Patient Safety Tip of the Week
June 6, 2017
NYS Mandate for Sepsis Protocol Works
In 2013 the New York
State Department of Health mandated that hospitals begin using protocols to
help with early identification and treatment of sepsis. Hospitals began
implementing these protocols in 2014 and outcomes related to this project were
reported in 2 recent publications (NYSDOH
2017, Seymour
2017). By the third quarter of 2016, 84.7% of adult patients and 85.3% of
pediatric patients with severe sepsis or septic shock were treated using
protocols (NYSDOH
2017). Adult in-hospital mortality fell from 30.2% in early 2014 to 25.4%
by late 2016. Pediatric mortality rates were more variable without clearcut trend. After
adjusting for patient factors, the NYSDOH analysis of the data showed that the
odds of dying were 21% less for adult patients who received protocol-driven treatments
compared to patients who do not receive protocol-driven treatments. The time
frame for management was also critical. After adjustment, the NYSDOH analysis showed
that the odds of dying were 27% less for adult patients who received all of the
recommended treatments within three hours compared to patients who did not
receive all of the recommended treatments.
Seymour et al. dove
deeper into the data in an article published in the New England Journal of
Medicine (Seymour
2017). Protocols were required to
include a 3-hour bundle consisting of receipt of the following care within 3
hours:
- obtaining of a blood culture before the administration of
antibiotics
- measurement of the serum lactate level
- administration of broad-spectrum antibiotics
Protocols were also
required to include a 6-hour bundle, consisting of:
- administration of a bolus of 30 ml of intravenous fluids per
kilogram of body weight in patients with hypotension or a serum lactate
level of 4.0 mmol or more per liter
- initiation of vasopressors for refractory hypotension
- remeasurement of the serum lactate level within 6
hours after the initiation of the protocol
Individual
facilities could further customize the protocols as they wished.
Of over 49,000
eligible patients in the emergency department at 149 hospitals, 82.5% had the 3-hour
bundle completed within 3 hours, with a median time to the completion of the
3-hour bundle of 1.30
hours. Median time to the administration of broad-spectrum antibiotics was 0.95
hours and median time to the completion of the initial bolus of intravenous
fluids was 2.56 hours.
Supporting the
importance of early treatment, they found that each hour of time to the completion
of the 3-hour bundle was associated with higher mortality (odds ratio of
death until completion of 3-hour bundle, 1.04 per hour). Patients who
had the bundle completed during hours 3 through 12 had 14% higher odds of dying
in the hospital than those whose bundle was completed by 3 hours. Those same
odds (1.04 per hour) were seen for time to administration of antibiotics and
in-hospital mortality and patients who received first dose of antibiotics
during hours 3 through 12 had 14% higher odds of dying in the hospital than
those receiving antibiotics by 3 hours. However, the researchers found no
association between the timing of the fluid bolus and mortality.
But the authors
caution against concluding that early administration of a fluid bolus is not
important. Early fluid resuscitation is likely important. In fact, another
recent study on pediatric sepsis patients noted that the nature of fluid
resuscitation in sepsis may be important. The Surviving Sepsis Campaign
guidelines updated in 2016 (Rhodes
2017) did not consider the evidence strong enough to recommend balanced
fluids over unbalanced fluids (“balanced” fluids are crystalloids such as
lactated ringers, while chloride-rich fluids such as normal saline are not
balanced). But Emrath and colleagues (Emrath
2017) recently compared outcomes in children with pediatric severe
sepsis receiving balanced fluids for resuscitation in the first 24 and 72 hours
of treatment to those receiving unbalanced fluids. After propensity matching,
they found the 72-hour balanced fluids group had lower mortality (12.5% vs
15.9%), lower prevalence of acute kidney injury (16.0% vs 19.2%), and fewer
vasoactive infusion days (3.0 vs 3.3 days) compared with the unbalanced fluids
group.
Overall, the New
York State experience re-emphasizes the importance of early recognition and
treatment of sepsis in reducing mortality. We have one additional comment
on the New York State studies. They used the Sepsis-2 consensus criteria for
diagnosis. Those include use of the SIRS criteria in making a diagnosis of
sepsis. We’ve done numerous columns on the pitfalls of the SIRS criteria and
have praised the newer criteria for sepsis that do not use the SIRS criteria
(see our What's New in the Patient Safety World columns for March 2016 “Finally…A
More Rationale Definition for Sepsis” and February 2017 “Yes,
the New Sepsis Criteria Fit the Bill”). We doubt, however, that the key conclusions reached in the NYS
studies would be altered if the newer Sepsis-3 criteria (Singer 2016)
had been used.
In a “Perspective” accompanying the Seymour article, Hershey
and Kahn (Hershey
2017) note that, even though 82.5% of hospitals in the New York State experience did complete the
3-hour bundle within 3 hours, there was still considerable variation across
hospitals. There are several potential reasons.
One possible reason
may relate to how busy the emergency departments are. In a study just
presented in abstract form (Peltan
2017), researchers found that patients received antibiotics within
three hours in 83 percent of cases in uncrowded ERs, but only 72 percent of the
time when the ER was crowded (exceeded the ERs’ licensed beds).
The New York State studies reported only the relationship of
mortality to the timing of the first dose of antibiotics. But subsequent
administration of antibiotics may also be important. Another recent study (Leisman
2017) found that major second
antibiotic dose delays were common, especially for patients given shorter
half-life pharmacotherapies and who boarded in the emergency department. They
also observed an association between
major second dose delay and increased mortality, length of stay, and mechanical
ventilation requirement. In fact, in their multivariable analysis, major
delay was associated with a 61%
increased odds of hospital mortality. Interestingly, they found that major
delays in second doses were paradoxically more frequent for patients receiving
compliant initial care. So the moral of this study is that we can’t pat
ourselves on the back when we meet the first 3 hours goals.
Those second dose delays should not be surprising. In our
January 29, 2013 Patient Safety Tip of the Week “A
Flurry of Activity on Handoffs” we noted that back in the 1990’s we
realized that patients with community-acquired pneumonia at some renowned
organizations were not getting their first dose of antibiotics for up to 18
hours. That, of course, was related to bottlenecks in moving patients from the
ED to the floor and problems with handoffs (relating to both information
transfer and transfer of responsibility for managing the patients).
Fortunately, we had performance improvement projects that focused on ensuring
timely administration of the antibiotics regardless of physical location of the
patient. But we likely still see ambiguities of coordination and responsibility
that occur in between-unit transfers that need to be resolved in the handoff.
The finding in the Leisman study that delays in a
second antibiotic dose were paradoxically more frequent in those patients who
had received a first antibiotic dose in a timely fashion suggests problems in
that coordination of care.
Some of the nuances of CPOE and standardized medication
administration times may also contribute to such delays in antibiotic
administration once the patient reaches the inpatient unit. For example, some
facilities consider an order for “drug X q6hours” will be given at the
facility’s standard times of 6AM, 12PM, 6PM, and 12AM. If the patient arrives
on that inpatient unit at 12:01 PM, he/she may not get that next dose until 6PM
even when the intent of the ordering physician was for earlier administration
of the next dose.
Given the magnitude of the increase in in-hospital mortality
(61%) seen with major delays in second dose of antibiotics in the Leisman study we would wholeheartedly endorse adding the
timing of the second antibiotic dose as a quality parameter to be measured in
patients with sepsis.
Our other columns on
sepsis:
- March 15, 2011 “Early
Warnings for Sepsis”
- April 1, 2014 “Expensive
Aspects of Sepsis Protocol Debunked”
- September 8, 2015 “TREWScore
for Early Recognition of Sepsis”
- October 2015 “Even
Earlier Recognition of Severe Sepsis”
- February 2, 2016 “Success
Against Sepsis”
- March 2016 “Finally…A
More Rationale Definition for Sepsis”
- February 2017 “Yes,
the New Sepsis Criteria Fit the Bill”
References:
NYSDOH (New York State Department of Health). New York State
report on sepsis care improvement initiative: hospital quality performance.
March 2017 https://www.health.ny.gov/press/reports/docs/2015_sepsis_care_improvement_initiative.pdf
Seymour CW, Gesten F, Prescott HC,
et al. Time to Treatment and Mortality during Mandated Emergency Care for
Sepsis. NEJM 2017; Online First May 23, 2017
http://www.nejm.org/doi/full/10.1056/NEJMoa1703058?query=featured_home
Rhodes A, Evans LE, Alhazzani W,
et al. Surviving Sepsis Campaign: International Guidelines for Management of
Sepsis and Septic Shock: 2016.
Critical Care Medicine 2017; 45(3): 486-552 March 2017
Emrath ET, Fortenberry
JD, Travers C, et al. Resuscitation With Balanced Fluids Is Associated With
Improved Survival in Pediatric Severe Sepsis. Critical Care Medicine 2017;
Published Ahead of Print Post Author Corrections: April 21, 2017
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
http://jama.jamanetwork.com/article.aspx?articleid=2492881
Hershey TB, Kahn JM. State Sepsis Mandates - A New Era for
Regulation of Hospital Quality. (Perspective). NEJM 2017; Online First May 23,
2017
http://www.nejm.org/doi/full/10.1056/NEJMp1611928
Peltan ID, Bledsoe JR, Oniki TA, et al. Increasing
ED Workload Is Associated with Delayed Antibiotic Initiation for Sepsis. Abstract
5505. 2017 American Thoracic Society International Conference. Presented
May 21, 2017
http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2017.195.1_MeetingAbstracts.A1155
Leisman D, Huang V, Zhou Q, et al. Delayed Second Dose Antibiotics for Patients Admitted
From the Emergency Department With Sepsis: Prevalence, Risk Factors, and
Outcomes. Critical Care Medicine 2017; 45(6): 956-965, June 2017
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