide standard of care treatment.

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.

Repeat neuroimaging of mild traumatic brain-injured patients with acute traumatic intracranial hemorrhage: clinical outcomes and radiographic features.

OBJECTIVES: Emergency department (ED) management of mild traumatic brain injury (TBI) patients with any form of traumatic intracranial hemorrhage (ICH) is variable. Since 2000, our center's standard practice has been to obtain a repeat head computed tomography (CT) at least 6 hours after initial imaging. Patients are eligible for discharge if clinical and CT findings are stable. Whether this practice is safe is unknown. This study characterized clinical outcomes in mild TBI patients with acute traumatic ICH seen on initial ED neuroimaging. METHODS: This retrospective cohort study included patients presenting to the ED with blunt mild TBI with Glasgow Coma Scale (GCS) scores of 14 or 15 and stable vital signs, during the period from January 2001 to January 2010. Patients with any ICH on initial head CT and repeat head CT within 24 hours were eligible. Cases were excluded for initial GCS < 14, injury > 24 hours old, pregnancy, concomitant nonminor injuries, and coagulopathy. A single investigator abstracted data from records using a standardized case report form and data dictionary. Primary endpoints included death, neurosurgical procedures, and for discharged patients, return to the ED within 7 days. Differences in proportions were computed with 95% confidence intervals (CIs). RESULTS: Of 1,011 patients who presented to the ED and had two head CTs within 24 hours, 323 (32%) met inclusion criteria. The median time between CT scans was 6 hours (interquartile range = 5 to 7 hours). A total of 153 (47%) patients had subarachnoid hemorrhage, 132 (41%) patients had subdural hemorrhage, 11 (3%) patients had epidural hemorrhage, 78 (24%) patients had cerebral contusions, and 59 (18%) patients had intraparenchymal hemorrhage. Four of 323 (1.2%, 95% CI = 0.3% to 3.2%) patients died within 2 weeks of injury. Three of the patients who died had been admitted from the ED on their initial visits, and one had been discharged home. There were 206 patients (64%) discharged from the ED, 28 (13.6%) of whom returned to the ED within 1 week. Of the 92 who were hospitalized, three (0.9%, 95% CI = 0.2% to 2.7%) required neurosurgical intervention. CONCLUSION: Discharge after a repeat head CT and brief period of observation in the ED allowed early discharge of a cohort of mild TBI patients with traumatic ICH without delayed adverse outcomes. Whether this justifies the cost and radiation exposure involved with this pattern of practice requires further study.

Airway management and out-of-hospital cardiac arrest outcome in the CARES registry.

BACKGROUND: Optimal out of hospital cardiac arrest (OHCA) airway management strategies remain unclear. We compared OHCA outcomes between patients receiving endotracheal intubation (ETI) versus supraglottic airway (SGA), and between patients receiving [ETI or SGA] and those receiving no advanced airway. METHODS: We studied adult OHCA in the Cardiac Arrest Registry to Enhance Survival (CARES). Primary exposures were ETI, SGA, or no advanced prehospital airway placed. Primary outcomes were sustained ROSC, survival to hospital admission, survival to hospital discharge, and neurologically-intact survival to hospital discharge (cerebral performance category 1-2). Propensity scores characterized the probability of receiving ETI, SGA, or no advanced airway. We adjusted for Utstein confounders. Multivariable random effects regression accounted for clustering by EMS agency. We compared outcomes between (1) ETI vs. SGA, and (2) [no advanced airway] vs. [ETI or SGA]. RESULTS: Of 10,691 OHCA, 5591 received ETI, 3110 SGA, and 1929 had no advanced airway. Unadjusted neurologically-intact survival was: ETI 5.4%, SGA 5.2%, no advanced airway 18.6%. Compared with SGA, ETI achieved higher sustained ROSC (OR 1.35; 95%CI 1.19-1.54), survival to hospital admission (1.36; 1.19-1.55), hospital survival (1.41; 1.14-1.76) and hospital discharge with good neurologic outcome (1.44; 1.10-1.88). Compared with [ETI or SGA], patients receiving no advanced airway attained higher survival to hospital admission (1.31; 1.16-1.49), hospital survival (2.96; 2.50-3.51) and hospital discharge with good neurologic outcome (4.24; 3.46-5.20). CONCLUSION: In CARES, survival was higher among OHCA receiving ETI than those receiving SGA, and for patients who received no advanced airway than those receiving ETI or SGA.

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.