1. Faculty Mitchell M. Levy, MD, FCCM
Professor of Medicine and Division Chief
Alpert Medical School of Brown University
Medical Director, MICU
Rhode Island Hospital
Providence , Rhode Island
Author 2004, 2008 & 2012 SSC Guidelines
SCCM SSC Executive and Steering Committees
Past President, SCCM

2. Starting the Clock: Time Zero Considerations
Mitchell M. Levy, MD, FCCM
Brown University
Providence, RI

3. Funded by a grant from the Gordon and Betty Irene Moore Foundation

4. Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock: 2012
R. Phillip Dellinger, Mitchell M. Levy, Andrew Rhodes, Djillali Annane, Herwig Gerlach, Steven M. Opal, Jonathan E. Sevransky, Charles L. Sprung, Ivor S. Douglas, Roman Jaeschke, Tiffany M. Osborn, Mark E. Nunnally, Sean R. Townsend, Konrad Reinhart, Ruth M. Kleinpell, Derek C. Angus, Clifford S. Deutschman, Flavia R. Machado,Gordon D. Rubenfeld, Steven A. Webb, Richard J. Beale, Jean-Louis Vincent, Rui Moreno, and the Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup.
Crit Care Med. 2013; 41:
Intensive Care Medicine 2013; ..

5. Current Surviving Sepsis Campaign Guideline Sponsors
American Association of Critical-Care Nurses
American College of Chest Physicians
American College of Emergency Physicians
Australian and New Zealand Intensive Care Society
Asia Pacific Association of Critical Care Medicine
American Thoracic Society
Brazilian Society of Critical Care(AIMB)
Canadian Critical Care Society
Chinese Society of Critical Care Medicine
Emirates Intensive Care Society
European Respiratory Society
European Society of Clinical Microbiology and Infectious Diseases
European Society of Intensive Care Medicine
European Society of Pediatric and Neonatal Intensive Care
Infectious Diseases Society of America
Indian Society of Critical Care Medicine
International Pan Arab Critical Care Medicine Society
Japanese Association for Acute Medicine
Japanese Society of Intensive Care Medicine
Pediatric Acute Lung Injury and Sepsis Investigators
Society Academic Emergency Medicine
Society of Critical Care Medicine
Society of Hospital Medicine
Surgical Infection Society
World Federation of Critical Care Nurses
World Federation of Pediatric Intensive and Critical Care Societies
World Federation of Societies of Intensive and Critical Care Medicine
Participation and endorsement:
German Sepsis Society
Latin American Sepsis Institute

6. “Time Zero” Time Zero = time of presentation ED, Medical Floors, ICU
Both bundles time based
Most important time based elements:
Antibiotic timing
Resuscitation timing (EGDT)

7. Antibiotic therapy
We recommend that intravenous antimicrobial therapy be started as early as possible and within the first hour of recognition of septic shock (1B) and severe sepsis without septic shock (grade1C).

8. Hospital Mortality by Time to Antibiotics

9. Fluid therapy
We recommend that initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemnic be started with ≥ 1000 mL of crystalloids (to achieve a minimum of 30ml/kg of crystalloids in the first 4 to 6 hours).
(Grade 1B).

10. Logistic Regression Model

11. SSC/NQF Bundle: Sepsis 0500
TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION † :
Measure lactate level
Obtain blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L
† “time of presentation” is defined as the time of triage in the Emergency Department or, if presenting from another care venue, from the earliest chart annotation consistent with all elements severe sepsis or septic shock ascertained through chart review.  

12. SSC/NQF Bundle: Sepsis 0500
TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION:
Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) ≥65mmHg)
In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate ≥4 mmol/L (36mg/dl):         - Measure central venous pressure (CVP)*               - Measure central venous oxygen saturation (ScvO2)*
Remeasure lactate*
* Targets for quantitative resuscitation included in the guidelines are CVP of ≥8 mm Hg, ScvO2 of ≥70% and lactate normalization.

13. So, What’s the Issue?
Many groups, especially ED physicians advocate for alternative time zero
Time of “diagnosis”
Physician-based
Chart based
Labs VS
Not all patients admitted from ED with severe sepsis present at triage with severe sepsis
Deteriorate in ED over hours
Triage time may not reflect true “time zero” of severe sepsis for all patients admitted to ICU from ED

14. Implications for Time Zero
New York State DOH
Mandated reporting of sepsis outcomes
Adherence to “evidence-based” protocols
NQF sepsis measures
Recently approved
Appeal issued by ACCP/ACEP
Fear of being “dinged” for patients who did not meet criteria on triage in ED
Public reporting
Pay for Performance

15. Alternatives to Triage Time as Time Zero
We considered several sources in making our conclusions:
Comments and concerns from other organizations represented on the 2012 SSC Guidelines Committee
Experts on the Infectious Disease Steering Committee of the National Quality Forum (NQF)
Public comments during NQF consensus measures process
SSC list serve discussion

16. Time Zero Determination: A Balancing Act
Time zero needs to offer the best balance of :
reliability and reproducibility
optimizing the overall performance improvement effort as to:
early diagnosis
appropriate treatment of severe sepsis.

17. The Importance of Early Detection
Efforts to just treat recognized sepsis alone are incomplete
A critical aspect of mortality reduction in the Campaign has been pushing practitioners to identify sepsis early.
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 Feb;38(2):
It may well be that earlier recognition accounts for much of the signal in mortality reduction and partially explains sharply increasing incidence.
Gaieski DF, Edwards JM, Kallan MJ, et al. Benchmarking the Incidence and Mortality of Severe Sepsis in the United States. Crit Care Med Feb 25. [Epub ahead of print]
Without recognition that the clock is ticking, there is simply no incentive to recognize a challenging diagnosis early.

18. Using “Time of Documentation” is Flawed as a Performance Improvement Approach
Some patients will not meet severe sepsis criteria on ED arrival, however altering time zero to chart annotation by a practitioner would:
Turn the bundle into a treatment only bundle (not a diagnosis and treatment bundle).
Diminish practitioners’ incentives to identify patients at risk based on history, symptoms and exam findings at ED presentation.
Reduce the reliability and reproducibility of time zero.
Make data collection more onerous and costly.

19. Lead time to Diagnosis & Treatment
Where Do The Gains Live? A B
Lead Time to Diagnosis
Delivery of Proper Treatment
Lead time to Diagnosis & Treatment

20. Could a fair criterion for time zero be onset of hypotension, with all previous blood pressures in the ED recorded as normotensive?
Such a time would:
falsely penalize sites for initiation of treatment prior to the onset of hypotension.
Fluids given first? Abx given first? Blood cultures already sent?
falsely decrease the number of observed cases meeting severe sepsis criteria.
diminish awareness of organ dysfunction other than hypotension.
not be the therapy that you want your loved one to receive

21. Fairness and the Bell Curve
Many discussions will be had about the “fairness” of making providers responsible for signs & symptoms that may not be initially present.
Such a viewpoint presupposes the veracity of the notion that the patient truly presented acutely to the ED for some other reason than impending quantifiable severe sepsis/shock.
Really??? Does that meet the test of most of the time for most cases???
Time zero as triage will lead to earlier and more frequent recognition  increased total number patients with improved outcomes.
Long ED stays are another real quality problem and one that hospitals should separately solve. CMS already measures this problem and there is no persuasive reason to confuse the issues.

22. The Patient’s Point of View
Despite a provider’s true occasional inability to achieve the time sensitive indicators:
due to late onset of symptoms
due to long elapsed time in the ED
“Early detection and treatment of my health problem is preferable.”

23. Strategies and Rational for Proceeding in the Next Phase of Sepsis Quality Improvement
Continue to use triage time as time zero in cases presenting to the ED.
Maximize the bundles’ effectiveness for diagnosis as well as treatment.
Acknowledge a percentage of patients will not meet criteria for severe sepsis or septic shock at ED triage and may miss the bundle.
Recognize that whatever compliance can be achieved will be converted to percentiles of performance by CMS for benchmarking.
Acknowledge that benchmarked performance even at possibly low levels of average raw compliance will still have a top decile; the decile determines compensation in CMS’s value based purchasing metrics.

24. QUESTIONS?