Do the surviving sepsis campaign guidelines work?

38 Do the Surviving Sepsis Campaign Guidelines Work? Laura Evans and Ariella Pratzer

WHAT ARE BUNDLES? The development and publication of guidelines seldom lead to changes in clinical behavior and guidelines are rarely integrated into bedside practice in a timely fashion.1 Used as a tool for implementation and practice change, bundles are a group of evidence-based interventions often based on guidelines that, when instituted together, may provide an impact greater than any single intervention alone.2 Ideally, a bundle provides a simple and uniform way to implement best practices.

THE NEED FOR BUNDLES IN SEVERE SEPSIS AND SEPTIC SHOCK Sepsis is the most common cause of intensive care unit (ICU) admission globally. The disorder accounts for 11% of all ICU admissions in high-income countries,3 and increases to 20% for noncardiac ICUs.4 There are approximately 750,000 new sepsis cases every year in the United States alone.5 It is the leading cause of ICU death, with a mortality rate between 18%-35%.6 It is also the single most expensive condition treated in the United States, with costs exceeding $20 billion annually.7 Sepsis, like poly-trauma, myocardial infarction, and stroke, is a medical emergency, for which early identification and management improves outcomes. Not surprisingly then, both mortality and healthcare costs associated with sepsis have been shown to be significantly decreased by the timely and coordinated application of a group of evidencebased interventions.8,9 Thus, sepsis is a syndrome that is particularly amenable to bundle-based management. Recognizing the global impact of sepsis and the growing evidence for interventions that would improve outcomes, the Surviving Sepsis Campaign (SSC) Guidelines were published initially in 2004, taking into account the best available evidence at that time. Beyond the guidelines, the SSC developed an international collaborative initiative to increase awareness of sepsis and to apply bundles as a means of translating the available evidence into improved patient outcomes on a global scale. Over the last 14 years, the SSC has progressed in phases with multiple goals: building awareness, educating healthcare professionals, and improving the management of sepsis. Thus, the SSC structured itself into an international practice 270

improvement project, with an in-depth collection of performance data and a goal of reducing sepsis mortality by 25% within five years (2004–09). Since the inception of the SSC, the bundles themselves have been adapted in response to an evolving evidence base and data collected from participants in the SSC effort (Table 38.1).

IS THERE EVIDENCE THAT APPLICATION OF THE SSC BUNDLES IMPROVES OUTCOMES? While the components of the bundles themselves have generated ample debate since their development, there is little doubt that the SSC bundles have been effective. In fact, the demonstrated association between compliance with bundles and improved survival in sepsis patients has led to the adoption of SSC measures by the National Quality Forum, the New York State Department of Health, and the Centers for Medicare and Medicaid Services.10,11 A national educational effort in Spain, based on the SSC guidelines, resulted in a reduction of in-hospital and 28-day mortality from severe sepsis or septic shock by 11% and 14%, respectively.12 A large, multicenter study by the Intermountain Healthcare Intensive Medicine Clinical Program, involving 11 hospitals and 18 ICUs, enrolled nearly 4500 patients and conducted a quality improvement study to evaluate the effects of implementation of sepsis bundles (Fig. 38.1).13 By the end of the study period, bundle compliance was almost 75% and in-hospital mortality rate had fallen below 10%. A study of over 49,000 patients at 149 hospitals in New York State in 2014-16, found that more rapid completion of the three-hour sepsis bundle was associated with lower riskadjusted in-hospital mortality.14 A prospective, observational study of compliance with SCC bundles across 62 countries found overall low compliance (19%), but also found that compliance with the three-hour bundle resulted in a 40% reduction in in-hospital mortality.15 The SSC itself has collected data from over 15,000 patients at 165 sites participating in the collaborative. Bundle compliance rates and their association with hospital mortality were examined. Compliance rates with both phases of the bundle improved over the two year campaign. Simultaneously, there was a 7% absolute risk reduction in unadjusted hospital

CHAPTER 38

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TABLE 38.1  Surviving Sepsis Campaign Care Bundles. Original Bundle (2005)

Updated Bundle (2012)

Most Recent Bundle (2018)

Resuscitation bundle (to be completed within the first 6 h) • Serum lactate measured • Blood cultures obtained prior to antibiotic administration • Broad spectrum antibiotics administered within 3 h for ED admissions, 1 h for non-ED admissions • If hypotensive or if lactate 4 mmol/L, initial bolus of 20 mL/kg crystalloid (or colloid equivalent) administered. If MAP still ,65 mm Hg, vasopressors applied • If hypotension or hyperlactemia persists, CVP .8 mm Hg and ScvO2 of .65% achieved (or MVO2 .65%)

To be completed within the first 3 h • Serum lactate measured • Blood cultures obtained prior to antibiotic administration • Broad spectrum antibiotics administered • 30 mL/kg of crystalloids administered for hypotension or lactate 4 mmol/L

To be initiated within the first hour • Serum lactate measured.a • Blood cultures obtained prior to antibiotic administration • Broad spectrum antibiotics administered • Administration of 30 mL/kg of crystalloids initiated for hypotension or lactate 4 mmol/L • Vasopressors applied for refractory hypotension to maintain MAP 65 mm Hg

Management bundle (to be completed within the first 24 h) • Low dose steroids administered for septic shock • Drotrecogin alpha (activated) administered • Glucose control maintained between lower limit of normal and ,150 mg/dL • Inspiratory plateau pressures maintained ,30 cm water for patients who are mechanically ventilated

To be completed within the first 6 h • Vasopressors applied for refractory hypotension to maintain MAP 65 mm Hg • If initial lactate .4 mmol/L or if hypotension persists after volume resuscitation, measure CVP and ScvO2 • Re-measure lactate if initial lactate was elevated

Remeasure lactate if elevated (does not need to be done in first hour). Data from Dellinger RP, Levy MM, Townsend SR, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637; Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367-374; Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Crit Care Med. 2018;44(6):925-928. a

80% 70% 60% 50% 40% 30% 20% 10% 0% 2004

2005

2006

2007

2008

2009

2010

Bundle compliance In-hospital mortality Fig. 38.1  ​Improving bundle compliance improves mortality. (Modified from Miller RR 3rd, Dong L, Nelson NC, et al. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med. 2013;188(1):77-82.)

mortality over this time period. As the authors noted, by instituting a practice improvement program grounded in evidence-based guidelines, the SSC successfully increased compliance with sepsis bundles, and this change was associated with better patient outcomes.16

In 2014, the SSC published the effects of bundle adoption over a 7.5 year period.8 Analysis of nearly 30,000 patients from three different continents and over 200 hospitals revealed the sustainability of improved outcomes with increasing bundle compliance. Participation in the SSC alone led to an overall decline in mortality. Higher compliance to either resuscitation or management bundles led to improvements in mortality. Continued participation in the SSC led to additional reductions in mortality by 7% per quarter. Additionally, for every 10% increase in bundle use, there were significant decreases in hospital and ICU lengths of stay. Overall, increased compliance with sepsis performance bundles was associated with a 25% relative reduction in mortality. While there are regional differences in bundle compliance and mortality, improved outcomes when adhering to the SSC bundles are not limited to resource intensive settings. Raymond and colleagues showed that bundle compliance in India reduced mortality from 35% to 21% (unpublished observations),2 including reductions in intensive care length of stay and ventilator-free days. Similar observations have been seen in China17 and Brazil.18 As of 2018, there are more than 50 studies showing that increased bundle compliance leads to improvements in mortality. As a corollary, noncompliance with these bundles was associated with increases in hospital mortality. In fact, a study in the United Kingdom showed that noncompliance with the 6 hour sepsis bundle was associated with a more than two-fold increase in hospital mortality.19

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SECTION 6 

Sepsis Through the bundles, the SSC has successfully created a paradigm shift in the approach to severe sepsis and septic shock. Therein lies the strength of bundles—guidelines that may take years to change clinical behavior can now be distilled into something easily implementable at the bedside. As new evidence becomes available, these bundle elements can continue to be adapted, and the new evidence quickly translated into improved patient care.

25,000

20,000

15,000

10,000

5,000

0 Total costs

ICU costs (roughly)

Costs in survivors

Preintervention Postintervention Fig. 38.2  ​Cost savings from implementation of a SSC bundle. (From Shorr AF, Micek ST, Jackson WL Jr, Kollef MH. Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs? Crit Care Med. 2007;35(5):1257-1262.)

IS THERE EVIDENCE THAT THE SSC BUNDLES ARE COST-EFFECTIVE? Treatment of severe sepsis and septic shock is resource-intensive, with annual costs exceeding $20 billion in the United States alone.7 Several studies have analyzed the cost effectiveness, from a health care perspective, of compliance with the SSC bundle elements. When implemented, the overall mean cost per patient may increase; however, this may be driven by improved survival leading to increased length of stay.9 The Incremental Cost-Effectiveness Ratio, a commonly used approach to decision making regarding health interventions, was as low as €4435 per life year gained (LYG) in one such study from Spain.9 These savings were significantly lower than the frequently used limit of €30,000 per LYG to gauge cost effectiveness of an intervention in that country. Data from the United States showed a reduction of nearly $5000/patient when the SSC bundles were implemented (Fig. 38.2).20 ICU costs fell by nearly 35%, and there was a simultaneous reduction in hospital length of stay by approximately 5 days. In a subgroup analysis, the cost savings was $8000 per survivor, despite an increase in hospital length of stay. In a period in which health care spending is being scrutinized, such cost saving measures have important economic implications. Extrapolating the data described earlier, to all patients with severe sepsis and septic shock, consistent adherence to the SSC bundle elements could potentially save $4 billion annually in the United States.

CONCLUSIONS There is substantial evidence that implementation of the SSC bundles saves lives as well as reduces healthcare spending.

AUTHORS’ RECOMMENDATIONS • Sepsis is a medical emergency for which early identification and management improves outcomes. • The Surviving Sepsis Campaign guidelines and bundles were introduced with the intention of reducing sepsis mortality by 25% over 5 years. • Numerous studies conducted since their introduction have consistently demonstrated association between compliance with bundles and improved survival in sepsis patients. • Sepsis guidelines and bundles will continue to be adapted to the most recent evidence, enabling this new evidence to be quickly translated to improved patient care.

REFERENCES 1. Fischer F, Lange K, Klose K, Greiner W, Kraemer A. Barriers and strategies in guideline implementation—a scoping review. Healthcare (Basel). 2016;4(3). 2. Khan P, Divatia JV. Severe sepsis bundles. Indian J Crit Care Med. 2010;14(1):8-13. 3. Perner A, Gordon AC, De Backer D, et al. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016;42(12):1958-1969. 4. Brun-Buisson C, Doyon F, Carlet J, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995;274(12):968-974. 5. Institute for Healthcare Improvement. Sepsis Care Enters New Era. 2006. Available at: http://www.ihi.org/resources/ Pages/ImprovementStories/SepsisCareEntersNewEra.aspx. Accessed September 25, 2018. 6. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. 7. Torio CM, Andrews RM. National inpatient hospital costs: the most expensive conditions by payer, 2011: Statistical Brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville, MD: Agency for Health Care Policy and Research; 2013. 8. Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015;43(1):3-12. 9. Suarez D, Ferrer R, Artigas A, et al. Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain. Intensive Care Med. 2011;37(3):444-452. 10. Dwyer J. One boy’s death moves state to action to prevent others. New York Times. December 20, 2012. Available at: http://www.nytimes.com/2012/12/21/nyregion/one-boysdeath-moves-state-to-action-to-prevent-others.html. Accessed September 25, 2018.

CHAPTER 38 11. Centers for Medicare & Medicaid Services. CMS to improve quality of care during hospital inpatient stays. CMS.gov. August 4, 2014. Available at: https://www.cms.gov/newsroom/fact-sheets/ cms-improve-quality-care-during-hospital-inpatient-stays. Accessed September 25, 2018. 12. Ferrer R, Artigas A, Levy MM, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294-2303. 13. Miller RR 3rd, Dong L, Nelson NC, et al. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med. 2013;188(1):77-82. 14. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235-2244. 15. Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med. 2015;41(9):1620-1628.

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16. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367-374. 17. Li ZQ, Xi XM, Luo X, Li J, Jiang L. Implementing surviving sepsis campaign bundles in China: a prospective cohort study. Chin Med J (Engl). 2013;126(10):1819-1825. 18. Shiramizo SC, Marra AR, Durão MS, Paes ÂT, Edmond MB, Pavão dos Santos OF. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. PLoS One. 2011;6(11):e26790. 19. Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care. 2005;9(6):R764-R770. 20. Shorr AF, Micek ST, Jackson Jr WL, Kollef MH. Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs? Crit Care Med. 2007;35(5):1257-1262.

e1 Abstract: Clinical practice guidelines should help clinicians improve patient care at the bedside. The Surviving Sepsis Guidelines are evidence-based guidelines with comprehensive recommendations about the management of sepsis and septic shock. Guidelines can be difficult to implement at the bedside, thus the Surviving Sepsis Campaign (SSC) has developed a series of bundled interventions that aim to improve outcomes by standardizing care. When bundled together, evidence-based interventions are thought to have a greater impact on outcomes than the sum of the individual components. To date, multiple publications have demonstrated a compelling relationship

between improved outcomes and compliance with the SSC bundles. This also has been shown to reduce health care spending. Worldwide, the SSC has been associated with reduced mortality in patients diagnosed with sepsis. It is unclear whether this universal benefit arises from bundle implementation, increased awareness of sepsis or both. The major benefit of bundles over guidelines is simplicity and plasticity. Bundles can be rapidly rolled out and easily implemented. Compliance is relatively easy to audit. Bundles can be changed quickly as new evidence emerges Keywords: bundles; guidelines; protocols; quality improvement; Surviving Sepsis Campaign.