Revisiting the Classification of Neuromuscular Blockade, Aligning Clinical Practice and Research No abstract available

Scholarly Activity of Anesthesiology Residents No abstract available

In Response No abstract available

The Age of Addiction: How Bad Habits Became Big Business No abstract available

Baseline Functional Connectivity Predicts Connectivity Changes Due to a Small Dose of Midazolam in Older Adults BACKGROUND: In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55–73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function. METHODS: We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults. RESULTS: Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration. CONCLUSIONS: Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults. Accepted for publication May 16, 2019. Funding: Institutional and/or departmental. The authors declare no conflicts of interest. Institutional review board: University of Alabama at Birmingham Institutional Review Board for Human. University of Alabama at Birmingham office of the Institutional review board, AB 470, 1720 2nd Ave South, Birmingham, AL 35294-0104. E-mail: irb@uab.edu. Clinical trial number and registry URL: NCT03089866, https://clinicaltrials.gov/ct2/show/NCT03089866. Reprints will not be available from the authors. Address correspondence to Michael A. Frölich, MD, MS, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, 619 19th St S, Office JT868C, Birmingham, AL 35249. Address e-mail to mfroelich@uabmc.edu. © 2019 International Anesthesia Research Society

Textbook of Neuroanesthesia and Neurocritical Care: Volume II – Neurocritical Care No abstract available

Gender Distribution in Professional Anesthesiology Activities No abstract available

Ropivacaine Activates Multiple Proapoptotic and Inflammatory Signaling Pathways That Might Subsume to Trigger Epidural-Related Maternal Fever BACKGROUND: Epidural-related maternal fever (ERMF) is an adverse effect of epidural analgesia during labor and is associated with perinatal and neonatal morbidity. Local anesthetics have been proposed to trigger ERMF via sterile inflammation. Ropivacaine is currently the most frequently used epidural anesthetic and considered least toxic. This study investigates molecular effects of ropivacaine on human umbilical vein endothelial cells (HUVECs) as model system for endothelial cells and human placental trophoblasts (TBs), compares the effects to the putative anti-inflammatory lidocaine and investigates the partially alleviating impact of the anti-inflammatory corticosteroid dexamethasone. METHODS: HUVECs and TBs were exposed to ropivacaine (35 μM–7 mM) or lidocaine (21 mM) with or without dexamethasone (1 μM). AnnexinV/propidium iodide staining and lactate dehydrogenase release were used to analyze apoptosis and cytotoxicity. Proinflammatory interleukins-6 (IL-6) and IL-8 as well as prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA), while activation of signaling pathways was detected by Western blotting. Oxidative stress was visualized by live cell imaging and quantification of antioxidant proteins, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, platelet endothelial cell adhesion molecule 1, cyclooxygenase 2, and mitochondrial deoxyribonucleic acid by real-time polymerase chain reaction. Dissipation of the mitochondrial membrane potential was assessed with cytofluorimetric analysis using the J-Aggregate (JC-1 staining [cytofluorimetric analysis using the J-Aggregate]). RESULTS: Ropivacaine exposure dose-dependently induced apoptosis and an increased release of IL-6, IL-8, and PGE2 from HUVECs and TBs. Furthermore, caspase-3, nuclear factor-κB, and p38 mitogen-activated protein kinase pathways were activated, while extracellular signal–regulated kinase 1/2 and protein kinase B (Akt) were dephosphorylated. Downregulation of antioxidative proteins induced oxidative stress and upregulation of ICAM1, VCAM1, and PECAM1 possibly facilitate leukocyte transmigration. Mitochondrial effects included increased release of the proinflammatory mitochondrial DNA damage–associated molecular patterns, but no significant dissipation of the mitochondrial membrane potential. Conversely, lidocaine exhibited repression of IL-6 and IL-8 release over all time points, and early downregulation of COX2 and cell adhesion molecules, which was followed by a late overshooting reaction. Dexamethasone reduced especially inflammatory effects, but as an inducer of mitophagy, had negative long-term effects on mitochondrial function. CONCLUSIONS: This study suggests that ropivacaine causes cellular injury and death in HUVECs and TBs via different signaling pathways. The detrimental effects induced by ropivacaine are only partially blunted by dexamethasone. This observation strengthens the importance of inflammation in ERMF. Accepted for publication July 23, 2019. Funding: Supported by a project grant of the Medical Scientific Fund of the Mayor of the City of Vienna, Austria (Peter Wohlrab, number AP17075). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org). Ethics approval for this study (Ethics Committee Nos. 1944/2014 for HUVECs and 084/2013 for TBs) was provided by the Medical University of Vienna Ethics Committee, Vienna, Austria. The experiments were performed after obtaining written, informed patient consent between January 2017 and July 2018. Reprints will not be available from the authors. Address correspondence to Stefan Boehme, MD, Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Address e-mail to stefan.boehme@meduniwien.ac.at. © 2019 International Anesthesia Research Society

Arterial Catheters for Early Detection and Treatment of Hypotension During Major Noncardiac Surgery: A Randomized Trial BACKGROUND: Continuous blood pressure monitoring may facilitate early detection and prompt treatment of hypotension. We tested the hypothesis that area under the curve (AUC) mean arterial pressure (MAP) <65 mm Hg is reduced by continuous invasive arterial pressure monitoring. METHODS: Adults having noncardiac surgery were randomly assigned to continuous invasive arterial pressure or intermittent oscillometric blood pressure monitoring. Arterial catheter pressures were recorded at 1-minute intervals; oscillometric pressures were typically recorded at 5-minute intervals. We estimated the arterial catheter effect on AUC-MAP <65 mm Hg using a multivariable proportional odds model adjusting for imbalanced baseline variables and duration of surgery. Pressures <65 mm Hg were categorized as 0, 1–17, 18–91, and >91 mm Hg × minutes of AUC-MAP <65 mm Hg (ie, no hypotension and 3 equally sized groups of increasing hypotension). RESULTS: One hundred fifty-two patients were randomly assigned to arterial catheter use and 154 to oscillometric monitoring. For various clinical reasons, 143 patients received an arterial catheter, while 163 were monitored oscillometrically. There were a median [Q1, Q3] of 246 [187, 308] pressure measurements in patients with arterial catheters versus 55 (46, 75) measurements in patients monitored oscillometrically. In the primary intent-to-treat analysis, catheter-based monitoring increased detection of AUC-MAP <65 mm Hg, with an estimated proportional odds ratio (ie, odds of being in a worse hypotension category) of 1.78 (95% confidence interval [CI], 1.18–2.70; P = .006). The result was robust over an as-treated analysis and for sensitivity analyses with thresholds of 60 and 70 mm Hg. CONCLUSIONS: Intraoperative blood pressure monitoring with arterial catheters detected nearly twice as much hypotension as oscillometric measurements. A. K. Khanna is currently affiliated with the Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina. Accepted for publication July 5, 2019. Funding: This study was supported by the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.anesthesia-analgesia.org). Clinical Trial Number: ClinicalTrials.gov NCT02453815. Reprints will not be available from the authors. Address correspondence to Daniel I. Sessler, MD, Department of Outcomes Research, Anesthesiology Institute, Cleveland, Clinic, 9500 Euclid Ave, P-77, Cleveland, OH 44195. Address e-mail to DS@OR.org. © 2019 International Anesthesia Research Society

Effect of Different Concentrations of Propofol Used as a Sole Anesthetic on Pupillary Diameter: A Randomized Trial BACKGROUND: Pupillometry monitoring under general anesthesia is based on the assumption that pupillary diameter variations reflect the adequacy of the provided analgesia to the intensity of the nociceptive surgical stimulus. The accurate interpretation of pupillometric data requires establishing clearly what the expected baseline unstimulated pupillary diameter at each specific level of hypnosis is. Opioids decrease pupillary diameter in a dose-dependent fashion. In contrast, the effects of hypnotic drugs on pupillary diameter are not well known. Our aim was to describe the potential relationship between propofol predicted effect-site concentrations (Cets) ranging from 1 to 3 µg/mL and pupillary diameter. METHODS: Patients were randomized to receive propofol by target-controlled infusion at a predicted Cet of 1, 2, or 3 µg/mL (groups P1, P2, and P3, respectively). Pupillary diameter measurements were performed after 10 minutes of steady-state propofol infusion at the randomized Cet. No stimulation was performed during the study. Heart rate and bispectral index (BIS) were continuously recorded. RESULTS: Forty patients were included: (13, 14, and 13 in groups P1, P2, and P3, respectively). Mean pupillary diameter was 5.7 mm (1 mm) in group P1, 4.8 mm (1.3 mm) in group P2, and 3.3 mm (0.8 mm) in group P3. Propofol had a dose-dependent effect on pupillary diameter (linear regression R2 = 0.45, P < .001). Pupillary diameter was positively correlated with the BIS (Spearman r = 0.75 [95% confidence interval (CI), 0.54 to −0.87] P < .001). CONCLUSIONS: From 1 to 3 µg/mL of predicted Cet, propofol has a dose-dependent effect on pupillary diameter. Within this concentrations range, there is a positive correlation between BIS and pupillary diameter. The subcortical effect of propofol on pupillary diameter is correlated to its effect on the cortex. Studies assessing pupillary diameter as a marker of the nociception–antinociception balance should be performed in patients with a standardized depth of hypnosis. Accepted for publication June 24, 2019. Funding: None. The authors declare no conflicts of interest. Registration was completed at clinicaltrials.gov (NCT02998424) before enrollment of the first patient. Reprints will not be available from the authors. Address correspondence to Nada Sabourdin, MD, Département d’anesthesiologie, Hôpital Armand Trousseau, 26 Avenue du Dr Arnold Netter, 75012 Paris, France. Address e-mail to nada.sabourdin@aphp.fr. © 2019 International Anesthesia Research Society