CẬP NHẬT GÓI 1H TRONG ĐIỀU TRỊ SỐC NHIỄM TRÙNG

INTRODUCTIONThe “sepsis bundle” has been central to the implementation of
the Surviving Sepsis Campaign (SSC) from the frst publication
of its evidence-based guidelines in 2004 through subsequent
editions (1-6). Developed separately from the guidelines publication by the SSC, the bundles have been the cornerstone of
sepsis quality improvement since 2005 (7-11). As noted when
they were introduced, the bundle elements were designed to
be updated as indicated by new evidence and have evolved
accordingly. In response to the publication of “Surviving Sepsis
Campaign: International Guidelines for Management of Sepsis
and Septic Shock: 2016” (12, 13), a revised “hour-1 bundle” has
been developed and is presented below (Fig. 1).
The compelling nature of the evidence in the literature,
which has demonstrated an association between compliance
with bundles and improved survival in patients with sepsis
and septic shock, led to the adoption of the SSC measures by
the National Quality Forum (NQF) and subsequently both by
the New York State (NYS) Department of Health (14) and the
Centers for Medicare and Medicaid Services (CMS) (15) in the
USA for mandated public reporting. The important relationship between the bundles and survival was confrmed in a publication from this NYS initiative (16).
Paramount in the management of patients with sepsis is the concept that sepsis is a medical emergency. As with
polytrauma, acute myocardial infarction, and stroke, early
identifcation and appropriate immediate management in the
initial hours after development of sepsis improves outcomes
(7-11, 14, 16-21). The guidelines state that these patients need
urgent assessment and treatment, including initial fluid resuscitation while pursuing source control, obtaining further laboratory results, and attaining more precise measurements of
hemodynamic status. A guiding principle is that these complex
patients need a detailed initial assessment and then ongoing
re-evaluation of their response to treatment. The elements of
the 2018 bundle, intended to be initiated within the frst hour,
are listed in Table 1 and presented in the following. Consistent with previous iterations of the SSC sepsis bundles, “time
zero” or “time of presentation” is defned as the time of triage
in the emergency department or, if referred from another care
location, from the earliest chart annotation consistent with
all elements of sepsis (formerly severe sepsis) or septic shock
ascertained through chart review. Because this new bundle is
based on the 2016 Guidelines publication, the guidelines themselves should be referred to for further discussion and evidence
related to each element and to sepsis management as a whole.HOUR-1 BUNDLEThe most important change in the revision of the SSC bundles is that the 3-h and 6-h bundles have been combined into
a single “hour-1 bundle” with the explicit intention of beginning resuscitation and management immediately. We believe
this reflects the clinical reality at the bedside of these seriously
ill patients with sepsis and septic shock—that clinicians begin
treatment immediately, especially in patients with hypotension, rather than waiting or extending resuscitation measures
over a longer period. More than 1 hour may be required for
resuscitation to be completed, but initiation of resuscitation
and treatment, such as obtaining blood for measuring lactate
and blood cultures, administration of fluids and antibiotics,
and in the case of life-threatening hypotension, initiation of
vasopressor therapy, are all begun immediately. It is also important to note that there are no published studies that have evaluated the effcacy in important subgroups, including burns and
immunocompromised patients. This knowledge gap needs to
be addressed in future studies specifcally targeting these subgroups. The elements included in the revised bundle are taken1Department of Medicine, Division of Pulmonary/Critical Care Medicine,
Alpert Medical School at Brown University, Providence, RI, USA.2New York University School of Medicine, New York, NY, USA.3St. George’s University Hospitals NHS Foundation Trust and St George’s
University of London, London, UK.
This article is being published simultaneously in Critical Care Medicineand Intensive Care Medicine (https://doi.org/10.1007/s00134-018-
5085-0) in the June 2018 issue of both journals.
Dr. Levy is a Member of the Surviving Sepsis Campaign Executive Committee and is a Surviving Sepsis Campaign Guidelines Author. Dr. Evans is
a Member of the Surviving Sepsis Campaign Steering Committee and is a
Surviving Sepsis Campaign Guidelines Co-Chair. Dr. Rhodes is a Member
of the Surviving Sepsis Campaign Executive Committee and is a Surviving
Sepsis Campaign Guidelines Co-Chair.
For information regarding this article, Email: mitchell_levy@brown.eduThe Surviving Sepsis Campaign Bundle:
2018 UpdateMitchell M. Levy, MD, MCCM1; Laura E. Evans, MD, MSc, FCCM2;
Andrew Rhodes, MBBS, FRCA, FRCP, FFICM, MD (res)3Copyright © 2018 by the Society of Critical Care Medicine and the European Society of Intensive Medicine. All Rights Reserved.DOI: 10.1097/CCM.0000000000003119
Copyright © 2018 by the Society of Critical Care Medicine and the European Society of Intensive Medicine. All Rights Reserved.
998 www.ccmjournal.org June 2018 • Volume 46 • Number 6from the Surviving Sepsis Campaign Guidelines, and the level
of evidence in support of each element can be seen in Table 1
(12, 13). We believe the new bundle is an accurate reflection of
actual clinical care.Measure Lactate LevelWhile serum lactate is not a direct measure of tissue perfusion (22), it can serve as a surrogate, as increases may represent tissue hypoxia, accelerated aerobic glycolysis driven by
excess beta-adrenergic stimulation, or other causes associated
with worse outcomes (23). Randomized controlled trials have
demonstrated a signifcant reduction in mortality with lactateguided resuscitation (24-28).
If initial lactate is elevated (> 2mmol/L), it should be
remeasured within 2-4 h to guide resuscitation to normalize
lactate in patients with elevated lactate levels as a marker of
tissue hypoperfusion (24).Obtain Blood Cultures Prior to AntibioticsSterilization of cultures can occur within minutes of the frst
dose of an appropriate antimicrobial (29, 30), so cultures
must be obtained before antibiotic administration to optimize the identifcation of pathogens and improve outcomes
(31, 32). Appropriate blood cultures include at least two sets
(aerobic and anaerobic). Administration of appropriate antibiotic therapy should not be delayed in order to obtain blood
cultures.Administer BroadSpectrum AntibioticsEmpiric broad-spectrum therapy with one or more intravenous antimicrobials to cover
all likely pathogens should be
started immediately (21) for
patients presenting with sepsis
or septic shock. Empiric antimicrobial therapy should be
narrowed once pathogen identifcation and sensitivities are
established, or discontinued
if a decision is made that the patient does not have infection.
The link between early administration of antibiotics for suspected infection and antibiotic stewardship remains an essential aspect of high-quality sepsis management. If infection is
subsequently proven not to exist, then antimicrobials should
be discontinued.Administer IV FluidEarly effective fluid resuscitation is crucial for the stabilization of
sepsis-induced tissue hypoperfusion or septic shock. Given the
urgent nature of this medical emergency, initial fluid resuscitation should begin immediately upon recognizing a patient with
sepsis and/or hypotension and elevated lactate, and completed
within 3 hours of recognition. The guidelines recommend
this should comprise a minimum of 30mL/kg of intravenous
crystalloid fluid. Although little literature includes controlled
data to support this volume, recent interventional studies have
described this as usual practice in the early stages of resuscitation,
and observational evidence is supportive (7, 8). The absence of
any clear beneft following the administration of colloid compared with crystalloid solutions in the combined subgroups of
sepsis, in conjunction with the expense of albumin, supports a
strong recommendation for the use of crystalloid solutions in
the initial resuscitation of patients with sepsis and septic shock.
Because some evidence indicates that a sustained positive fluid
balance during ICU stay is harmful (33-37), fluid administration beyond initial resuscitation requires careful assessment of
the likelihood that the patient remains fluid responsive.TABLE 1. Bundle Elements With Strength of Recommendations and Under-Pinning Quality
of Evidence (12, 13)Bundle Element Grade of Recommendation and Level of EvidenceMeasure lactate level. Re-measure if initial lactate is
> 2 mmol/L
Weak recommendation, low quality of evidence
Obtain blood cultures prior to administration of antibiotics Best practice statement
Administer broad-spectrum antibiotics Strong recommendation, moderate quality of evidence
Rapidly administer 30mL/kg crystalloid for hypotension or
lactate ≥ 4 mmol/L
Strong recommendation, low quality of evidence
Apply vasopressors if patient is hypotensive during or after
fluid resuscitation to maintain mean arterial pressure≥ 65mm Hg
Strong recommendation, moderate quality of evidenceFigure 1. Hour-1 Surviving Sepsis Campaign Bundle of Care.*
Copyright © 2018 by the Society of Critical Care Medicine and the European Society of Intensive Medicine. All Rights Reserved.Special ArticleCritical Care Medicine www.ccmjournal.org 999Apply VasopressorsUrgent restoration of an adequate perfusion pressure to the
vital organs is a key part of resuscitation. This should not be
delayed. If blood pressure is not restored after initial fluid
resuscitation, then vasopressors should be commenced within
the frst hour to achieve mean arterial pressure (MAP) of≥ 65 mm Hg. The physiologic effects of vasopressors and combined inotrope/vasopressor selection in septic shock are outlined in a large number of literature reviews (38-47).SUMMARYPrevious iterations of the sepsis bundle were introduced as a
means of providing education and improvement related to
sepsis management. The literature supports the use of sepsis
bundles for improving outcomes in patients with sepsis and
septic shock. This new sepsis “hour-1 bundle,” based on the
2016 guidelines, should be introduced to emergency department, floor, and ICU staff as the next iteration of ever-improving tools in the care of patients with sepsis and septic shock as
we all work to lessen the global burden of sepsis.ACKNOWLEDGMENTSThe authors gratefully acknowledge Deb McBride and Lori
Harmon for their invaluable assistance with manuscript preparation and editing (D.M.) and overall support for this work
(D.M. and L.H.).REFERENCES1. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign
Management Guidelines Committee. Surviving Sepsis Campaign
guidelines for management of severe sepsis and septic shock. Crit
Care Med 2004; 32:858–873
2. Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign
Management Guidelines Committee. Surviving Sepsis Campaign
guidelines for management of severe sepsis and septic shock.Intensive Care Med 2004; 30:536–555
3. Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign:
International guidelines for management of severe sepsis and septic
shock: 2008. Crit Care Med 2008; 36:296–327
4. Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign:
International guidelines for management of severe sepsis and septic
shock: 2008. Intensive Care Med 2008; 34:17–60
5. Dellinger RP, Levy MM, Rhodes A, et al: Surviving Sepsis
Campaign: International guidelines for management of severe
sepsis and septic shock, 2012. Intensive Care Med 2013; 39:
165–228
6. Dellinger RP, Levy MM, Rhodes A, et al: Surviving sepsis campaign:
International guidelines for management of severe sepsis and septic
shock: 2012. Crit Care Med 2013; 41:580–637
7. Levy MM, Dellinger RP, Townsend SR, et al: Surviving Sepsis
Campaign. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting
severe sepsis. Crit Care Med 2010; 38:367–374
8. Levy MM, Rhodes A, Phillips GS, et al: Surviving Sepsis Campaign:
Association between performance metrics and outcomes in a 7.5-year
study. Crit Care Med 2015; 43:3–12
9. Levy MM, Pronovost PJ, Dellinger RP, et al. Sepsis change bundles:
Converting guidelines into meaningful change in behavior and clinical
outcome. Crit Care Med 2004; 32:S595–S597
10. Damiani E, Donati A, Serafni G, et al: Effect of performance improvement programs on compliance with sepsis bundles and mortality: A
systematic review and meta-analysis of observational studies. PLoS
One 2015; 10:e0125827
11. Rhodes A, Phillips G, Beale R, et al: The Surviving Sepsis Campaign
bundles and outcome: Results from the International Multicentre
Prevalence Study on Sepsis (the IMPreSS study). Intensive Care
Med 2015; 41:1620–1628
12. Rhodes A, Evans L, Alhazzani W, et al: Surviving sepsis campaign:
International guidelines for management of sepsis and septic shock:
2016. Crit Care Med 2017; 45:486–552
13. Rhodes A, Evans L, Alhazzani W, et al: Surviving sepsis campaign:
International guidelines for management of sepsis and septic shock:
2016. Intensive Care Med 2017; 43:304–377
14. Dwyer J: One Boy’s Death Moves State to Action to Prevent Others.
2012. Available at: http://www.nytimes.com/2012/12/21/nyregion/one-boys-death-moves-state-to-action-to-prevent-others.html.
Accessed December 27, 2017
15. Centers for Medicare & Medicaid Services: CMS to Improve
Quality of Care during Hospital Inpatient Stays. 2014. Available at:
https://www.cms.gov/Newsroom/MediaReleaseDatabase/Factsheets/2014-Fact-sheets-items/2014-08-04-2.html. Accessed
December 28, 2017
16. Seymour CW, Gesten F, Prescott H, et al: Time to treatment and
mortality during mandated emergency care for sepsis. N Engl J Med2017; 376: 2235–2244
17. Liu VX, Morehouse JW, Marelich GP, et al: Multicenter implementation
of a treatment bundle for patients with sepsis and intermediate lactate
values. Am J Respir Crit Care Med 2016; 193(11):1264–1270
18. Leisman DE, Doerfler ME, Ward MF, et al: Survival beneft and cost
savings from compliance with a simplifed 3-hour sepsis bundle in a
series of prospective, multisite, observational cohorts. Crit Care Med2017; 45:395–406
19. Ferrer R, Martin-Loeches I, Phillips G, et al: Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the
frst hour: Results from a guideline-based performance improvement
program. Crit Care Med 2014; 42:1749–1755
20. Kumar A, Roberts D, Wood KE, et al: Duration of hypotension before
initiation of effective antimicrobial therapy is the critical determinant of
survival in human septic shock. Crit Care Med 2006; 34:1589–1596
21. Kumar A. Systematic bias in meta-analyses of time to antimicrobial in
sepsis studies. Crit Care Med 2016; 44:e234–e235
22. Levy B: Lactate and shock state: The metabolic view. Curr Opin Crit
Care 2006; 12:315–321
23. Casserly B, Phillips GS, Schorr C, et al: Lactate measurements in
sepsis-induced tissue hypoperfusion: Results from the Surviving
Sepsis Campaign database. Crit Care Med 2015; 43:567–573
24. Jansen TC, van Bommel J, Schoonderbeek FJ, et al: LACTATE study
group. Early lactate-guided therapy in intensive care unit patients: A
multicenter, open-label, randomized controlled trial. Am J Respir Crit
Care Med 2010; 182:752–761
25. Jones AE, Shapiro NI, Trzeciak S, et al: Emergency Medicine Shock
Research Network (EMShockNet) Investigators. Lactate clearance vs
central venous oxygen saturation as goals of early sepsis therapy: A
randomized clinical trial. JAMA 2010; 303:739–746
26. Lyu X, Xu Q, Cai G, et al: Effcacies of fluid resuscitation as guided by
lactate clearance rate and central venous oxygen saturation in patients
with septic shock. Zhonghua Yi Xue Za Zhi 2015; 95:496–500
27. Tian HH, Han SS, Lv CJ, et al: The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2012; 24:42–45
28. Yu B, Tian HY, Hu ZJ, et al: Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous
oxygen saturation in patients with sepsis. Zhonghua Wei Zhong Bing
Ji Jiu Yi Xue 2013; 25:578–583
29. Zadroga R, Williams DN, Gottschall R, et al: Comparison of 2 blood
culture media shows signifcant differences in bacterial recovery for
patients on antimicrobial therapy. Clin Infect Dis 2013; 56:790–797
30. Kanegaye JT, Soliemanzadeh P, Bradley JS: Lumbar puncture in pediatric bacterial meningitis: Defning the time interval for recovery of
cerebrospinal fluid pathogens after parenteral antibiotic pretreatment.Pediatrics 2001; 108:1169–1174
Copyright © 2018 by the Society of Critical Care Medicine and the European Society of Intensive Medicine. All Rights Reserved.Levy et al1000 www.ccmjournal.org June 2018 • Volume 46 • Number 6
31. Cardoso T, Carneiro AH, Ribeiro O, et al: Reducing mortality in severe
sepsis with the implementation of a core 6-hour bundle: results from
the Portuguese community-acquired sepsis study (SACiUCI study).Crit Care 2010; 14:R83
32. De Sousa AG, Fernandes Junior CJ, Santos GPD, et al: The impact of
each action in the Surviving Sepsis Campaign measures on hospital
mortality of patients with severe sepsis/septic shock. Einstein 2008;
6:323–327
33. Acheampong A, Vincent JL: A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015;
19:251
34. Brotfain E, Koyfman L, Toledano R, et al: Positive fluid balance
as a major predictor of clinical outcome of patients with sepsis/
septic shock after ICU discharge. Am J Emerg Med 2016; 34:
2122–2126
35. Mitchell KH, Carlbom D, Caldwell E, et al: Volume overload:
Prevalence, risk factors, and functional outcome in survivors of septic
shock. Ann Am Thorac Soc 2015; 12:1837–1844
36. de Oliveira FS, Freitas FG, Ferreira EM, et al: Positive fluid balance
as a prognostic factor for mortality and acute kidney injury in severe
sepsis and septic shock. J Crit Care 2015; 30:97–101
37. Malbrain ML, Marik PE, Witters I, et al: Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: A systematic
review with suggestions for clinical practice. Anaesthesiol Intensive
Ther 2014; 46:361–380.
38. Day NP, Phu NH, Bethell DP, et al: The effects of dopamine and
adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet 1996; 348:219–223
39. De Backer D, Creteur J, Silva E, et al: Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic
shock: Which is best? Crit Care Med 2003; 31:1659–1667
40. Martin C, Papazian L, Perrin G, et al: Norepinephrine or dopamine
for the treatment of hyperdynamic septic shock? Chest 1993;
103:1826–1831
41. Martin C, Viviand X, Leone M, et al: Effect of norepinephrine on the
outcome of septic shock. Crit Care Med 2000; 28:2758–2765
42. Bollaert PE, Bauer P, Audibert G, et al: Effects of epinephrine on
hemodynamics and oxygen metabolism in dopamine-resistant septic
shock. Chest 1990; 98:949–953
43. Levy B, Bollaert PE, Charpentier C, et al: Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate
metabolism, and gastric tonometric variables in septic shock: A prospective, randomized study. Intensive Care Med 1997; 23:282–287
44. Zhou SX, Qiu HB, Huang YZ, et al: Effects of norepinephrine, epinephrine, and norepinephrine-dobutamine on systemic and gastric
mucosal oxygenation in septic shock. Acta Pharmacol Sin 2002;
23:654–658
45. Mackenzie SJ, Kapadia F, Nimmo GR, et al: Adrenaline in treatment
of septic shock: Effects on haemodynamics and oxygen transport.Intensive Care Med 1991; 17:36–39
46. Moran JL, O’Fathartaigh MS, Peisach AR, et al: Epinephrine as an
inotropic agent in septic shock: a dose-profle analysis. Crit Care Med1993; 21:70–77
47. Yamazaki T, Shimada Y, Taenaka N, et al: Circulatory responses to
afterloading with phenylephrine in hyperdynamic sepsis. Crit Care
Med 1982; 10:432–435