Evaluating Target: Stroke guideline implementation on assessment and treatment times for patients with suspected stroke.

OBJECTIVES: Immediate ischemic stroke treatment improves outcomes and early alteplase administration is recommended for patients within window. We implemented stroke guidelines through a neuro-resuscitation initiative (NRI) and hypothesized that the intervention would decrease times to assessment and treatment. METHODS: We analyzed quality assurance data for EMS and triage patients arriving to our academic emergency department with suspected ischemic stroke to compare outcomes 12 months before to 6 months after initiative implementation at an academic certified primary stroke center in the U.S. Southwest. We examined four time-based outcomes: neurology at bedside, CT head without contrast, CT head angiogram, and alteplase administration. We summarized times with median and IQR values and compared pre and post times to event (in minutes) with Wilcoxon rank sum tests and Kaplan-Meier survival curves. RESULTS: We identified 203 EMS (83 pre, 120 post) and 66 (11 pre, 55 post) triage Stroke Alert patients. We observed decreased times for all outcomes in both the EMS and triage samples; however, only those in the EMS sample were significant. In the EMS sample, neurology at bedside median times decreased from 20 min to 2 min (p < 0.001); median minutes to CT head without contrast decreased from 16 min to 9 min (p < 0.001); median minutes to CT head angiogram decreased from 71 min to 21 min (p = 0.007); and, median minutes to alteplase decreased from 72 min to 49.5 min (p = 0.04). CONCLUSIONS: An academic ED led stroke care initiative streamlined evaluation and care with significantly shortened times to all four events.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Frailty Predicts 30-day mortality following major complications in neurosurgery patients: The risk analysis index has superior discrimination compared to modified frailty index-5 and increasing patient age.

Background: Postoperative complications after cranial or spine surgery are prevalent, and frailty can be a key contributing patient factor. Therefore, we evaluated frailty's impact on 30-day mortality. We compared the discrimination for risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for predicting 30-day mortality. Methods: Patients with major complications following neurosurgery procedures between 2012- 2020 in the ACS-NSQIP database were included. We employed receiver operating characteristic (ROC) curve and examined discrimination thresholds for RAI, mFI-5, and increasing patient age for 30-day mortality. Independent relationships were examined using multivariable analysis. Results: There were 19,096 patients included in the study and in the ROC analysis for 30-day mortality, RAI showed superior discriminant validity threshold C-statistic 0.655 (95% CI: 0.644-0.666), compared to mFI-5 C-statistic 0.570 (95% CI 0.559-0.581), and increasing patient age C-statistic 0.607 (95% CI 0.595-0.619). When the patient population was divided into subsets based on the procedures type (spinal, cranial or other), spine procedures had the highest discriminant validity threshold for RAI (Cstatistic 0.717). Furthermore, there was a frailty risk tier dose response relationship with 30-day mortalityy (p<0.001). Conclusion: When a major complication arises after neurosurgical procedures, frail patients have a higher likelihood of dying within 30 days than their non-frail counterparts. The RAI demonstrated a higher discriminant validity threshold than mFI-5 and increasing patient age, making it a more clinically relevant tool for identifying and stratifying patients by frailty risk tiers. These findings highlight the importance of initiatives geared toward optimizing frail patients, to mitigate long-term disability.

Postprocedural Complications of External Ventricular Drains: A Meta-Analysis Evaluating the Absolute Risk of Hemorrhages, Infections, and Revisions.

BACKGROUND: External ventricular drain (EVD) insertion is often a lifesaving procedure frequently used in neurosurgical emergencies. It is routinely done at the bedside in the neurocritical care unit or in the emergency room. However, there are infectious and noninfectious complications associated with this procedure. This meta-analysis sought to evaluate the absolute risk associated with EVD hemorrhages, infections, and revisions. The secondary purpose was to identify and characterize risk factors for EVD complications. METHODS: We searched the MEDLINE (PubMed) database for "external ventricular drain," "external ventricular drain" + "complications" or "Hemorrhage" or "Infection" or "Revision" irrespective of publication year. Estimates from individual studies were combined using a random effects model, and 95% confidence intervals (CIs) were calculated with maximum likelihood specification. To investigate heterogeneity, the t2 and I2 tests were utilized. To evaluate for publication bias, a funnel plot was developed. RESULTS: There were 260 total studies screened from our PubMed literature database search, with 176 studies selected for full-text review, and all of these 176 studies were included in the meta-analysis as they met the inclusion criteria. A total of 132,128 EVD insertions were reported, with a total of 130,609 participants having at least one EVD inserted. The pooled absolute risk (risk difference) and percentage of the total variability due to true heterogeneity (I2) for hemorrhagic complication was 1236/10,203 (risk difference: -0.63; 95% CI: -0.66 to -0.60; I2: 97.8%), infectious complication was 7278/125,909 (risk difference: -0.65; 95% CI: -0.67 to -0.64; I2: 99.7%), and EVD revision was 674/4416 (risk difference: -0.58; 95% CI: -0.65 to -0.51; I2: 98.5%). On funnel plot analysis, we had a variety of symmetrical plots, and asymmetrical plots, suggesting no bias in larger studies, and the lack of positive effects/methodological quality in smaller studies. CONCLUSIONS: In conclusion, these findings provide valuable information regarding the safety of one of the most important and most common neurosurgical procedures, EVD insertion. Implementing best-practice standards is recommended in order to reduce EVD-related complications. There is a need for more in-depth research into the independent risk factors associated with these complications, as well as confirmation of these findings by well-structured prospective studies.

A comprehensive analysis of the triad of frailty, aging, and obesity in spine surgery: the risk analysis index predicted 30-day mortality with superior discrimination.

BACKGROUND CONTEXT: The United States has experienced substantial shifts in its population dynamics due to an aging population and increasing obesity rates. Nonetheless, there is limited data about the interplay between the triad of frailty, aging, and obesity. PURPOSE: To investigate discriminative thresholds and independent associations of the Risk Analysis Index (RAI), Modified Frailty Index-5 (mFI-5), and greater patient age. STUDY DESIGN: An observational retrospective cohort study. PATIENT SAMPLE: We analyzed 49,754 spine surgery patients from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. OUTCOME MEASURE: A total of 30-day postoperative mortality. METHODS: Using receiver operating characteristic (ROC) and multivariable (odds ratios [OR] and 95% confidence intervals [CI]) analyses, we compared the discriminative thresholds and independent associations of RAI, mFI-5, and greater patient age in elderly obese patients who underwent spine surgery. RESULTS: There were 49,754 spine surgery patients, with a median age of 71 years (IQR: 68-75), largely white (82.6%) and male (51.9%). The ROC analysis for 30-day postoperative mortality demonstrated superior discrimination for RAI (C-statistic 0.779, 95%CI 0.54-0.805) compared to mFI-5 (C-statistic 0.623, 95% CI 0.594-0.651) and greater patient age (C-statistic 0.627, 95% CI 0.598-0.656). Multivariable analyses revealed a dose-dependent association and a larger effect magnitude for RAI: frail patients OR: 19.52 (95% CI 18.29-20.82) and very frail patients OR: 65.81 (95% CI 62.32-69.50). A similar trend was observed in the interaction evaluating RAI-age-obesity (p<.001). CONCLUSION: Our study highlights a strong association between frailty and 30-day postoperative mortality in elderly obese spine patients, revealing a dose-dependent relationship. The RAI has superior discrimination than the mFI-5 and greater patient age in predicting 30-day postoperative mortality after spine surgery. Using the RAI in preoperative assessments may improve outcomes and help healthcare providers effectively communicate accurate surgical risks and potential benefits, set realistic recovery expectations, and enhances patient satisfaction.

Clinical and demographic factors associated with antipyretic use in gram-negative severe sepsis and septic shock.

BACKGROUND: Antipyretic therapy is commonly prescribed for patients with infection, but studies of its impact on clinical outcomes have yielded mixed results. No data exist to characterize the use of antipyretic medications in patients with severe sepsis or septic shock. OBJECTIVE: To identify clinical and demographic factors associated with antipyretic medication administration in severe sepsis and septic shock. METHODS: This single-center, retrospective, cohort study assessed febrile patients (temperature ≥ 38.3 °C) with gram-negative severe sepsis or septic shock at an 1111-bed academic medical center between January 2002 and February 2008. Patients were excluded if they had liver disease, acute brain injury, or allergy to acetaminophen. Generalized estimating equations were used to estimate the effect of clinical factors on treatment of patients with antipyretic medications. RESULTS: Although 76% of patients in this febrile cohort (n = 241) were prescribed an antipyretic agent, only 42% received antipyretic therapy; 95% of the doses were acetaminophen. Variables associated with antipyretic treatment were maximum body temperature (OR 2.11, 95% CI 1.53 to 2.89), time after sepsis diagnosis (OR 0.88, 95% CI 0.82 to 0.95), surgery during hospitalization (OR 0.49, 95% CI 0.31 to 0.80), death within 36 hours (OR 0.35, 95% CI 0.15 to 0.85), and mechanical ventilation (OR 0.58, 95% CI 0.34 to 0.98). Severity of illness factors, demographic factors, and patient treatment location did not predict who would receive antipyretic therapy. CONCLUSIONS: Most febrile episodes in patients with gram-negative severe sepsis or septic shock were not treated with antipyretic medications. Further studies are needed to demonstrate the effect of antipyretics on clinically relevant outcomes in severe sepsis and septic shock.

Decision-making for decompressive craniectomy in traumatic brain injury aided by multimodality monitoring: illustrative case.

BACKGROUND: Severe traumatic brain injury (TBI) requires individualized, physiology-based management to avoid secondary brain injury. Recent improvements in quantitative assessments of metabolism, oxygenation, and subtle examination changes may potentially allow for more targeted, rational approaches beyond simple intracranial pressure (ICP)-based management. The authors present a case in which multimodality monitoring assisted in decision-making for decompressive craniectomy. OBSERVATIONS: This patient sustained a severe TBI without mass lesion and was monitored with a multimodality approach. Although imaging did not seem grossly worrisome, ICP, pressure reactivity, brain tissue oxygenation, and pupillary response all began worsening, pushing toward decompressive craniectomy. All parameters normalized after decompression, and the patient had a satisfactory clinical outcome. LESSONS: Given recent conflicting randomized trials on the utility of decompressive craniectomy in severe TBI, precision, physiology-based approaches may offer an improved strategy to determine who is most likely to benefit from aggressive treatment. Trials are underway to test components of these strategies.

A systematic review of second line therapies in toxic seizures.

BACKGROUND: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. METHODS: We searched PubMed, Embase, PsychINFO, Cochrane Library, Web of Science, Google Scholar, and International Pharmaceutical Abstracts from inception through August of 2018, following PRISMA Guideline. The MESH terms focused on identifying treatments for seizures induced by drugs or other potentially toxic substances. We excluded the articles if they involved animals, had seizures resulting from alcohol withdrawal, were case reports, or not peer-reviewed. Our primary outcome was seizure termination and/or suppression by the second-line agent as agreed upon by two authors. We used descriptive statistics for analysis. RESULTS: We identified six case series that met inclusion and exclusion criteria. Included case series contained nine to 235 patient cases each. The most common xenobiotic exposures were bupropion, isoniazid, and anti-psychotics. The description of seizure type and duration was diverse. First-line treatments were primarily benzodiazepines. Secondary treatments included propofol, barbiturates, phenytoin, valproic acid, and levetiracetam. Patient outcomes differed, attributable to any of the following: mixed toxic substances, drug-drug interactions, inability to control seizures, or toxicity of the anti-epileptic drugs (AED) themselves. Few cases specifically discussed the success of secondary treatment administration to suppress or terminate seizures. CONCLUSIONS: Available literature discussing second-line treatment for toxic seizures is of poor quality with high heterogeneity. Although the majority of articles used similar second-line agents, it is difficult to compare the efficacy of the regimens. Additional studies are necessary to identify the most efficacious second-line therapies in toxic seizures.

Spreading depolarization in acute brain injury inhibited by ketamine: a prospective, randomized, multiple crossover trial.

OBJECTIVERetrospective clinical data and case studies support a therapeutic effect of ketamine in suppression of spreading depolarization (SD) following brain injury. Preclinical data strongly support efficacy in terms of frequency of SD as well as recovery from electrocorticography (ECoG) depression. The authors present the results of the first prospective controlled clinical trial testing the role of ketamine used for clinical sedation on occurrence of SD.METHODSTen patients with severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) were recruited for this pilot trial. A standard ECoG strip was placed at the time of craniotomy, and the patients were then placed on an alternating every-6-hour schedule of ketamine or other sedation agent. The order of treatment was randomized. The ketamine dose was adjusted to clinical effect or maintained at a subanesthetic basal dose (0.1 mg/kg/hr) if no sedation was required. SD was scored using standard criteria, blinded to ketamine dosing. Occurrence of SD was compared with the hourly dose of ketamine to determine the effect of ketamine on SD occurrence.RESULTSSuccessful ECoG recordings were obtained in all 10 patients: 8 with SAH and 2 with TBI. There were a total of 1642 hours of observations with adequate ECoG: 833 hours off ketamine and 809 hours on ketamine. Analysis revealed a strong dose-dependent effect such that hours off ketamine or on doses of less than 1.15 mg/kg/hr were associated with an increased risk of SD compared with hours on doses of 1.15 mg/kg/hr or more (OR 13.838, 95% CI 1.99-1000). This odds ratio decreased with lower doses of 1.0 mg/kg/hr (OR 4.924, 95% CI 1.337-43.516), 0.85 mg/kg/hr (OR 3.323, 95% CI 1.139-16.074), and 0.70 mg/kg/hr (OR 2.725, 95% CI 1.068-9.898) to a threshold of no effect at 0.55 mg/kg/hr (OR 1.043, 95% CI 0.565-2.135). When all ketamine data were pooled (i.e., on ketamine at any dose vs off ketamine), a nonsignificant overall trend toward less SD during hours on ketamine (χ2 = 3.86, p = 0.42) was observed.CONCLUSIONSKetamine effectively inhibits SD over a wide range of doses commonly used for sedation, even in nonintubated patients. These data also provide the first prospective evidence that the occurrence of SD can be influenced by clinical intervention and does not simply represent an unavoidable epiphenomenon after injury. These data provide the basis for future studies assessing clinical improvement with SD-directed therapy.Clinical trial registration no.: NCT02501941 (clinicaltrials.gov).

Levetiracetam in toxic seizures.

BACKGROUND/OBJECTIVES: The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures. METHODS: We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV. RESULTS: Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy was 1.6 days (0-49). CONCLUSIONS: Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results.

Early antipyretic exposure does not increase mortality in patients with gram-negative severe sepsis: a retrospective cohort study.

Existing data suggest that antipyretic medications may have deleterious effects on immune function and may increase mortality in human infection. This study was designed to evaluate the impact of antipyretic therapy on 28-day in-hospital mortality when administered early in the course of gram-negative severe sepsis or septic shock. This study was a single-center retrospective cohort study at a 1,111-bed academic medical center of all febrile patients with gram-negative bacteremia hospitalized with severe sepsis or septic shock (n = 278) between Jan 2002 and Feb 2008. Although the raw mortality was lower in the group that received an early antipyretic medication (22 vs. 35 %, p = 0.01), patients in the early antipyretic group had higher mean arterial pressure (58.0 vs. 52.7, p = 0.01) and higher 24-h T (max) (39.3 vs. 39.0, p < 0.01). Early antipyretic therapy was not significantly associated with 28-day in-hospital mortality (adjusted OR 0.55, 0.29-1.03) in a multivariable logistic regression model controlling for APACHE-II score, hypotension, pneumonia, surgery during hospitalization, persistent fever, and in-hospital dialysis. In conclusion, early antipyretic therapy is not associated with increased mortality.

Psychogenic seizures: a focused clinical review for the emergency medicine practitioner.

Psychogenic seizures sometimes mimic neurogenic seizures and may occur concomitantly. Unlike neurogenic seizures, psychogenic seizures do not have abnormal electrical discharges on electroencephalogram, and their presence generally reflects an underlying psychiatric disorder. No single clinical observation can definitively distinguish psychogenic from neurogenic seizures. Evidence in support of the diagnosis includes asynchronous extremity movements, rapid turning of the head from side to side, forward pelvic thrusting, out-of-phase limb movements, presence of a light reflex, and geotropic eye movements. Video electroencephalogram monitoring is a particularly valuable method of distinguishing psychogenic from neurogenic seizures. When the diagnosis is suspected by history, physical examination, maneuvers, and laboratory tests, and after the proper stabilization steps have been taken, the emergency medicine practitioner should consult a neurologist and a psychiatrist to assist in the patient's further evaluation and management. Although the diagnosis of psychogenic seizures cannot always be secured in the emergency department, identifying patients with this condition is important because it can obviate unnecessary pharmacologic interventions and help patients obtain proper psychiatric care.