OHSU

Clinical Effectiveness of Video Laryngoscopy in Perioperative Airway Management
Michael Aziz, MD

We have made advances in the field of airway management with respect to video laryngoscopy. In a large-scale database evaluation in collaboration with the multicenter perioperative outcome group (MPOG), we demonstrated that video laryngoscopy is the preferred tool to rescue the airway in the situation when direct laryngoscopy fails (unanticipated difficult airway). Furthermore, its use in this rescue scenario resulted in higher intubation success than alternate intubation techniques.

In a large multicenter, randomized, controlled trial, we compared two commonly employed acute-angle video laryngoscopy techniques. In this study of patients with predictors of a difficult airway, we observed that video laryngoscopy is successful in securing the airway in 98% of cases with some minor differences between the two studied techniques: Glidescope vs. C-MAC with D-blade (abstract presented at IARS 2015).

Funding:
Karl Storz Endoscopy America: A Multi-centered Randomized Controlled Trial to Investigate Two Video Laryngoscopes in Difficult Airway Scenarios.
Covidien: Prospective Clinical Evaluation of the Taperguard Endotracheal Tube.

Publications:
Michael F. Aziz, M.D., Amy W. Chu, B.S., David Healy, M.D., Amy Shanks, M.S., Leslie C. Jameson, M.D., William C. Paganelli, M.D. Sachin Kheterpal. Comparative Approaches to the Unanticipated Difficult Airway: Results from the Multi-Centered Perioperative Outcomes Group. American Society of Anesthesiologists, Annual Meeting Program Webpage, 2014.

Kheterpal S, Healy D, Aziz MF, Shanks AM, Freundlich RE, Linton F, Martin LD, Linton J, Epps JL, Fernandez-Bustamante A, Jameson LC, Tremper T, Tremper KK. Multicenter Perioperative Outcomes Group (MPOG) Perioperative Clinical Research Committee. Incidence, predictors, and outcome of difficult mask ventilation combined with difficult laryngoscopy: a report from the multicenter perioperative outcomes group. Anesthesiology. 2013, 119:1360-9.

Aziz MF, Kim D, Mako J, Hand K, Brambrink AM. A retrospective study of the performance of video laryngoscopy in an obstetric unit. Anesth Analg. 2012; 115:904-6.

Aziz MF, Dillman D, Fu R, Brambrink AM. Comparative effectiveness of the C-MAC video laryngoscope versus direct laryngoscopy in the setting of the predicted difficult airway. Anesthesiology. 2012; 116(3):629-36.

Aziz MF, Healy D, Kheterpal S, Fu RF, Dillman D, Brambrink AM. Routine clinical practice effectiveness of the Glidescope in difficult airway management: an analysis of 2,004 Glidescope intubations, complications, and failures from two institutions. Anesthesiology. 2011; 114:34-41.

Anesthesia Induced Morphologic and Functional Injury In Developing Brain
Ansgar Brambrink, MD, PhD

Our current research pertains to the adverse effects of anesthetic drugs on the developing non-human primate brain. Over the last several years we have generated a large data base and numerous publications demonstrating that clinically relevant exposure of infant or fetal monkeys to several anesthetic drugs (isoflurane, ketamine, propofol) triggers a toxic reaction in the developing brain consisting of acute apoptosis of neurons and also of glial cells, which we have determined are of the oligodendrocyte lineage. The highly productive line of research is conducted in collaboration with the Washington University (St. Louis) and in part with the University of Geneva, Switzerland, and experts at the Oregon National Primate Research Center. We are currently following a cohort of non-human primates that will determine whether exposure of infant monkeys to isoflurane (ISO) anesthesia on one occasion, or on three successive occasions over the first weeks of life, is associated with long-term neurobehavioral disturbances. Our early behavioral observations indicate that ISO exposure x3 and possibly x1 is associated with measurable neurobehavioral deficits which remain to be fully characterized as the infants mature over their first 2 years of life. We are also pursuing morphologic and functional assessments of the surviving brain, and apply neuroimaging methods to determine whether acute and long-term brain changes following anesthesia exposure can be detected non-invasively. We are also exploring factors that worsen the injury and those that have neuroprotective potential. The overarching goal is to advance our knowledge pertaining to toxic effects of anesthetics in the developing non-human primate brain, which is very similar to that of young humans.

Funding:
NIH/NICHD, RO1: Anesthesia-Induced Developmental Neuroapoptosis in Non-Human Primates (subcontract).
IARS“ Frontiers in Anesthesiology Award: Long-Term Outcome of Single vs. Triple Anesthesia Exposure of Infant Monkeys

Publications:
Brambrink AM, Dissen GA, Martin LD, Kristich RA, Noguchi KK, Olney JW. Lithium protects against isoflurane-induced neurotoxicity in infant non-human primates. American Society of Anesthesiologists, Annual Meeting Program Webpage, 2014, A4046

Brambrink AM, Dissen GA, Martin LD, Johnson SA, Olney JW. Three hours of isoflurane anesthesia are sufficient to cause significant cell death in the brain of neonatal nonhuman primates. American Society of Anesthesiologists, Annual Meeting Program Webpage, 2014, LBB03

Martin LD, Dissen GA, McPike MJ, Brambrink AM. Differential effects of isoflurane, ketamine and propofol anesthesia on physiologic parameters in neonatal rhesus macaques (macaca mulatta). J Am Assoc Lab Anim Sci. 2014; 53(3):290-300.

Creeley CE, Dikranian KT, Dissen GA, Back S, Olney JW, Brambrink AM. Isoflurane-induced apoptosis of neurons and oligodendrocytes in the fetal Rhesus macaque brain. Anesthesiology. 2014; 120(3):626-38.

Creeley CE, Dikranian KT, Evers A, Dissen GA, Olney JW, Brambrink AM. Propofol-induced apoptosis of neurons and oligodenrocytes in the fetal and the neonatal Rhesus macaque brain. Br J Anaesth. 2013; 110 Suppl 1:i29-38

Brambrink AM, Back S, Riddle A, Gong X, Moravee M, Dissen GA, Creeley CE, Dikranian KT, Olney JW. Isoflurane-Induced Oligodendrocyte Apoptosis of oligodendrocytes in the neonatal primate brain. Ann Neurol. 2012, 72:525-35

Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Martin, LD, Dissen GA, Creeley CE, Olney JW. Ketamine-induced Neuroapoptosis in the Fetal and Neonatal Rhesus Macaque Brain. Anesthesiology 2012, 116:372-84.

Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, Dissen GA, Creeley CE, Olney JW. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010, 112:834-41.

The Role of Estrogen in Renal Reperfusion Injury
Michael Hutchens, MD

My research program focuses on sex and renal ischemia-reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation. In particular, after finding a sex difference characterized by female protection, I found that estrogen was a protective factor. Tubular epithelial cell death is the hallmark of renal ischemia-reperfusion injury, but the factors that initiate this process are poorly understood. As an anesthesiologist, my focus is on the minutes after ischemic injury as a potential therapeutic interval. We have found that an early functional deficit following ischemia-reperfusion is sexually-dimorphic filtration failure. This observation along with the finding of estrogen protection has directed my research efforts into the study of the effects of cardiac arrest and cardiopulmonary resuscitation on glomerular permeability and its downstream effects on tubular epithelium. I have found that estrogen abrogates the early failure of the glomerular filtration barrier following ischemic insult, and that this barrier failure may itself influence the downstream fate of tubular epithelial cells, which we are currently investigating.

Funding:

NIH/NIDDK, KO8: Sex Difference in Renal Injury after Cardiac Arrest: Mechanisms of Estrogen Action.

Publications:

Hutchens MP, Fujiyoshi T, Koerner IP, Herson PS. Extracranial hypothermia during cardiac arrest and cardiopulmonary resuscitation is neuroprotective in vivo. Ther Hypothermia Temp Manag. 2014, 4:79-87.

Hutchens MP, Kosaka Y, Zhang W, Fujiyoshi T, Murphy S, Alkayed N, Anderson S. Estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation is robust to GPR30 gene deletion. PLoS One. 2014, 9:e99910.

Hutchens MP, Fujiyoshi T, Komers R, Herson PS, Anderson S. Estrogen protects renal endothelial barrier function from ischemia-reperfusion in vitro and in vivo. Am J Physiol Renal Physiol. 2012, 303:F377-85.

Hutchens MP, Traystman RJ, Fujiyoshi T, Nakayama S, Herson PS. Normothermic cardiac arrest and cardiopulmonary resuscitation: a mouse model of ischemia-reperfusion injury. J Vis Exp. 2011, 54.pii: 3116.

Hutchens MP, Nakano T, Kosaka Y, Dunlap J, Zhang W, Herson PS, Murphy SJ, Anderson S, Hurn PD. Estrogen is renoprotective via a nonreceptor-dependent mechanism after cardiac arrest in vivo. Anesthesiology. 2010, 112:395-405.

Switching the Microglial Response to Injury Improves Neurologic Function After Cardiac Arrest.
Ines P. Koerner, MD PhD

Advances in resuscitation technique and post-resuscitation critical care have dramatically improved the number of survivors of cardiac arrest. Unfortunately, many of the survivors suffer permanent brain injury and are left with disabling deficits of memory and executive function. No specific treatments exist currently to prevent brain injury. We investigate whether blocking the brain inflammatory response after cardiac arrest and resuscitation can reduce the extent of the resulting brain injury. Any insult to the brain activates the immune system, which is necessary for defense against pathogens as well as scar formation and repair after brain injury. After sterile injury such as brain ischemia during cardiac arrest, however, the immune response can also exacerbate neuronal death and worsen functional deficit. Microglia, the brain resident immune cells, are activated after cardiac arrest and retain an inflamed phenotype for many months after the insult. We hypothesize that the inflamed microglia become neurotoxic, worsening the initial injury and interfering with regeneration and brain plasticity during recovery after cardiac arrest. We have identified several candidate proteins that contribute to the toxic microglial activation after cardiac arrest, including a microglial protein that can be inhibited to transition the toxic microglial phenotype to a supportive, anti-inflammatory one. More recently, we have also identified a novel danger molecule that is released from injured neurons after cardiac arrest and induces the neurotoxic inflamed microglial phenotype. We anticipate that our work will lead to new drug targets that will help ameliorate functional deficit for survivors of cardiac arrest.

Funding:

NIH/NINDS K02: Microglial uptake and inactivation of epoxyeicosatrienoic acid in stroke injury.
American Heart Association Grant-in-Aid: Mechanisms of microglia-mediated secondary brain injury after cardiac arrest.

Publications:

Ikeda M, Fujiyoshi T, Mader S, Koerner IP. Peroxiredoxin-1 and Toll-like receptor 2 pathway contributes to neurotoxic microglial activation after cardiac arrest. American Society of Anesthesiologists, Annual Meeting Program Webpage, 2014. (“Best Abstracts: Basic Science”)

Wang J, Fujiyoshi T, Kosaka Y, Raybuck JD, Lattal KM, Ikeda M, Herson PS, Koerner IP. Inhibition of soluble epoxide hydrolase after cardiac arrest/cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival. J Cereb Blood Flow Metab. 2013, 33:1574-81.

Weinstein JR, Koerner IP, MÃller T. Microglia in ischemic brain injury. Future Neurol. 2010, 5:227-246.

The Role of Gene-Polymorphism in Postoperative Decline in Cognition and Functional Status
Katie Schenning, MD, MPH

Individuals aged 65 years and older receive more than 1/3 of the over 40 million anesthetics delivered yearly in the United States, and evidence suggests that older adults are most at risk for postoperative deleterious neurocognitive outcomes. Alzheimer’s disease is caused by interplay between environmental and genetic risk factors, and it is unknown whether one such environmental factor is the exposure to anesthesia and surgery. We hypothesized that exposure to surgery and general anesthesia in older adults is associated with an accelerated rate of decline in cognition, function, and brain volumes, and the rate of decline is higher in those with the presence of an APOE4 allele. Using a retrospective cohort design, we tested our hypothesis by interrogating two longstanding aging databases, the Oregon Brain Aging Study and Intelligent Systems for Assessment of Aging Changes Study. Out of a total of 527 participants, 182 participants had a combined total of 331 surgeries under general anesthesia after enrollment in the cohort. The mean follow-up after study enrollment was 7 years (SD 4.6). This retrospective cohort analysis demonstrated that exposure to general anesthesia and surgery in older adults was associated with an accelerated rate of decline in cognition and functional status and a more dramatic increase in ventricular size. Importantly, we found that among the exposed participants, the rate of deterioration in cognition, function, and ventricular size was more pronounced in participants with at least one copy of the APOE4 allele.

Funding:

Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) K12: Influence of Sex and Genetics in Postoperative Cognitive and Functional Decline
Oregon Alzheimer Disease Center Award: Anesthesia in the elderly: effects on cognitive decline and dementia

Publications:

Schenning KJ, Murchison C, Mattek N, Kaye J, Quinn J. Effects of Anesthesia, Surgery, and APOE4 in the Elderly. International Anesthesia Research Society; Annual Meeting Program Webpage, 2015.

Hogan KJ, Koscik RL, Schenning KJ, Boncyk JC, Wenzel AL, La Rue AA, Hermann BP, Johnson SC, Sager MA. Cognitive Deficits after Surgery in Persons with a Family History of Alzheimer’s Disease. American Society of Anesthesiologists, Annual Meeting Program Webpage, 2014.

Schenning KJ, Murchison C, Mattek N, Kaye J, Quinn J. Postoperative Dementia: Role of Anesthesia and APOE4. Euroanesthesia; 4th International Workshop on Perioperative Neurotoxicity in the Elderly; Annual Meeting Program Webpage, 2014.

Schenning KJ, Murchison C, Mattek N, Kaye J, Quinn J. Postoperative Dementia: Role of Anesthesia and APOE4. Association of University Anesthesiologists, Annual Meeting Program Webpage, 2014.

We have made advances in the field of airway management with respect to video laryngoscopy. In a large scale database evaluation with the multicenter perioperative outcome group (MPOG), we demonstrated that video laryngoscopy is the preferred tool to rescue the airway in the situation when direct laryngoscopy fails (unanticipated difficult airway). Furthermore, its use in this rescue scenario results in a higher intubation success rate than alternate intubation techniques.
(http://www.asaabstracts.com/strands/asaabstracts/searchArticle.htm;jsessionid=350D77BC365CE848AA6914C5365B8F0A?index=0&highlight=false&highlightcolor=0&bold=false&italic=false)

In a large multicenter randomized control trial, we compared two commonly employed acute-angle video laryngoscopy techniques. In this study of patients with predictors of a difficult airway, we observed that video laryngoscopy is successful in securing the airway in 98% of cases with some minor differences between the two studied techniques: Glidescope vs. C-MAC with D-blade (pending abstract at IARS 2015).