Dr. Geert W. Schmid-Schoenbein, who has been involved in this research for over 25 years, led the team in the Department of Bioengineering at UCSD’s Jacobs School of Engineering. Other authors include David B. Hoyt and Frank DeLano, with contributions made by several other UCSD researchers and graduates.

The research conducted focused on the digestive enzymes that underwent a process called autodigestion and the negative effects that the process has on patients in shock. Autodigestion results in damage to the intestine as well as other organs, which can lead to multi-organ failure and death.

The mucosal barrier in the intestine generally prevents the digestive enzymes from leaving the intestine. However, problems arise in severely ill patients — such as those in shock — because their mucosal barrier breaks down, allowing the enzymes to escape and begin autodigestion.

This research suggests that blocking digestive enzymes through intravenous infusion may stop autodigestion and save the lives of patients.

Intravenous infusion is the process of administering a solution through an infusion set, a bag or bottle containing the solution that enters a patient through tubing connected to a catheter or needle in the patient’s vein. The research also called attention to the fact that there are factors other than bacterial infections that lead to death. Bacterial products, such as endotoxins, cause the breakdown of the mucosal barrier.

“We show that the intervention reduces organ injury and death rate in several experimental forms of shock,” Schmid-Schoenbein said. “The temporary blockade of digestion was actually tried in a very sick patient the first time in 2010, for whom the physicians had exhausted all other options. This patient is alive and well today.”

The researchers started out by examining blood, bacteria and bacterial products, and other markers for inflammation. They discovered, through a bioengineering analysis of the sequence of events that cause organ damage during shock, that none of the factors they examined was the main cause of organ failure, since inflammation remained after the factors were taken away.

The researchers then looked to see which organ became inflamed first and discovered it was the pancreas. They already knew that the pancreas synthesizes digestive enzymes, and they found the intestines also had a lot of inflammation only when those digestive enzymes were present, which made it clear that the digestive enzymes “play a central role in shock.”

“Most clinicians and surgeons are surprised, interested, but also skeptical,” Schmid-Schoenbein said. “This is not surprising, since not a single intervention against organ failure in shock patients has been approved, in spite of clinical trials.”