What follows is a post that you will see on a number of websites this week explaining the petition to retract the 2018 Surviving Sepsis Campaign guidelines. You can read the guideline here. Although many of the individual recommendations seems reasonable, I think these guidelines could end up harming patients.
One concern that I have is the lack of recognition of clinician judgement. For example, it is recommended that all patients receive a 30 ml/kg bolus in the first hour, without any caveats. Although reasonable for many patients, a minority will certainly be harmed if this recommendation is implemented, or worse integrated into measures used to judge or pay physicians.
More concerning is the insistence that the entire sepsis bundle be completed within one hour of arrival at triage, ignoring the fact that the diagnosis of sepsis requires time and clinical expertise. I probably could have lived with these guidelines if they suggested aggressive care in the first hour after diagnosing sepsis, but they insist that “time zero” is defined as the time of triage in the emergency department. In order to complete the 1 hour bundle, hospitals would simply have to assume that every patient has sepsis. The patient presenting altered and hypotensive will have to immediately receive a 30 ml/kg bolus, which will be disastrous when the real diagnosis of cardiogenic shock is discovered an hour later. Demanding the completion of a 1 hour bundle within one hour of the patient being triaged, without any evidence, is misguided and irresponsible.
Finally, I cannot understand guidelines that make “strong recommendations” based on “low quality of evidence”. (This is a recurrent problem across all medical guidelines). If you are writing an evidence based guideline, make strong recommendations only when the evidence is strong. If you want to provide expert opinion on a topic, that is fine, but it should be clear that the recommendation is weak and should never be mandated. Historically, recommendations from the surviving sepsis guidelines became core measures used to judge and remunerate physicians despite weak evidence, and that should never be allowed to happen.
Concern regarding the Surviving Sepsis Campaign (SSC) guidelines dates back to their inception. Guideline development was sponsored by Eli Lilly and Edwards Life Sciences as part of a commercial marketing campaign (1). Throughout its history, the SSC has a track record of conflicts of interest, making strong recommendations based on weak evidence, and being poorly responsive to new evidence (2-6).
The original backbone of the guidelines was a single-center trial by Rivers defining a protocol for early goal-directed therapy (7). Even after key elements of the Rivers protocol were disproven, the SSC continued to recommend them. For example, SSC continued to recommend the use of central venous pressure and mixed venous oxygen saturation after the emergence of evidence that they were nonbeneficial (including the PROCESS and ARISE trials). These interventions eventually fell out of favor, despite the slow response of SSC that delayed knowledge translation.
SSC has been sponsored by Eli Lilly, manufacturer of Activated Protein C. The guidelines continued recommending Activated Protein C until it was pulled from international markets in 2011. For example, the 2008 Guidelines recommended this, despite ongoing controversy and the emergence of neutral trials at that time (8,9). Notably, 11 of 24 guideline authors had financial conflicts of interest with Eli Lilly (10).
The Infectious Disease Society of America (IDSA) refused to endorse the SSC because of a suboptimal rating system and industry sponsorship (1). The IDSA has enormous experience in treating infection and creating guidelines. Septic patients deserve a set of guidelines that meet the IDSA standards.
Guidelines should summarize evidence and provide recommendations to clinicians. Unfortunately, the SSC doesn’t seem to trust clinicians to exercise judgement. The guidelines infantilize clinicians by prescribing a rigid set of bundles which mandate specific interventions within fixed time frames (example above)(10). These recommendations are mostly arbitrary and unsupported by evidence (11,12). Nonetheless, they have been adopted by the Centers for Medicare & Medicaid Services as a core measure (SEP-1). This pressures physicians to administer treatments despite their best medical judgment (e.g. fluid bolus for a patient with clinically obvious volume overload).
We have attempted to discuss these issues with the SSC in a variety of forums, ranging from personal communications to formal publications (13-15). We have tried to illuminate deficiencies in the SSC bundles and the consequent SEP-1 core measures. Our arguments have fallen on deaf ears.
We have waited patiently for years in hopes that the guidelines would improve, but they have not. The 2018 SSC update is actually worse than prior guidelines, requiring the initiation of antibiotics and 30 cc/kg fluid bolus within merely sixty minutes of emergency department triage (16). These recommendations are arbitrary and dangerous. They will likely cause hasty management decisions, inappropriate fluid administration, and indiscriminate use of broad-spectrum antibiotics. We have been down this path before with other guidelines that required antibiotics for pneumonia within four hours, a recommendation that harmed patients and was eventually withdrawn (17).
It is increasingly clear that the SSC guidelines are an impediment to providing the best possible care to our septic patients. The rigid framework mandated by SSC doesn’t help experienced clinicians provide tailored therapy to their patients. Furthermore, the hegemony of these guidelines prevents other societies from developing better guidelines.
We are therefore petitioning for the retirement of the SSC guidelines. In its place, we would call for the development of separate sepsis guidelines by the United States, Europe, ANZICS, and likely other locales as well. There has been a monopoly on sepsis guidelines for too long, leading to stagnation and dogmatism. We would hope that these new guidelines are written by collaborations of the appropriate professional societies, based on the highest evidentiary standards. The existence of several competing sepsis guidelines could promote a diversity of opinions, regional adaptation, and flexible thinking about different approaches to sepsis.
We are disseminating an international petition that will allow clinicians to express their displeasure and concern over these guidelines. If you believe that our septic patients deserve more evidence-based guidelines, please stand with us.
Scott Aberegg MD MPH
Jennifer Beck-Esmay MD
Steven Carroll DO MEd
Joshua Farkas MD
Jon-Emile Kenny MD
Alex Koyfman MD
Michelle Lin MD
Brit Long MD
Manu Malbrain MD PhD
Paul Marik MD
Ken Milne MD
Justin Morgenstern MD
Segun Olusanya MD
Salim Rezaie MD
Philippe Rola MD
Manpreet Singh MD
Rory Speigel MD
Reuben Strayer MD
Anand Swaminathan MD
Adam Thomas MD
Scott Weingart MD
Lauren Westafer DO MPH
- Eichacker PQ, Natanson C, Danner RL. Surviving Sepsis – Practice guidelines, marketing campaigns, and Eli Lilly. New England Journal of Medicine 2006; 16: 1640-1642.
- Pepper DJ, Jaswal D, Sun J, Welsch J, Natanson C, Eichacker PQ. Evidence underpinning the Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Management Bundle (SEP-1): A systematic review. Annals of Internal Medicine 2018; 168: 558-568.
- Finfer S. The Surviving Sepsis Campaign: Robust evaluation and high-quality primary research is still needed. Intensive Care Medicine 2010; 36: 187-189.
- Salluh JIF, Bozza PT, Bozza FA. Surviving sepsis campaign: A critical reappraisal. Shock 2008; 30: 70-72.
- Eichacker PQ, Natanson C, Danner RL. Separating practice guidelines from pharmaceutical marketing. Critical Care Medicine 2007; 35: 2877-2878.
- Hicks P, Cooper DJ, Webb S, Myburgh J, Sppelt I, Peake S, Joyce C, Stephens D, Turner A, French C, Hart G, Jenkins I, Burrell A. The Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. An assessment by the Australian and New Zealand Intensive Care Society. Anaesthesia and Intensive Care 2008; 36: 149-151.
- Rivers ME et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine 2001; 345: 1368-1377.
- Wenzel RP, Edmond MB. Septic shock – Evaluating another failed treatment. New England Journal of Medicine 2012; 366: 2122-2124.
- Savel RH, Munro CL. Evidence-based backlash: The tale of drotrecogin alfa. American Journal of Critical Care 2012; 21: 81-83.
- Dellinger RP, Levy MM, Carlet JM et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: Intensive Care Medicine 2008; 34: 17-60.
- Allison MG, Schenkel SM. SEP-1: A sepsis measure in need of resuscitation? Annals of Emergency Medicine 2018; 71: 18-20.
- Barochia AV, Xizhong C, Eichacker PQ. The Surviving Sepsis Campaign’s revised sepsis bundles. Current Infectious Disease Reports 2013; 15: 385-393.
- Marik PE, Malbrain MLNG. The SEP-1 quality mandate may be harmful: How to drown a patient with 30 ml per kg fluid! Anesthesiology and Intensive Therapy 2017; 49(5) 323-328.
- Faust JS, Weingart SD. The past, present, and future of the centers for Medicare and Medicaid Services quality measure SEP-1: The early management bundle for severe sepsis/septic shock. Emergency Medicine Clinics of North America 2017; 35: 219-231.
- Marik PE. Surviving sepsis: going beyond the guidelines. Annals of Intensive Care 2011; 1: 17.
- Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Intensive Care Medicine. Electronic publication ahead of print, PMID 29675566.
- Kanwar M, Brar N, Khatib R, Fakih MG. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic administration rule. Chest 2007; 131: 1865-1869.