Gas PipeLine Summer 2017

Celebrate Research at Stanford Anesthesia

In recent years, Stanford Anesthesia has been a top department in terms of research nationally. The department’s annual research award dinner is a major event to celebrate and enhance excellence with posters and abstracts presenting the latest achievements. It is also an attractive social occasion to connect with each other as our faculty and staff are scattered widely, not only at the main medical center and VA Palo Alto Hospital, but also across the Bay Area. Demands for attending have grown so drastically that a restriction to limit one abstract submission per person has to be imposed. More than 100 people, ranging from student to senior faculty, participated in this year’s event, and the 2017 Research Awards are:

Best Basic Research

An Immune Clock of Human Pregnancy

Aghaeepour N, Ganio EA, Mcilwain D, Tsai AS, Tingle M, Van Gassen S, Gaudilliere DK, Baca Q, McNeil L, Okada R, Furman D, Wong RJ, Winn VD, Druzin ML, El-Sayed YY, Qyaintance C, Gibbs R, Darnstady GL, Shaw GM, Stevenson DK, Tibshirani R, Nolan GP, Lewis DB, Angst MS, Gaudilliere B

Best Clinical Research

A Randomized Trial of Perioperative Gabapentin to Promote Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort

Hah J, Mackey S, Efron B, McCue R, Goodman S, Curtin C, Carroll I 

Best Data Analysis Research

Predictors of postoperative pain in a cohort of 1,008 patients undergoing spine surgery

Baca QJ, Marti F, Gaudilliere B, Aghaeepour N, Angst MS

Best T-32 or FARM Fellow Research

The hippocampal extracellular matrix regulates pain and memory dysfunction after peripheral injury

Tajerian M, Hung V, Nguyen H, Huang TT, Clark DJ

The 2017 awards reflect a number of new research trends at Stanford Anesthesia. For example, data analysis research has developed rapidly with the establishment of several major databases such as Collaborative Health Outcomes Information Registry (CHOIR) and the recent recruitments of core faculty and staff in big data.  In addition, increasing cross-departmental and cross-institutional collaboration are seen. The Guest Commentator of Research Award Dinner, Dr. Michael Gropper, Chairman, Department of Anesthesia and Perioperative Care at UCSF, applauded the broad research topics of 2017 awards and urged greater collaboration between Stanford and UCSF anesthesia, which have a strong tradition of working together. The two departments started a biennial joint research retreat several years ago and planning of this year’s event is currently underway.

Photos from the Event

Dr. Jennifer Hah (right) in Q&A with Dr. David Clark after award presentation. Her perspective trial with 422 patients showed no effect of perioperative gabapentin on time to pain cessation after surgery but a 24% increase in the rate of opioid cessation, with more impaired coordination and rash, and less constipation. 

Dr. Quentin Baca presenting the research which identified 8 robust predictive factors (Sex, preoperative pain, duration of surgery, remifentanil use, ketamine use, non-opioid intraoperative pain medication use, volatile anesthetic use, and PACU morphine equivalent consumption) and 3 less robust predictive factors (Age, premedication with opioids, and combined IV and volatile anesthetic use.) for postoperative pain.

Dr. David Clark presenting the award to Dr. Maral Tajerian (right), a T32 fellow. Her study used tibia fracture male mouse model of chronic pain, and found that deficits in working and location memory was associated with increased hippocampal LTP, decreased dendritic complexity, altered extracellular matrix microarchitecture and decreased extracellular matrix rigidity. Hippocampal extracellular matrix exhibited various biochemical changes and a reduction in specialized extracellular matrix nets around inhibitory interneurons potentially accounted for the increased LTP.

Guest Commentator of the evening, Dr. Michael Gropper (center), Chairman, Department of Anesthesia and Perioperative Care at UCSF with Dr. Ronald Pearl (right), Chairman, and Dr. David Clark (left), Vice Chair of Research, Stanford Anesthesia

Dr. Brice Gaudilliere (right) receiving award from Dr. David Clark, Vice Chairman of Research. The study collected all major immune cell subsets in serial blood samples throughout pregnancy and demonstrated the chronology of immune adaptations 

Anesthesia’s Early Career Faculty in Full Bloom to World-Class Principal Investigators

Dr. Gregory Scherrer in his laboratory

Stanford Anesthesia has a rich history of research. Our faculty have set standards and changed practices, from George Albright’s research that changed the use of bupivacaine, David Gabba/ Kevin Fish/Steven Howard’s publication on Crisis Management in Anesthesiology, to Sean Mackey’s work in imaging and pain funded by the National Institutes of Health. Now, a new generation of faculty carry on the tradition. Their topnotch research breakthroughs in basic and clinical areas were published in prestigious journals recently.

In Nature Medicine, a multidisciplinary team from our laboratories at 1050 Arastradero and VA Palo Alto reports identifying the source of opioids’ side effects and their potential remedy. This will pave the way to separate them from pain relief properties and to make the painkillers safer.

Patients taking opioid painkillers inevitably face two side effects: a growing tolerance and a paradoxical increased sensitivity to pain.  As a result, higher doses of opioids are needed to maintain pain relief. This increases both the risk of addiction and respiratory failure. Opioid overdoses were responsible for more than 20,000 deaths nationwide in 2015, and are now the leading cause of accidental death in the United States.

Dr. Gregory Scherrer, an Assistant Professor who joined Anesthesia 5 years ago, led the study which identified the receptors for opioids producing tolerance and increased sensitivity to pain in animal model. The research also revealed that a commercially available drug could eliminate the two side effects without reducing pain relief.  “We demonstrate that these two side effects can be drastically reduced with co-administration of methylnaltrexone bromide, currently used to combat constipation, which is another unwanted side effect of opioids” Scherrer said. Methylnaltrexone bromide has been approved by the Food and Drug Administration. It’s a safe drug. Therefore, there is a great potential for translating the discovery made in laboratory to the clinic. In fact, the future implications for possibly reducing the opioid dose needed to maintain pain relief go beyond the clinic. “The issues of drug abuse and exposure which can lead to heroin abuse are huge problems,” Dr. David Clark, Professor and Department’s Vice Chair of Research, adds. “By limiting the dosages of the drugs given to the patient, we also reduce the amount of these drugs leaking out into the community.”

In addition to the immediate translational value, the study also brings a conceptual advance in our understanding of molecular mechanism of action of opioid. It shows that contrary to the prevailing view in the field, nociceptors, the sensory neurons detecting pain signals, but not microglia, specialized macrophages capable of phagocytosis that protect neurons of the central nervous system, are the initiators for opioids’ side effects. This will have far-reaching impact on the development of therapeutic strategies. 

In Journal of Immunology, a clinical study on next generation of precision medicine from our “immune signature research cluster” was lauded in a commentary section reserved for the most impactful articles published in the journal.  

Dr. Brice Gaudilliere and his team used a single-cell mass cytometry assay to compare all major immune cell subsets from maternal peripheral blood with fetal cells from umbilical cord blood at the time of scheduled Caesarian delivery following healthy pregnancy. A graphical approach was developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. These data build the core reference for better understanding the factors contributing to preterm birth and other complications of pregnancy and derive personalized diagnosis and treatment of adverse maternal and neonatal outcomes.

Dr. Gaudilliere joined Stanford Anesthesia as a resident and established his independent research group 2 years ago with the appointment to faculty. The team’s work is an example of Stanford Medicine’s focus on precision health - to better predict individual risks for specific diseases and arm clinicians with information to care for patients with individualized diagnosis and treatment. 

… and Organized to Collaborate

From front left- Eric Sun, Catherine Chen, Manch Lee, Boris Heifets, Brice Gaudilliere, Zhonghui Guan, Viv Tawfik, Liz Whitlock, Mike Bokoch

Academic excellence is often achieved when people break down boundaries to work together. Anesthesia has been actively promoting collaborations within and beyond Stanford.

The UCSF and Stanford Departments of Anesthesiology have a long, collegial history. Before  1960 and briefly in 1997-1998, two medical faculties were actually one combined health care system. In order to keep this longstanding relationship going, a UCSF/Stanford Resident and Junior Faculty Research Dinner was organized to get junior anesthesiologist-scientists from both institutions together to discuss research and mentorship. The dinner was attended by 5 people from UCSF including Catherine Chen, Liz Whitlock and Michael Bokoch- all junior faculty graduates from the UCSF research track, Man-cheung Lee, a current T32 fellow and Zhonghui Guan, an Assistant Professor pain clinician and researcher. Representing Stanford were four recent FARM graduates: Brice Gaudilliere, Boris Heifets, Eric Sun and Vivianne Tawfik. Topics discussed were the newly formed early-Stage Anesthesiology Scholars (eSAS) group, an international networking forum for junior academic anesthesiologists (esashq.org) as well as grant writing and career planning. The best part of the evening was celebrating grants awarded as several attendees had recently received fundable scores on their applications to NIH R- and K-awards. This collegial tradition will continue with the strong supports from both institutions, Drs. David Clark and Ron Pearl at Stanford and Drs. Judith Hellman and Michael Gropper at UCSF.

New Textbook Published

Stanford anesthesiologists have made major contributions to medical education. Since 1990’s, a number of reference books published by our faculty members, such as Anesthesiologist’s Manual of Surgical Procedures by Richard Jaffe and Stanley Samuels, have become must-reads in the field. Dr. Jaffe, together with Dr. Philip Larson (Chairman of Anesthesia at Stanford during the 1980’s), now add a new one, Practical Anesthetic Management: The Art of Anesthesiology, with a difference.

In the era of evidence-based medicine with the hype of precision health, the quest for pragmatic balance in maintaining the highest quality of anesthesia care ushers an important role for the art of anesthesia. “The art of anesthesia encompasses a whole host of practices that are based on long- standing, effective experiences and common sense.” Dr. Jaffe comments, “When combined with the science of anesthesia, the art of anesthesia gives clinicians powerful tools that will make their practices safer, more effective, and efficient and will bring greater satisfaction to their patients.”

This book is quite different from ordinary references of anesthesiology, which usually contain an encyclopedic knowledge of the specialty, documented by double-blind studies and scientific validation. Drs. Larson and Jaffe have supervised tens of thousands of anesthetics, and taught hundreds of residents the finer points of clinical care. Together, they own decades of anesthesia wisdom. The book shares their experience and addresses key topics where the art of anesthesiology has been generally overlooked, misunderstood, or forgotten. Written for anesthesiology residents in training and practicing physicians, this practical guide focuses on giving clinicians the tools to create better practices while cater to patient satisfaction. It also covers topics like preoperative evaluation, tips on blood-gas analysis, and essentials of airway management, completed with accompanying videos. 

Sir William Osler famously said, “The practice of medicine is an art based on science”. It is equally important for clinicians to know when the science of medicine should not be applied to patients. Practical Anesthetic Management: The Art of Anesthesiology provides teachers and students of anesthesia a refresher - There is an art to anesthesia and anesthesiologists should not limit patient care to the exclusion of common sense and clinical experience.

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