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NIH RECORD, JUNE 27, 2000

Oxygen found to reduce infections after surgery

Pennies' worth of extra oxygen could save millions of dollars in hospital costs by helping to prevent post-surgical wound infection, nausea and vomiting, researchers report.

Clinical researchers have recently demonstrated that a simple and inexpensive change in basic surgical procedures – giving patients more oxygen during and immediately after surgery – can cut the rate of wound infections in half. The work was conducted by the Outcomes Research Institute (http://www.or.org), led by Dr. Daniel Sessler, associate dean and professor of anesthesiology at the University of Louisville in Kentucky. The study, which was largely funded by the National Institute of General Medical Sciences and conducted by Sessler while at the University of California, San Francisco, appeared in the New England Journal of Medicine in January.

Wound infection is a serious and costly complication of surgery. Wound infections can develop into sepsis, an infection in the bloodstream, which is difficult to treat and can be fatal. On average, 2-3 percent of general surgeries result in a wound infection; however, the rate increases to 27 percent in some types of colorectal surgery.

"Our experimental treatment, giving extra oxygen, costs only 3 cents per patient," said Sessler. This inexpensive treatment dramatically reduced the number of infections after colorectal surgery. Patients who suffer an infection after abdominal surgery typically spend an extra week in the hospital at an average cost of $12,500.

Sessler and his team designed the study to test whether higher doses of oxygen would stimulate immune function. A higher level of oxygen is believed to increase the ability of immune system cells known as neutrophils to kill bacteria in wound tissues. Neutrophils surround invading bacteria and expose them to a highly reactiveform of oxygen in a process known as oxidative killing. The researchers reasoned that providing the neutrophils with more oxygen would increase their killing efficiency.

The first step in neutralizing bacteria is phagocytosis, during which the neutrophil literally engulfs a bacterium, walling it off in an internal chamber. The neutrophil then shoots free-radical oxygen molecules into the chamber, killing the microbe. If insufficient oxygen is available, the microbe soon wriggles free of the neutrophil and continues to invade and infect the wound tissue. Ordinary air contains around 20 percent oxygen. The researchers gave the patients four times that amount to raise the level of oxygen in the patient's body tissues. In theory this makes more oxygen available to the neutrophils, ensuring that they never run out of microbe-killing ammunition.

The study involved 500 patients undergoing colorectal surgery in one of three European hospitals. Participants were assigned at random to receive either 30 or 80 percent oxygen along with their anesthesia. Thirty percent oxygen is the minimum concentration used by anesthesiologists in the United States and Europe. The supplemental oxygen treatment continued for 2 hours after surgery. Half of the patients received the lower dose of oxygen, and 28 of them developed wound infections. Only 13 of the patients who received the higher dose of oxygen developed infections.

Researchers working independently of the surgical team evaluated each patient's wounds daily during their hospital stay. These researchers did not know which treatment a patient had received. Patients who were kept in the hospital longer by the surgeons were the same ones noted by the researchers to have wound infections, lending even more strength to the study.

For years, doctors have resisted giving high levels of oxygen during surgery because they feared that it could cause impaired lung function or even partial collapse of the lungs. But an earlier study, also done by the Outcomes Research Institute, demonstrated no difference in lung function after surgery between a group given 30 percent oxygen and one given 80 percent oxygen. The additional oxygen has no known side effects.

Increasing the amount of oxygen during surgery had other benefits as well. A study on a subset of the patients showed that increased oxygen cut in half the rate of nausea and vomiting associated with general anesthesia. Although not life-threatening like a wound infection, nausea and vomiting occur much more frequently – in as many as 7 out of 10 patients – and are the leading cause of unexpected hospital admission after outpatient surgery. In addition to being extremely unpleasant for the patient, these complications place additional burdens on hospitals and may require an ambulance to transport the patient from an outpatient clinic to a hospital. In a subsequent study, the researchers demonstrated that extra oxygen prevented nausea and vomiting as effectively as the leading anti-nausea medication.

While the rate of wound infection in general surgery is not as high as in colorectal surgery, even a small reduction in the rate of infection could produce huge benefits. "You have to multiply that reduction by the 25 million surgeries performed in the U.S. each year," said Sessler. Standardizing the level of oxygen given during surgery at 80 percent has an impressive number of potential benefits. But they are even more striking simply because the cost of the extra oxygen is trivial and administering it is so simple. "The anesthesiologist has to set the dial to something. It's just as easy to make it 80 instead of 30," said Sessler.

-Michael Vatalaro

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