The development of a personalized lung protective breathing method by William “Gabe” Tharp, M.D., Ph.D., associate professor of anesthesiology at the Larner College of Medicine, is supported by a $923,000 K23 award from the National Institutes of Health.
This new technique will be especially helpful for patients who are at high risk for post-operative lung damage. This includes people who have obesity, people who have experienced chest trauma, or those with lung diseases such as asthma, chronic obstructive pulmonary disease, emphysema, or cardiovascular dysfunction. The method may be particularly effective for patients undergoing surgical procedures in which they are placed in a head-down position for surgery. This means the technique could be used daily in operating rooms around the world.
“During some common surgical procedures, such as removal of ovarian and prostate cancers, the surgeon tilts the patient’s head down so that the patients organs and innards fall away from the surgical site. This places physical pressure on the chest and abdomen that can restrict normal mechanical breathing patterns and cause damage to the delicate gas exchange surfaces of the lungs,” explained Dr. Tharp, who is an investigator in the Vermont Lung Center.
Over the past nine years, Tharp’s research team has measured the forces impacting the lungs during surgery for gynecologic or prostate cancers. They have found that patients with obesity are at high risk for lung damage during these procedures and are more likely to need a lengthy stay in the hospital and sometimes the Intensive Care Unit (ICU).
During surgery, anesthesia causes a patient’s spontaneous breathing to cease. The anesthesiologist uses a mechanical ventilator to deliver breaths to the patient’s lungs while monitoring key settings, such as the positive end-expiratory pressure (PEEP)—the pressure remaining in the airways and alveoli at the end of exhalation. Standard PEEP settings keep a small amount of air pressure in the lungs during the resting phase of breathing to prevent they tiny air sacs in the lungs—alveoli—from fully collapsing when the patient exhales. This stops the air sacs from opening and closing repeatedly, lowering the effort needed for the next breath. Tharp’s research shows, however, that standard PEEP settings are too low for many patients, leading to lung bruising and tissue tears that make it difficult to breathe after the surgery.
“The way we help people breathe needs to be adjusted for different body types.” — William “Gabe” Tharp, M.D., Ph.D.
“The way we help people breathe needs to be adjusted for different body types, and there’s a ton of science and sophisticated imaging that support giving more PEEP,” Tharp said. “Our work has shown that patients exposed to potentially injurious ventilation forces during surgery demonstrate biochemical evidence of alveolar-capillary damage, a sign of lung injury. These data are important because they clearly show that the current paradigm of mechanical ventilation does not prevent injury in a high-risk patient population undergoing a common surgical procedure.”
Tharp’s new study focuses on measuring air movement during each mechanical breath, and piloting the intervention—that is, increasing PEEP. Tharp is recruiting patients scheduled for ovarian or prostate cancer surgeries at the University of Vermont Medical Center. Participants will agree to having tissues from their lungs sampled during surgery, using a bronchoalveolar lavage. Some of the patients will receive standard PEEP while others will receive increased PEEP. The researchers will assess the lung samples for molecular evidence of tissue damage and white blood cells involved in inflammatory reactions. They anticipate recruiting more than 50 subjects for the study over the next five years.
“This potential intervention is elegantly simple and generally safe, it just falls way outside the normal guidelines we use for ventilation,” Tharp said. “These factors make the work very cutting edge with the potential for rapid translation from research to the operating room.”
A K23 award supports the career development of investigators who commit to focus on patient-oriented research. It provides protected time and funding for supervised clinical investigations, working directly with patients to test a new treatment. Tharp’s mentors include pulmonary medicine professors Jason Bates, Ph.D., D.Sc., and Anne Dixon, B.M.B.Ch., M.A., the E. L. Amidon endowed chair of the Department of Medicine.
“This potential intervention is elegantly simple and generally safe … the work [is] very cutting edge with the potential for rapid translation from research to the operating room.” — William “Gabe” Tharp, M.D., Ph.D.
Beyond this specific study, Tharp’s research team will use the biochemical data generated to answer questions about pulmonary dysfunction in obesity. This builds on Tharp’s doctoral dissertation work at the Larner College of Medicine, which focused on obesity and the molecular pathology of neurodegenerative diseases. Tharp’s current research team includes post-doctoral fellow Dylan Casey, Ph.D.’23, who is working on refining the tools and methods for Tharp’s intraoperative respiratory monitoring techniques.
Tharp is the inaugural holder of the Michael O’Reilly, M.D.’90, G’89, Green and Gold Professorship in Anesthesiology. Dr. O’Reilly is an internationally renowned expert in medical technology.
Research like this has contributed to the University of Vermont’s designation by the Carnegie Classification of Institutions of Higher Education as an R1 institution, placing it in the top tier of research universities in the U.S.
