One of the best advantages when starting a company is ignorance. Ask Pramod Bonde, MD, an associate professor of surgery, and a recipient of the 2023 Yale Faculty Innovation Award. His project targets harmful reflux and aspiration in patients who are intubated and supported by mechanical ventilation.
“I always say that ignorance is an opportunity because if you don't know anything it forces you to look at the old problems in a novel way. We assume that solutions are complex. But solutions are extremely easy. It's asking the right questions that is complex. And that's exactly what we did,” said Dr. Bonde.
Dr. Bonde founded PiroGon Inc. in 2022. For two decades he studied the interaction of electromagnetic spectrum with biological systems and how gastroesophageal reflux leads to aspiration related lung injury. During the COVID pandemic he served in the Intensive Care Unit (ICU) using a heart-lung machine called ECMO (Extra Copper Membrane Oxygenation Support). The experience inspired a novel electromechanical approach to treat aspiration-related lung injury due to acute gastroesophageal reflux.
An ECMO machine removes carbon dioxide and returns oxygen-filled blood back to the body. “Every other heart surgeon in the country pitched in during the COVID pandemic. There was a lot that we learned through that process,” he said.
After the initial viral insult, over 50 percent of survivors continued to get lung injury due to aspiration of gastric contents while on ventilator hampering recovery, leading to ventilator associated pneumonia. When looking at non-COVID patients needing ventilatory support, this also poses risk if they were to need ventilatory support for more than 48 hours.
“The stomach contains a highly acidic solution to digest food. The lower esophageal sphincter prevents backward flow of this gastric contents. However, this lower esophageal valve becomes dysfunctional when patients receive sedatives, opiates, and anesthetic agents to help them tolerate the breathing tube which is inserted to help them breath on a ventilator,” said Dr. Bonde. This allows gastric contents to spread and spill over into the lungs causing injury. To prevent this injury a patient’s head at the end of bed is raised 30 to 45 degrees. This may not happen consistently due to low blood pressure or procedures where the patient lies flat. Antiacids lead to bacterial overgrowth due to reduced acidity and randomized clinical trials have shown that promotility drugs are ineffective at preventing aspiration related lung injury. Current guidelines for preventing aspiration-related lung injury requires additional training for ICU staff.
“This was a problem that was there for all along. We do a successful surgery, only to lose the patient because they get aspiration related lung injury, and they go on to develop ventilator-associated pneumonia,” said Dr. Bonde. Despite the availability of anti-acid drugs, ventilator-associated pneumonia is a recurring cause of morbidity and mortality. “There are many surgical and endoscopic ways of regaining the control, but none of those options are available for what we call acute reflux in patients,” he added.
Aspiration can lead to ventilator associated pneumonia, which is associated with 1 in 25 deaths in ventilated patients. Each year in United States, 15 million patients undergo insertion of a breathing tube in operating rooms. Outside of operating room another 650,000 breathing tubes are inserted in the hospital and 350,000 in the emergency room to prevent aspiration. “This is the most vulnerable population of patients because they can't speak for themselves and they're dependent on healthcare providers to be their advocate,” he said.
PiroGon stops this reflux by using a neuromodulation exoskeleton which can accommodate existing feeding tubes that maintains the right pressure between the food pipe and the stomach and prevents the backward flow of gastric acid. Such fundamental exoskeleton has wide application besides stopping reflux as it can be used in situations where neuromodulation is desired within the human body. PiroGon has a fully functional product prototype with robust preclinical data and is in talks with the FDA for the best way forward to bring this technology to patients.
Tools developed through PiroGon could become a standard of care for surgical procedures. “A third of the anesthetic deaths can be attributed to the sudden reflux and the lungs getting damaged because of this stomach acid. So, it's a significant problem,” said Dr. Bonde.
The Yale Faculty Innovation Award provides an opportunity to solicit feedback from members of the Yale community and other innovators. “Yale believes in innovation and entrepreneurship,” said Dr. Bonde. “Innovation and research are only worthwhile if it improves patient outcomes and save lives. That is what we are striving for.”
Dr. Bonde believes that every physician or surgeon is capable of innovation. His first company developed a mechanical circulatory support device for chronic heart failure.
“The first question an innovator should ask is, ‘What is going to put me out of business?’ It begins with tweaking a suture or the way to remove certain diseased organs, or part or whole of a tumor. The difference is whether are you able to take that innovation and turn that into a viable venture.”
The first question an innovator should ask is what is going to put me out of business?’
Pramod Bonde, MD
Dr. Bonde received the Sezai Award for developing the novel wireless energy transfer system for powering ventricular assist devices and Willem Kolff/Don B Olsen award for Innovation in artificial heart development. He serves as the president of American Society for Artificial Internal Organs (ASAIO), which addresses complex challenges in medical devices and artificial heart development.
“How you come up with these things is simple. Do you really believe in it? Do you follow up with it and work across your comfort zone? Talk to engineers. Look at fundamental physical processes and mechanisms, their limitations and see if you can apply them. Then you work on a solution and validate it. Once you pass that first hurdle, you need to persevere and convert that idea into a viable option. The next task is to convince the business community that this will benefit people and have a revenue stream.”
Dr. Bonde shared additional advice for aspiring inventors. “You need something that you can put together, but at the same time something that you can intellectually protect because you owe it to your patients, their families, your investors, the engineers, and the physicians who are working with you to have a secure intellectual property. Even if you are the busiest surgeon you need to ask what is going to replace me and then work towards that. Know the limitations of what you are currently doing. That's the only way you can invent tomorrow's technology.”
Know the limitations of what you are currently doing. That's the only way you can invent tomorrow's technology.
Pramod Bonde, MD
“No operation has lasted for more than 50 years. History is evidence of that. We started with bypass surgery and now there are a subset of patients who benefit more from stents than surgery. You need to constantly have an open mind. It's wrong to think that surgery is bad and non-surgery is good but should continue to explore how you can move to the next solution.”
The Yale Faculty Innovation Awards supports innovations that impact the world's greatest challenges. To learn more about funding for faculty-led projects visit, Yale Ventures.