Comparison of Anesthetic Agents Dexmedetomidine and Midazolam During Mechanical Thrombectomy.

OBJECTIVES: The ideal anesthetic for mechanical thrombectomy (MT) is a subject of debate. Recent studies have supported the use of monitored anesthesia care (MAC), but few have attempted to compare MAC neuroanesthetics. Our study directly compares midazolam and dexmedetomidine (DEX) on blood pressure control during thrombectomy and functional outcomes at discharge. MATERIALS AND METHODS: We performed a retrospective review of an MT database, which consisted of 612 patients admitted between 2010-2019 to our tertiary stroke center. 193 patients who received either midazolam or DEX for MAC induction were identified. Primary and secondary outcomes were >20% maximum decrease in mean arterial pressure during MT and functional independence respectively. RESULTS: 146 patients were administered midazolam, while 47 were administered DEX. Decrease in blood pressure (BP) during MT was associated with lower rates of functional independence at last follow-up (p=0.034). When compared to midazolam, DEX had significantly higher rates of intraprocedural decrease in MAP at the following cut-offs: >20% (p<0.001), >30% (p=0.001), and >40% (p=0.006). On multivariate analysis, DEX was an independent predictor of >20% MAP decrease (OR 7.042, p<0.001). At time of discharge, NIHSS scores and functional independence (mRS 0-2) were statistically similar between DEX and midazolam. Functional independence at last known follow-up was statistically similar between DEX and midazolam (p = 0.643). CONCLUSIONS: Use of DEX during MT appears to be associated with increased blood pressure volatility when compared to midazolam. Further investigation is needed to determine the impact of MAC agents on functional independence.

Observational study of the effect of ketamine infusions on sedation depth, inflammation, and clinical outcomes in mechanically ventilated patients with SARS-CoV-2.

Severely ill patients with COVID-19 are challenging to sedate and often require high-dose sedation and analgesic regimens. Ketamine can be an effective adjunct to facilitate sedation of critically ill patients but its effects on sedation level and inflammation in COVID-19 patients have not been studied. This retrospective, observational cohort study evaluated the effect of ketamine infusions on inflammatory biomarkers and clinical outcomes in mechanically ventilated patients with SARS-CoV-2 infection. A total of 186 patients were identified (47 received ketamine, 139 did not). Patients who received ketamine were significantly younger than those who did not (mean (standard deviation) 59.2 (14.2) years versus 66.3 (14.4) years; P = 0.004), but there was no statistically significant difference in body mass index (P = 0.25) or sex distribution (P = 0.91) between groups. Mechanically ventilated patients who received ketamine infusions had a statistically significant reduction in Richmond Agitation-Sedation Scale score (-3.0 versus -2.0, P < 0.001). Regarding inflammatory biomarkers, ketamine was associated with a reduction in ferritin (P = 0.02) and lactate (P = 0.01), but no such association was observed for C-reactive protein (P = 0.27), lactate dehydrogenase (P = 0.64) or interleukin-6 (P = 0.87). No significant association was observed between ketamine administration and mortality (odds ratio 0.971; 95% confidence interval 0.501 to 1.882; P = 0.93). Ketamine infusion was associated with improved sedation depth in mechanically ventilated COVID-19 patients and provided a modest anti-inflammatory benefit but did not confer benefit with respect to mortality or intensive care unit length of stay.

Clinical Outcomes After Ultra-Early Cranioplasty Using Craniectomy Contour Classification as a Patient Selection Criterion.

BACKGROUND: Although not a technically difficult operation, cranioplasty is associated with high rates of complications. The optimal timing of cranioplasty to mitigate complications remains the subject of debate. OBJECTIVE: To report outcomes between patients undergoing cranioplasty at ultra-early (0-6 weeks), intermediate (6 weeks to 6 months), and late (>6 months) time frames. We report a novel craniectomy contour classification (CCC) as a radiographic parameter to assess readiness for cranioplasty. METHODS: A single-institution retrospective analysis of patients undergoing cranioplasty was performed. Patients were stratified into ultra-early (within 6 weeks of index craniectomy), intermediate (6 weeks to 6 months), and late (>6 months) cranioplasty cohorts. We have devised CCC scores, A, B, and C, based on radiographic criteria, where A represents those with a sunken brain/flap, B with a normal parenchymal contour, and C with "full" parenchyma. RESULTS: A total of 119 patients were included. There was no significant difference in postcranioplasty complications, including return to operating room ( P = .212), seizures ( P = .556), infection ( P = .140), need for shunting ( P = .204), and deep venous thrombosis ( P = .066), between the cohorts. Univariate logistic regression revealed that ultra-early cranioplasty was significantly associated with higher rate of functional independence at >6 months (odds ratio 4.32, 95% CI 1.39-15.13, P = .015) although this did not persist when adjusting for patient selection features (odds ratio 2.90, 95% CI 0.53-19.03, P = .234). CONCLUSION: In appropriately selected patients, ultra-early cranioplasty is not associated with increased rate of postoperative complications and is a viable option. The CCC may help guide decision-making on timing of cranioplasty.

Neuregulin-1-human epidermal receptor-2 signaling is a central regulator of pulmonary epithelial permeability and acute lung injury.

The mechanisms behind the loss of epithelial barrier function leading to alveolar flooding in acute lung injury (ALI) are incompletely understood. We hypothesized that the tyrosine kinase receptor human epidermal growth factor receptor-2 (HER2) would be activated in an inflammatory setting and participate in ALI. Interleukin-1ß (IL-1ß) exposure resulted in HER2 activation in human epithelial cells and markedly increased conductance across a monolayer of airway epithelial cells. Upon HER2 blockade, conductance changes were significantly decreased. Mechanistic studies revealed that HER2 trans-activation by IL-1ß required a disintegrin and metalloprotease 17 (ADAM17)-dependent shedding of the ligand neuregulin-1 (NRG-1). In murine models of ALI, NRG-1-HER2 signaling was activated, and ADAM17 blockade resulted in decreased NRG-1 shedding, HER2 activation, and lung injury in vivo. Finally, NRG-1 was detectable and elevated in pulmonary edema fluid from patients with ALI. These results suggest that the ADAM17-NRG-1-HER2 axis modulates the alveolar epithelial barrier and contributes to the pathophysiology of ALI.

High Incidence of Burst Suppression during Propofol Sedation for Outpatient Colonoscopy: Lessons Learned from Neuromonitoring.

BACKGROUND: Although anesthesia providers may plan for moderate sedation, the depth of sedation is rarely quantified. Using processed electroencephalography (EEG) to assess the depth of sedation, this study investigates the incidence of general anesthesia with variable burst suppression in patients receiving propofol for outpatient colonoscopy. The lessons learned from neuromonitoring can then be used to guide institutional best sedation practice. METHODS: This was a prospective observational study of 119 outpatients undergoing colonoscopy at Thomas Jefferson University Hospital (TJUH). Propofol was administered by CRNAs under anesthesiologists' supervision. The Patient State Index (PSi™) generated by the Masimo SedLine® Brain Root Function monitor (Masimo Corp., Irvine, CA) was used to assess the depth of sedation. PSi data correlating to general anesthesia with variable burst suppression were confirmed by neuroelectrophysiologists' interpretation of unprocessed EEG. RESULTS: PSi values of <50 consistent with general anesthesia were attained in 118/119 (99.1%) patients. Of these patients, 33 (27.7%) attained PSi values <25 consistent with variable burst suppression. The 118 patients that reached PSi <50 spent a significantly greater percentage (53.1% vs. 42%) of their case at PSi levels <50 compared to PSi levels >50 (p=0.001). Mean total propofol dose was significantly correlated to patient PSi during periods of PSi <25 (R=0.406, p=0.021). CONCLUSION: Although providers planned for moderate to deep sedation, processed EEG showed patients were under general anesthesia, often with burst suppression. Anesthesiologists and endoscopists may utilize processed EEG to recognize their institutional practice patterns of procedural sedation with propofol and improve upon it.

Challenges of pain management in neurologically injured patients: systematic review protocol of analgesia and sedation strategies for early recovery from neurointensive care.

BACKGROUND: A recent paradigm shift within the intensive care discipline has led to implementation of protocols to drive early recovery from the intensive care unit (ICU). These protocols belong to a large knowledge, translation and quality improvement initiative lead by the Society of Critical Care Medicine, aiming to "liberate" patients from the ICU. They "bundle" evidence-based elements shown to lower ICU stay and mortality and optimize pain management. The bundled elements focus on Assessing, preventing and managing pain; Both spontaneous awakening trials and spontaneous breathing trials; Choice of analgesia and sedation; assessment, prevention, and management of Delirium; Early mobility and exercise; and Family engagement and empowerment (ABCDEF). It is evident that analgesia and sedation protocols either directly relate to or influence most of the bundle elements. A paucity of literature exists for neurologically injured patients, who create unique challenges to bundle implementation and often have limited external validity in existent studies. We will systematically search the literature, present the unique challenges of neurointensive care patients, conduct a stratified analysis of subgroups of interest, and disseminate the evidence of analgesia and sedation protocols in the neurointensive care unit (NICU). We hope the relevant stakeholders can adapt this information through knowledge translation-to make formal recommendations in clinical practice guidelines or a position statement. METHODS/DESIGN: The authors will search MEDLINE (PubMed), EMBASE, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate, and a Cohen's Kappa coefficient of agreement will be reported. Provided the data retrieved from studies is suitable, results will be combined statistically using meta-analysis. We aim to evaluate the impact of ABCDEF bundle components on multiple endpoints of NICU recovery. Our primary outcomes will be time to successful discontinuation of mechanical ventilation and time to early mobility. The authors will guide the methodological design of the study using the PRISMA-statement and the checklist compliance will be available. DISCUSSION: Using the evidence from this systematic review, we anticipate disseminating knowledge of analgesia and sedation protocols in the NICU. The results of this systematic review are imperative to close the knowledge gap in a patient population that is often excluded from studies, and to add to the body of literature aiming to enhance early recovery from the NICU and mitigate iatrogenic harm. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017078909.

Chronic Skull Base Erosion from Temporomandibular Joint Disease Causes Generalized Seizure and Profound Lactic Acidosis.

This report displays a rare presentation of lactic acidosis in the setting of status epilepticus (SE). The differential diagnosis of lactic acidosis is broad and typically originates from states of shock; however, this report highlights an alternative and rare etiology, SE, due to chronic skull base erosion from temporomandibular joint (TMJ) disease. Lactic acidosis is defined by a pH below 7.35 in the setting of lactate values greater than 5 mmol/L. Two broad classifications of lactic acidosis exist: a type A lactic acidosis which stems from global or localized tissue hypoxia or a type B lactic acidosis which occurs once mitochondrial oxidative capacity is unable to match glucose metabolism. SE is an example of a type A lactic acidosis in which oxygen delivery is unable to meet increased cellular energy requirements. This report is consistent with a prior case series that consists of five patients experiencing generalized tonic-clonic (GTC) seizures and lactic acidosis. These patients presented with a pH range of 6.8-7.41 and lactate range of 3.8-22.4 mmol/L. Although severe lactic acidosis following GTC has been described, this is the first report in the literature of chronic skull base erosion from TMJ disease causing SE.

Lung fluid immunoglobulin from HIV-infected subjects has impaired opsonic function against pneumococci.

BACKGROUND: The incidence of pneumococcal pneumonia is greatly increased among human immunodeficiency virus (HIV)-infected subjects, compared with among non-HIV-infected subjects. Lung fluid levels of immunoglobulin G (IgG) specific for pneumococcal capsular polysaccharide are not reduced in HIV-infected subjects; therefore, we examined immunoglobulin subtypes and compared lung fluid IgG opsonic function in HIV-infected subjects with that in healthy subjects. METHODS: Bronchoalveolar lavage (BAL) fluid and serum samples were collected from 23 HIV-infected and 26 uninfected subjects. None of the subjects were receiving highly active antiretroviral therapy, and none had received pneumococcal vaccination. Pneumococcal capsule-specific IgG levels in serum and BAL fluid were measured by enzyme-linked immunosorbent assay, and IgG was concentrated from 40 mL of BAL fluid. Opsonization and opsonophagocytosis of pneumococci with serum, BAL fluid, and BAL IgG were compared between HIV-infected subjects and healthy subjects. RESULTS: The effect of type 1 pneumococcal capsular polysaccharide-specific IgG in opsonizing of pneumococci was significantly less using both serum and BAL IgG from HIV-infected subjects, compared with serum and BAL IgG from healthy subjects (mean level, 8.9 fluorescence units [95% confidence interval, 8.1-9.7 fluorescence units] vs. 12.1 fluorescence units [95% confidence interval, 9.7-15.2 fluorescence units]; P=.002 for lung BAL IgG). The opsonophagocytosis of pneumococci observed using BAL IgG from HIV-infected subjects was significantly less than that observed using BAL IgG from healthy subjects (37 fluorescence units per ng of IgG [95% confidence interval, 25-53 fluorescence units per ng of IgG] vs. 127 fluorescence units per ng of IgG [95% confidence interval, 109-145 fluorescence units per ng of IgG]; P<.001). CONCLUSION: HIV infection is associated with decreased antipneumococcal opsonic function in BAL fluid and serum.

Perioperative Management of Adult Patients With External Ventricular and Lumbar Drains: Guidelines From the Society for Neuroscience in Anesthesiology and Critical Care.

External ventricular drains and lumbar drains are commonly used to divert cerebrospinal fluid and to measure cerebrospinal fluid pressure. Although commonly encountered in the perioperative setting and critical for the care of neurosurgical patients, there are no guidelines regarding their management in the perioperative period. To address this gap in the literature, The Society for Neuroscience in Anesthesiology & Critical Care tasked an expert group to generate evidence-based guidelines. The document generated targets clinicians involved in perioperative care of patients with indwelling external ventricular and lumbar drains.

Efficiency of spinal anesthesia versus general anesthesia for lumbar spinal surgery: a retrospective analysis of 544 patients.

BACKGROUND: Previous studies have shown varying results in selected outcomes when directly comparing spinal anesthesia to general in lumbar surgery. Some studies have shown reduced surgical time, postoperative pain, time in the postanesthesia care unit (PACU), incidence of urinary retention, postoperative nausea, and more favorable cost-effectiveness with spinal anesthesia. Despite these results, the current literature has also shown contradictory results in between-group comparisons. MATERIALS AND METHODS: A retrospective analysis was performed by querying the electronic medical record database for surgeries performed by a single surgeon between 2007 and 2011 using procedural codes 63030 for diskectomy and 63047 for laminectomy: 544 lumbar laminectomy and diskectomy surgeries were identified, with 183 undergoing general anesthesia and 361 undergoing spinal anesthesia (SA). Linear and multivariate regression analyses were performed to identify differences in blood loss, operative time, time from entering the operating room (OR) until incision, time from bandage placement to exiting the OR, total anesthesia time, PACU time, and total hospital stay. Secondary outcomes of interest included incidence of postoperative spinal hematoma and death, incidence of paraparesis, plegia, post-dural puncture headache, and paresthesia, among the SA patients. RESULTS: SA was associated with significantly lower operative time, blood loss, total anesthesia time, time from entering the OR until incision, time from bandage placement until exiting the OR, and total duration of hospital stay, but a longer stay in the PACU. The SA group experienced one spinal hematoma, which was evacuated without any long-term neurological deficits, and neither group experienced a death. The SA group had no episodes of paraparesis or plegia, post-dural puncture headaches, or episodes of persistent postoperative paresthesia or weakness. CONCLUSION: SA is effective for use in patients undergoing elective lumbar laminectomy and/or diskectomy spinal surgery, and was shown to be the more expedient anesthetic choice in the perioperative setting.

Molecular and cellular basis of hepatic fibrogenesis in experimental schistosomiasis mansoni infection

Morbidity in schistosomiasis mansoni occurs primaryly as a result of the complications of hepatic fibrosis. Yet, the pathogenesis of schistosomal hepatic fibrosis is poorly understood. The fact that hepatic egg granuloma is the hallmark of this infection suggests a potential role for granulomatous inflamation in hepatic fibrogenesis. Our studies in a murine schistosomiasis model indicate that hepatic granuloma cells secrete a variety of fibrogenic cytokines that may initiate the scarring process. Among these cytokines, we identified a novel protein that we designated fibroplast stimulating factor-1 (FsF-1). FsF-1 is a lymphokine that can stimulate fibroplast growth and matrix synthesis. A notable feature of hepatic fibrosis in this model is that production of FsF-1 and other granuloma-derived fibrogenic cytokines is down-regulated in chronic infection, an event that may be under immunological control. The spontaneous reduction of FsF-1 secretion presumably accounts for reduced scar formation late in infection of mice. In the context of relevant clinical studies, our findings engender the hypothesis that Symmer's fibrosis may develop in a small suppopulation of individuals as a result of immunogenetically-determined dysregulation of fibrogenic cytokine production