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.”
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.