Neurosurgical patients admitted via the emergency department initiating comfort care measures: a prospective cohort analysis.

BACKGROUND: Given the serious nature of many neurosurgical pathologies, it is common for hospitalized patients to elect comfort care (CC) over aggressive treatment. Few studies have evaluated the incidence and risk factors of CC trends in patients admitted for neurosurgical emergencies. OBJECTIVES: To analyze all neurosurgical patients admitted to a tertiary care academic referral center via the emergency department (ED) to determine incidence and characteristics of those who initiated CC measures during their initial hospital admission. METHODS: We performed a prospective, cohort analysis of all consecutive adult patients admitted to the neurosurgical service via the ED between October 2018 and May 2019. The primary outcome was the initiation of CC measures during the patient's hospital admission. CC was defined as cessation of life-sustaining measures and a shift in focus to maintaining the comfort and dignity of the patient. RESULTS: Of the 428 patients admitted during the 7-month period, 29 (6.8%) initiated CC measures within 4.0 ± 4.0 days of admission. Patients who entered CC were significantly more likely to have a medical history of cerebrovascular disease (58.6% vs. 33.3%, p = 0.006), dementia (17.2% vs. 1.5%, p = 0.0004), or cancer with metastatic disease (24.1% vs. 7.0%, p = 0.001). Patients with a presenting pathology associated with cerebrovascular disease were significantly more likely to initiate CC (62.1% vs. 35.3, p = 0.04). Patients who underwent emergent surgery were significantly more likely to enter CC compared with those who had elective surgery (80.0% vs. 42.7%, p = 0.02). Only 10 of the 29 (34.5%) patients who initiated CC underwent a neurosurgical operation (p = 0.002). Twenty of the 29 (69.0%) patients died within 0.8 ± 0.8 days after the initiation of CC measures. CONCLUSION: CC measures were initiated in 6.8% of patients admitted to the neurosurgical service via the ED, with the majority of patients entering CC before an operation and presenting with a cerebrovascular pathology.

A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage.

OBJECTIVE: An inflammatory response occurs after aneurysmal subarachnoid hemorrhage (aSAH) and predicts poor outcomes. Glucocorticoids suppress inflammation and promote fluid retention. Dexamethasone is often administered after aSAH for postoperative cerebral edema and refractory headache. Our objective was to examine the impact of dexamethasone use on functional outcomes and delayed cerebral ischemia (DCI) after aSAH. METHODS: Patients with aSAH admitted between 2010 and 2015 were included; the data source was a single-center subarachnoid hemorrhage registry. The intervention of interest was a dexamethasone taper used <7 days from ictus. The primary outcome was poor discharge functional outcome, with a modified Rankin Scale score >3. Other outcomes included DCI and infection. A propensity score for use of dexamethasone was calculated using a logistic regression model that included potential predictors of dexamethasone use and outcome. The impact of dexamethasone on outcomes of interest was calculated and the propensity score was controlled for. RESULTS: A total of 440 patients with subarachnoid hemorrhage were admitted during the study period and 309 met eligibility criteria. Dexamethasone was administered in 101 patients (33%). A total of 127 patients (41%) had a discharge modified Rankin Scale score >3, 105 (34%) developed DCI, and 94 (30%) developed an infection. After propensity score analysis, dexamethasone use was associated with a significant reduction in poor functional outcomes (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.19-0.66) but showed no significant association with DCI (OR, 0.93; 95% CI, 0.53-1.64) or infection (OR, 0.60; 95% CI, 0.34-1.06). CONCLUSIONS: Dexamethasone use after aSAH was associated with a reduction in poor functional outcomes at discharge but not DCI, controlling for predictors of dexamethasone use.

Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

OBJECTIVE: To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. METHODS: This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) <50% or required NIV for clinical symptom management. RESULTS: In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. CONCLUSIONS: The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar.

A Randomized Trial of Central Venous Catheter Type and Thrombosis in Critically Ill Neurologic Patients.

BACKGROUND: Observational studies suggest peripherally inserted central venous catheters (PICCs) are associated with a high risk of catheter-related large vein thrombosis (CRLVT) in critically ill neurologic patients. We evaluated the difference in thrombosis risk between PICCs and centrally inserted central venous catheters (CICVCs). METHODS: We conducted a pragmatic, randomized controlled trial of critically ill adult neurologic patients admitted to neurological and trauma critical care units at two level I trauma centers. Patients were randomized to receive either a PICC or CICVC and undergo active surveillance for CRLVT or death within 15 days of catheter placement. RESULTS: In total, 39 subjects received a PICC and 41 received a CICVC between February 2012 and July 2015. The trial was stopped after enrollment of 80 subjects due to feasibility affected by slow enrollment and funding. In the primary intention-to-treat analysis, 17 (43.6 %) subjects that received a PICC compared to 9 (22.0 %) that received a CICVC experienced the composite of CRLVT or death, with a risk difference of 21.6 % (95 % CI 1.57-41.71 %). Adjusted common odds ratio of CRLVT/death was significantly higher among subjects randomized to receive a PICC (adjusted OR 3.08; 95 % CI 1.1-8.65). The higher adjusted odds ratio was driven by risk of CRLVT, which was higher in those randomized to PICC compared to CICVC (adjusted OR 4.66; 95 % CI 1.3-16.76) due to increased large vein thrombosis without a reduction in proximal deep venous thrombosis. CONCLUSIONS: Our trial demonstrates that critically ill neurologic patients who require a central venous catheter have significantly lower odds of ultrasound-diagnosed CRLVT with placement of a CICVC as compared to a PICC.

Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest.

OBJECTIVE: To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Pigs. INTERVENTIONS: Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. CONCLUSIONS: In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Adolescent knowledge and attitudes related to clinical trials.

BACKGROUND OR AIMS: Poor enrollment plagues most clinical trials. Furthermore, despite mandates to improve minority representation in clinical trial participation, little progress has been made. We investigated the knowledge and attitudes of adolescents related to clinical trials and made race/ethnicity comparisons in an attempt to identify a possible educational intervention target. METHODS: Students aged 13-18 years in southeast Michigan were offered participation through a class at one high school or two academic summer enrichment programs that drew from multiple high schools (73% response). Questionnaires previously validated in adults were administered. Non-Hispanic whites were compared with minorities using Wilcoxon rank-sum tests. RESULTS: Of the 82 respondents, the median age was 16 years (interquartile range: 15-17 years); 22 (28%) were white, 41 (51%) were African American, 11 (14%) were multiracial, 2 (2%) were American Indian or Alaska Native, 1 (1%) was Asian, 3 (4%) were Native Hawaiian or other Pacific Islander, and 2 respondents did not report a race (but did report Hispanic ethnicity). Nine (12%) were Hispanic. Only 27 (33%) had ever heard of a clinical trial. On a scale from 1 (most receptive) to 5 (least receptive) for learning more about a clinical trial for a relevant medical condition, the median score was 2 (interquartile range: 1-3) and for participating in a clinical trial for a relevant medical condition was 2 (interquartile range: 2-3). Overall knowledge was poor, with a median of 46% (interquartile range: 23%-62%) of knowledge answers correct. Knowledge was reduced (p = 0.0006) and attitudes were more negative (p = 0.05) in minorities than non-Hispanic whites, while minorities also endorsed more substantial barriers to trial participation (p = 0.0002). Distrust was similar between minority students and non-Hispanic whites (p = 0.15), and self-efficacy was greater in non-Hispanic whites (p = 0.05). CONCLUSION: Educational interventions directed toward adolescents that address knowledge, attitudes, and distrust in order to improve clinical trial awareness and receptivity overall are needed and may represent a tool to address disparities in minority enrollment in clinical trials.

Efficacy of antibiotic-impregnated external ventricular drains in reducing ventriculostomy-associated infections.

Use of an external ventricular drain (EVD) is essential for managing patients with hydrocephalus or intracranial hypertension. While this procedure is safe and efficacious, ventriculostomy-associated infections (VAI) continue to cause significant morbidity. In this study, we evaluated the efficacy of antibiotic-coated EVD (AC-EVD) in reducing the occurrence of VAI. Between July 2007 and July 2009, 203 patients underwent placement of an EVD. A total of 145 of these patients met the inclusion criteria, with 76 patients (52.4%) receiving AC-EVD and 69 patients (47.6%) receiving uncoated EVD. Ten patients (6.9%) developed VAI, of whom three were in the AC-EVD group and seven were in the uncoated EVD group (p=0.19). The mean duration between catheter insertion and positive cerebrospinal fluid culture was significantly greater in the AC-EVD group versus the uncoated EVD group (15±4days versus 4±2days, respectively; p=0.001). In the uncoated EVD group, 17 of 69 patients (24.6%) were dead at 3years versus 12 of 76 (15.8%) patients in the AC-EVD group (p=0.21). The overall VAI rate was 6.9% with a trend toward lower infection rates in the AC-EVD group compared to the uncoated EVD group (3.9% versus 10.1%, respectively; p>0.05).

Inter-observer agreement on the diagnosis of neurocardiogenic injury following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurocardiogenic injury results from increased sympathetic nervous system activation following acute brain injury. No diagnostic criteria for neurocardiogenic injury exist, and agreement has not been tested. We investigated the agreement by neurointensivists for the presence of neurocardiogenic injury on routine cardiac studies. METHODS: Six neurointensivists rated 100 consecutive cases of aneurysmal subarachnoid hemorrhage (aSAH) for the presence of neurocardiogenic injury. A fixed-panel design was employed for the agreement among the whole cohort, as well as stratified by modified Fisher Scale (mFs), Hunt and Hess grade, gender, and the presence of elevated cardiac enzymes. Overall percent agreement, paired agreement, and agreement above change (Fleiss' Kappa) were calculated. Overall percent agreement between groups was compared using Chi square tests. RESULTS: Six raters completed the survey for a total 600 responses. Overall percent agreement was 79.3 %, and agreement among cases at least one rater thought had neurocardiogenic injury was 66.5 % (paired agreement). Fleiss' Kappa was 0.66 (95 % CI, 0.1-0.71; p < 0.0001), indicating substantial agreement above chance. Similarly, on subgroup analysis, significant agreement beyond chance was seen in all groups (p < 0.001). Overall percent agreement was significantly better among mFs 3-4 compared to mFs ≤ 2 (81.3 vs. 63.6 %; p = 0.018) and among cases with positive cTI (96.9 vs. 70.1 %; p ≤ 0.001). CONCLUSIONS: Overall, we demonstrated substantial agreement for the presence of neurocardiogenic injury on early cardiac studies following aSAH. However, inter-observer variability increased when evaluating patients without the objective finding of elevated cTI and among those with lower clinical and radiographic grades.

Low pulsatility index on transcranial Doppler predicts symptomatic large-vessel vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Elevated mean cerebral blood flow velocity (mCBFV) on transcranial Doppler predicts vasospasm of the large intracranial arteries after aneurysmal subarachnoid hemorrhage (aSAH). The pulsatility index (PI) is a measure of distal vascular resistance, which may be low when there is compensatory distal vasodilatation following hypoperfusion caused by large-vessel vasospasm. OBJECTIVE: To study the predictive value of low PI for symptomatic large-vessel vasospasm (SLVVS) after aSAH. METHODS: Medical records of patients admitted with aSAH between January 2007 and April 2009 were reviewed. Transcranial color-coded duplex (TCCD) sonography was performed daily between days 2 and 14. Patients with unexplained acute neurological decline underwent catheter- or computed tomography-angiography. The lowest recorded PI and the highest mCBFV on TCCD were correlated to the occurrence of SLVVS, angiographic vasospasm, and delayed cerebral infraction in multivariate analysis by use of logistic regression. Functional outcome was assessed at first follow-up. RESULTS: Eighty-one patients met inclusion criteria. Mean lowest PI was 0.71 + 0.19. Median highest mCBFV was 135 cm/s (interquartile range 99-194 cm/s). SLVVS was seen in 21 of 81 (26%) patients, whereas 27 of 55 (49%) patients with repeat angiography had moderate or severe angiographic vasospasm. Following multivariate analysis, only the lowest PI was an independent predictor of SLVVS (P = .03, odds ratio 0.04, 95% confidence interval 0.001-0.54), whereas only the highest mCBFV was an independent predictor of angiographic vasospasm (P = .02, odds ratio 1.01, 95% confidence interval 1.002-1.02). SLVVS was independently associated with functional outcome at follow-up. CONCLUSION: Low PI on TCCD is an independent predictor of SLVVS after aSAH, whereas mCBFV is a better predictor of angiographic vasospasm.

The association between proton pump inhibitor use and outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: For many patients with aneurysmal subarachnoid hemorrhage (SAH), initiation of acid suppression therapy is concordant with guidelines and has become standard of care in neurological intensive care units. The aim of this study was to evaluate the association between type of acid suppression therapy and outcome following aneurysmal SAH. METHODS: Retrospective cohort study of consecutive aneurysmal SAH patients identified over a 5 year period. Of 297 patients identified, 148 met inclusion criteria for analysis. Multivariable logistic regression was performed to evaluate the independent association between type of acid suppression therapy (proton pump inhibitor (PPI) vs histamine 2 receptor antagonist (H2A)) and the outcomes of delayed neurological deficits (DNDs), delayed infarction and favorable functional outcome defined as a modified Rankin Scale ≤ 2. RESULTS: Forty-two patients were treated with a PPI and 106 with a H2A. Baseline characteristics were well-matched between groups with the exception of year of treatment and prophylactic antiepileptic medication. Patients placed on a PPI were less likely to have a favorable functional outcome than those on a H2A (45 vs 64%; P = 0.035). In adjusted analysis, no association was identified between PPI use and DNDs (OR 1.18 (95% confidence interval: 0.48-2.88)) or delayed infarction (OR 1.64 (0.64-4.16)); however, PPI use was associated with a lower odds of favorable functional outcome (OR 0.37 (0.16-0.85)). CONCLUSIONS: Type of acid suppression therapy was not associated with DNDs or delayed infarction following aneurysmal SAH. However, PPI use was associated with poorer functional outcome. Further study of acid suppression therapy and PPI use following SAH is warranted.

Real-time ultrasound-guided percutaneous dilatational tracheostomy: a feasibility study.

INTRODUCTION: Ultrasound (US) performed prior to percutaneous tracheostomy (PT) may be useful in avoiding injury to pretracheal vascular structures and in avoiding high placement of the tube. Bedside real-time US guidance with visualization of needle path is routinely utilized for other procedures such as central venous catheterization, and may enhance the safety and accuracy of PT without causing airway occlusion or hypercarbia. Our objective was to demonstrate that PT performed under real-time US guidance with visualization of needle path during tracheal puncture is feasible, including in patients with features that increase the technical difficulty of PT. METHODS: Mechanically ventilated patients with acute brain injury requiring tracheostomy underwent US guided PT. The orotracheal tube was withdrawn using direct laryngoscopy. The trachea was punctured under real-time US guidance (with visualization of the needle path) while using the acoustic shadows of the cricoid and the tracheal rings to identify the level of puncture. After guidewire passage the site and level of entry was verified using the bronchoscope, which was then withdrawn. Following dilatation and tube placement, placement in the airway was confirmed using auscultation and the "lung sliding" sign on US. Bronchoscopy and chest X-ray were then performed to identify any complications. RESULTS: Thirteen patients successfully underwent US guided PT. Three patients were morbidly obese, two were in cervical spine precautions and one had a previous tracheostomy. In all 13 patients bronchoscopy confirmed that guidewire entry was through the anterior wall and between the first and fifth tracheal rings. There was no case of tube misplacement, pneumothorax, posterior wall injury, significant bleeding or other complication during the procedure. CONCLUSIONS: Percutaneous tracheostomy performed under real-time ultrasound guidance is feasible and appears accurate and safe, including in patients with morbid obesity and cervical spine precautions. Larger studies are required to further define the safety and relative benefits of this technique. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000005023.

Lack of association between decompressive craniectomy and conversion to donor status.

There has been a recent resurgence in the use of decompressive craniectomy (DC) following severe brain injury. The aim of this study was to evaluate any association between DC and solid organ donation. We performed a retrospective, single-center, cohort study involving referrals to the local organ procurement organization, excluding those with anoxic brain injury. Of subjects referred, 64 (53%) were deemed eligible for donation and 29 (24%) converted to donor status. DC was performed with similar frequency in donors and non-donors (41% vs. 29%; p = 0.23). Patients with DC had similar odds of donation as those without DC (odds ratio 1.70, 95% CI 0.72-4.03), including after adjustment for age and Glasgow Coma Scale score (odds ratio 1.31, 95% CI 0.53-3.24). The most common reason eligible patients failed to convert to donor status was failure to pursue organ procurement because of the belief that the patient would not progress to neurological death or be a candidate for donation following cardiac death. Decompressive craniectomy was not uncommon among referrals to organ procurement organizations who ultimately become solid organ donors. Continued communication between the organ donation coordinators and the treating team has potential to decrease missed opportunities for organ donation.

CT angiography is cost-effective for confirmation of internal carotid artery occlusions.

BACKGROUND AND PURPOSE: While sensitive to internal carotid artery (ICA) occlusion, carotid ultrasound can produce false-positive results. CT angiography (CTA) has a high specificity for ICA occlusion and is safer and cheaper than catheter angiography, although less accurate. We determined the cost-effectiveness of CTA versus catheter angiography for confirming an ICA occlusion first suggested by carotid ultrasound. METHODS: A Markov decision-analytic model was constructed to estimate the cost-effectiveness of CTA compared with catheter angiography in a hypothetical cohort of symptomatic patients with a screening examination consistent with an ICA occlusion. Costs in 2004 dollars were estimated from Medicare reimbursement. Effectiveness was measured in quality-adjusted life years. RESULTS: The 2-year cost in the CTA scenario was $9,178, and for catheter angiography, $11,531, consistent with a $2,353 cost-savings per person for CTA. CTA resulted in accrual of 1.83 quality-adjusted life years while catheter angiography resulted in 1.82 quality-adjusted life years. CTA was less costly and marginally more effective than catheter angiography. In sensitivity analyses, when CTA sensitivity and specificity were allowed to vary across a plausible range, CTA remained cost-effective. CONCLUSIONS: After screening examination has suggested an ICA occlusion, confirmatory testing with CTA provides similar effectiveness to catheter angiography and is less costly.