Anesthesia Research

Yale University and Yale-New Haven Medical Center are among the premier research and training institutions in the country. As part of this rich tradition, the areas of research interest in the department of Anesthesiology encompass both “traditional” areas of anesthesia research, and new areas of science and medicine. Expanding and enhancing the research mission in the department is one of the top priorities in Anesthesia at Yale.

Our research program encompasses clinical, translational and basic areas of investigation.  It ranges from neuroscience and cellular and molecular biology and tissue engineering to clinical and translational research.  Under the direction of Dr. Laura Niklason, Vice Chair for Research, this program offers an ideal platform for training the next generation of physician scholars in anesthesiology.

The following projects are occurring in the investigational stages:

  • Repetitive Transcranial Magnetic Stimulation for Neuropathic Pain
  • Electroanalgesia for Musculoskeletal Paina nd Post-Traumatic Stress Disorder
  • Sub-Anesthetic IV Infusions of NMDA Antagnoists for Complex Regional Pain Syndrome
  • Cognitive-Behavior Therapy for Diabetic Peripheral Neuropathic Pain
Learn more about our Research Faculty.

Investigative Basic Research

LaMotte(1)

The LaMotte Lab»

There are thought to be many similarities between itch and pain, including similar neurophysiology and some common pharmacology. Itch is a significant clinical problem but one for which there is little that can be done at present. We continue our work to examine anti-itch properties of a series of compounds that are being tested in a recently validated animal behavioral model for itch. We are also pursuing collaborative studies focused on the types of primary afferents that convey information about itch from the periphery to the central nervous system. Our current focus in that area is on identifying relationships between contents of mast cells that may be able to initiate the sensation of itch.

Ma

The Ma Lab»

Shuangge (Steven) Ma has been involved in developing novel statistical and bioinformatics methodologies for analysis of cancer (NHL, breast cancer, melanoma, lung cancer), mental disorders, and cardiovascular diseases. He has also been involved in health economics research, with special interest in health insurance in developing countries.

Clinical Research

Members of our faculty have maintained their significant contributions to medical/scientific literature and have continued to play active roles in professional and research societies. Our clinical research faculty examine acute and chronic pain, acupuncture, noninvasive monitoring of cardiovascular function, echocardiography, myocardial preservation during open heart surgery, psychological evaluations of children undergoing surgery, noninvasive monitoring of brain temperature and many other topics.

Among its outstanding features, the Yale University School of Medicine/Yale- New Haven Hospital medical complex offers the potential for collaboration with experts in a wide variety of fields. In addition to the aforementioned collaboration among clinical investigators and basic scientists within our Department, members of our Department have collaborated with clinicians and scientists in a variety of Departments within our Medical Center.

One area of focus in clinical research is the non-invasive assessment of cardiovascular function and volume status. Using a multi-dimensional computerized data acquisition system, we are integrating input from arterioles and capillaries (laser Doppler flowmetry), arteries and veins (plethysmography), with continuous monitors of blood pressure and heart rate to gain insight into two major areas of cardiovascular physiology: a) the regulation of microvascular perfusion, with a focus on autonomically- mediated autoregulatory processes in patients (with disorders such as diabetes) and helathy volunteers; b) the assessment of the cardiovascular responses to volume loss intraoperatively and in healthy volunteers (withdrawal and reinfusion of two units of blood; simulated hypovolemia with the use of lower body negative pressure).

To study the impact of anesthetics on brain function and metabolism, faculty members use magnetic resonance imaging. Functional MR imaging is an objective method of studying the subjective effects of anesthesia. fMRI can measure BOLD (blood oxygen level dependent contrast) a qualitative measure of cerebral metabolism and regional cerebral blood flow (rCBF). BOLD and rCBF are indirect measures of neuronal activity. In collaboration with the MRRC (magnetic resonance research center) we have been studying healthy ASA I volunteers under sevoflurane anesthesia. We study the effect of sevoflurane 0.25 and 0.5 MAC as well as the effect of activation under anesthesia. So far, close to 80 subjects have been imaged. In our first protocol the effect of visual, auditory and motor activation was studied under 0.25 MAC sevoflurane. Cerebral metabolism (BOLD) as well as rCBF was measured, providing direct information on the physiological effects on anesthetics on brains of normal patients.

Other faculty have looked at the effects of hypnosis on perioperative setting. In addition, our faculty have worked to implement a wellness program in anesthesiology residents at Yale, to study its impact on quality of life, stress levels, etc.

Dr. Barash, a former chairman of Anesthesia at Yale, is currently conducting research in two areas: (1) peri-operative cardiovascular anesthesia and (2) healthcare delivery. In particular working with Dr. John Elefteriades (Chief Cardiac Surgery), he is utilizing intra-operative echocardiographic imaging techniques to elucidate the mechanical properties of thoracic aortic aneurysms. Using Quality Assurance databases and information directly gathered in the operating rooms, Dr. Barash and his team are evaluating the logistics of delivering anesthetic care in an inpatient operating room suite of an academic medical center.

Yale Center for Analgesic Research

Integral to the pain rotation is the collection of safety, efficacy, and outcome data. This subsection of the Pain Management Service provides numerous research opportunities for residents and fellows assigned to the Pain Service. In recent years, a number of residents have participated as investigators in clinical trials and have had their research presented at major Anesthesiology meetings. Basic and clinical research at Yale, and at other major medical centers, has increased our understanding of pain pathways, and has helped to develop novel analgesics and routes of administration improving analgesic efficacy and postoperative outcome. Optimal therapy employs preemptive analgesia (administration of analgesics prior to surgical incision) and multi-modal analgesia (utilizing a variety of medications in an effort to provide additive analgesic effects). Current research efforts are focused on determining whether analgesic regimens that emphasize these concepts lead to improvements in patient functionality and post-surgical outcome.

Analgesic Investigations

  • The multimodal administration of non-opioid analgesics in an effort to improve pain control, reduce epidural and IV PCA opioid requirements. We are currently evaluating preoperative administration of IV acetaminophen and Oral COX-2 inhibitors as adjuncts to opioid-based analgesia. These agents were noted to reduce morphine requirements by 35-44%, while reducing pain with effort, such as ambulation and deep breathing or cough. We continue to test the hypothesis that reduction in opioid exposure may lead to improvements in cognitive function, particularly in elderly patients, and may reduce the incidence of opioid induced ileus. We are also testing whether multimodal improvements in effort dependent pain may improve post-surgical pulmonary function and reduce the incidence of pneumonia.
  • We continue our leadership role documenting the safety and efficacy of hydromorphone for epidural infusions and patient-controlled epidural infusion. To date over 10,000 patients have been treated with solutions containing hydromorphone and hydromorphone plus bupivacaine. The quality of pain relief and the incidence of adverse effects have been entered into a large prospective database.
  • We continue as a lead site evaluating the post-surgical application of E-TRANS Fentanyl, an iontophoretic transdermal PCA device that patients can use to self administer small doses of fentanyl, Dilaudid CR a 24hr sustained release oral opioid for control of moderate to severe acute pain, and DepoDur® a substantial release epidural formulation of morphine that provides up to 48 hours of pain relief. We will be testing our preparation for pain control in women recovering from cesarean delivery.
  • We are the lead site evaluating EDLA-40K for post-orthopedic pain management. EDLA is a solution of extended release bupivacaine that can provide up to 72hrs of pain control following peripheral neural injection.

The Yale Center for Medical Informatics

Professor Perry Miller is Director of the Yale Center for Medical Informatics (YCMI) and of Yale's Biomedical Informatics research training program. Biomedical Informatics is a discipline at the intersection of biomedicine and the computing and information sciences. The field focuses on the creative application of computers in clinical medicine, biomedical research, and medical education. In clinical medicine, the growing use of computers in patient care, education, and research makes the field increasingly important. In biomedical research, informatics is rapidly becoming a critical component of virtually all bioscience fields.

Projects at the YCMI include major initiatives in clinical, neuro-, and genome informatics. In these projects, the YCMI collaborates with faculty and staff from many departments at Yale. Additional information is available at the YCMI web site.

Research Projects

  • Biomedical informatics research training. Since 1985, Dr. Miller has been Director of Yale's Biomedical Informatics Research Training Program, supported in part by the National Library of Medicine. This program currently supports trainees whose activities are roughly equally divided between clinical informatics and bioscience informatics.
  • Genomic and genetic informatics. Over the past 15 years, the YCMI has been involved in a number of projects involving genomics and genetics. An early project involved exploring the use of parallel computation in biological sequence analysis, genetic linkage analysis, and molecular dynamics, in collaboration with Prof. David Gelernter (Computer Science) and his colleagues. Another project provided Internet-based informatics support for a collaborative Genome Center involving the Albert Einstein College of Medicine and Yale to map human chromosome 12. Current projects include 1) developing and maintaining a variety of databases that are used actively within the laboratory of Dr. Kenneth Kidd (Genetics), 2) working with Dr. Michael Snyder to develop and refine databases for a) yeast gene expression data and b) yeast proteome chip data, and tools to help analyze that data, and 3) working with several groups to provide University-wide informatics support for microarray experiments. Dr. Kei Cheung (Assistant Professor, YCMI) plays a central role in many of these activities.
  • Neuroinformatics. Dr. Miller directs the informatics components of a collaborative Program Project involving Drs. Gordon Shepherd (Neurobiology), Michael Hines (Computer Science), and Prakash Nadkarni (YCMI), supported as part of the national Human Brain Project. The project is developing informatics support for neuroscience research and computer-based neural simulation using the olfactory system as a model system.
  • Informatics in support of clinical research. Since 1996, the YCMI has had a major project to develop, refine, and use Trial/DB, a client-server, Web-accessible database designed to support clinical research projects. Trial/DB is currently being used for a growing number of clinical trials and clinical research projects at Yale. It is also supported by two cooperative grants to Dr. Prakash Nadkarni (Associate Professor, YCMI): a) to serve as the special studies database for the NCI's multisite Cancer Genetics Network, and b) to help support the NIH's multisite Pharmacogenetics Network. Dr. Cynthia Brandt (Assistant Professor, YCMI) also plays a central role in many phases of this project.
  • The PathMaster cell image database. Dr. Miller directs a collaborative research contract from the National Library of Medicine to build a database of cell images indexed by computationally-derived descriptors, implemented using parallel computation, as a testbed to explore desirable Next Generation Internet capabilities.
  • Clinical informatics activities. The YCMI is also involved in a number of collaborative clinical informatics activities. A longstanding research activity has involved the development of programs which bring computer-based advice to the practicing clinician. One current project directed by Dr. Richard Shiffman (Associate Director, YCMI) involves developing GEM (Guideline Elements Model), an XML-based standard to help organize the creation and use of clinical practice guidelines. Another recent clinical informatics project involves Personal Digital Assistants (PDAs) which offer a lightweight, mobile platform that can be used at the point-of-care.

Research in Environmental Factors

The World Health Organization calls climate change the defining issue for health systems in the 21st century. Ironically, the health care industry itself is a leading emitter of climate change-causing gases and other types of pollution that adversely affect public health. In 2009, health care in the United States (US) accounted for 17% of the total GDP, consumed 73 billion kWh of electricity, spent nearly $320 billion on goods and services, and produced 8% of national greenhouse gas (GHG) emissions. One third of health care’s GHG emissions come from pharmaceuticals and medical equipment alone, and the health care sector is one of the single largest purchasers of chemicals. Seemingly small changes in how medical supplies are produced and used, magnified over this large sector, can have significant implications for resource use and public health. There is an increasing need to accurately measure and track human health and environmental impacts associated with health care practice itself. 

The environmental impact of perioperative services is among the largest in all of medicine. Inhaled anesthetics account for 5% of hospital emissions, and 33% of hospital solid waste is generated in the ORs. Anesthesiologists have a unique opportunity and responsibility to improve the pollution profile of our specialty, however little is presently known where to target our efforts. The central goal of Dr. Jodi Sherman research in the Yale University Department of Anesthesiology is to quantify the environmental and public health effects of common drugs and devices for entire anesthetic pathways, so these results may aid in targeted waste reduction and pollution prevention strategies where choices exist, as they often do in clinical practice. Dr. Sherman collaborates with Dr. Julie Zimmerman, Ph.D. and other environmental engineers from the Yale School of Forestry and Environmental Sciences, applying Life Cycle Assessment (LCA) scientific modeling to questions in anesthetic practice, quantifying energy, greenhouse gas emissions, human health impacts, and economic densities of therapeutic drugs, OR devices, and perioperative behaviors to help guide clinical decision making toward more ecologically sustainable practices. Dr. Sherman also serves on the Environmental Task Force of the American Society of Anesthesiologists.

Translational Research


Niklason, Laura E

Professor of Anesthesiology and of Biomedical Engineering; Division Chief; Vice Chair, Research

Biography

Dr. Niklason is Professor of Anesthesia and Biomedical Engineering at Yale.She received her Bachelors degrees in Physics and Biophysics from the University of Illinois, and went on to the University of Chicago for her PhD in Biophysics in 1988. Dr. Niklason subsequently received her MD from the University of Michigan, where she did her internship. She then went on tothe Massachusetts General Hospital for residency in Anesthesia, followed by fellowship training in Critical Care Medicine....

Dr. Niklason is Professor of Anesthesia and Biomedical Engineering at Yale.She received her Bachelors degrees in Physics and Biophysics from the University of Illinois, and went on to the University of Chicago for her PhD in Biophysics in 1988. Dr. Niklason subsequently received her MD from the University of Michigan, where she did her internship. She then went on tothe Massachusetts General Hospital for residency in Anesthesia, followed by fellowship training in Critical Care Medicine. During her time in Boston, Dr.Niklason was also a post-doctoral researcher at MIT with Dr. Robert Langer,where she developed techniques for the tissue engineering of autologous arteries. Dr. Niklason joined the faculty at Duke University in 1998, where she continued her work in cardiovascular tissue engineering, and founded a biotechnology company designed to bring tissue engineered cardiovascular products to the clinic. Dr. Niklason has received national and international recognition for her work in this field, receiving the Discover Magazine award for Technological Innovation in 2000. In January of 2006, Niklason moved to Yale University, where she is expanding her research program in tissue engineering of blood vessels and lung, as well as understanding the basic aspects of cellular aging.

Currently, Dr. Niklason's research program has several areas of focus. With regard to engineered arteries, Niklason is engaged in preclinical studies in large animals to validate the method for generating engineered tissues that are available "off the shelf". Large animal studies on vascular grafts are centered on immune/inflammatory response minimization to these off-the-shelf tissues, and on the long-term function of the grafts in the arterial circulation. In addition, Niklason is developing tissue engineering approaches to generating vascularized cardiac muscle, as well as vascularized lungtissue. In addition, Niklason has active research interests in vascularremodeling that is associated with various disease states, including atherosclerosis and arterial vasospasm.

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Selected Recent Publications

1.

Tissue-engineered lungs for in vivo implantation.

Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE.

Science. 2010 Jul 30;329 (5991) :538-41. Epub 2010 Jun 24. PMID: 20576850

2.

Enabling tools for engineering collagenous tissues integrating bioreactors, intravital imaging, and biomechanical modeling.

Niklason LE, Yeh AT, Calle EA, Bai Y, Valentín A, Humphrey JD.

Proc Natl Acad Sci U S A. 2010 Feb 23;107 (8) :3335-9. Epub 2009 Dec 1. PMID: 19955446

3.

Blood vessels engineered from human cells.

Gong Z, Niklason LE.

Trends Cardiovasc Med. 2006 Jul;16 (5) :153-6. PMID: 16781948

4.

Relevance and safety of telomerase for human tissue engineering.

Klinger RY, Blum JL, Hearn B, Lebow B, Niklason LE.

Proc Natl Acad Sci U S A. 2006 Feb 21;103 (8) :2500-5. Epub 2006 Feb 13. PMID: 16477025