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Opinion

VIEWPOINT
Surviving Sepsis Guidelines
A Continuous Move Toward Better Care of Patients
With Sepsis
Daniel De Backer, MD Sepsis is a life-threatening condition that affects cases; for example, those with a history of cardiac dys-
Department of more than 1 million patients a year in the United States function who develop pneumonia, when the nature of
Intensive Care, CHIREC and even more patients around the globe and is one of circulatory failure is not always obvious).
Hospitals, Universit
the leading causes of death. Since the Declaration of Another important advance is that the new guide-
Libre de Bruxelles,
Brussels, Belgium. Barcelona in 2002, the European Society of Intensive lines recommend the use of dynamic (ie, pulse or
Care Medicine and the Society of Critical Care Medicine stroke volume variations induced by mechanical venti-
Todd Dorman, MD, (SCCM) have launched several initiatives to decrease lation or passive leg raise test) over static variables (in-
PhD the mortality of patients with sepsis. The Surviving Sep- travascular pressures or volumes) to predict fluid
Department of
sis Campaign (SSC) was launched in 2002 and has a responsiveness. This is a significant change, as previous
Anesthesiology and
Critical Care Medicine, 7-point agenda: building awareness of sepsis, improv- guidelines recommended that clinicians should target
Johns Hopkins ing diagnosis and recognition, defining and increasing specific values of central venous pressure. Subsequent
University School of the use of appropriate treatment and care, educating data have shown that central venous pressure has lim-
Medicine, Baltimore,
Maryland. health care professionals, improving postintensive ited value for the prediction of the response to fluids.7
care unit care, developing guidelines of care, and imple- Importantly, the guidelines recommend that when fluid
menting a performance improvement program. administration is initiated, clinicians should use the fluid
The mortality of patients with sepsis has improved challenge technique to evaluate the effect (and safety)
Related article over time.1 In an observational study that included of fluid administration. When hemodynamic factors
29 470 patients in sepsis worldwide, every quarter of continue to improve in response to fluids, further fluid
participation in the SSC initiative was associated with a administration can be considered. However, fluid
significant decrease in the odds of hospital mortality administration should be discontinued when the
(odds ratio, 0.96; 95% CI, 0.95-0.97; P < .001).2 response to fluids is no longer beneficial, a step often
The Surviving Sepsis Guidelines were first pub- neglected in clinical practice.7 This is particularly impor-
lished in 2004, with revisions in 2008 and 2012. tant because multiple studies have shown that exces-
In January 2017, the fourth revision of the Surviving sive net fluid status is associated with a poorer out-
Sepsis Guidelines was presented at the 46th annual come, including an increase in mortality. Hence, the
SCCM meeting and published online jointly in Critical guidelines moved from a protocolized, quantitative
Care Medicine and Intensive Care Medicine.3,4 A synop- resuscitation strategy to a more patient-centered
sis of the guidelines also has been published.5 resuscitation approach guided by hemodynamic
The updated guideline was generated by 55 inter- assessment including dynamic variables for fluid
national experts representing 25 international organi- responsiveness and ongoing reevaluation of the
zations involved in the care of patients with sepsis and response to treatment.
providing 93 recommendations on early management Infection source control (eg, retrieval of catheter/
of sepsis and septic shock. There are numerous major device suspected to be infected, surgical procedure) and
advances in the revision of the guidelines. Among the early antibiotic therapy remain mainstays of treat-
various topics covered, initial resuscitation and antibi- ment. Source control should always be obtained as rap-
otic therapy are the domains in which the most impor- idly as possible. The new guidelines recommend that an-
tant changes and advances were made. tibiotics should be administered as soon as possible and
For initial resuscitation, previous guidelines were within 1 hour maximum. This recommendation is based
mostly based on early goal-directed therapy, which has on multiple observational studies showing that any de-
been challenged by recent trials,6 and this approach is lay in antibiotic administration is associated with an in-
no longer recommended. Of note, no harm was dem- creased risk of death. In addition to the timing of anti-
onstrated in those trials, so there was not a recommen- biotics, it is important to ensure the adequacy of
Corresponding dation to avoid early goal-directed therapy targets. antibiotics in terms of both doses and drug selection. The
Author: Todd Dorman, The guidelines recommend (mostly as best practice new guidelines state that best practice includes the use
MD, PhD, statements) the use of hemodynamic assessment for of dosing strategies based on pharmacokinetics/
The Johns Hopkins
Hospital, Department
further fluid administration after the initial fluid bolus pharmacodynamics principles in patients with sepsis
of Anesthesiology/ (including available physiological variables but also when such tests are available. This statement is based
Critical Care Medicine, noninvasive or invasive hemodynamic monitoring) and on the observation that recommended initial doses of
Turner 17, 720 Rutland
hemodynamic assessment to determine the type of antibiotics are often insufficient because of an increase
Ave, Baltimore, MD
21205-2195 shock if the clinical diagnosis does not lead to clear in volume of distribution and also, in some patients, aug-
(tdorman@jhmi.edu). diagnosis (this is particularly important in complex mented renal clearance.8

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Opinion Viewpoint

The issue of combination therapy, which reflects the use of 2 a few paragraphs in the adult guidelines, and the evolving evidence
different classes of antibiotics to cover a single putative pathogen justified the development of the SSC Pediatric Guideline. Thus, a new
sensitive to both agents, is also addressed in the new guidelines. guideline development committee specifically designed to de-
Even though combination therapy is not recommended for routine velop pediatric guidelines has been established as part of the SSC.
treatment of neutropenic sepsis (even with bacteremia), a weak The pediatric committee will include pediatric intensivists and other
recommendation was made for the use of empirical combination experts in pediatrics involved in the care of children with sepsis, and
therapy in patients with septic shock (but not in sepsis without publication of these guidelines is expected to occur in approxi-
shock). The latter was based on the increasing frequency of patho- mately 2 years. In addition, an SSC research committee has now been
gen resistance to antimicrobial agents and that multidrug combina- established with the aim of outlining research priorities in sepsis care,
tions of different classes of antibiotics decrease the likelihood of with particular attention to areas of the current guidelines in which
inadequate coverage. Several observational studies have sug- inadequate information exists.
gested benefit with empirical combination therapy in high-risk but Finally, the SSC guidelines will be translated into bundles that
not low-risk patients, justifying this quite complex 3-level recom- are key elements in sepsis improvement efforts. In a 1-day observa-
mendation on combination therapy. tional study conducted in 62 countries worldwide, adherence to the
The SSC has also developed other initiatives. The Sepsis in bundles, even though not present in the majority of patients, was
Resource Limited Nations initiative is designed to improve the qual- associated with a marked reduction in the odds of death.9 In re-
ity and reliability of patient-centered care to patients in developing sponse to the changes in the SSC guidelines, these bundles will be
and emerging countries, based on the adaptation of the current updated later this year and will be available online.10
evidence to these specific areas. Unlike previous editions, the 2016 This fourth revision of the SSC guidelines based on up-to-date
iteration of the SSC guidelines does not include recommendations evidence should prove helpful for clinicians to continue to improve
for the care of pediatric patients with sepsis. The specific aspects the care of patients with sepsis and improve the outcome of these
involved in treatment of pediatric patients could not be covered in critically ill patients.

ARTICLE INFORMATION 2. Levy MM, Rhodes A, Phillips GS, et al. Surviving 7. Cecconi M, Hofer C, Teboul JL, et al; FENICE
Published Online: January 19, 2017. Sepsis Campaign: association between Investigators; ESICM Trial Group. Fluid challenges in
doi:10.1001/jama.2017.0059 performance metrics and outcomes in a 7.5-year intensive care: the FENICE study: a global inception
study. Crit Care Med. 2015;43(1):3-12. cohort study. Intensive Care Med. 2015;41(9):1529-
Conflict of Interest Disclosures: The authors have 1537.
completed and submitted the ICMJE Form for 3. Rhodes A, Evans L, Alhazzani W, et al. Surviving
Disclosure of Potential Conflicts of Interest and Sepsis Campaign: international guidelines for the 8. Roberts JA, Paul SK, Akova M, et al; DALI Study.
none were reported. management of sepsis and septic shock: 2016. Crit DALI: defining antibiotic levels in intensive care unit
Care Med. doi:10.1097/CCM.0000000000002255 patients: are current -lactam antibiotic doses
Additional Information: Dr De Backer is immediate sufficient for critically ill patients? Clin Infect Dis.
past cochair of the Surviving Sepsis Campaign and 4. Rhodes A, Evans L, Alhazzani W, et al. Surviving
Sepsis Campaign: international guidelines 2014;58(8):1072-1083.
immediate past president of the European Society
of Intensive Care Medicine. Dr Dorman is president for the management of sepsis and septic shock: 9. Rhodes A, Phillips G, Beale R, et al. The Surviving
of the Society of Critical Care Medicine. 2016. Intensive Care Med. doi:10.1007/s00134 Sepsis Campaign bundles and outcome: results
-017-4683-6 from the International Multicentre Prevalence
REFERENCES 5. Howell MD, Davis AM. Management of sepsis Study on Sepsis (the IMPRESS study). Intensive
and septic shock. JAMA. doi:10.1001/jama.2017.0131 Care Med. 2015;41(9):1620-1628.
1. Kaukonen KM, Bailey M, Suzuki S, Pilcher D,
Bellomo R. Mortality related to severe sepsis and 6. Angus DC, Barnato AE, Bell D, et al. A systematic 10. Surviving Sepsis Campaign. http://www
septic shock among critically ill patients in Australia review and meta-analysis of early goal-directed .survivingsepsis.org. Accessed January 11, 2017.
and New Zealand, 2000-2012. JAMA. 2014;311 therapy for septic shock: the ARISE, PROCESS and
(13):1308-1316. PROMISE Investigators. Intensive Care Med. 2015;41
(9):1549-1560.

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