A nationwide randomized clinical trial led by experts at the University of Pittsburgh School of Medicine found a structured, standardized approach to diagnose and treat sepsis in its early stages did not change survival chances for people who develop this deadly condition.
Their findings, available online and published in the May 1 edition of the New England Journal of Medicine
, could change the way sepsis is diagnosed and treated. Each year, sepsis, the body's response to severe infections, kills more people than breast cancer, prostate cancer and HIV/AIDS combined.
"We found no overall differences in two protocolized approaches when compared to conventional treatment. The study provides strong evidence that will have immediate consequences," said Derek C. Angus, M.D., M.P.H., Distinguished Professor and Mitchell P. Fink Chair, Department of Critical Care Medicine at Pitt, and investigator of the study. "Many organizations have endorsed structured guidelines for sepsis treatment that often call for invasive devices early in care. But with prompt recognition and treatment of the condition, we found that these approaches do not improve outcomes but do increase the use of hospital resources," said Dr. Angus.
The five-year, multicenter study, called "Protocolized Care for Early Septic Shock" or ProCESS, was sponsored by an $8.4 million grant from the National Institute of General Medical Sciences (NIGMS), part of the National Institutes of Health.
"More than 750,000 cases of severe sepsis and septic shock occur in the U.S. each year, most receiving care initially in an emergency department. We've found that if early recognition and treatment happen, one approach to supporting circulation while giving antibiotics is not better than another," said Donald M. Yealy, M.D., a ProCESS investigator and professor and chair of Pitt's Department of Emergency Medicine.
"ProCESS set out to determine whether a specific protocol would increase the survival rates of people with septic shock. Instead, it showed something far more importantthat over the past decade, the care of people with sepsis has significantly improved nationwide," said Sarah Dunsmore, Ph.D., who managed the ProCESS trial for NIGMS. "ProCESS showed that regardless of how the delivery of the interventions was monitored, sepsis patients in these clinical settings are receiving effective treatments."
A 2001 study in a Detroit hospital suggested that early, goal-directed therapy (EGDT), a treatment protocol that includes placing a catheter called a central line in the jugular vein to monitor blood pressure and oxygen levels, as well as delivery of drugs, fluids and blood transfusions according to target levels, reduced mortality by 16 percent.
ProCESS tested whether EGDT was superior to either protocolized standard care (PSC), a simpler strategy that still requires vein access but no central catheter, or the usual care in hospitals across the country, in which the bedside physician directs the course of treatment. All patients in ProCESS were diagnosed quickly and received prompt intravenous antibiotics and fluid resuscitation, but only EGDT required central venous catheterization, sophisticated monitoring and blood transfusions.
Between March 2008 and May 2013, 1,351 patients with septic shock at 31 U.S. hospital emergency departments were enrolled in the trial. They were randomly chosen to receive EGDT, PSC or usual care for the first six hours of resuscitation.
The researchers found no difference in outcomes among the three interventions: at 60 days post-intervention, 21 percent of the EGDT group, 18.2 percent of the PSC group and 18.9 percent of the standard care group had died in the hospital. There were also no differences in mortality after 90 days or one year.
"There have been many improvements in the management of sepsis in the past decade. We examined whether giving the medical team step-by-step instructions to monitor and treat the effects of sepsis could improve survival rates as the previous study suggested," Dr. Angus said. "EGDT, PSC and usual care all offer early diagnosis and methods to deliver fluids, restore blood pressure and monitor cardiovascular function; one was not better than the other to treat the condition effectively." Added Dr. Yealy, "We are not suggesting that sepsis care should be delayed or can be limited."