Sepsis is a serious and often deadly illness, yet it remains an unfamiliar threat to most of the general public, as well as one of the most difficult diseases for doctors to diagnose and treat. The condition, which begins with an aggressive immune system reaction to an infection, kills 18 million people around the world every year, including around 260,000 in the U.S. By many estimates, sepsis—and its most severe form, septic shock—is the leading cause of death for intensive care patients in the U.S. and the 10th most common cause of death for everyone else in the country. Yet only one in five Americans recognizes the term, according to a 2011 study commissioned by the nonprofit group Sepsis Alliance, and of those survey participants who had heard of sepsis, most could not define it.
Even physicians, who learn about sepsis in medical school, often miss its early signs because they mimic other disorders and because the illness progresses so rapidly from what looks like a mild infection to a life-threatening situation. As a result of these difficulties, doctors are often late to launch the necessary interventions, such as antibiotics to obliterate the infection, drugs to counteract a perilous drop in blood pressure, and a mechanical ventilator to raise dangerously low oxygen levels.
“The timing of antibiotics is a critical determinant for whether someone lives or dies,” says James O'Brien, who is medical director of quality and patient safety at Riverside Methodist Hospital in Columbus, Ohio, and serves as an adviser to Sepsis Alliance. But some of the most compelling data out there, he says, shows that only 50 percent of patients with septic shock get appropriate antibiotics within six hours of first being seen by a health professional. “If we had a similar record with getting heart attack patients to the catheterization lab, there would be an uproar,” he adds.
To further complicate the picture, better treatments have been slow in coming. Some are on the horizon—such as an experimental blood test and filtration therapy—but failure of four potential antisepsis drugs in the past two years has discouraged researchers and advocates alike. Carl Flatley, a retired dentist, founded Sepsis Alliance after his daughter died of the syndrome in 2002. “In the 10 years since, we have lost 2.5 million people to this [in the U.S.], and it could take another 10 years before we have something that works,” he says. “We need to move faster.”
Sepsis begins innocuously enough when the immune system performs its usual task of recognizing invading bacteria, viruses or fungi. Immune cells release signaling proteins called cytokines to stimulate one another and overcome the invaders—but for poorly understood reasons, the immune cells release far more cytokines and other inflammatory molecules than is typical. All the extra immune molecules surging through the bloodstream have the inadvertent effect of making blood vessels slack and permeable, reducing blood pressure and allowing the fluid component of the blood to seep into surrounding tissues. The blood components left behind clot in the smallest vessels, preventing oxygen from reaching major organs. At this point, someone with sepsis has transitioned from the earliest stage of the disease, known as systemic inflammatory response syndrome, to the later stages of severe sepsis and septic shock. Confusion sets in, the heart's electrical activity becomes erratic, the kidneys and other organs fail, and blood pressure cannot be raised even with large amounts of intravenous fluids and drugs.
Because the immune system's reaction is responsible for the destructive progression of sepsis, researchers have tried using various drugs to interrupt the chemical cascade that triggers inflammation and clotting. Recent attempts have been disappointing.