2014 BluePrint

BLUE PRINT Duke Anesthesiology

HTTP://BLUEPRINT.DUHS.DUKE.EDU

DUKE ANESTHESIOLOGY’S FORMALIZED MENTORSHIP PROGRAM IS SET UP TO ATTRACT AND RETAIN THE BRIGHTEST PHYSICIANS FROM AROUND THE COUNTRY.

Mark F. Newman, MD CELEBRATING 13 YEARS OF LEADERSHIP AS CHAIR OF THE DEPARTMENT OF ANESTHESIOLOGY AT DUKE

Volume 5 | 2014

WELCOME

Volume 5 | 2014

From the Interim Chair

Editors: Elizabeth T. Perez, RN, BSN Ratna Swaminathan Tiffany A. Nickel Contributing Editors: Joseph Mathew, MD, MHSc, MBA Miles Berger, MD, PhD Miklos Kertai, MD, PhD Michael Manning, MD, PhD Steve Melton, MD Karthik Raghunathan, MD, MPH Thomas Van de Ven, MD, PhD Zhiquan Zhang, PhD Mark Newman, MD Adam Hartz Thomas Buchheit, MD Ru-Rong Ji, PhD Sven-Eric Jordt, PhD Adeyemi Olufolabi, MB BS Holly Muir, MD Richard Moon, MD, CM, MSc, FRCP(C), FACP, FCCP Eugene Moretti, MD, MHSc Christopher Young, MD Copy Writer: Tiffany A. Nickel Creative Director: Elizabeth T. Perez, RN, BSN Photography Contributions: Elizabeth T. Perez, RN, BSN Tiffany A. Nickel Adeyemi Olufolabi, MB BS Richard Moon, MD, CM, MSc, FRCP(C), FACP, FCCP Duke Photography Mark Newman, MD Miklos Kertai, MD, PhD Michael Manning, MD, PhD Karthik Raghunathan, MD, MPH Thomas Van de Ven, MD, PhD Zhiquan Zhang, PhD www.iStockphoto.com Duke Anesthesiology faculty & friends Production: Elizabeth T. Perez, RN, BSN Tiffany A. Nickel Duke Anesthesiology Alumni & Development Affairs Your comments, ideas, and letters are welcome.

Please contact us at: BluePrint Magazine Anesthesia Alumni & Development Affairs DUMC 3094 Durham, NC 27710 blueprint@mc.duke.edu http://blueprint.duhs.duke.edu

Greetings!

It is my privilege to introduce our 2014–2015 BluePrint publication and share the exciting news and highlights of Duke Anesthesiology over the past year.

Since our last issue, Dr. Newman has stepped into his new role as president of the Duke Private Diagnostic Clinic. During his time as Chair, he elevated Duke Anesthesiology to be one of the best anesthesiology departments in the world by successfully balancing the clinical, educational, and research missions while ensuring the financial integrity necessary for long-term success. The department is on an incredibly solid foundation because of his tireless work. Furthermore, and perhaps more importantly, an entire generation of clinicians, educators, scientists, and leaders have been developed over the last 13 years—these are the people who are changing our world.

Another significant appointment for our department this past year has been the selection of Dr. Cathy Kuhn, our program director for 20 years and Vice-Chair for Education since 2007, as the Director and Associate Dean for Graduate Medical Education and the Designated Institutional Official for the ACGME. As most of you already know, Dr. Kuhn has received national recognition for her leadership contributions and the innovative education programs that have transformed the Duke Anesthesiology residency into one of the top programs in the country. In her new role, Dr. Kuhn has oversight and responsibility for over 80 accredited training programs and dozens of non-accredited programs at Duke, which in total comprise nearly 1,000 trainees. Dr. Mark Stafford-Smith, a committed and innovative educator whose experience crosses the divide between education and research, has taken over as the Vice-Chair for Education, and Dr. Annemarie Thompson has joined the department as our new Residency Program Director. Dr. Thompson comes from Vanderbilt University, where she was an Associate Professor of Anesthesiology and Medicine (dually trained at UCSF) and served as Director of the Adult Cardiothoracic Anesthesiology Fellowship since 2006. I am grateful that all our leaders, past and present, are committed to the achievement of excellence and recognize that it can only occur if we promote a culture of creative dissatisfaction.

The Department of Anesthesiology has always stood for excellence, and I would like to thank all of the faculty, staff, trainees, alumni, donors, and friends of the department who have made this possible. In this issue of BluePrint, we highlight the work of a few from our family but by no means should it be considered a complete list; everyone plays a unique and valued role, and I am proud of all of you who are a part of this incredible department. I am humbled and honored to serve you.

Sincerely,

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Joseph P. Mathew, MD, MHSc, MBA

Facebook: https://www.facebook.com/DukeAnes

Interim Chair, Department of Anesthesiology

Jerry Reves, MD, Professor of Cardiac Anesthesiology and

Featured Stories DIG

LEADERSHIP

PAIN

OUTREACH

Our 2013 DREAM Innovation Grant (DIG) recipients reveal what they have discovered during the one-year funding period of the DIG, as well as what the future holds for their promising research studies. Also, meet the 2014 DIG recipients as they share their ambitious research projects and what they hope to accomplish.

A reflection on the past 13 years, during which time the Department of Anesthesiology at Duke has flourished under the chairmanship of Mark F. Newman, MD, the Merel H. Harmel Professor of Anesthesiology, and a look to the future as he steps into his new role as president of the Duke Private Diagnostic Clinic (PDC).

A multi-pronged approach to pain management is now a reality at Duke. A comprehensive Pain Program that dovetails top-ranked research with an equally powerful clinical program has been designed to investigate the causes of pain and develop the optimal methods for prevention and treatment.

Since 2005, Drs. Adeyemi Olufolabi and Holly Muir, along with a team of nurse anesthetists (CRNAs), obstetricians, neonatologists, residents, and others interested in improving maternal care on a global scale, have seen their efforts in Ghana bear tremendous results.

- PA G E 4 -

- PA G E 1 4 -

- PA G E 2 2 -

- PA G E 2 8 BLUEPRINT 2014 | 3

GroundBreaking Research

The DREAM Innovation Grant (DIG) program was started in 2011 at Duke to support innovative, high-risk, and potentially high-reward investigations to accelerate anesthesia and pain management research. As the majority of extramural funding agencies require pilot data, the DIG program funds faculty at any level to conduct a one-year pilot study to demonstrate the feasibility of a new line of research and generate data to support applications for peerreviewed funding.

Research deemed innovative may introduce a new paradigm, challenge current paradigms, look at existing problems from new perspectives, or exhibit other uniquely creative qualities. The DIG promotes new ideas; therefore, proposals need not include preliminary data. However, a solid rationale for the work must be provided. Proposed work should not be the next logical step of previous work, but should have a high probability of revealing new avenues of investigation. This program aims to provide pilot funding that will lead to successful competition for additional funding beyond the pilot period. The research concept, scientific team, and explicit plans for how this work will lead to follow-on funding will be the primary criteria for judging proposals.

4 | DUKE ANESTHESIOLOGY

Eligibility All faculty members within the Department of Anesthesiology at Duke are eligible to apply. One of the grants will be reserved to support a scientist early in their career (within 5 years of completion of residency or fellowship) by encouraging and adequately funding projects that can contribute to bridging the gap between training and progression to independent investigator status. The other award(s) will be used as a seed grant to help investigators with promising science obtain preliminary data to support follow-on funding applications.

Become a DDC partner The success of the DREAM Campaign depends on donations and grants from individuals and businesses.

The discoveries developed as a result of your donation can have a life-changing impact on millions of people on a global basis.

To learn more, please visit us online at dukedream.org.

To date, six of our thirteen DIG recipients have

Comparative Effectiveness in Perioperative and Critical Care Medicine: Crystalloid Fluid Therapy $206,944 grant from the Baxter Healthcare Corporation Fluids franchise and $94,680 APSF/ASA Endowed Research Award from the APSF Scientific Evaluation Committee

received $1,326,374 in extramural funding! That’s

$180,000 in donations that have led to over a million dollars in external grants!

- Karthik Raghunathan, MD, MPH 2013

Functional Neuroimaging to Assess Cognitive Function after Cardiac Surgery $431,750 Exploratory/Developmental research grant from the National Heart, Lung, and Blood Institute

- Joseph P. Mathew, MD 2011

Pharmacogenomics of β-blockers: Implication for Postoperative Atrial Fibrillation

- Miklos Kertai, MD, PhD 2013

Cardiopulmonary Bypass Induced Inflammatory Changes in the Atrial Wall: The Novel Role for Cardiac Chymase produced Angiotensin II in the Development of Atrial Fibrillation Two-year, $50,000 Society of Cardiovascular Anesthesiologists (SCA) Starter Grant

Gender-based Differences in Genetic Expression after Acute Brain Injury in Mice

- Michael “Luke” James, MD 2011

- Michael Manning, MD, PhD 2013

Role of SUMO2/3 Conjugation Pathway in Cerebral Ischemia/Stroke $308,000 NCRP Winter 2012 Scientist Development Grant from the American Heart Association

- Wei Yang, PhD2011

Neurointerventional Regional Anesthesia to Improve Hand Rehabilitation in Stroke

- Steve Melton, MD 2013

Elucidating Adaptive Mechanisms of Perioperative Cardioprotection Following Ischemia-reperfusion in Hibernating Arctic Ground Squirrels $75,000 Foundation for Anesthesia Education and Research Grant, and a $10,000 Duke SOM Voucher Award - Mihai V. Podgoreanu, MD2012

Determination of the Role of Alzheimer’s Disease Pathways in Post-Operative Cognitive Dysfunction Two-year, $150,000 International Anesthesia Research Society Mentored Research Award

- Miles Berger, MD, PhD 2014

Sirtuin-3 Modulation of Acetylation in the Treatment of Perioperative Myocardial Reperfusion Injury

Effect of an Mn-Porphyrin in Neuropathic Pain

- Huaxin Sheng, MD 2012

- Zhiquan Zhang, PhD 2014

Determinants of Intestinal Epithelial Wound Healing

- Joern A. Karhausen, MD 2012

The role of FXR, TGR5, and the Bile Acid Pathway in the Prevention and Treatment of Chronic Post-Nerve Injury Pain

- Thomas Van de Ven, MD, PhD 2014

BLUEPRINT 2014 | 5

2013 Final DIG Report: Miklos Kertai, MD, PhD Pharmacogenomics of β-blockers: Implication for Postoperative Atrial Fibrillation Figure 2.

Normalized Signal Intensities

One of the objectives of our study was to identify differences in gene expression in human heart tissue in a sample of 47 patients treated with beta-blockers. Of these patients, 13 developed atrial fibrillation after heart surgery, and 34 patients did not. In order to evaluate the pattern of the gene expression data across our samples, signal intensity of each expressed gene was measured and plotted as shown in figure 1. We found that for one patient without atrial fibrillation, the average signal intensity deviated from the rest of the study sample, and thus had to be excluded from subsequent analyses.

Unnormalized Signal Intensities

In table 1, a summary of the probe counts is presented with the range of their corresponding P-values.

Based on the results presented in table 1, only the top two (P<10-5) probes met the adjusted P-value <0.05, indicating genome wide significance. Table 2 summarizes the top four probes that met <20% false discovery rate (adjusted p-value <0.2, a slightly relaxed criteria).

Table 1: Summary of the probe counts based on P-value ranges

Figure 1: Box-plot for the average signal intensity per subject Next, the so-called quintile normalization was used to normalize average signal intensity prior to the data analysis. The data postnormalization is shown in figure 2.

Subsequently, using a designated statistical package, a linear regression analysis was conducted to test the gene expression of each probe between samples that originated from patients with and without atrial fibrillation after heart surgery. This analysis was then adjusted for the so-called atrial fibrillation risk index. Given that these types of analyses are subject to multiple testing, a false discovery rate (FDR) was computed to correct for multiple testing.

6 | DUKE ANESTHESIOLOGY

Table 2: Top four probes that met <20% false discovery rate (adjusted p-value <0.2, a slightly relaxed criteria)

Figure 3: Volcano plot showing our gene expression data

Figure 3 shows a “volcano” plot, which is a type of scatter-plot used to identify changes in large datasets composed of replicated data. It plots significance (P-values in –log10(P) scale) on the y-axis versus fold-change on the x-axis. This plot indicated to us that probe ILMN_1 was up-regulated, while probe ILMN_2 was down-regulated in patients with atrial fibrillation after heart surgery.

-log10 p-value

The top gene identified by the most significant probe has been previously described in association with transcriptional regulation of cell death.

Our next step is to perform a pathway analysis that will help us identify plausible mechanistic pathways involving these top genes in the pathogenesis of atrial fibrillation and lack of effectiveness of beta-blockers for preventing this postoperative complication.

log2 fold change

2013 Final DIG Report: Michael Manning, MD, PhD

Cardiopulmonary Bypass Induced Inflammatory Changes in the Atrial Wall: The Novel Role for Cardiac Chymase produced Angiotensin II in the Development of Atrial Fibrillation Figure 1: Transesophageal burst pacing induces atrial fibrillation.

Three lead EKG demonstrating 30 sec of burst pacing induces Postoperative atrial fibrillation (POAF)

atrial fibrillation with spontaneous conversion back to sinus rhythm.

is the most common complication patients. It is associated with increased lengths of hospital stay, stroke, and both short and long-term mortality. While the

Lead I (mV)

following cardiac surgery and occurs in 40 to 60 percent of

evidence suggest that acute inflammation may play a role in its development. There is further evidence that points to a role

Lead II (mV)

exact mechanism of how POAF develops is unknown, current

these complications have been associated with development of POAF. My long-term goal is to understand the mediators of acute

Esophageal Probe (mV)

inflammation, oxidative stress, fibrosis, and hypertrophy. All of

Lead aVR (mV)

for Angiotensin II as both a promoter and modulator of acute

inflammation that lead to alterations within the myocardium and can promote development of POAF. The DREAM Innovation Grant (DIG) allowed me to conduct initial tests to determine a possible mechanism of this problem. My hope is that these studies will ultimately identify pharmacologically modifiable points in a pathway of damage that would allow for development of a way to

a baseline measurement of how long this atrial fibrillation would last, I exposed the animals to cardiopulmonary bypass with circulatory arrest (CPB/CA). After the animals recovered, I would

prevent POAF and improve patient outcomes.

induce atrial fibrillation again, and what I observed was an

Initially, I found that I could induce atrial fibrillation in a rat

suggested that the heart had undergone some injury that allowed

specimen by episodes of burst pacing (fig. 1). Once I established

increase in the time the animals stayed in atrial fibrillation. This abnormal conduction to persist following induction.

BLUEPRINT 2014 | 7

Following these findings, I began to look inside the hearts of the animals used in the experiments to see what changes had occurred. It appeared that an acute inflammatory reaction had been induced in the heart, with inflammatory cells moving from the blood vessels into the surrounding tissues (see figs. 2, 3).

These histological changes included both increased inflammatory cells and new collagen deposition within the heart where it should not be. These changes were much quicker than previously recognized. Moreover, this inflammatory process was still actively occurring 48 hours after the conclusion of the CPB/CA, and was not associated with a surgical stimulus.

Next, I looked for evidence of increased Angiotensin II signaling within the hearts. Not only were the major components of the angiotensin pathway present in the heart, but they were all upregulated following exposure to cardiopulmonary bypass, with the main enzyme (angiotensin converting enzyme) being up-regulated

Figure 2: CPB/CA results in increased cellular infiltration and collagen deposition. Slides A & D show sham animals undergoing anesthesia and sham procedure. Slides B and E, along with C and F, are two representative hearts demonstrating increased inflammation and collagen deposition. (Forty-eight hours following CPB/CA; Massonâ&#x20AC;&#x2122;s Trichrome stains collagen blue; H&E staining details inflammatory cells-purple from myocardium-pink.)

the most (fig. 4).

Both the increased level of collagen deposition and increased presence of inflammatory cells paired with the changes in the RAS pathway proteins are seen in figure 4. This suggests that these two processes are occurring simultaneously, however this does not demonstrate cause and effect.

Taken together, exposure to CPB/CA appears to increase both key proteins of the RAS pathway, as well as inflammatory cell infiltration in the heart, and produces changes in the heart that supports dysrhythmias â&#x20AC;&#x201C; specifically atrial fibrillation.

I am now expanding my studies in order to better understand the interactions between the molecular changes that I observed

Figure 3: Active inflammation at two days postoperatively.

Inflammatory cells are visible adherent within the vessel, traversing the vessel wall (*), and present in the adventitial space.

within the heart and the conduction abnormalities that lead to atrial fibrillation. I am using the heart tissue and looking to directly measure the levels of Angiotensin II produced during bypass.

Additionally, I have started comparison studies using human atrial tissue samples to validate my findings from the animal studies.

This work was presented at the 36th Annual Meeting of the Society of Cardiovascular Anesthesiologists in New Orleans in April of 2014. I have also received funding from the Society of Cardiovascular Anesthesiologists to continue this important research.

Figure 4: CPB with CA increases regulatory protein levels. Renin, ACE, Chymase, as well as receptor protein levels are increased within 24 hours and remain elevated by 48 hours. (** p<0.05, mean +/- SEM; 8 | DUKE ANESTHESIOLOGY

n=4/group)

2013 Final DIG Report: Steve Melton, MD

Neurointerventional Regional Anesthesia to Improve Hand Rehabilitation in Stroke

our group is confident that we have built a solid foundation for Over the course of this year, collaboration between investigators from anesthesiology, physical therapy, neurology, and the Brain Imaging and Analysis Center has provided the detailed groundwork, preparation, and coordination necessary to facilitate successful recruitment, enrollment, and implementation for this study. While the process of introducing a novel therapeutic strategy into a clinical research setting has been challenging,

The DREAM Innovation Grant (DIG) program was

safety and success.

Having completed manuscripts related to our preliminary fMRI investigation in healthy, human subjects, our group was able to successfully translate data from our previous work to the current project in stroke-affected individuals. After much planning, our group is excited to begin enrollment. Having received partial funding through the DREAM Innovation Grant, enrollment will depend on additional funding. Our group has submitted proposals for extramural funding.

2013 Final DIG Report: Karthik Raghunathan, MD, MPH Comparative Effectiveness in Perioperative and Critical Care Medicine: Crystalloid Fluid Therapy

We studied patients with serious illness that received both Intravenous electrolyte fluids (crystalloid solutions) are routinely used to resuscitate seriously ill patients that have actual or perceived signs of inadequate circulation. There are two major alternatives to intravenous electrolyte fluids: saline or balanced fluids. While the difference in price is small and both are widely available, balanced fluids have been observed to have some theoretical benefits in patients. Despite these benefits, saline currently remains the overwhelming choice in real-world medical ICUs across the United States, with 95% of patients receiving this type of fluid almost exclusively.

Our research aims to answer the question: â&#x20AC;&#x153;Are balanced fluids more effective than saline at lowering the risk of death among seriously ill patients?â&#x20AC;?

fluids, using data from nearly one in five hospital discharges across the country between 2005 and 2010. This data was captured in a large administrative and financial database that had been used for safety studies by the Food and Drug Administration. We used this database to look for differences in the rates of death among similarly ill patients receiving varying proportions of balanced fluids compared with saline.

We found that the use of greater proportions of balanced fluids during initial resuscitation was comparatively safer.

Our observations will be reported in an original manuscript accepted for publication by Critical Care Medicine, a leading journal in the field. While our findings still need to be confirmed in large clinical experiments, our study indicates the potential for substantial benefit to society from switching to balanced fluids. Saline is routinely given to hundreds of thousands of

BLUEPRINT 2014 | 9

patients with serious illnesses each year, and balanced fluids might represent a viable, cost-effective alternative with modestly lower

Figure 1: Receipt of balanced fluids versus in-hospital mortality

risk of death. A figure in the accepted manuscript, shown in figure 1, demonstrates the steady reduction in the risk of death among patients in the hospital who are receiving increasing proportions of balanced fluids early during resuscitation.

The knowledge gained through this study prompted applications for further funding from two sources and, as included in the previous report, the Anesthesia Patient Safety Foundation and Baxter, a major fluid manufacturer.

2014 DIG Report: Miles Berger, MD, PhD

Determination of the Role of Alzheimer’s Disease Pathways in Post-Operative Cognitive Dysfunction

Foundation for Anesthesia Education and Research (FAER).

Over the past year, we have enrolled 48 patients in the ACTIVATE (Alzheimer’s Disease Markers and Cognitive Testing after Inhaled vs.

IntraVenous Anesthetic Treatment in the Elderly) study. These patients will undergo cognitive testing before anesthesia and surgery, as well as six weeks after surgery, and donate samples of the fluid surrounding their brain and spinal cord, called the cerebrospinal fluid (CSF), at these points in time.

Our goal is to identify patients who have post-operative cognitive decline, and then perform a global analysis of the levels of proteins involved in Alzheimer’s disease pathways in these CSF samples using a technique called, “unbiased proteomics.” Our hypothesis is that post-operative cognitive decline is associated with changes in these Alzheimer’s disease pathways.

Over the past year our group has also applied for three extramural grants to further this work. We have submitted grants to the American Foundation for Aging Research (AFAR) and the

10 | DUKE ANESTHESIOLOGY

In May of 2014, we were awarded a two-year, $150,000 International Anesthesia Research Society (IARS) Mentored Research Award, entitled, “The trajectory and significance of perioperative changes in AD biomarkers.” This IARS grant will allow us to expand the ACTIVATE trial by performing functional MRI scans before and after patients go through anesthesia and surgery. This will allow us to look for subtle changes in brain function and connectivity that may underlie post-operative cognitive dysfunction. We greatly appreciate the DREAM Innovation Grant donors for helping us to turn our dream of performing this project into a reality!

2014 DIG Report: Thomas Van de Ven, MD, PhD The role of FXR, TGR5 and the Bile Acid Pathway in the Prevention and Treatment of Chronic Post-Nerve Injury Pain

Thanks to the generous support of the Duke Anesthesiology DREAM Campaign, we have made significant progress toward our goal of understanding a previously unknown molecular pathway the TGR5 - that regulates the unwanted transition from acute to chronic neuropathic pain after surgery. We have found that activating this pathway may be an effective way to reduce inflammation and prevent pain.

Figure 1: Treatment with the TGR5 agonists deoxycholate (DCA) and oleanolic acid (OA) prevents pro-inflammatory chemokine (MCP-1) release in cultured astrocytes

We used cells collected from spinal cord tissue to show that activation of the TGR5 pathway prevents release of substances that cause inflammation (see figs. 1, 2). This result was very exciting because we believe that an inappropriate inflammatory response causes chronic pain after surgery. In addition, weâ&#x20AC;&#x2122;ve shown that activating this pathway in mice relieves acute pain.

Our next important experiment will determine whether activating this pathway can prevent or treat chronic pain in mice after surgery. We have applied for a $1.5 million Department of Defense grant using the preliminary data described above as supporting evidence. I am extremely grateful for the DREAM Innovation Grant award that made this work possible.

Figure 2: Intrathecal injection of 25 micrograms DCA reduced pain behavior in a mouse acute pain capsaicin model

DREAM Campaign Executive Board Joe Farrell

Dr. Joseph Mathew

Chair, Duke DREAM Campaign

Interim Chair, Department of Anesthesiology

Elizabeth Allardice

James Forrest

James Anthony

Jaime Kulow

Dr. Maria Arias

Dr. Jerry Levy

Bud Doughton

Asun Mathew

Elizabeth Perez, RN, BSN Kevin McNeilly, PhD Director, Strategic Planning & Development, Department of Anesthesiology

Catherine Miller Tiffany Nickel

Director of Marketing, Duke DREAM Campaign

Jon Stewart Michele Stone

Steve Steff

BLUEPRINT 2014 | 11

2014 Final DIG Report: Zhiquan Zhang, PhD Sirtuin-3 Modulation of Acetylation in the Treatment of Perioperative Myocardial Reperfusion Injury

The overall goal of this study is to determine how to manipulate Sirtuin-3 (SIRT3), a longevity factor in mammals, to protect the heart from perioperative myocardial injury (PMI). SIRT3 is a protein enzyme that has emerged as a novel target for small molecule activators in extending life span, and for developing new drugs to treat a variety of human diseases, including cardiovascular diseases, like cardiac hypertrophy and heart failure, and cancer, diabetes as well as other degenerative diseases. With the support of this DREAM Innovation Grant (DIG), we have shown the novel role that SIRT3 plays in controlling the cell survival/death decision in a

Nature Communications. Furthermore, our results have been selected for podium presentations at several local, national, and international meetings, including the annual scientific sessions of the American Society of Anesthesiology and the AHA. Using a rat model of heart surgery, we will compare SIRT3 levels in normal rats, rats overexpressing SIRT3 (via ANXA1sp or transgenic methods), and rats lacking SIRT3 or SIRT3-knockout rats, and determine the effect of deleting SIRT3 on cell damage and cardiac function. The findings and the tools derived from this study will provide basic in vivo observations that will guide mechanistic studies.

model of simulated PMI. Figure 1

We have demonstrated the pharmacologic activation of SIRT3, and its capacity to protect heart cells from death induced by simulated surgical stress, such as glucose-oxygen deprivation (OGD). In cultured heart cells, we compared the effect of OGD in normal cells versus SIRT3-deficient cells. To test the effect of OGD on cell survival in SIRT3-deficient cells, we pharmacologically re-introduced SIRT3 activity by treating the

Figure 2

cells with ANXA1sp, a novel small molecule SIRT3 activator.

Cells were then isolated from the heart of an adult rat. SIRT3deficient cells were achieved by introducing SIRT3-specific siRNA. The siRNA-mediated knockdown of SIRT3 expression was confirmed by Western blotting (fig. 1). Normal cells and

Figure 3

SIRT3-deficient cells were pretreated with 10 ÎźM ANXA1sp for 1 hour and subjected to 2 hours OGD. At 24 hours, reoxygenation, necrosis (fig. 2), and apoptosis (fig. 3) were significantly increased in SIRT3-deficient cells compared to SIRT3-deficient cells pretreated with ANXA1sp. For the first time, our findings indicate that SIRT3 plays a pivotal role in controlling the cell survival/death decision in response to surgical stress.

Based on our novel findings, we recently submitted an NIH R01 grant application, an American Heart Association (AHA) Grantin-Aid application, and we will submit a grant proposal to the Mathers Foundation in March. We have filed a US provisional patent (Duke Ref. No. 4227/5405-467PR) and are preparing a manuscript for publication in the peer-reviewed journal, 12 | DUKE ANESTHESIOLOGY

Heart cells deficient in SIRT3 by introducing siRNA (figure 1: Western Blot) showed increased necrosis (figure 2: ELISA) and apoptosis (figure 3: ELISA), which was partially rescued by ANXA1sp. (Ctrl, control; scrR, scrambled RNA; siR, siRNA; SP, ANXA1sp. Data were presented as mean +/- SD, n=3. *P<0.05 and #P<0.01.)

Photo credit:Elizabeth T. Perez

RESIDENCY PROGRAM

Duke ranked 4th among US anesthesia residency programs in the 2014 Doximity/U.S. News & World Report poll

BLUEPRINT 2014 | 13

Photo credit: Elizabeth T. Perez

14 | DUKE ANESTHESIOLOGY

MARK F. NEWMAN, MD

13 YEARS OF LEADERSHIP AS CHAIR OF DUKE ANESTHESIOLOGY For the past 13 years, the Department of Anesthesiology at Duke has flourished under the chairmanship of Mark F. Newman, MD, the Merel H. Harmel Professor of Anesthesiology. With his indomitable spirit, an unwavering commitment to patient care, and a relentless pursuit of knowledge, Dr. Newman has elevated Duke Anesthesiology to be one of the best academic anesthesia departments in the world. In March of 2014, Dr. Newman was elected president of the Duke Private Diagnostic Clinic (PDC), which is the faculty practice group for Duke physicians.

“It has been an honor to work with so many great individuals. Duke Anesthesiology clearly has the best team in the game,” says Dr. Newman.

A Pioneer in Research Dr. Newman’s relationship with Duke University began in 1988 when he joined the fellowship program in cardiac anesthesiology following medical school at the University of Louisville and residency at Wilford Hall United States Air

BLUEPRINT 2014 | 15

Photo credit: Oivind Toyen

Photo courtesy: Dr. Mark Newman

Photo courtesy: Dr. Mark Newman

Photo courtesy: Dr. Mark Newman

Photo courtesy: Dr. Mark Newman

Above (top to bottom, left to right): (a) Dr. Mark Newman in the Duke North operating room, (b) Dr. Newman, with daughters Catherine (Duke 2016) and Sarah (Duke 2007), being honored as the University of Louisville School of Medicine Distinguished Alumni Fellow in 2010, (c) Dr. Newman in Beijing, China, as the invited speaker for the 12th International Congress of Cardiothoracic and Vascular Anesthesia in September 2010, and (d) Long-time faculty, Drs. Fiona Clements and Norbert de Bruijn, with Dr. Newman at their retirement dinner

Force Medical Center (USAF). While training under

interventional trials attempting to reduce the incidence of this

Jerry Reves, MD, and James Blumenthal, PhD, during his

devastating post-surgical outcome.

fellowship at Duke, Dr. Newman developed an interest in neurological outcomes research.

In 2001, Dr. Newman developed the Multicenter Perioperative Outcomes Research Group of the Duke Clinical Research

Dr. Newman turned his passion for research into a lifelong

Institute to study strategies that would improve outcomes of

mission to improve perioperative patient outcomes. This research

patients undergoing surgery and anesthesia. Several grants

has shaped his career and strongly impacted his success.

from organizations, such as the National Institute on Aging;

Considered a pioneer in the field of perioperative neurological

the American Heart Association; the National Heart, Lung, and

research, Dr. Newman has largely defined the now widely

Blood Institute; the Anesthesia Patient Safety Foundation; and

accepted demographic, procedural, and genetic risk factors

the International Anesthesia Research Society, facilitated his

for neurocognitive dysfunction after surgery. Most importantly,

research on the impact of perioperative outcomes (neurocognitive

he has been the prime force behind several, including the first,

decline, stroke, myocardial infarction, and renal injury) on quality

16 | DUKE ANESTHESIOLOGY

Photo courtesy: Dr. Mark Newman Photo courtesy: Dr. Mark Newman Photo courtesy: Dr. Mark Newman

Above (top to bottom, left to right): (a) Division of Cardiothoracic Anesthesiology in 1997, (b) Dr. Newman with emeritus chairs, Drs. Jerry Reves and Merel Harmel, and (c) Drs. Mark Newman, Joseph Mathew, Solomon Aronson, and Stan Shernan at the Duke Cardiothoracic Anesthesiology meeting in Hilton Head, SC

of life following cardiac surgery. Consequently, his research has

alongside the traditional residency program, that allows trainees

resulted in numerous seminal publications in the New England

to get the skills and experience necessary for successful

Journal of Medicine, JAMA, and Lancet.

careers in academic anesthesiology.

Advancing the Department

Dr. Newman also focused on the career development of faculty

During his chairmanship, Dr. Newman worked diligently to

members over the past 20 years. He has personally mentored

further the departmentâ&#x20AC;&#x2122;s educational program, develop faculty,

over 30 Duke fellows in cardiothoracic anesthesiology. Many

and improve department-wide, clinical operations as a whole.

of his protĂŠgĂŠs have gone on to become successful leaders

Within the residency program, Dr. Newman constructed two

of academic medicine in their own right. More recently, he has

continuums designed to integrate advanced clinical and research

implemented a mentorship program within the anesthesiology

training without prolonging the duration of the traditional

department that is designed to support and develop faculty

residency and fellowship. This resulted in the development of

members from the time they enter the department.

the Academic Career Enrichment Scholars (ACES) program, BLUEPRINT 2014 | 17

Photo credit: Elizabeth T. Perez

Above (left to right): Current interim chair, Dr. Joseph Mathew, with former chairs, Drs. Jerry Reves and Mark Newman

To further improve patient care, Dr. Newman expanded the perioperative outcomes database beyond cardiac surgery to assess patients undergoing all types of surgery. He increased operating room throughput and efficiency, and redesigned the departmental compensation plan.

Finally, to ensure that the department would continue to attract the brightest faculty, Dr. Newman successfully created five endowed professorships through philanthropy and sound financial management.

Accolades Over the last 20 years at Duke, Dr. Newman has received numerous

Dr. Newman constructed two continuums designed to integrate advanced clinical and research training without prolonging the duration of the traditional residency and fellowship.

awards, including the Bernard H. Eliasberg Medal for significant contributions to the field of anesthesia, critical care, and pain management; the Golden Stump Award for key contributions to the field of perioperative neuroprotection; and the 2012 Duke Distinguished Faculty Award. Dr. Newman is the senior editor of the textbook Perioperative Medicine: Managing for Outcome and a co-editor of Anesthesiology, a principal textbook of anesthesiology used globally for teaching and reference. He has also written book chapters, editorials, and over 200 manuscripts.

New Beginnings With Dr. Newman taking on his new role at the PDC, the Department of Anesthesiology is under the leadership of the interim chair, 18 | DUKE ANESTHESIOLOGY

Dr. Joseph Mathew, the Jerry Reves, MD, Professor of Anesthesiology. Dr. Mathew came to Duke University in 1998. He has since served the department as the director of perioperative echocardiography; director of the Neurological Outcomes Research Group; director of the Clinical Anesthesia Research Endeavors (CARE) Group; chief of the Division of Cardiothoracic Anesthesiology; and, most recently, as the Executive Vice-Chair of Performance and Operations. â&#x20AC;&#x153;Joseph will work to create an even better reality from our strong departmental vision. He has shown strong leadership and commitment to all of our missions,â&#x20AC;? says Dr. Newman.

Department of Anesthesiology New Faculty Appointments & Promotions July 1, 2013 - July 31, 2014

Warwick Ames, MBBS Associate Professor Track IV Pediatric Division

Miles Berger, MD, PhD Assistant Professor Track IV Neuroanesthesiology Division

Richard Boortz-Marx, MD, MS Associate Professor Track IV Pain Medicine

Thomas Buchheit, MD Chief, Division of Pain Medicine

Anne Cherry, MD Assistant Professor Track IV Cardiothoracic Division

Brian Colin, MD Assistant Residency Program Director GVTCCM Division

Sean Daley, MD Assistant Professor Track IV Cardiothoracic Division

Jennifer Dominguez, MD Assistant Professor Track IV Womenâ&#x20AC;&#x2122;s Division

John Eck, MD Director of Education Development Pediatric Division

Tong Joo Gan, MD, MHS, FRCA Chair, Department of Anesthesiology Stony Brook University

Andrea Goodrich, MD Assistant Professor Track IV Pediatric Division

Nathaniel Greene, MD Assistant Professor Track IV Pediatric Division

BLUEPRINT 2014 | 19

Jason Guercio, MD, MBA Assistant Professor Track IV Neuroanesthesiology Division

Nicole Guinn, MD Director of Center for Blood Conservation Neuroanesthesiology Division

Ashraf Habib, MB BCh, MSc, MHSc, FRCA Interim Chief, Division of Womenâ&#x20AC;&#x2122;s Anesthesia

Thomas Hopkins, MD, MMCi Assistant Professor Track IV Pain Medicine

Hung-Lun (John) Hsia, MD Assistant Professor Track IV Pain Medicine, VAMC

Sven-Eric Jordt, PhD Associate Professor Track III with Tenure Basic Science Division

Miklos Kertai, MD, PhD Associate Professor Track IV Cardiothoracic Division

Nancy Knudsen, MD Professor Track IV GVTCCM

Ryan Konoske, MD Assistant Professor Track IV VAMC

John Lemm, MD Catherine Kuhn, MD Director and Associate Dean, Graduate Assistant Professor Track IV GVTCCM Medical Education Designated Institutional Official

Kelly Machovec, MD, MPH Assistant Professor Track IV Pediatric Division

Elizabeth Malinzak, MD Assistant Professor Track IV GVTCCM Division

Joseph Mathew, MD, MHSc, MBA Jerry Reves, MD, Professor of Cardiac Anesthesiology and Interim Chair

20 | DUKE ANESTHESIOLOGY

Boyi Liu, PhD Assistant Professor Track V Basic Science Division

Cory Maxwell, MD Assistant Professor Track IV Cardiothoracic Division

Holly Muir, MD Professor Track IV Womenâ&#x20AC;&#x2122;s Division

Mark F. Newman, MD Merel H. Harmel Professor of Anesthesiology President, Duke PDC Cardiothoracic Division

Brian Ohlendorf, MD Assistant Professor Track IV Regional Division

Mihai Podgoreanu, MD, FASE Chief, Division of Cardiothoracic Anesthesiology Cardiothoracic Division

Steven Prakken, MD Assistant Professor Track IV Pain Medicine

Quintin Quinones, MD, PhD Assistant Professor Track IV Cardiothoracic Division

Scott Runyon, MD Assistant Professor Track IV Pain Medicine

Scott Schulman, MD, MHS Medical Director of Pediatric Cardiac Anesthesia UCSF School of Medicine

Andrew Shaw, MB BS, FRCA Chief, Division of Cardiothoracic Anesthesiology Vanderbilt University

Mark Stafford-Smith, MD, CM, FRCP(C), FASE Vice Chair of Education Cardiothoracic Division

Madhav Swaminathan, MD Clinical Director, Division of Cardiothoracic Anesthesiology Cardiothoracic Division

Lenny Talbot, MD Assistant Professor Track IV Neuroanesthesiology Division

Shannon Tew, MD Medical Instructor Pediatric Division

Annemarie Thompson, MD Professor Track IV Residency Program Director Cardiothoracic Division

Ankeet Udani, MD Assistant Professor Track IV GVTCCM Division

Ian Welsby, MB BS Associate Professor Track I with Tenure Cardiothoracic and Critical Care Divisions

BLUEPRINT 2014 | 21

d e k n a ch R - ar p To ese R

W Cl or ini ldca C l P las ro s gr am

POWERHOUSE TWO POWERHOUSES JOIN FORCES TO CREATE A COMPREHENSIVE AND COLLABORATIVE PAIN PROGRAM 22 | DUKE ANESTHESIOLOGY

Photo credit: Elizabeth T. Perez

Above (left to right): Leader of the Medical Pain Service, Dr. Steven Prakken; Director of the Clinical Pain Program, Dr. Thomas Buchheit; and Section Chief for Interventional Pain Medicine, Dr. Richard Boortz-Marx

Introducing Duke Anesthesiologyâ&#x20AC;&#x2122;s New Pain Program:

Clinically, Dr. Buchheit saw an opportunity to improve patient

Comprehensive and Collaborative Care

care at Duke by restructuring the Pain Program to include three synchronized services: an outpatient Medical Pain Service

A multi-pronged approach to pain management is now a reality at

(MPS), an expanded outpatient Interventional Pain Service,

Duke. A comprehensive Pain Program that dovetails top-ranked

and a Hospital Consultation Service. These services coordinate

research with an equally powerful clinical program has been designed

medical care across the Duke University Health System (DUHS)

to investigate the causes of pain and develop the optimal methods for

by working with specialists and primary care physicians to risk-

prevention and treatment.

stratify and manage both low and high-risk patients.

Director of the Clinical Pain Program, Thomas Buchheit, MD, and

Medical Pain Service

Director of Pain Research, Ru-Rong Ji, PhD, along with fellow clinicians

Responding to DUHS needs, the MPS team was recruited

and researchers, have been spearheading this initiative to provide a

to not only care for patients with more complex issues, but

comprehensive pain medicine program built on a foundation of basic

to coordinate care with both referring specialists and primary

science and translational research.

care physicians. The MPS team is led by Steven Prakken, MD, a board-certified pain specialist with a clinical background

A Clinical Transformation

in psychiatry. Dr. Prakken has an extensive background in

After managing a multi-hospital pain practice, Dr. Buchheit returned

the pharmacological and clinical treatment of chronic pain

to Duke in 2010 to pursue translational scientific work in pain and to

and manages a team that includes three advanced practice

take on the role of re-organizing and expanding the Pain Management

providers: Karen McCain, Ashley Underwood, and Lisa

Program. He became Director of Pain Medicine in 2013, and has been

Peoples. The MPS team evaluates and manages high-risk pain

working diligently with Dr. Ji to strengthen the critical bond between

patients, assists with physician education in pain treatment, and

bench research and clinical practice.

coordinates pain management throughout DUHS. BLUEPRINT 2014 | 23

The Department of Anesthesiology and the Pain Program are defining standards and best practices not just for DUHS, but also Photo credit: Elizabeth T. Perez

for the state and the region.

Above: The new Center of Pain Medicine

Along with the charge to risk-stratify patients, the Pain Program

was chosen due to its close proximity to the Davis Ambulatory

and MPS also build care pathways, particularly for the high-risk

Surgery Center (where surgical implants and advanced pain

patient groups, throughout DUHS. These initiatives align with

interventions are performed) and also because it has parking

parallel projects that members of the Duke Pain Medicine faculty are

facilities immediately adjacent to the building giving easy access

carrying out across the state in conjunction with the Pain Society of

to patients with limited mobility. Patients will also be able to

the Carolinas and the Community Care of North Carolina’s Chronic

receive complementary Medical Psychology and Physical

Pain Initiative, Project Lazarus. The Department of Anesthesiology

Therapy services in one patient-centered facility.

and the Pain Program are defining standards and best practices not just for DUHS, but also for the state and the region.

Hospital Consultation Service “Across the United States, patients in chronic pain or on chronic

Interventional Pain Service

opioid therapy tend to have longer and more complicated

To further strengthen the new Pain Program, the Department of

postoperative courses, putting them at a higher risk for

Anesthesiology also recruited a new section chief for Interventional

emergency visits and readmission,” explains Dr. Buchheit.

Pain Medicine (IPM), Richard Boortz-Marx, MD, MS. With decades

Therefore, a Hospital Consultation Service, led by one of the

of experience in interventional therapies, implantation techniques,

first advocates for multi-modal analgesia and Medical Director

and cancer pain care, Dr. Boortz-Marx has continued to expand

of Acute Pain Therapy, Brian Ginsberg, MB BCh, was formed at

the role of the IPM team in providing cutting-edge interventional

Duke to work with these patients. Thomas Hopkins, MD, MMCi,

and implantation techniques for the benefit of chronic pain and

a fellowship-trained pain medicine physician, also joined

cancer patients. Along with Dr. Buchheit, the team includes

Dr. Ginsberg. With advanced training in the electronic patient

Scott Runyon, MD; Lance Roy, MD; Anne Marie Fras, MD; and

medical record system, Epic, Dr. Hopkins plays a key role in

Dianne Scott, MD. Two nurse practitioners, Jennifer Parsons and

defining and tracking outcomes through Maestro Care. This

Emily Davis, have also recently joined the team to play a vital role in

outcomes-based research, including the length of a patient’s

coordinating the surgical implant program. They currently coordinate

stay and number of clinic visits, will allow physicians track data to

care for over 100 intrathecal pump patients.

improve patient care and reduce repeat emergency room visits.

The third core member of this team is Dr. Scott Runyon, who

A New Center of Pain Medicine

cares for patients in both the outpatient clinic and the inpatient

In January 2014, the Duke Pain Medicine clinic was relocated to

Consult Pain Service. His work in both services is critical to

a new facility on Medical Park Drive to facilitate teamwork and

further facilitating and defining the best practices for care

enable practitioners to work in the same clinical space. This location

transition. This team is also working with patients in the cancer

24 | DUKE ANESTHESIOLOGY

A world-renowned researcher in pain mechanisms, Dr. Ji was recruited from Harvard in 2012 and entrusted with the responsibility of formalizing and strengthening the research arm of the Pain Program, as well as promoting pain research across Duke.

Research Labs Dr. Ji runs his research operations in the newly renovated Genome Sciences Research Building-I (GSRB-I) on LaSalle Street. This facility houses not only his lab, but also the pain labs run by Sven-Eric Jordt, PhD; Thomas Van de Ven, MD, PhD; and Dr. Buchheit. The close proximity of the labs allows for collaboration and coordination between researchers. Dr. Ji also mentors budding researchers by assisting in grant proposals

Photo credit: Elizabeth T. Perez

and advising them on funding.

Dr. Jiâ&#x20AC;&#x2122;s lab, which is supported by four NIH R01 grants, currently examines pain signaling by working on animal models of pain.

His study focuses on how glial cells regulate pain and how antiinflammatory and lipid mediators derived from fish oil can be used to mediate pain.

Dr. Jiâ&#x20AC;&#x2122;s goal is to move his basic science research forward into translational studies. He has been working with a team of and spine centers, and continues to build initiatives across surgical and medical specialties within DUHS. Research Initiatives In concert with the clinical growth of the Pain Program was an expansion in pain research. A world-renowned researcher in pain mechanisms, Dr. Ji was recruited from Harvard in 2012 and entrusted with the responsibility of formalizing and strengthening the research arm of the Pain Program, as well as promoting pain research across Duke.

In addition to running a state-of-the art lab, Dr. Ji holds pain seminars, journal clubs, and a Duke club. Students interested in pain research from any department (such as neurology, neurobiology, and psychiatry), as well as principal investigators and fellows, are encouraged to attend. Dr. Ji eventually plans to organize both local and regional symposiums, and coordinate pain research on a global scale.

seven investigators, including six fellows recruited from Harvard, and is in the process of hiring more candidates to expand the qualitative scientific base necessary for research.

The second pain lab is run by Dr. Jordt and focuses on the mechanisms that enable humans to sense touch, pain, and irritation. His lab, which is supported by five NIH grants and supplements, aims to identify the molecular components of these pathways and to understand how sensory neurons become sensitized during injury and chronic painful conditions, such as inflammation.

Dr. Jordtâ&#x20AC;&#x2122;s lab is also conducting a new line of research, which focuses on chemosensory mechanisms in sensory neurons and their role in chemical environmental exposures to respiratory and skin irritants. His lab has been able to identify new interactions between the immune and nervous systems that control inflammation in acute and chronic conditions such as infections, asthma, dermatitis, and neuropathies that have revealed novel targets for pharmacological interference.

BLUEPRINT 2014 | 25

Photo credit: Elizabeth T. Perez

Drs. Van de Ven and Buchheit hope to identify new genes and mediators involved in chronic pain and glean information necessary to help alleviate pain in patients, including veterans and the elderly.

Photo credit: Elizabeth T. Perez

Above (top to bottom, left to right): (a) Rou-Gang Xie, PhD student, conducting research in Dr. Jiâ&#x20AC;&#x2122;s lab, (b) The researchers who work in Dr. Jiâ&#x20AC;&#x2122;s pain lab at GSRB-I: Sarah Taves, PhD; Temugin Berta, PhD; Chul-Kyu Park, PhD; Alexander Chamessian, MD/PhD student; Gang Chen, PhD; Rou-Gang Xie, PhD student; Zhen-Zhong Xu, PhD; Qingjian Han, PhD; Sangsu Bang, PhD; and Dr. Ru-Rong Ji

26 | DUKE ANESTHESIOLOGY

Photo credit: Elizabeth T. Perez

Photo credit: Elizabeth T. Perez

Above (left to right): The researchers who work in Dr. Jordtâ&#x20AC;&#x2122;s lab: Maya Kaelberer, BS; Satya Achanta, DVM, PhD; Dr. Sven-Eric Jordt; Anabel Caceres, PhD; and Boyi Liu, MD

In addition to the basic science research in the labs, Drs. Van de Ven and Buchheit are finishing work on their $1.5 million Department of Defense grant that is investigating biomarkers, genetics, and pain phenotypes in a population of injured

Together, we are defining the mechanisms involved in the transition of acute to chronic pain and aim to develop therapies that would reduce the burden of suffering in the future generations.

military service members. They hope to identify new genes and mediators involved in chronic pain and glean information necessary to help alleviate pain in patients, including veterans and the elderly. They now have $2.2 million in follow-up funding for a clinical intervention trial, which they hope will be able to reduce the incidence of chronic pain after injury and allow them to study the genetic and epigenetic mechanisms that occur in the transition from acute to chronic pain.

A Winning Combination The Pain Program at Duke is poised to make huge strides under the able leadership of Drs. Buchheit and Ji. Bolstered by state-of-the-art basic and translational science, the pain team has put in place a plan for coordinated and comprehensive care.

Together, they are defining the mechanisms involved in the transition of acute to chronic pain and aim to develop therapies that would reduce the burden of suffering in the future generations.

BLUEPRINT 2014 | 27

Global Health Update: Ghana

28 | DUKE ANESTHESIOLOGY

Photo courtesy: Dr. Adeyemi Olufolabi

O

Photo courtesy: Dr. Adeyemi Olufolabi

Left to right: (a) Dr. Olufolabi teaching nurse anesthesia interns in the operating room, (b) Dr. Olufolabi and Dr. Bill Nelson, a third-year anesthesia resident, examining an anesthetic machine before it is used

ne of Adeyemi “Yemi” Olufolabi’s, MB BS, fondest

and Ghana. The team members include nurse anesthetists

memories while working in the operating room at Ridge

(CRNAs), obstetricians, neonatologists, residents, and others

Hospital in Ghana was of a patient who came there in

interested in improving maternal care on a global scale. Most

labor. She was in severe pain. Along with Holly Muir, MD,

recently, Duke Anesthesiology’s presence has been particularly

and the rest of the Duke Global Health team, Dr. Olufolabi gave her

strong in Ghana. Duke has partnered with Kybele, a non-profit

analgesia, relieved her pain, and safely delivered the baby.

organization founded by an anesthesiologist, Medge Owen, MD, at Wake Forest University. Kybele’s mission is to improve birthing

Dr. Olufolabi recounted how the patient kept in touch with him

conditions and outcomes for babies worldwide by providing

and expressed gratefulness to the team for the smooth delivery

training and resources to host countries. Consequently, Drs.

of her baby. A few years later, the woman had another child at

Olufolabi and Muir have seen their efforts in Ghana bear

a different hospital. With few healthcare workers and resources

tremendous results, impacting the lives of both patients and

available, she did not receive the same level of attention and

healthcare workers there.

pain relief during delivery. Drawing a sharp contrast in the quality of care she received there, she told Dr. Olufolabi emotionally how she hoped

A Rising Demand in Ghana

that everyone in Ghana could have access to the type of care that she

“At Ridge Hospital in Ghana there are 11,000 child deliveries

received at Ridge Hospital.

annually, up from 4,000 in 2005, with only 3 anesthesia attendings available. At Duke, there are approximately 3,000

Global Health Updates - Ghana

child deliveries annually with 8 attendings. The fundamental

Since 2005, Drs. Olufolabi and Muir, along with other current and former

difference is the sheer number of births and few healthcare

doctors at Duke (Drs. Ashraf Habib, Terrence Allen, Evelyn Lockhart,

workers,” Dr. Olufolabi explains. With the rising number of

and John Schultz) have been taking multi-disciplinary teams to Turkey,

deliveries at Ridge Hospital and few attending physicians

Croatia, Republic of Georgia, Egypt, Armenia, Haiti, Uganda, Nigeria,

present, well qualified CRNAs and midwives have to fill in the BLUEPRINT 2014 | 29

Photo courtesy: Dr. Adeyemi Olufolabi

Dr. Olufolabi teaching students how to give a general anesthetic during Caesarean section

gap in providing quality care. To meet this growing demand, Drs. Olufolabi and Muir helped create a Bachelor’s degree program for CRNAs in Northern Ghana to provide a career pathway for qualified nurse anesthetists. Eventually, they would like to

program, I bought finger pulse oximeters for all of them. A number of students came to the airway course the following year, and told me, ‘I still have my pulse oximeter and it’s the best gift you could have given us. We go to places that don’t have any monitors.’

implement a Master’s Degree program for CRNAs as well.

They are so grateful to become well-qualified CRNAs.”

They have also seen the graduation of the fourth class of nurse

To help their colleagues in Ghana, who have access to minimal

anesthetists from the Nurse Anesthetist School at Ridge Regional Hospital. Before the implementation of this school, Ghana had approximately 500 nurse anesthetists. Now, with nearly 100 new nurse anesthetist graduates, they have been able to increase the

resources, the CRNAs and student CRNAs at Duke have followed Dr. Muir’s lead and launched a drive to collect disposable items, including finger pulse oximeters, to send to Ridge Hospital.

capacity for those delivering safe anesthesia.

A New Maternity Operating Room

Drs. Muir and Olufolabi have been providing additional, on-going

dedicated maternity operating room at Ridge Hospital through

training and leadership programs to keep healthcare workers engaged and informed throughout their careers. Besides holding courses that focus on performing safe and efficient Caesarean sections, they have held two airway courses for CRNAs, a high-risk procedure course, and continuous skill improvement sessions.

Healthcare workers in Ghana appreciate the efforts of the Duke team. Recalling an airway course in January 2012, Dr. Muir says: “After the first class of 120 participants graduated from the CRNA

30 | DUKE ANESTHESIOLOGY

Drs. Olufolabi and Muir have also been successful in opening a collaboration with Kybele, Ridge Hospital, the Ghana’s Woman’s Club (a group of educated women who came together to make a difference in Ghana), and the United States Agency for International Development (USAID).

Originally, Ridge Hospital had four, shared operating rooms (ORs).

Women in need of emergency Caesarean sections had to often wait for an OR to become available. With a dedicated maternity OR, doctors and nurses can now safely care for the large number

Photo courtesy: Dr. Adeyemi Olufolabi

Dr. Olufolabi tutoring new students who are being introduced to the concept of safe anesthesia practice

of cases that come in. According to Dr. Olufolabi, since the

made by the department that must be sustained and developed

team from Duke began their work at Ridge Hospital, the rate of

further.” Duke Anesthesiology has partnered with the Duke Global

mortality and stillbirths has decreased (stillbi r t h s b y 50% at one point), despite the rising delivery rate.

Health Institute to develop a two-year Global Health Fellowship.

An advanced computer system has been set up in the new maternity suite and the OR to collect data. The data from the labor ward is used for presentations both for the stakeholders as well as government officials who

Those accepted into the program will have the opportunity to spend one year of fellowship in the field, and one year at Duke.

The fellowship will enable fellows to make valuable contributions to medical care in underdeveloped countries as well as earn their Master’s Degree in global health. To get more information

control funding.

on the global health efforts at Duke and to learn more about the

Dr. Olufolabi explains: “Each visit has one major conference

www.dukeglobalhealth.org.

Anesthesiology Global Health Fellowship, please visit us online at:

where all the stakeholders come, where we present what we’ve done and where we’re going, so that there is a buy-in of the progress from local stakeholders.”

The Future of Global Health Residents have also been involved in the department’s global health endeavors in Ghana. Dr. Olufolabi, who spent January of 2014 with a resident from Duke, explains: “The residents at Duke are keen in supporting and being a part of the global community. There is definitely a growing interest among our

“There is definitely a growing interest among our trainees to make a difference in the global community.”

- Dr. Adeyemi Olufolabi

trainees to make a difference in the global community, and they recognize that this is an important contribution being

BLUEPRINT 2014 | 31

Photo courtesy: Dr. Richard Moon

CLUES TO SURVIVING LOW OXYGEN ENVIRONMENTS Updates from the Duke Xtreme Everest 2 Project

I

n March of 2013, Richard Moon, MD, CM, MSc, FRCP(C), FACP,

The Trek

FCCP; his son, Peter Moon; Eugene Moretti, MD, MHSc;

After 21 hours of air travel, the Xtreme Everest 2 group arrived in

and Chris Young, MD, along with a group of adventure-seeking

Kathmandu, the first leg of the trek. The team spent two nights at

trekkers from around the world, ventured out with some

Kathmanduâ&#x20AC;&#x2122;s Summit Hotel, where the trek leader, Rob Wymer,

like-minded fellow travellers from the University College, London, UK,

briefed the members on their onward journey. Thereafter, the group

as part of the Xtreme Everest 2 project, to the Mount Everest Base

took a short flight to Lukla, the next stop on the trek to the Everest

Camp. Their goal was to learn how humans successfully adapt to low

Base Camp. Over 10 days, this team trekked 40 miles and climbed

oxygen environments as altitude increases. More importantly, they

8,300 feet to reach the Everest Base Camp at an altitude of

aimed to use this knowledge to develop new therapies for illnesses,

17,598 feet.

like heart attack, stroke, and lung disease, especially as hypoxia or the lack of oxygen can be devastating to the patientâ&#x20AC;&#x2122;s brain and other organs in these diseases.

32 | DUKE ANESTHESIOLOGY

Photo courtesy: Dr. Richard Moon

Photo credit: Dr. Richard Moon

Above (left to right, top to bottom): The Xtreme Everest 2 trekkers: Petrus Fourie, MB; Tsz Hin Kwok; Dr. Anna Grodecki; Dr. Eugene Moretti; Peter Moon; Dr. Chris Young; Ken Stapleton; Mike Teanby; Dr. Richard Moon; Janice Woo; Belinda Schepers; Hemanta Maharaj, MB; and Rob Wymer, trek leader, at 11,300 feet at Namche Bazaar

The Mount Everest expedition enabled the group to collect valuable data on the effects of chronic hypoxia and obtain nearly 3,500 hours of continuous blood oxygen saturation monitoring.

On the way to and from the Everest Base Camp, the members continuously recorded their oxygen saturation, by using pulse oximeters, as well as their heart rates. Their oxygen saturation, which was around 85% in Lukla, decreased to the 70% range as soon as they began to walk. It took around 6 hours to reach their next stop at Monjo, where they recorded an oxygen saturation of less than 80%.

The next day, the group started their 2,000-foot climb to Namche Bazaar, the historic Sherpa capital. At an altitude of 11,500 feet, Namche Bazaar has a population of around 2,000. It also hosted the Xtreme Everest Lab, headed by former Duke faculty member, Monty Mythen, MB BS, MD, FRCA, who is the anesthesia chair at the University College, London. The group spent 2 days in Namche Bazaar acclimatizing for the next uphill trek towards the Everest Base Camp.

BLUEPRINT 2014 | 33

Photo courtesy: Dr. Richard Moon Photo courtesy: Dr. Richard Moon

Above: Trekker with high altitude cerebral edema (HACE) being assisted by helicopter in Lukla, Nepal

Everest Team Reaches Base Camp On April 10, 2013, the Duke team reached the Everest Base Camp and collected data on altitude sickness and oxygen saturation. Unfortunately, on the way downhill towards Dingboche, a team member developed high altitude cerebral edema (HACE) and had to be airlifted by helicopter. Dr. Moon cut short his trek to accompany her to the medical facility in Kathmandu, where the team member made a full recovery. The rest of the team rejoined them in Kathmandu on April 21.

Above: Duke trekkers at Everest Base Camp

This expedition enabled the group to collect valuable data on the effects of chronic hypoxia and obtain nearly 3,500 hours of continuous blood oxygen saturation monitoring.

With this data, the team hopes to gain new insight into the Photo courtesy: Dr. Richard Moon

effects of decreases in oxygen saturation on performance under hypoxia as well as learn how humans adapt to high altitude environments.

Above: Peter Moon at the top of Kala Patthar

34 | DUKE ANESTHESIOLOGY

SPECIAL THANKS TO OUR DONORS A heart-felt thanks goes out to our donors who have given to the Duke DREAM Campaign. This list represents Lifetime DREAM Campaign supporters and those who gave between January 2013 and June 2014. Individuals who have donated for three or more consecutive years are honored as members of the Chairmanâ&#x20AC;&#x2122;s Circle, indicated by an asterisk (*). The names of those who are lifetime donors are indicated by italics.

Doctors Aaron and Genevieve Ali

Drs. Merel H. Harmel and Ernestine Friedl*

Dr. and Mrs. Lloyd F. Redick*

Mr. and Mrs. Robert D. Allardice*

Dr. Albert Michael Hasson

Dr. and Mrs. Joseph G. Reves

Dr. and Mrs. Mike Alvis

Mr. and Mrs. Peter R. Heath

Ms. Lucille Rosenberg

Mr. and Mrs. James I. Anthony, Jr.

Dr. and Mrs. Steven Ellis Hill

Dr. Kenneth Sauve

Anthony & Co.

Dr. and Mrs. Luke James*

Ms. Mimi Seidman

Dr. Paul G. Barash

Dr. and Mrs. Joannes H. Karis*

Dr. Paul R. Shook

Mr. and Mrs. John Borrelli*

Dr. and Mrs. John P. Karis*

Dr. Donat R. Spahn

Dr. Randall P. Brewer*

Dr. Kathryn King & Mr. Douglas King

Mr. Steve Steff

Mr. & Mrs. Paul Bronson

Dr. and Mrs. Stephen M. Klein

Mr & Mrs. Jon Stewart*

Dr. Thomas Buchheit*

The Klurfeld Family

Ms. Sarah L. Stogner

Dr. William Paul Bundschuh

Mr. & Mrs. Stanley Kritzik

Ms. Michele Stone

Dr. James J. Chien and Dr. Michelle W. Lau*

Dr. Catherine Kuhn

SunTrust Investment Services, Inc. (Mrs. Anne Lloyd)

Dr. James Michael Chimiak

Ms. Jaime Kulow

Ms. Leah D. Temkin

Mr. UI IL Chung

Dr. and Mrs. Stephen Kushins*

Mr. & Mrs. Royal Taxman

Clancy & Theys (Mr. Tim Clancy)

Dr. and Mrs. Michael Henry Lasecki*

Mr. & Mrs. Charles Vogel

Dr. Carrie Clarke & Mr. Robert Clarke

Drs. Jerry Levy & Maria Arias

Dr. and Mrs. Anil M. Vyas

Dr. Thomas H. Collawn*

Dr. Labrini C. Liakonis*

Mr. and Mrs. John Wagner

Dr. Brian Alan Craig

Ms. Shelli P. Lieberman*

Dr. and Mrs. David S. Warner*

Ms. Sabrina S. Deaver

Dr. Steve F. Lipson*

Dr. Deryl Hart Warner*

Mr. and Mrs. James H. Doughton*

Dr. and Mrs. Walker A. Long*

Dr. Gregory J. Waters*

Mr. & Mrs. Cy Dudnick

Dr. Andrew G. Lutz*

The Weingarten Family

Dr. Sharon Elias

Dr. Elizabeth Malinzak

Dr. and Mrs. Stanley W. Weitzner

The Herbert H. & Fern Elliott Family Foundation

Martin Marietta Materials*

Dr. and Mrs. Ian Welsby

Dr. & Mrs. Robert Frederick Evans

Dr. and Mrs. Joseph P. Mathew*

Dr. and Mrs. Andrew R. Wiksten*

Mr. & Mrs. Joseph Farrell

Ms. Kit McConnell

Mr. and Mrs. John D. Wolfe

Mrs. Margaret D. Fikrig*

Drs. David L. McDonagh and Anne Tuveson*

Dr. Richard Lee Wolman*

Mr. Robert Finkelstein

Dr. Kevin McNeilly

Dr. Jaimie Yamat

Dr. and Mrs. Paolo Flezzani

Mr. and Mrs. Steven K. Miller*

Mr. & Mrs. Harold Young

Mr. James Forrest

Dr. and Mrs. Richard E. Moon

Dr. Elisabeth J. Fox

Dr. Holly A. Muir

Dr. Angelo V. Gagliano*

Mrs. Gloria R. Newman

Dr. Tong Joo Gan

Dr. and Mrs. Mark F. Newman

Dr. and Mrs. Lynn Darcy George*

Dr. Wendy Pabich

Dr. Mark Allen Gerhardt*

Dr. & Mrs. Tom Pagedas

Mr. & Mrs. Eugene Gilbert

Dr. John V. Parham, Jr.

Mr. & Mrs. Melvin Goldin

Dr. & Mrs. Wulf D. Paschen

Dr. Josef P. Grabmayer*

Ms. Helen M. Pavilonis*

Dr. William J. Greeley and Ms. Cece M. Fortune Greeley

Dr. Ann M. Pflugrath

Ms. Betty Grenda

Mr. and Mrs. Philip Perez*

Drs. James and Katherine Grichnik

Dr. Keith Norris Phillippi*

Dr. Alina and Mr. Sorin Grigore

Ms. Laurie Platt

Dr. Elliott B. Guerrero and Mrs. Karin Bagan*

Dr. and Mrs. Anthony Pollizzi

Ms. Jane Guhl

Mr. and Mrs. Francis T. Quinn, Jr.*

Dr. Nicolas Guillard

Ms. Carol Redding

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Our Mission: Extraordinary care through a unique culture of innovation, education, research, and professional growth.

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