This issue is the 2nd annual special issue featuring research from a pioneering institution in our field. The cover is a compilation of images presented in Washington University research published in this issue.

Washington University and the Why of Anesthesiology 1145

James C. Eisenach 

Memories and Dreams: Building an Academic Department at Washington University in St. Louis 1147

Alex S. Evers and William D. Owens 

Depth of Anesthesia: Perhaps the Patient Isn’t a Submarine 1149

Jamie W. Sleigh 

From Bedside to Bench and Back: Perfecting Lipid Emulsion Therapy for Local Anesthetic Toxicity 1151

Peter V. Killoran and Davide Cattano 

Perioperative Pharmacokinetics of Methadone in Adolescents 1153

Anshuman Sharma, Danielle Tallchief, Jane Blood, Thomas Kim, Amy London, and Evan D. Kharasch 

This investigation determined the pharmacokinetics of intravenous methadone in adolescents undergoing surgery. Methadone disposition was similar to that in healthy adults

A Gain-of-function Mutation in Adenylate Cyclase Confers Isoflurane Resistance in Caenorhabditis elegans  1162

Owais Saifee, Laura B. Metz, Michael L. Nonet, and C. Michael Crowder 

A gain-of-function mutation in an adenylate cyclase gene was discovered in the nematode Caenorhabditis elegans  that strongly reduces the potency of isoflurane. This mutation acts in neurons to regulate neurotransmitter release and isoflurane sensitivity

Perioperative Nerve Injury after Total Hip Arthroplasty: Regional Anesthesia Risk during a 20-year Cohort Study 1172

Adam K. Jacob, Carlos B. Mantilla, Hans P. Sviggum, Darrell R. Schroeder, Mark W. Pagnano, and James R. Hebl 

This cohort study determined the overall incidence of perioperative nerve injury after total hip arthroplasty to be 0.72. Use of neuraxial or peripheral regional anesthesia techniques did not increase the risk for perioperative nerve injury

First-line Therapy with Coagulation Factor Concentrates Combined with Point-of-Care Coagulation Testing Is Associated with Decreased Allogeneic Blood Transfusion in Cardiovascular Surgery: A Retrospective, Single-center Cohort Study 1179

Klaus Görlinger, Daniel Dirkmann, Alexander A. Hanke, Markus Kamler, Eva Kottenberg, Matthias Thielmann, Heinz Jakob, and Jürgen Peters 

First-line fibrinogen and/or prothrombin complex concentrate administration combined with point-of-care testing (thromboelastometry, impedance aggregometry) was associated with a markedly decreased incidence of allogeneic blood transfusion and of thrombotic/thromboembolic events in cardiovascular surgery

Pharmacogenomic Strain Differences in Cardiovascular Sensitivity to Propofol 1192

Thomas A. Stekiel, Stephen J. Contney, Richard J. Roman, Craig A. Weber, Anna Stadnicka, Zeljko J. Bosnjak, Andrew S. Greene, and Carol Moreno 

There is a pharmacogenomic difference in Dahl Salt Sensitive rats compared with Brown Norway control rats manifesting as enhanced cardiovascular sensitivity to propofol. This is attributable to altered renin gene function in the Dahl strain

Use of Recombinant Factor VIIa in Patients with Amniotic Fluid Embolism: A Systematic Review of Case Reports 1201

Barbara L. Leighton, Michael H. Wall, Ellen M. Lockhart, Louise E. Phillips, and Amanda J. Zatta 

Amniotic fluid embolism patients who received recombinant factor VIIa had significantly worse outcomes than cohorts who did not receive recombinant factor VIIa. Death and major organ thrombosis were common in patients receiving recombinant factor VIIa

Relationship between Bispectral Index Values and Volatile Anesthetic Concentrations during the Maintenance Phase of Anesthesia in the B-Unaware Trial 1209

Elizabeth L. Whitlock, Alexander J. Villafranca, Nan Lin, Ben J. Palanca, Eric Jacobsohn, Kevin J. Finkel, Lini Zhang, Beth A. Burnside, Heiko A. Kaiser, Alex S. Evers, and Michael S. Avidan 

Individual and population concentration response characteristics limit the feasibility of titrating volatile anesthetic administration against processed electroencephalographic indices such as the Bispectral Index

Lipid Resuscitation of Bupivacaine Toxicity: Long-chain Triglyceride Emulsion Provides Benefits over Long- and Medium-chain Triglyceride Emulsion 1219

Zhengqian Li, Yun Xia, Xiaoxi Dong, Hongfei Chen, Fangfang Xia, Xianqin Wang, Huimin Dong, Zhousheng Jin, Xili Ding, Thomas J. Papadimos, and Xuzhong Xu 

The results of resuscitation effects of two commercially available lipid emulsions of different compositions on the recovery from bupivacaine toxicity in rats displayed long-chain triglyceride emulsion’s superiorities over long- and medium-chain triglyceride emulsion

Neuroprotective Effect of Curcumin in an Experimental Rat Model of Subarachnoid Hemorrhage 1229

Chang-Po Kuo, Chueng-He Lu, Li-Li Wen, Chen-Hwan Cherng, Chih-Shung Wong, Cecil O. Borel, Da-Tong Ju, Chun-Mei Chen, and Ching-Tang Wu 

Treatment with multiple doses of curcumin after subarachnoid hemorrhage reduced mortality rate and improved functional and histological outcomes. Possible mechanisms include attenuation of glutamate level by preservation of glutamate transporter-1 protein expression and attenuation of oxidant stress

Metabotropic Glutamate Receptor 5 Antagonism with Fenobam: Examination of Analgesic Tolerance and Side Effect Profile in Mice 1239

Michael C. Montana, Beth A. Conrardy, Laura F. Cavallone, Benedict J. Kolber, Lesley K. Rao, Suellen C. Greco, and Robert W. Gereau IV 

Daily administration of the mGlu5 antagonist fenobam for up to 2 weeks does not result in tolerance to fenobam’s analgesic effects and is well tolerated in mice

Buprenorphine Metabolites, Buprenorphine-3-glucuronide and Norbuprenorphine-3-glucuronide, Are Biologically Active 1251

Sarah M. Brown, Michael Holtzman, Thomas Kim, and Evan D. Kharasch 

Buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide had moderate to high affinity for human μ, δ, and/or nociceptin receptors, and elicited mild analgesic responses. Norbuprenorphine-3-glucuronide but not buprenorphine-3-glucuronide caused sedation and decreased tidal volume. Glucuronide metabolites may contribute to buprenorphine effects

Isozyme-specific Effects of Protein Kinase C in Pain Modulation 1261

Chengshui Zhao, Michael Leitges, and Robert W. Gereau IV 

This study utilizes a panel of genetically modified mice to demonstrate the diverse roles of the α, β, γ, and δ isoforms of protein kinase C in mediating hypersensitivity after inflammation or nerve injury

Rewarding Electrical Brain Stimulation in Rats after Peripheral Nerve Injury: Decreased Facilitation by Commonly Abused Prescription Opioids 1271

Eric E. Ewan and Thomas J. Martin 

Spinal nerve ligation in rats suppresses opioid facilitation of rewarding brain stimulation in a manner that is distinct from analgesia-related manipulations

Shifts in Cell-type Expression Accompany a Diminishing Role of Spinal P38-Mapkinase Activation over Time during Prolonged Postoperative Pain 1281

Liang Huang, Yong-Jing Gao, Jeffrey Wang, and Gary Strichartz 

During prolonged, postoperative pain, expression of activated mitogen-activated protein kinase p38 shifts from microglia to neurons. Inhibition of P-p38 at early times prevents later postoperative pain, but later inhibition causes only transient pain relief

Case Scenario

Opioid Association with Serotonin Syndrome: Implications to the Practitioners 1291

Rahul Rastogi, Robert A. Swarm, and Trusharth A. Patel 

Serotonin syndrome is an uncommon but potentially life-threatening drug-induced toxicity, from interaction of opioids to other serotonergic agents. This toxic reaction can either be avoided, through knowing a patient’s detailed medicinal history, or be diagnosed early to prevent severe morbidity and mortality. It is even more critical for a practicing anesthesiologist to understand this entity, as the syndrome will be even more difficult to diagnose if secondary to overlapping symptoms from anesthetic. This case scenario focused on serotonin syndrome pathophysiology and management, and its association to routinely used opioids

Images in Anesthesiology

Inflammatory Myofibroblastic Tumor within Intrahepatic Inferior Vena Cava 1299

Andrea Vannucci, Lan Chi Tran, and Ivan M. Kangrga 

Subglottic Airway Foreign Body: A Near Miss 1300

Jacob AuBuchon, Catherine Krucylak, and David J. Murray 

Necrotizing Fasciitis after Cesarean Delivery 1301

Kathleen W. Nissman, Daniel B. Nissman, Barbara L. Leighton, Swarup S. Varaday, and Ellen M. Lockhart 

Pus in the Ventricles of a Patient with a Lumbar Cerebrospinal Fluid Drain for a Thoracoabdominal Aneurysm Repair 1302

Jonathan E. Charnin, Brian T. Bateman, and Edward A. Bittner 

Anesthesia Literature Review 1303

Original Investigations in Education

Simulation-based Assessment of Pediatric Anesthesia Skills 1308

James J. Fehr, John R. Boulet, William B. Waldrop, Rebecca Snider, Megan Brockel, and David J. Murray 

A multiple scenario simulation-based assessment of pediatric perioperative care demonstrated that anesthesia residents with more training achieved higher scores, with a wide range of ability among subjects

Review Articles

Genetic Variation, β-blockers, and Perioperative Myocardial Infarction 1316

Peter Nagele and Stephen B. Liggett 

Perioperative myocardial infarction (MI) is a common and potentially fatal complication after noncardiac surgery. The use of β-adrenergic receptor blocking drugs for prevention and treatment of perioperative MI has become controversial. Interindividual genetic variation may determine the clinical response to β-blocker therapy. This article reviews the molecular, cellular, and physiologic consequences of polymorphisms in the adrenergic signaling pathway and CYP2D6 gene, and shows that these are likely relevant factors influencing efficacy, safety, and toxicity of β-blocker therapy in prevention and treatment of perioperative MI

Use of Concatemers of Ligand-Gated Ion Channel Subunits to Study Mechanisms of Steroid Potentiation 1328

Joe Henry Steinbach and Gustav Akk 

Neurosteroids potentiate responses to neurotransmitter at multiple sites on receptors. The authors review the use of covalently linked channel subunits to characterize the sites individually and provide insights into the mechanisms of neurosteroid potentiation

Structural Studies of the Actions of Anesthetic Drugs on the γ-Aminobutyric Acid Type A Receptor 1338

Gustav Akk and Joe Henry Steinbach 

The γ-aminobutyric acid type A receptor is the major target for many clinically used anesthetic drugs. The authors describe the current state of knowledge of the structural rearrangements taking place during receptor activation and modulation

Advances in the Management of Sepsis and the Understanding of Key Immunologic Defects 1349

Lee P. Skrupky, Paul W. Kerby, and Richard S. Hotchkiss 

Anesthesiologists increasingly face the difficult challenge of managing patients with sepsis both in the operating room and intensive care unit. This review discusses advances in current therapy and an evolving immunologic understanding of sepsis.

Molecular Mechanisms of Opioid Receptor-dependent Signaling and Behavior 1363

Ream Al-Hasani and Michael R. Bruchas 

This review highlights the recent advances in opioid receptor signaling and discusses their potential for the development of novel opioids in the treatment of pain and neurologic disorders

Mind To Mind

“… And I Was Born” 1382

Ezzat I. Abouleish 

Blue Baby 1385

Thomas W. Quigley 

The Sea Politic 1386

Jennifer Root 

Hernia Repair, Anesthetic Exposure, and Academic Performance in Children 1387

Randall P. Flick and David O. Warner 

In Reply

Tom G. Hansen, Steen W. Henneberg, Jacob K. Pedersen, and Kaare Christensen 

New Dreams: Back to the Future 1388

Louis Jacobson and Anthony J. Mariano 

Pain Treatment and Opioids 1389

Rosemary J. Orr 

Intraoperative Transesophageal Echocardiography Guides Liver Transplant Surgery in a Patient with Thrombosed Transjugular Intrahepatic Portosystemic Shunt 1389

Andrea Vannucci, Joshua Johnston, Truman M. Earl, Majella Doyle, and Ivan M. Kangraga 


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