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ProCESS Study: Identify sepsis early and treat aggressively


sepsismanagementchartToday, the New England Journal of Medicine just released a landmark paper by the ProCESS (Protocolized Care for Early Septic Shock) trial investigators. There has already been much buzz about this on various blogs and websites, including St. Emlyn’s, MedPageToday, and MDAware. I received an email from my colleague Dr. Michael Callaham, who shared some direct comments and pearls from Dr. Donald Yealy, (professor and chair of emergency medicine from the University of Pittsburgh Medical Center) who was the first author of this writing team. Thank you to Dr. Yealy for allowing me to share your team’s comments with the ALiEM readership.


ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock. New Engl J Med. 2014 (early online release – free PDF download)1

Google Hangout on April 1, 2014 with Dr. Yealy

Here is the Surviving Sepsis Campaign response to the ProCESS Trial mentioned, which advocates for still the full sepsis bundle despite the ProCESS Trial findings.

Donald Yealy, MD

Donald Yealy, MD

A few key points we see (though not exhaustive):

  • The different resuscitative approaches did not create one clear superior method, and while some resource use varied, the primary and secondary analyses largely agreed on this observation. Of our three, no one resuscitative path is bad or better; this allows sites the flexibility of crafting best local approach to care within these constructs.
  • The study groups were treated differently – in other words, we did an experiment. There is no evidence of contamination.
  • Overall, adherence to protocols was very good, and ancillary care – esp. antibiotic delivery – was also very good. These are key features.
  • While our cohort differs in some ways from the 2001 Rivers cohort – not a surprise –both trials included very sick patients with similar vital signs and APACHE on presentation.
  • Overall, mortality is much lower than reported in 2001 – a very good thing and reason why this isn’t a ”negative trial”, but a refining trial showing early recognition and resuscitation are key – there is more than one way to do the latter. However, sepsis remains a killer, more than many other ED/ICU illnesses like acute MI/CVA.
  • We did not study delayed recognition or care – these results validate the Rivers dictum that seeking sepsis in all forms early and treating to deter the cycle of propagation is key.Our observations apply to settings where sepsis is aggressively sought and treated early.

Bottom line

We relearn that more care is not always better care.
— Derek, Don, John, David, Amber, and the ProCESS Team


JAMA also published a paper today, supporting the ProCESS study view that shifting definitions alone do not explain the improved mortality.

Further Reading:

  • Kaukonen KM, Bailey M, Suzuki S et al. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012. JAMA.
  • Iwashyna TJ, Angus DC. Declining Case Fatality Rates for Severe Sepsis: Good Data Bring Good News With Ambiguous Implications. JAMA. 2014.
ProCESS I, Yealy D, Kellum J, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-1693. [PubMed]
Michelle Lin, MD
ALiEM Editor-in-Chief
Academy Endowed Chair of EM Education
Professor of Clinical Emergency Medicine
University of California, San Francisco
Michelle Lin, MD
Michelle Lin, MD

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  • Anand Swaminathan

    This is a wonderful study with important conclusions. The commentary/editorial for this is extremely important to read as it shines a light on the importance of Dr. Rivers work. Mortality in the “standard non-protocalized care” group was lower than what we would expect. This doesn’t mean that the protocol isn’t important but rather that since Dr. Rivers’ publication, we have shifted our basic management to improve care. Streamlining EGDT is a necessary step but should not be at the expense of lapsing back to where we were 13 years ago.

  • Donald M Yealy

    We agree!
    Dr Rivers’ durable message is that early recognition and fluid/vasopressor therapy thwarts mortality; our trial refines that message. While CVC, oximetric or not, can add information and drive other actions (blood, iontropes), that approach is not superior in septic shock patients IF the basics are done well.
    ED care matters; there are now a few paths a person or group can take that deliver better outcomes. Recognize (especially cryptic shock, where blood pressure “looks ok”) and treat early – with fluids, vasopressors, and antibiotics. Simple is good, and more isn’t always better.
    Without Dr. Rivers, we couldn’t be at this point of clarity – each of the ProCESS investigators kniows this fact and thanks him for creating this opportunity.

  • LALynn

    Unfortunately all these trials are based on oversimplifief threshold science from the 1980s, guessed threshold criteria, and simplistic thresold targets.

    Threhsold scientists may think this is enough data but those of us who conider the relational time patterns of sepsis in its management consider more comprehensive relational analysis of timed sepsis trial data necessary. Aggregated data is not enough. It is like getting only the stats on a football game. Cant learn to win with only aggregated data and stats. We need the time series data of lab vitals and treatment. “THE SEPSIS GAMEFILMS”. ProCESS leaves us guessing. We need more data disclosure to interpret results.

    Read the link to learn the incredible but true state of threshold science in sepsis.

    • Michelle Lin

      Excellent point, Dr Lynn – your nice editorial in Patient Safety in Surgery provides an interesting argument. I think the future of published research in general should move towards the release of all the raw data so that the interpretation of the findings can be vetted by the public and “crowdsourced” in a way. Transparency is key. Thanks for commenting.

      Here’s the free PDF to the editorial:

  • RO

    Dr Yealy’s comment that none of the sites had a pre-existing sepsis program is inaccurate. Intermountain (one of sites from PROCESS) published their data of bundle compliance in 2013 in the blue journal: Miller RR, Nelson L, Multicenter implementation of severe sepsis and septic shock treatment bundle. Am J Resp Crit Care 2013 Jul 1; 188 (1) 77-82.
    To state that emergency physicians should ” worry less” on how you “do these things” is not a good bit of advice. Emergency physicians should be diagnosticians not “disposition technicians”. Emergency physicians should be able to determine if a patient is in a supply dependent or supply independent state when a patient has severe sepsis or septic shock. Being relegated to starting IVFs, start gorillacillin and admit to ICU is an insult to emergency physicians

    • MRS

      I cannot speak for the US, but emergency physicians in the UK and, in the near future, in Australia are indeed becoming disposition technicians. The political emphasis on time-based targets for patient disposition, with knock-on effects on funding, guarantee this, to the detriment of the specialty. The Emergency Physician you describe is the one that most of us would like to be. The reality is different, hence the flight of EPs to ICU.

  • andrew

    metabolic theory of septic shock