In 2018, the Surviving Sepsis Campaign (SSC) revised their care bundle . The 3-hour bundle that was recommended in their 2016 guidelines included blood culture, lactate measurement, broad-spectrum antibiotics and 30 ml/kg crystalloid fluid administration in case of hypotension or hyperlactatemia . Although this was based on moderate level evidence, several large retrospective studies subsequently confirmed an association between compliance with the sepsis bundle and better prognosis [3–5].
The 2018 update recommends completing the sepsis bundle within 1-hour instead of three. Similar to other scientific societies (including the Society for Critical Care Medicine, the Infectious Disease Society of America and the American College of Emergency Physicians), the European Society of Emergency Medicine (EuSEM) wishes to express its concerns regarding the following points:
- Overall, the sepsis bundle is based on low to moderate quality evidence, which is acknowledged by their authors . We regret the repeated use of the term ‘demonstrate’ in the SSC 2018 update, because most of the cited studies of the recommendation describe an association between sepsis bundle compliance and outcomes rather than a demonstration of causality and—more importantly—other studies have failed to confirm the reported relation [6,7]. Consequently, the empirical basis for the reduced time frame of the sepsis bundle is too weak to be mandatory. We believe that further studies are needed to allow the conclusion that the first hour bundle or one of its components could be used as quality markers. Seymour et al.  have shown that only the timely completion of blood cultures, lactate measurement and the administration of broad-spectrum antibiotics are correlated with hospital mortality while fluid administration was without effect. The 2018 update also includes measurement of lactate within 1 hour. We agree with Marik et al.  and their rebuttal on the weak quality of evidence of most of the literature that constitutes the basis of the SSC sepsis bundle, and do not support a lactate measurement within 1 hour as a quality indicator. Although lactate measurement is widely utilised as part of the assessment of the severity of sepsis, it is based on low quality evidence .
- After the release of the third international consensus definition of sepsis (SEPSIS-3), and since the Sequential Organ Failure Assessment (SOFA) score is rarely available within 60 minutes of triage, the SSC allows that patients can be identified based on a quick SOFA (qSOFA) score of two or more only, despite this not being a definition of sepsis . However, lactate was found to have no added prognostic value to SOFA and qSOFA scoring in some studies [10,11]. Moreover, the requirement of a repeated lactate measurement, if the first one is more than 2 mmol/l is also based on low quality of evidence . In an alternative to lactate, it was recently reported that a repeated qSOFA at 3 hours can be easily applicable and a good prognostic tool in the emergency department (ED) . Because there was no improvement in outcome with fluid therapy and the evidence for lactate measurement is poor, we therefore conclude that the key element of the sepsis bundle is early antibiotic administration, as soon as the diagnosis of sepsis is the most likely .
- The choice of ‘time zero’ being the time of triage further reduces the mandatory time frame for both identification and treatment of patients with potential sepsis. In busy EDs the chances of seeing this bundle completed in 1 hour are low, and particularly so for patients that are not in shock. The authors of the SSC acknowledge this by suggesting in their guidelines that physicians ‘may not complete all bundle elements within 1 hour of recognition’. In emergency medicine, unrealistic time targets taken as quality indicators may cause unexpected harm [14,15]. This short time frame, combined with unclear and broad criteria for starting the sepsis bundle could expose patients to unnecessary antibiotic therapy and fluids. Specifically, patients with acute heart failure may also have hyperlactatemia and unnecessary fluid challenges are potentially harmful. We believe this should be reconsidered, as up to one in five patients diagnosed with sepsis in the ED were ultimately found to have a non-infectious diagnosis .
- Time-based key performance indicators are a common proxy measure of quality in emergency care. There may even be financial incentives associated with adhering to or achieving a particular target. Endorsement by an organisation such as the SSC could be used by commissioners of care to alter an existing or create a new incentivized target. This target, which would require all patients with suspicion of sepsis to have a care bundle completed within 1 hour of arrival at an ED, is unlikely to be achievable in most EDs as sepsis cannot be definitely recognised within this time frame due to medical reasons. Furthermore, as outlined above may be hazardous to those with other diseases. Another possible unintended consequence of the endorsement of such an indicator would be that EDs could be confronted with reduced reimbursement for not attaining this target, given the already critical budget situation of many European EDs.
We agree that implementation of sepsis protocols and sepsis bundles in the ED helps to increase attention and places the emphasis on the early diagnosis and management of sepsis, and that it is an important and common diagnosis associated with significant mortality. However, treatment protocols and bundles must be evidence-based. We fully recognise the potential increased risk of mortality associated with delayed administration of antibiotics for severely ill infected patients and suggest that emergency physicians focus on this evidence-based component of the bundle. We would like to point out the prominent role for emergency physicians in the timely recognition and care of patients with sepsis since roughly a third of sepsis is diagnosed in ED . In this regard, the sepsis bundle could be regarded as a driver for improved processes in EDs.
However, completion of the sepsis bundle within 1 hour after triage is not evidence-based and may even be potentially harmful. Therefore, EuSEM cannot support the new SSC guidance, but emphasises the early recognition of sepsis and timely administration of antibiotics in appropriately selected patients within 1 hour of triage.
Conflicts of interest
There are no conflicts of interest.
1. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign
bundle: 2018 update.. Crit Care Med. 2018; 46:997–1000.
2. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign
: international guidelines for management of sepsis and septic shock: 2016.. Crit Care Med. 2017; 45:486–552.
3. Leisman DE, Doerfler ME, Ward MF, Masick KD, Wie BJ, Gribben JL, et al. Survival benefit and cost savings from compliance with a simplified 3-hour sepsis bundle in a series of prospective, multisite, observational cohorts.. Crit Care Med. 2017; 45:395–406.
4. Liu VX, Morehouse JW, Marelich GP, Soule J, Russell T, Skeath M, et al. Multicenter implementation of a treatment bundle for patients with sepsis and intermediate lactate values.. Am J Respir Crit Care Med. 2016; 193:1264–1270.
5. Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency
care for sepsis.. N Engl J Med. 2017; 376:2235–2244.
6. Rhee C, Filbin MR, Massaro AF, Bulger AL, McEachern D, Tobin KA, et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Compliance with the national SEP-1 quality measure and association with sepsis outcomes: a multicenter retrospective cohort study.. Crit Care Med. 2018; 46:1585–1591.
7. Finfer S. The Surviving Sepsis Campaign
: robust evaluation and high-quality primary research is still needed.. Intensive Care Med. 2010; 36:187–189.
8. Marik PE, Farkas JD, Spiegel R, Weingart S; collaborating authors. POINT: should the Surviving Sepsis Campaign
guidelines be retired? Yes.. Chest. 2019; 155:12–14.
10. Freund Y, Lemachatti N, Krastinova E, Van Laer M, Claessens YE, Avondo A, et al; French Society of Emergency
Medicine Collaborators Group. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department
.. JAMA. 2017; 317:301–308.
11. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3).. JAMA. 2016; 315:762–774.
12. Gu WJ, Zhang Z, Bakker J. Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomised controlled trials.. Intensive Care Med. 2015; 41:1862–1863.
13. Lemachatti N, Ortega M, Penaloza A, Le Borgne P, Claret P-G, Occelli C, et al. Early variation of quick sequential organ failure assessment score to predict in-hospital mortality in emergency department
patients with suspected infection.. Eur J Emerg Med. 2019; 26:234–241.
14. Mason S, Weber EJ, Coster J, Freeman J, Locker T. Time patients spend in the emergency department
: England’s 4-hour rule-a case of hitting the target but missing the point?. Ann Emerg Med. 2012; 59:341–349.
15. Locker TE, Mason SM. Analysis of the distribution of time that patients spend in emergency
departments.. BMJ. 2005; 330:1188–1189.
16. Jones AE, Heffner AC, Horton JM, Marchick MR. Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department
.. Clin Infect Dis. 2010; 50:814–820.
17. Lo RS, Brabrand M, Kurland L, Graham CA. Sepsis—where are the emergency
physicians?. Eur J Emerg Med. 2016; 23:159.