CHESTCHEST NewsSEP-1 protocol to manage severe sepsis and septic shock

SEP-1 protocol to manage severe sepsis and septic shock

Based on a long-standing commitment to reducing death and disability resulting from delayed early sepsis care, the American College of Chest Physicians (CHEST), together with the Society for Critical Care Medicine (SCCM), issued a letter to the National Quality Forum regarding #0500 (SEP-1) measure - Severe Sepsis and Septic Shock: Management Bundle.

The appeal surrounding the SEP-1 measure judged the antibiotic recommendations to be based on low quality evidence based on the idea that the Surviving Sepsis Campaign’s (SSC) guidelines for the diagnosis and treatment of sepsis and septic shock utilizes the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

This approach assumes that all studies showing an association of antibiotic delays with increased sepsis mortality are retrospective. However, because the vast majority of such studies shows that early antibiotics save lives, the NQF appropriately gives credence to them. CHEST and SCCM believe that NQF standards for antibiotics are medically sound and keep patients’ interests in the forefront.

In the letter, CHEST and SCCM reference four studies – recently published and not available to the SSC panel – that directly address the gaps in the SSC guidelines.

“Managing sepsis is all about timing, and Sep-1 requires that basic elements of sepsis care, including antibiotics and IV fluids, are not delayed. If I were a patient and my doctor did not come back in less than 6 hours to check on my shock status, I would be disappointed, to say the least. Nevertheless, some physicians and professional societies see no reason why these should be standards,” says Steven Q. Simpson, MD, FCCP, sepsis expert and Immediate Past President of the American College of Chest Physicians. “Meanwhile, according to CMS’ own evaluation, national compliance with the [SEP-1] measure is less than 50%, while being compliant with the measures reduces absolute overall mortality by approximately 4%. This would translate to between 14,000 and 15,000 fewer patients dying from sepsis per year, if all patients received bundled, measure-compliant care.”

Read the full correspondence below and a commentary from Dr. Simpson in CHEST Physician here.

March 16, 2022

Dear NQF Panel:

The American College of Chest Physicians (CHEST) is the largest organization of pulmonologists, intensivists, and sleep physicians in the United States. In conjunction with the Society of Critical Care Medicine (SCCM), CHEST sponsored the first consensus conference on the definitions of sepsis and published those definitions in its flagship journal CHEST in 1992.

CHEST and SCCM also partnered in the second sepsis definitions conference in 2001, published in Critical Care Medicine. Since that time, a third definition was independently published in JAMA in 2016.

CHEST has supported SCCM in efforts to continue providing evidence-based guidelines and bundles to improve the care of patients with sepsis and septic shock. With acknowledgement of the long-standing commitment of both societies to reducing death and disability resulting from delayed early sepsis care, CHEST and SCCM reaffirm our support of endorsement of the NQF #0500 (SEP-1) measure.

A number of organizations including American College of Emergency Physicians (ACEP), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society (PIDS), Society for Healthcare Epidemiology of America (SHEA), Society of Hospital Medicine (SHM) and Society of Infectious Diseases Pharmacists (SIDP) have objected to NQF’s continuing endorsement of the SEP-1 measure on the grounds that they are based on low quality evidence. They reference as support the most recent, updated version of the Surviving Sepsis Campaign’s (SSC) guidelines for the diagnosis and treatment of sepsis and septic shock. Of note, several of the objecting organizations were instrumental in developing the same guidelines, specifically the sections pertaining to the administration of antibiotics. The IDSA in particular did not support the 2016 SSC guidelines during the last SEP-1 measure NQF approval.1

The SSC laudably utilizes the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach in its guideline development and partners with McMaster University Canada’s GUIDE group using highly skilled, intensivist trained methodologists for guidelines development. We acknowledge the evidence that was available to the most recent SSC panel was determined to be low quality based on the GRADE approach. All available evidence at the time the guidelines were developed was observational. However, we believe that NQF has rated the quality of evidence informing measure #0500 to be of moderate quality. Understanding GRADE and NQF quality of evidence ratings is critical to avoid unclear or perhaps misleading references to low quality of evidence classifications.

It is axiomatic that patients with life threatening illness, such as sepsis or septic shock, should not be randomized in a prospective study to an arm that is riskier than the prevailing standard of care. The standard of care in the United States for patients with sepsis is to administer broad spectrum antibiotics as soon as sepsis is recognized. Both the SSC guidelines and the SEP-1 measure allow a reasonable time window for this intervention. The guidelines encourage action within 3 hours for delivering antibiotics to patients with sepsis, and 1 hour for patients with septic shock. The one controlled PHANTASi trial randomized patients of comparably lower mortality than the SEP-1 population to receive antibiotics earlier than the standard, i.e. in the ambulance on the way to the hospital.2 While the trial did not find a mortality difference, patients in the intervention group had a significantly lower hospital re-admission rate within 28 days.

Concerns about antimicrobial resistance may also be contributing to the appellant’s objections. It is important to keep in mind that antibiotic use at the most proximal point of presentation are not the main driver of resistance. Resistance is a function of: 1) over-prescribing of antibiotics which is more typical in the outpatient setting where antibiotic prescribing is not guided by culture findings; 2) patients not completing antibiotic prescriptions (which is not the case in the inpatient setting); 3) overuse of antibiotics in livestock farming; and 4) poor hygiene and sanitation. Antimicrobial stewardship and de-escalation at the earliest opportunity are prioritized in the SSC guidelines to ensure antibiotics are not over-prescribed. Instead of moving away from endorsement of SEP-1 by NQF, further support of antimicrobial stewardship would address resistance concerns. To that end, early infectious disease consultation as a component of sepsis bundles in the Emergency Department is associated with lower mortality in patients who complete the 3-hour part of the measure with severe sepsis and septic shock.3

When possible, standardizing care (such as procedures, operations, protocols and guidelines) ensures consistent and equitable patient management. For example, the plan to enhance equitable care by New York City (NYC) Health and Hospitals includes standardization of patient care practices as a primary goal. This NYC initiative recognized that racial and ethnic disparities in sepsis care exist.4 Additionally, critical care among racial and ethnic minority groups was made equitable throughout the COVID-19 pandemic with the implementation of standardized protocols ensuring unbiased care.5 The SEP-1 measure, which has received continued endorsement since 2008, underpins the management of critically ill septic patients and reinforces equitable care for all patients.

We also would like to inform you of 4 recent studies published in CHEST and Critical Care Medicine since the release of the 2021 revision of the SSC guidelines. We hope that these studies are of aid to the panel as it deliberates.

1) Schinkel M, Paranjape K, Kundert J, Nannan Panday RS, Alam N, Nanayakkara PWB. Towards Understanding the Effective Use of Antibiotics for Sepsis. CHEST 2021 Oct;160(4):1211-1221. doi: 10.1016/j.chest.2021.04.038. Epub 2021 Apr 24. PMID: 33905680; PMCID: PMC8546240.

In this study the authors of the aforementioned PHANTASi trial of antibiotics in the ambulance applied an unsupervised machine learning algorithm to their data as a novel mechanism of retrospective subgroup analysis. While the original trial was reported as showing no mortality benefit to earlier antibiotics, the authors retrospectively discovered an interaction of age and response to antibiotics, such that patients younger than 75 years of age were benefitted by earlier antibiotics, whereas the benefit was not seen in older patients. Such an interaction had not been considered at the time the prospective trial was designed.

2) Bisarya R, Song X, Salle J, Liu M, Patel A, Simpson SQ. Antibiotic Timing and Progression to Septic Shock Among Patients in the ED With Suspected Infection. CHEST 2022 Jan;161(1):112-120. doi: 10.1016/j.chest.2021.06.029. Epub 2021 Jun 26. PMID: 34186038.

This retrospective study analyzed over 74,000 patients with suspected infection in the emergency department to determine whether time to antibiotics was associated with increased progression from infection to septic shock. Importantly, this study stratified by severity of illness at presentation and demonstrated that a significant association exists, regardless of the illness severity. It also found that this association was most pronounced in the first 5 hours following presentation to the emergency department, underscoring an association of improved outcome with more rapid treatment. These findings address specific limitations of previous similar analyses, limitations emphasized by the organizations that object to SEP-1’s renewal.

3) Townsend SR, Phillips GS, Duseja R, Tefera L, Cruikshank D, Dickerson R, Nguyen HB, Schorr CA, Levy MM, Dellinger RP, Conway WA, Browner WS, Rivers EP. Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study. CHEST 2022 Feb;161(2):392-406. doi: 10.1016/j.chest.2021.07.2167. Epub 2021 Aug 6. PMID: 34364867.

This study evaluates the first 14 months of CMS’ own data on SEP-1 compliance and outcomes using propensity score matching and a hierarchical general linear model. The study demonstrates a mortality benefit to receiving the full bundle and each of the components, regardless of whether patients were in a high or a low propensity group for receiving it. In other words, using the SEP-1 components saves lives and decreases hospital length of stay by 1 day, compared with not using them. This study avoids the common mistake of comparing overall sepsis mortality before and after the presence of the SEP-1 measures.

Such studies, to date, have not taken into consideration the extent to which the hospitals they studied had implemented the bundle elements either before or after SEP-1’s effective date in October, 2015, nor do the studies address how well sepsis was diagnosed in those hospitals before and after SEP-1.

4) Tarabichi Y, Cheng A, Bar-Shain D, et al. Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative. Crit Care Med 2022 March;50(3):418-427. doi:10.1097/CCM.0000000000005267. PMID: 34415866.

In this study using pharmacists in addition to providers and the electronic health record, patients were prospectively randomized to standard sepsis care or standard care augmented by the display of a sepsis early warning system–triggered flag in the electronic health record combined with electronic health record–based emergency department pharmacist notification. A total of 598 patients were included in the study (285 in the intervention group and 313 in the standard care group). Time to antibiotic administration from emergency department arrival was shorter in the augmented care group than that in the standard care group (median, 2.3 hr [interquartile range, 1.4–4.7 hr] vs 3.0 hr [interquartile range, 1.6–5.5 hr]; p = 0.039). The hierarchical composite clinical outcome measure of days alive and out of hospital at 28 days was greater in the augmented care group than that in the standard care group (median, 24.1 vs 22.5 d; p = 0.011). Rates of fluid resuscitation and antibiotic utilization did not differ. There was no increase in undesirable or potentially harmful clinical interventions. This study addresses the issues brought forth by the Society of Infectious Diseases Pharmacists, a co-sponsor of the measure appeal.

These 4 studies, which were not available to the SSC panel, directly address some of the shortcomings in data that were extant at the time the 2021 guidelines were written. While these studies might be considered low quality evidence within the GRADE approach, we believe that NQF panel members will recognize them as moderate-to-high quality, since they are well performed retrospective, prospective and randomized analyses that take steps to recognize and eliminate bias, where possible.

We absolutely believe that NQF takes seriously its responsibility to the patients and potential patients of America, and that your deliberations will be fair and judicious. Both CHEST and SCCM wish to ensure that you have access to some of the most up to date information on the topic, information that reinforces the validity of the previous actions taken by the NQF panel in 2021.

Respectfully,

American College of Chest Physicians (CHEST)

Society of Critical Care Medicine (SCCM)

References:

1. Gilbert DN, Kalil AC, Klompas M, Masur H, Winslow DL. IDSA POSITION STATEMENT: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines. Clinical Infectious Diseases. 2017:cix997-cix997.

2. Alam N, Oskam E, Stassen PM, van Exter P, et al. Prehospital Antibiotics in the Ambulance for Sepsis: A Multicentre, Open Label, Randomised Trial. Lancet Respir Med 2018;6(1):40-50.

3. Madaline T, Wadskier Montagne F, Eisenberg R, et al. Early Infectious Disease Consultation Is Associated With Lower Mortality in Patients With Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle. Open Forum Infect Dis. 2019;6(10):ofz408.

4. Corl K, Levy M, Phillips G, Terry K, Friedrich M, Trivedi AN. Racial And Ethnic Disparities In Care Following The New York State Sepsis Initiative. Health Aff (Millwood). 2019;38(7):1119-1126.

5. Lopez DC, Whelan G, Kojima L, Dore S, et al. Critical Care Among Disadvantaged Minority Groups Made Equitable: Trends Throughout the COVID-19 Pandemic. J Racial Ethnic Health Dis 2022; Epub Feb 4.