Defeating Sepsis: 25 Percent by 2009
When someone contracts an infection, the body’s natural defense system usually fights back, routing the infection and restoring equilibrium. Not so for the estimated 750,000 Americans per year who develop severe sepsis, septic shock, or septicemia. Because of what is thought to be a chemical reaction gone awry, when these patients encounter a dangerous pathogen, passed along by an infected person or object, their defense systems overreact, setting off chain reactions that can be catastrophic. The “sepsis syndrome,” as it’s often called, includes gross inflammation, low blood pressure, and many dispersed, tiny blood clots, all of which deprive the body of vital oxygen, damaging — even destroying — major organ function and body tissue.[1]
Unusually lethal, severe sepsis quickly kills about 30 percent of those who develop it and, as a result of lingering damage, another 20 percent die within six months. Quick diagnosis and thorough treatment are key to saving lives but also can be difficult to achieve. Sepsis often develops suddenly, with symptoms — fever, chills, nausea, diarrhea, rapid heart and respiration rates — that can easily be misinterpreted, delaying treatment past the point of effective intervention. Once treatment begins, it may not be comprehensive, leaving a patient vulnerable to ancillary insults, such as a depressed heart rate and hyperglycemia. The disease can frustrate even the most vigilant caregivers. Common infection sites are the lungs, urinary tract, abdomen, and pelvis, but, in 30 percent of patients, the infection source cannot be traced and the course of the disease is often unpredictable.
Anyone whose immune system has been weakened by physical trauma, substance abuse, or debilitating medical treatments is at higher risk for sepsis, but seriously ill hospitalized patients are the most vulnerable. Surrounded by the drug-resistant pathogens often found in hospitals, these patients are the most likely to suffer from other underlying diseases, have a history of extensive use of antibiotics, and tend to be hooked up to invasive equipment — any one of which increases the odds of developing a serious infection.
With aging populations, increased use of invasive medical technologies, and a growing number of cancer and HIV patients, experts predict a steady increase in the global incidence of severe sepsis — currently estimated at 13 million cases — over coming decades. However, efforts to alter this bleak picture are accelerating. In 2002 the US Society of Critical Care Medicine, the European Society of Intensive Care Medicine, and the International Sepsis Forum launched the Surviving Sepsis Campaign (SSC), to reduce the relative risk of sepsis deaths by 25 percent globally by 2009. The focus of the initiative has been to build awareness of the issue, improve early and accurate diagnosis and treatment of sepsis, and develop global standards of care.
By early 2004, evidence-based clinical guidelines for the resuscitation and management of patients with severe sepsis were published in leading medical journals and on the SSC website (translated into six languages), along with educational materials, advice, and support for both clinicians and families of patients. Health systems around the world were invited to join the global effort, simply by implementing the site’s recommendations or, if willing, by also sharing patient charts so the SSC can analyze what progress is being made toward the goal of 25 percent reduction in the risk of death from sepsis.
To help integrate the clinical guidelines into bedside practice, the SSC joined forces with the Institute for Healthcare Improvement (IHI), distilling the guidelines into articulated protocols, or “bundles.” In 2007, the SSC unveiled two bundles for effective intervention and management of sepsis. “The objective of both bundles is to improve blood and oxygen flow throughout the body, particularly to the organs,” explains Sean Townsend, MD, an IHI faculty member who supervised the project and who serves on the SCC executive committee.“One bundle addresses the acute phase of severe sepsis; the other addresses the non-acute phase, which is just as important.”
The Severe Sepsis Resuscitation Bundle contains up to seven steps, depending on circumstances, which must be started immediately and accomplished within six hours of when a patient first presents with the infection. The steps include: confirming the presence of sepsis; identifying the exact type of infection and administering the antibiotic appropriate to that infection; restoring blood pressure levels, generally by administering fluids; and verifying that oxygen is reaching vital organs.
The Sepsis Management Bundle contains four back-up steps to be considered immediately and, if indicated, completed within 24 hours of sepsis being diagnosed. These steps are: use of low-dose steroids if fluids were not effective in restoring blood pressure; an evaluation to determine if other drug therapies are needed based on disease severity; control of glucose levels; and, for patients on mechanical ventilation, maintenance of proper settings to avoid tissue damage.
To date, 41 countries — from Brazil to Wales, including Colombia, Slovakia, and five hospitals in China — are participating in the Surviving Sepsis Campaign, and roughly 10,000 patient charts have been submitted via downloadable data collection software available on the SSC site. The US has the largest number of SSC sites: 54 in 19 states, plus Washington, DC.
Among the first to sign on was the Colorado Critical Care Collaborative, a coalition of 14 hospitals across the state affiliated with the Colorado Hospital Association. Dubbed “C4” by its members, the voluntary multi-professional critical care provider organization seeks “to improve outcomes in the most cost-effective manner through multidisciplinary efforts.” The SSC’s objectives and approach were considered a good fit as an initial collaborative project. In 2005, C4 members agreed to adopt the SSC guidelines — now codified into bundles. The experience of the intervening two years shows that they have the potential for significant impact, according to Ivor Douglas, MD, MRCP (UK), vice-chair of C4 and Chief of Pulmonary and Critical Care at Denver Health, an integrated community academic health care system. “Our data indicate that, when both bundles are perfectly administered to a patient with severe sepsis, twice as many patients survive as when only one or partial bundle of care is used.” Unfortunately, says Douglas, progress has been uneven in both uptake of the bundles and perfect adherence to the protocol. “Unless there’s an in-house champion and the hospital has really bought in to the notion of protocol-driven, bundled care for sepsis, it can be a struggle,” he observes. “Even then, there may be competing interests that take attention away.”
Still, he says, “the sepsis domain has set an important precedent” for the entire C4 effort. “The strength of the SSC approach has set up the framework for future campaigns.”
Sentara Healthcare
In September 2006, Sentara Healthcare — a network of seven hospitals in southeast Virginia — became the largest, most integrated US system to join the Surviving Sepsis Campaign, adopting the SSC goals as part of its 2007 performance improvement program. System-wide, 15 in-service educational sessions were held for physicians, nurses, therapists, and administrators. Bolstering the training are new resources to encourage and facilitate consistent use of the bundles, such as revamped order sets and the addition of sepsis screenings to nursing shift change reports.
Sentara has implemented a data collection system that takes accumulated sepsis patient information from each individual hospital site and submits it nightly into a system-wide database that ultimately merges it with all other important clinical information about that patient (identifiers are scrubbed before the data is submitted to the SSC). Bundle performance is monitored weekly at the individual hospital level to assess compliance with the SSC goals and address local process-related issues. The merged database is utilized to analyze system-level outcomes on a monthly basis and reported to Sentara’s system quality leadership team. Based on early extrapolation, the clinical leaders at Sentara expect the SSC bundles will save about 200 lives per year.
University of Minnesota Medical Center
At the University of Minnesota Medical Center in Minneapolis, SSC guidelines have been used informally since their 2004 publication, says Henry Mann, Pharm D, FCCP, FCCM, FASHD, Director of the Center for Excellence in Critical Care at the University of Minnesota College of Pharmacy. “Sepsis management has always been a focus of ours, but there wasn’t a formal move to promote these particular guidelines until 2006.”
In June of that year, Mann and others organized the Minnesota Surviving Sepsis Network to accelerate use of the SSC guidelines. Conducting a survey of the state’s 15 largest hospitals, they found that nine were already using at least some portion of the SSC guidelines, but six were not, and no hospitals had adopted all of the guidelines. “Several of the sites that were not considering using the guidelines thought their outcomes were already better than average,” says Mann, “but few had data to support that view.” During 2007, the Center for Excellence in Critical Care provided educational programs on best practices in sepsis to develop the Network throughout the state.
Mann has also applied for a grant from the federal Agency for Healthcare Research and Quality to underwrite the cost of hiring “change agents” or improvement advisors at willing hospitals. Change can be slow work, admits Mann. “I’m constantly surprised by how hard it is to get hospitals to do what they say they want to do but, when it comes down to it, they just have other priorities. One of the major obstacles that sites who have adopted the guidelines continue to identify is a lack of data collection resources. This factor has kept submissions to the SSC databank low. We’re exploring ways that the Center for Excellence in Critical Care can help overcome this hurdle.”
Survive Sepsis Program in the UK
The official launch of the SCC in the United Kingdom took place in Summer 2004. However, while initial buy-in to the guidelines and take-up of the database were brisk, progress was slow outside units with local SSC champions. To address this issue, a new education initiative was launched in September 2007 with the aim of improving compliance with the SSC guidelines. Known as Survive Sepsis, the program has already trained 750 individuals with a four-part strategy consisting of a day’s worth of tutorials, workshops, lectures, and case studies; a 45-minute bedside demonstration; a toolkit of evaluative screens and care pathways, plus a provider manual.
The main goal of Survive Sepsis in the UK is to raise awareness of the Sepsis Resuscitation Bundle, particularly among junior nursing and medical staff in acute care. “Of course, we’re interested in both bundles,” says Ron Daniels, MD, who heads the project, “but the greatest gaps in delivery currently exist for the Resuscitation Bundle, which demands early recognition and immediate action from individuals in all disciplines and at all levels. Rarely, if ever, has such a wide-scale application of such a complex diagnostic and therapeutic package been required.” The challenge, says Daniels, is “the identification of a response to a disease, rather than simply the disease itself. The skills required are unfamiliar to many outside critical care units. Achieving them requires a level of interdisciplinary cohesion previously unseen in the UK.”
In contrast, says Daniels, “When recognition and emergency therapy is timely, the Sepsis Management Bundle will be more readily achieved.” Indeed, he points out, “At roughly 36 percent, compliance with the Management Bundle in the UK and globally is already more than three times higher than with the Resuscitation Bundle at 11 percent.”
So far, the Survive Sepsis program has trained more than 700 people, says Daniels. By the end of 2007, he expects that another 360 will have been trained. “By the end of 2008, we should be providing training to more than 400 staff per month.”
While some individual efforts are sure to progress faster than others, says IHI faculty Dr. Sean Townsend, the global Surviving Sepsis Campaign is on track to deliver a huge impact in lives saved. “Based on the data that’s coming in, I’m confident that we’re going to reach our 2009 goal of reducing the risk of dying from sepsis by 25 percent. Worldwide, that’s a lot of people.”
[1] Surviving Sepsis Campaign
Implement the Sepsis Management Bundle
Reducing mortality due to severe sepsis requires an organized process that guarantees early recognition and consistent application of evidence-based practices. The Severe Sepsis Bundles are a series ofevidence-based therapiesthat, when implemented together, will achieve better outcomes thanif implemented individually.
There are twosepsis bundles.Each bundle articulates requirements for specific timeframes.
- Sepsis Resucitation Bundle: Evidence-based goals that must be completed within 6 hours for patients with severe sepsis, septic shock and/or lactate > 4 mmol/L (36 mg/dl).
- Sepsis Management Bundle: Evidence-based goals that must be completed within 24 hours for patients with severe sepsis, septic shock and/or lactate > 4 mmol/L (36 mg/dl).
For patients with severe sepsis, as many as seven Sepsis Resuscitation Bundle elementsmay be necessary to accomplish within the first 6 hours of presentation, and as many as four Sepsis Management Bundle elements must be accomplished within the first 24 hours of presentation.Somebundle elements may not be completed if the clinical conditions described in the bundle do not prevail, but clinicians should stillassess for those conditions and make a determination. Theintention in applyingthe Sepsis Management Bundleis to perform all indicated tasks 100 percent of the time within the first 24 hours of indication for severe sepsis.
Changes for Improvement
Administer Drotrecogin Alfa (Activated) by a Standard Policy
Maintain Adequate Glycemic Control
Prevent Excessive Inspiratory Plateau Pressures
Implement the Sepsis Management Bundle:
Administer Low-Dose Steroids by a Standard Policy
Corresponding Bundle Item:
Low-dose steroids administered for septic shock in accordance with a standardized ICU policy.
Related Measures
Low-Dose Steroid Administration
Background:
Intravenous corticosteroids (hydrocortisone 200–300 mg/day, for 7 days in three or four divided doses or by continuous infusion) are suggested for adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy. We believe hospitals should strive to develop a standardized policy in their ICU for the administration of steroids in accordance with the available evidence for use.
For decades, the rationale for the use of glucocorticoids in sepsis trials has been the fundamental role that they play in the stress response to infection and the anti-inflammatory effects that they exert. Randomized, controlled, high-dose glucocorticoid trials failed to improve outcomes, leading to skepticism and the avoidance of using any glucocorticoids in septic patients by most intensive care unit physicians.However, recent randomized, controlled trials with low doses of hydrocortisone in septic shock have evoked a renewed interest.
In the context of corticosteroid therapy for septic shock, high doses of glucocorticoids mainly refer to 30 mg/kg methylprednisolone or equivalent steroid preparations administered up to four times during a short course of 1 or 2 days. [1,2] Recent low-dose glucocorticoid trials refer to a daily dose of 200–300 mg of hydrocortisone or equivalent administered for 5 to 7 days or longer. [3–8]
Possible Decreased Mortality:
Preliminary data from a 2005 Cochrane meta-analysis considering 15 randomized controlled trials of low- and high-dose corticosteroids in 2,022 patients with septic shock summarizes available evidence on the use of steroids in septic shock. [9]Pooled 28-day all-cause mortality did not differ between placebo and verum (relative risk, 0.98; 95 percentCI, 0.87–1.10; p=0.7).Subgroup analysis of five trials [3–7] with low-dose corticosteroids reduced 28-day all-cause mortality significantly (relative risk, 0.8; 95 percentCI, 0.67– 0.95; p=0.01), whereas high-dose trials did not (relative risk, 0.99; 95 percentCI, 0.83–1.17; p=0.9). The number needed to treat with low-dose corticosteroids to save one additional life was nine (95 percentCI, 5–33). In addition, low-dose corticosteroids significantly reduced intensive care unit and hospital all-cause mortality and significantly increased the number of patients with shock reversal on day 7 and day 28.
These data stand in contrast to results from a large European trial, CORTICUS, which failed to show a mortality benefit from administration of low-dose steroids in septic shock. [12] In this multicenter, randomized, double-blind, placebo-controlled trial, 251 patients were assigned to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test. Of the 499 patients in the study, 233 (46.7 percent) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2 percent in the hydrocortisone group and 36.1 percent in the placebo group, p=0.69) or between those who had a response to corticotropin (28.8 percent in the hydrocortisone group and 28.7 percent in the placebo group, p=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3 percent) and 78 of 248 patients in the placebo group (31.5 percent) had died (p=0.51). Possible interpretations and concerns about CORTICUS are detailed below.
Earlier Shock Reversal:
Low-dose corticosteroids promote more rapid shock reversal than when they are not administered to patients with septic shock. Numerous randomized, controlled trials with low-dose corticosteroids in patients with septic shock confirm shock reversal and reduction of vasopressor support within a few days after initiation of therapy in most patients. [3–7] The median time to cessation of vasopressors decreased in one study from 13 to 4 days [5] and, in the other study, from 7 to 3 days. [8] CORTICUS, although finding no overall decreased mortality from low-dose steroid administration, confirmed the finding of more rapid shock reversal. [12]