On the alert for a quiet killer

Patients developing sepsis may go undiagnosed because the early symptoms can be subtle or suggest other disorders.

Severe sepsis is the top cause of death in non-cardiac intensive care units (ICUs), according to research in the February 2010 Critical Care Medicine. The Surviving Sepsis Campaign (SSC) in 2002 provided evidence-based guidelines and tools for managing the condition, yet progress has been uneven in different areas of the hospital. In particular, physicians who work on general hospital wards are less likely than emergency and critical care specialists to recognize the warning signs and begin treatment soon enough, experts said.

“We know that the mortality of patients who become septic on the wards is higher than if they come in septic to the emergency department or if they develop sepsis in the ICU,” said Mitchell M. Levy, MD, director of critical care services at Rhode Island Hospital in Providence, professor of medicine at Brown University School of Medicine, and a member of the SSC executive committee.

Bacterial sepsis image with scanning electron microscope Courtesy of Phototake
Bacterial sepsis image with scanning electron microscope. Courtesy of Phototake.

“We suspect patients languish on the wards and go undiagnosed until they get much sicker, and obviously ill with sepsis, and we've missed an opportunity to intervene early,” Dr. Levy added. “The next area of the hospital that I think could have a significant impact on the survival of patients with severe sepsis is the hospitalists in the wards.”

Stealthy menace

Patients developing sepsis may go undiagnosed because the early symptoms can be subtle or characteristic of other disorders. Altered mental status in an elderly patient, for example, may be chalked up to delirium or stroke rather than the organ dysfunction associated with sepsis. Physicians also may focus on patients' underlying infection and lose sight of the more immediate threat of sepsis.

“A hospitalist may get called to the bed of a patient with fever and think, is it a urinary tract infection, is it pneumonia? Without thinking about the systemic response to infection, the doctor focuses on antibiotics and diagnostics as opposed to rapid treatment of sepsis,” said Mark J. Rosen, FACP, professor of medicine at Hofstra North Shore-LIJ School of Medicine and pulmonologist in the division of pulmonary, critical care and sleep medicine at North Shore-LIJ Health System. “Treating the infection and neglecting the septic systemic response may be a killer.”

A patient with some but not all of the criteria for sepsis can look relatively well and still be on the verge of a medical emergency, said Morgan Moncada, MD, director of the hospitalist program at Reid Hospital in Richmond, Ind. “Many physicians don't understand how quickly sepsis can take a patient who looks good,” he said. “I hear that all the time: ‘Oh, he looks good, his BP's fine.’ And I say, ‘Yes, but he still meets the criteria for sepsis.’”

Recognizing SIRS

According to the SSC, patients with an existing infection or a suspected new infection and who meet any two of the criteria for systemic inflammatory response syndrome (SIRS) are considered septic. Those criteria are: hyperthermia (>38.3° C), hypothermia (<36° C), tachycardia (>90 bpm), tachypnea (>20 bpm), acutely altered mental status, leukocytosis (white blood count >12,000 µL), leukopenia (white blood count <4,000 µL), and hyperglycemia (plasma glucose >120 mg/dL) in the absence of diabetes. An SSC screening tool and treatment guidelines are available online.

The next step is to obtain lactic acid levels, blood cultures and complete blood count, the SSC says. A lactate level exceeding 4 mmol/L, in particular, can help identify patients with severe sepsis who have normal blood pressure or who don't appear seriously ill.

“A patient can come in with a normal blood pressure, with a fever but not looking too bad, and then you find out the lactate is 5 or 6,” said Margaret M. Parker, FACP, professor of pediatrics, anesthesia and medicine at Stony Brook University in Stony Brook, N.Y. “That patient is a lot sicker than we sometimes appreciate.”

The importance of education

Educating staff on how to recognize sepsis and customizing a screening tool are key to improving early diagnosis, experts said. The sepsis initiative at Stony Brook University Medical Center, for example, includes group and individual instruction for nurses, and lectures for house staff, residents and hospitalists on how to use the screening tool, said Dr. Parker, who also served on the SSC executive committee.

Mortality from sepsis at Stony Brook has dropped from about 28% in 2006 to about 18% currently, though most of that improvement occurred in the ED, Dr. Parker said.

“Hospital-wide, it has not been easy to get timely diagnosis of sepsis, so over the past few months we've been trying to direct our efforts toward earlier diagnosis on the floors,” she said. “Our rapid response teams screen every patient for sepsis. We're also working with information technology to have the computer flag patients identified with altered mental status and a positive blood culture.”

Unlike the ED and ICU, which essentially have one team of doctors and nurses, there are often several teams on the floors—as well as more patients per nurse. That makes it more difficult to implement processes, such as daily SIRS screening, on the floors than in the ICU, she said.

“We've tried to implement the screening tool on the (general medicine) floors to be done each shift, but that hasn't been as successful,” Dr. Parker said. “Finding the right resident to order labs and make the determination about new infection can be quite a challenge.”


Creating a checklist of criteria to identify sepsis is an idea that sounds simple and can work, although getting physicians to refer to it can be challenging, experts said.

“Getting doctors to agree that protocolized medicine is better than ‘I think’ or ‘in my experience’ is the most difficult part,” said Marc T. Zubrow, FACP, director of critical care medicine at Christiana Care Health System in Newark, Del. “When I get asked to review a sepsis case for quality issues, it's rarely a diagnostic mystery. The problem was that someone didn't realize they were looking at SIRS criteria early on.”

Launched in early 2004, the Sepsis Alert program at Christiana Care began with an intensive educational program focused on early identification of patients with SIRS. Tactics included presentations to nursing and physician grand rounds and to all incoming residents, in-service seminars, videos, posters and internal newsletter articles. Physicians and nurses in the EDs and ICUs received a Sepsis Alert packet (including a care management guideline, a treatment algorithm, a poster, and information to streamline patient identification and management).

In addition, the Sepsis Alert team created a first-dose kit containing single-dose vials of antibiotics and corticosteroids with administration guidelines. Providing members of the rapid response team with the Sepsis Alert packet and medication kit brought these key elements of the program to the bedside of hospitalized inpatients, Dr. Zubrow said; the program achieved a 49.4% decrease in mortality over three years.

“After the initial development phase, we've devoted most of our efforts into reawakening the education process,” said Dr. Zubrow. “I think for the hospitalist, success depends on keeping that radar screen up all the time that this could be sepsis. Think of that diagnosis, and if you're not sure, give them antibiotics anyhow because, clearly, that's what's going to improve your outcomes.”

Keeping vigilant

In addition to those with known infections, patients at higher risk for developing sepsis include the elderly, those who are immunocompromised and those with indwelling catheters, tubes and lines, Dr. Parker said. “The elderly can be particularly difficult to diagnose because they are less likely to have fever with sepsis, which is one of the common flags most health professionals look for, and they are more likely to have nonspecific signs such as changes in mental status,” she added.

Comorbidities such as diabetes, chronic lung disease and heart disease also predispose patients to develop severe sepsis, Dr. Levy said.

“When a patient comes to the ward with bronchitis or low-level pneumonia, or a diabetic patient has a small skin ulcer, those are the patients that physicians and nurses need to watch closely,” Dr. Levy said. “We need to have a heightened sense of anxiety so that we're able to pick up the transition earlier between a simple infection and the development of sepsis or severe sepsis.”

Coordination and communication among departments and between physicians and nurses are also essential to ensuring that septic patients aren't missed. “It's a team effort, and the nurses are my eyes and ears when I'm not here,” said Dr. Moncada. “Everyone needs to be able to recognize a problem and notify the rapid response team, if necessary.”

The sepsis initiative at Reid Hospital, which is not yet a formalized program, began with Dr. Moncada and his hospitalist group. Dr. Moncada, who became a sepsis “champion” after studying critical care and sepsis medicine through a fellowship in 2006, said the first step was educating his hospitalist team about sepsis. As the team became better at identifying sepsis patients, it brought that information to the ED, he said.

“When the ED would call me about a patient, and I would fire questions about white count, fever, etc., they started putting it on their radar,” Dr. Moncada said.

Now, two years later, when the ED calls the hospitalists with an admission, the physicians say, “I think this guy's septic, he's got these criteria,” he noted. “A well-trained hospitalist can bridge the gap between intensive care medicine and floor medicine, and that's exactly what I was doing when I started this effort,” Dr. Moncada said.