2022 IARS Mentored Research Award

William TharpWilliam Tharp, MD, PhD
Assistant Professor, Anesthesiology
University of Vermont Medical Center (UVM)
Burlington, VT

Dr. Tharp’s Research

Impaired Lung Mechanics and Intraoperative Ventilator Induced Lung Injury

Post-operative pulmonary complications are common, costly, and difficult to predict. Impaired intraoperative lung mechanics may lead to alveolar injuries arising from combinations of patient or procedural factors. The magnitude at which impaired lung mechanics leads to pathological damage is not known. Concerted clinical trial efforts at refining lung protective ventilation have yielded marginal improvement in patient outcomes. Human biological data on intraoperative lung injury are nearly absent.

Previously we found a high degree of impairment in lung mechanics during robotic assisted laparoscopic surgery. The data suggested regionally heterogenous ventilation and potential for atelectrauma. The impairment was increasingly severe in subjects with obesity, leading us to speculate about the potential for subclinical lung injury.

This integrated respiratory physiology study aims to determine the relationships between impaired lung mechanics, regional alveolar damage, and obesity. We will first collect blood and bronchoalveolar lavage before and after surgery and measure intraoperative pulmonary mechanics in a cross-sectional study. We will assay for markers of alveolarcapillary disruption and examine their association with lung mechanics and patient factors. We will then conduct a proof-of concept interventional trial, using transpulmonary pressure guided ventilation to improve intraoperative lung mechanics and look for changes in markers of alveolar-capillary damage in blood and bronchoalveolar lavage.

This research is designed to address important, unanswered questions about intraoperative ventilation, lung injury, and obesity. The data from this study will potentially provide biochemical targets and mechanical ventilation parameters useful in refining lung protective ventilation methods. The results will be relevant to a wide audience ranging from basic scientists to clinical anesthesiologists.

Related Publications

Effects of obesity, pneumoperitoneum, and body position on mechanical power of intraoperative ventilation: an observational study
William G. Tharp, et al.

Mechanical power can describe the complex interaction between the respiratory system and the ventilator and may predict lung injury or pulmonary complications, but the power associated with injury of healthy human lungs is unknown. Body habitus and surgical conditions may alter mechanical power but the effects have not been measured. In a secondary analysis of an observational study of obesity and lung mechanics during robotic laparoscopic surgery, researchers comprehensively quantified the static elastic, dynamic elastic, and resistive energies comprising mechanical power of ventilation. They stratified by body mass index (BMI) and examined power at four surgical stages: level after intubation, with pneumoperitoneum, in Trendelenburg, and level after releasing the pneumoperitoneum. Esophageal manometry was used to estimate transpulmonary pressures. Mechanical power of ventilation and its bioenergetic components increased over BMI categories. Respiratory system and lung power were nearly doubled in subjects with class 3 obesity compared with lean at all stages. Power dissipated into the respiratory system was increased with class 2 or 3 obesity compared with lean. Increased power of ventilation was associated with decreasing transpulmonary pressures. Body habitus is a prime determinant of increased intraoperative mechanical power. Results indicate that obesity and surgical conditions increase the energies dissipated into the respiratory system during ventilation. The observed elevations in power may be related to tidal recruitment or atelectasis, and point to specific energetic features of mechanical ventilation of patients with obesity that may be controlled with individualized ventilator settings.