For critically ill patients in hospitals, severe sepsis and septic shock are a major cause of death. In fact, severe sepsis strikes about 750,000 Americans every year and between 28 and 50 percent of these people die. A new study conducted in Australia and New Zealand found a decrease in the risk of death from severe sepsis or septic shock between 2000 and 2012, which coincides with changes in the pattern of discharge of intensive care unit (ICU) patients to home, rehabilitation, and other hospitals. The study, which appears in the Journal of the American Medical Association, may have important implications for hospitals worldwide.

What is sepsis?

A potentially life-threatening complication of an infection, sepsis occurs when chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body. Next, a cascading effect may occur, where organ systems may become damaged and begin to fail. If sepsis progresses to septic shock, a person’s blood pressure drops dramatically, and this may also lead to death. Anyone can develop sepsis and any type of infection can lead to sepsis, but most commonly it begins with pneumonia, abdominal infections, kidney infections, and bloodstream infections that start. In the U.S., the incidence of sepsis appears to be increasing. Early treatment of sepsis, usually with antibiotics and large amounts of intravenous fluids, improves a person’s chance of surviving.

Because invasive devices, such as intravenous catheters or breathing tubes, often lead to infections, sepsis more frequently occurs among patients in intensive care units than the general population. For this reason, the researchers conducted a retrospective study using data from the Australian and New Zealand Intensive Care Society adult patient database and also retrieving population data from the Australian Bureau of Statistics and Statistics New Zealand. They isolated records of 1,037,115 patients treated in 171 ICUs between 2000 and 2012. Of these patients, 101,064 (or 9.7 percent) had severe sepsis, while 15,471 (or 15.3 percent) were 44 years old or younger. Comorbidities were present in 36,915 patients (or 36.5 percent).

The researchers discovered that overall hospital mortality was 24.2 percent over the entire study period: 33.1 percent in patients with comorbidities and 19.1 percent in those without. Yet mortality from severe sepsis decreased from 35.0 percent to 18.4 percent between 2000 and 2012, a relative risk reduction of 47.5 percent. Mortality also decreased in nonseptic patients during that time span similar to patients with severe sepsis. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy according to severity of the disease contributed to this change,” wrote the authors. “The observation that an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings." This result may be key to reducing sepsis in the U.S., where a recent study investigated treatment protocols.

American Study

In a recent five-year study conducted in 31 American hospitals, survival of patients with septic shock was the same regardless of whether patients received the usual standard of care or two other protocols of care. “The good news from this study is that, as long as sepsis is recognized promptly and patients are adequately treated with fluid and antibiotics, there is not a mandated need for more invasive care in all patients,” said Dr. Derek C. Angus, one of the authors of the study.

For this study, researchers randomly assigned patients to receive either Early Goal-Directed Therapy, Protocolized Standard Care, or Standard Care. In each case, the patient was 18 years old or older and the treating physician suspected sepsis. For patients in the Early Goal-Directed Therapy group, doctors inserted a central venous catheter — a long, thin tube placed close to a patient’s heart — to continuously monitor blood pressure and blood oxygen levels. For the first six hours of care, doctors kept these levels within tightly specified ranges using intravenous fluids, cardiovascular drugs and blood transfusions. For patients in the Protocolized Standard Care group, doctors used standard bedside measures like blood pressure (taken using an arm cuff), heart rate, and clinical judgment to evaluate patient status and guide treatment decisions. Doctors kept patient blood pressure and fluid levels within specified ranges for the first six hours of care. For patients in the Standard Care group, doctors administered fluids until the team leader decided that the patient's fluids were replete. The standard protocol did not specify the type of fluid, and doctors did not follow specific guidelines but instead proceeded as they would normally.

The study helped “resolve a long-standing clinical debate about how best to manage sepsis patients, particularly during the critical first few hours of treatment,” said Dr. Donald M. Yealy, University of Pittsburgh. The study was supported by the National Institutes of Health.



 Kaukonen K-M,  Bailey M,  Suzuki S,  Pilcher D,  Bellomo R. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012. JAMA. 2014.

Yealy DM, Kellum JA, Huang DT, et al. A Randomized Trial of Protocol-Based Care for Early Septic Shock. NEJM. 2014.