Sepsis—a systemic inflammatory response to a bacterial infection—can lead to tissue damage, organ failure, and death. Estimates of U.S. incidence range from 894,000 to 3.1 million patients annually, while mortality figures range from 14.7% to 29.9%. In response, the Centers for Medi­care and Medicaid Services (CMS) in October imple­mented a new sepsis care quality improvement measure that requires hospital compliance with multiple pages of checklists detailing actions to be completed within specific windows of time. Based on research and a National Quality Forum (NQF) measure that previously defined the condition, the Severe Sepsis/Septic Shock Early Manage­ment Bundle (SEP-1) emphasizes prompt recognition and early resuscitation and antibiotic administration to improve outcomes and reduce mortality.

Before October, not all hospitals had been using SEP-1’s exact definitions of severe sepsis and septic shock and many are now grappling with the tremendous amount of interdepartmental coordination necessary to meet the measure’s requirements. No matter the challenges, the measure’s goal of saving lives is worth the effort, according to experts.

“If done right, meeting SEP-1 requirements can reduce mortality rates, length of stay, and ICU utilization,” said James Sverha, MD, vice chair of emergency medicine at Virginia Hospital Center in Arlington, Virginia.

Definitions and Debate

SEP-1’s definition of severe sepsis includes a suspected source of infection and two systemic inflammatory response syndrome criteria, plus evidence of end-organ dysfunction. That evidence includes specified systolic blood pressure or drop in this measure, mean arterial pressure, and urine output, and/or particular lab values. The latter include creatinine, bilirubin, platelets, international normalized ratio, partial thromboplastin time, and lactate ≥2 mmol/L.

Many institutions had not been using lactate ≥2 mmol/L as part of the definition for end-organ dysfunction in severe sepsis, according to Sverha and Alison Woodworth, PhD, director of esoteric chemistry, associate director of clinical chemistry, and associate professor of pathology, microbiology, and immunology at Vanderbilt University Medical Center in Nashville.

However, the SEP-1 lactate levels used to define end-organ function are not new, said Craig Coopersmith, MD, president of the Society of Critical Care Medicine (SCCM) and associate director of the Center for Critical Care at Emory University School of Medicine in Atlanta. Indeed, the latest 2012 recommendations from the Surviving Sepsis Campaign—a global initiative to reduce sepsis-related mortality—suggest resuscitation of severe sepsis patients with hypoperfusion defined as hypotension persisting after initial fluid challenge or blood lactate concentration ≥4 mmol/L, he noted. SCCM and the European Society of Intensive Care Medicine (ESICM) direct the Surviving Sepsis campaign.

Some have also questioned the focus on organ failure, Woodworth noted. “People have organ failure for reasons other than sepsis. The concern is that you might treat someone who doesn’t have sepsis.”

SEP-1 defines septic shock as an initial lactate ≥4 mmol/L or evidence of hypotension documented in the first hour following a completed 30 cc/kg intravenous fluid bolus.

To better clarify which patients have sepsis, SCCM and ESICM expect to issue new, outcomes-based definitions later this month, according to Coopersmith. The forthcoming definitions, intended to complement SEP-1, will discuss different concentrations of lactate “as a prognostic factor of mortality in sepsis,” both in isolation and in combination with hypotension, he noted.

Treatment Protocols

SEP-1 sets specific criteria for care of patients with severe sepsis and septic shock. Hospitals have 3 hours from presentation to draw lactate, send blood samples for culture, and begin patients on broad-spectrum antibiotics included in the SEP-1 list. If lactate is ≥2 mmol/L, hospitals have 6 hours to repeat the test. Within 3 hours, septic shock patients must have been started on a 30 cc intravenous bolus and vasopressors. Within 6 hours, they need a volume status and tissue perfusion assessment.

SEP-1’s list of antibiotics that CMS deems appropriate for sepsis includes some medications that are not currently available or may not be appropriate treatment for sepsis and septic shock, explained Ronald Nahass, MD, chair of the Infectious Disease Society of America’s Quality Committee and president of Hillsborough, N.J.-based ID Care. “Furthermore, although the criteria incorporated in the measure create some objectivity, not all patients with those criteria will have sepsis, as such, [and] patients without infection could receive unnecessary broad-spectrum antibiotics which could lead to proliferation of drug-resistant bacteria and Clostridium difficile infection,” he noted. If the causative organism is known, a narrow-spectrum drug may be more appropriate, but SEP-1 does not allow them, he pointed out.

Changes to Improve Sepsis Care

In all, diagnosis and care under SEP-1 has multiple process and outcomes measures and “requires many handoffs and a significant coordination of care between clinicians and hospital units,” observed Christopher Seymour, MD, assistant professor of critical care and emergency medicine at the University of Pittsburgh School of Medicine. He noted that while patients usually present in the emergency department (ED), they will be assessed in another department, and both must document specific care stipulated in SEP-1.

Successfully meeting SEP-1 requirements will involve ED screening tools as part of triage, an electronic notification system, established protocols, and clear and frequent communication among several hospital departments, according to Sverha.

Mayo Clinic Hospital in Jacksonville, Florida used these tactics between September 2013 and September 2014 to achieve a 15.4% mortality rate for septic shock patients, compared to a 30.9% rate for patients who did not receive such coordinated care.

This success hinged on several factors. One is a sepsis “sniffer” computer algorithm that triggered text pages to the ED team lead nurse, who then notified the ED physician responsible for sepsis diagnoses. Especially key was care by a multidisciplinary sepsis and shock response team which evaluated patients within 15 minutes of diagnosis, noted Pablo Moreno Franco, MD, the study’s first author and medical director in the intensive care unit (ICU) and assistant professor of medicine at Mayo Clinic. The team consisted of an ICU physician, fellow, resident, and nurse, respiratory therapist, pharmacist, as well as staff from the laboratory and radiology. ED physicians triaged patients to the medical ICU or progressive care unit, Moreno Franco explained. An internal website, updated weekly, showed how well care complied with sepsis performance metrics.

Using similar tactics, Mayo Clinic Hospital has achieved more than 80% compliance with four key SEP-1 resuscitation elements, Moreno Franco said. These include: lactate testing before or within 1 hour after blood culture; blood culture drawn before antibiotics; antibiotics administered within an hour of severe sepsis or septic shock onset; and appropriate use of fluid bolus.

Help From the Lab

Noting that tests for lactate, platelets, and coagulation are important parts of SEP-1, Seymour suggested that labs set up point-of-care testing (POCT), especially for lactate. That’s already happening at Vanderbilt, which has established a small ED satellite that measures lactate quickly and accurately on a standard automated chemistry platform, as well as metabolic panels, cardiac markers, and coagulation for heart attack and stroke patients, Woodworth noted. Once patients are admitted to the ICU, computer algorithms help flag sepsis patients and guide treatment, she added.

Until POCT costs drop, Mayo Clinic Hospital will use standard lactate tests, according to Moreno Franco. However, with appropriate lab involvement the hospital consistently achieves a 1-hour turnaround time or less, he noted.

Based on his own experiences, Moreno Franco encouraged labs to think of sepsis management as a “team sport.” Meeting the SEP-1 requirements and saving lives of more seriously ill patients requires labs—and all other hospital departments involved in their care—“to engage early, perform at the top of their game, and communicate effectively,” he emphasized.

Deborah Levenson is a freelance writer in College Park, Maryland. +Email: dlwrites@verizon.net.