Newswise — Despite continuing improvements in overall delivery of care to critically injured patients, many trauma victims who survive their initial injury will often die of multiple-organ failure following an operation. In a study presented at the 2008 Clinical Congress of the American College of Surgeons (ACS), Bryan A. Cotton, MD, FACS, reported that "implementation of high-dose antioxidant protocol (vitamins C, E, and selenium) resulted in a reduction of pulmonary complications, in general, as well as infectious complications, including central line and catheter-related infections."

Dr. Cotton, who is assistant professor of surgery at Vanderbilt University Medical Center, Nashville, TN, also observed a remarkable decrease in abdominal wall complications—including abdominal compartment syndrome and surgical site infections. When an abdominal wound opens up, the result is not just an infection to be treated with antibiotics, he explained. The wounds need packing and some of them open up to the point where they have to be reconstructed with expensive agents.

"This is a high mortality, high morbidity, may-never-return-to-work-again problem in a young healthy patient," he said. "Abdominal wall complications are enormous, yet we noted a reduction in some of these complications with implementation of antioxidants. Importantly, the biggest difference was in those patients who had a predicted mortality exceeding 50 percent."

Immediately prior to completing this study, Dr. Cotton and his colleagues at Vanderbilt demonstrated that this same high-dose antioxidant protocol resulted in a stunning 28 percent reduction in mortality in acutely injured patients. In addition, patients' length-of-stay in both the hospital and intensive care unit (ICU) were reduced. After the team observed the reduction in mortality after initiating the protocol, they wanted to learn exactly how antioxidants might work. It is all related to addressing the overwhelming oxidative stress, Dr. Cotton said.

He explained that any time a patient has an acute injury, an operation, or some kind of infection, it places a huge stress on the body. This stress can result in injured oxygen molecules called free radicals being released in the body. These molecules roam around, causing considerable damage at the cellular level. This damage is called oxidative stress.

Dr. Cotton said that past research by some renowned scientists in this field has shown a depletion in the store of antioxidants in critically stressed, critically injured patients. Essentially, it appears that antioxidants work as a team in mopping up some of the oxidative stress waste byproducts, reducing the stressors that cause harm.

As Dr. Cotton explains it, antioxidants are like an army of molecular warriors that rush to the site of an injury to fight infection. In the course of doing battle on the front lines, however, most troops are lost early on. When infectious insurgents rise up later on, patients are highly vulnerable to infections. Depletion of antioxidants is one of the mechanisms that explains why we are vulnerable. Antioxidant therapy replenishes those troops to help keep us safe.

"Antioxidant therapy is so simple and that's what throws people off," Dr. Cotton said, confessing that he had some doubts about it at first as well. Then he saw an impressive randomized prospective trial conducted by Avery B. Nathens, MD, MPH, which showed that some inflammatory states and responses were remarkably improved in patients who had received antioxidants versus those who did not. Dr. Nathens' trial did not have enough patients in each arm of the study, though, so they were limited in their mortality conclusions.

"Based on these results, we were inspired to initiate a study with vitamins C and E. When we looked at the literature, however, there were some concurrent studies showing that selenium had an impact too, especially on sepsis and other infectious complications. So we combined all the existing research and did a cost analysis. When we learned it would cost only $11 a patient for a seven-day course of antioxidants, we decided to give it a try."

This retrospective study followed a total of 4,279 patients admitted to the Vanderbilt University Medical Center trauma unit during the study period. High-dose antioxidant protocol was administered to all acutely injured patients (2,258 individuals) admitted to the center between October 1, 2005, and September 30, 2006. This treatment included 1,000 mg. vitamin C (ascorbic acid) and 1,000 IU vitamin E (DL--tocopherol acetate), each routinely given every eight hours by mouth, if the patient could take it that way. In addition, 200 mcg. selenium was given once daily intravenously. Patients received these supplements upon arrival, and they were continued for seven days or until discharge, whichever happened first. Patients who were pregnant or had serum creatinine levels >2.5mg/dL did not receive antioxidants.

A comparison cohort was made up of all patients (2,021 individuals) admitted to the trauma center between October 1, 2004, and September 30, 2005—prior to implementation of the antioxidant protocol. While pneumonia and renal failure were similar between the groups, the incidence of abdominal compartment syndrome was significantly less (90 versus 31), as were catheter-related infections (75 versus 50) and surgical site infections (101 versus 44). Pulmonary failure—meaning the patient could not get off the ventilator—was less as well (721 versus 528).

Dr. Cotton is now prescribing high-dose antioxidants only to the most seriously ill patients in the ICU, as they seem to derive the greatest benefit. He and his colleagues will now focus on dose adjustments and length of administration to see if the doses and duration they are currently using are optimal. They have been approached by several groups that are interested in collaborating and investigating these agents as part of multiinstitutional trials and expanding their use to critically ill nontrauma patients.

"While we are all looking for that magic bullet to cure some of the horrible things that can happen after someone is injured or has an operation, we have something at our disposal," Dr. Cotton said. "It might not be that magic bullet, but it is a very inexpensive and safe way to reduce complications and mortality in the sickest patients."

Assisting Dr. Cotton with this study were Aviram Giladi, BS; Bryan R. Collier, DO, FACS; Lesly A. Dossett, MD; and Sloan B. Fleming, PharmD, all from Vanderbilt. He received no funding for this research.

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2008 American College of Surgeons Clinical Congress