Guidelines Summary
The initial sepsis guidelines were published in 2004 and then revised in 2008 and 2012. The 2016 clinical practice guidelines are a revision of the 2012 Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis and septic shock. The latest guidelines were 2021 Surviving Sepsis Campaign Guidelines that were revised by IDSA/ Emergency Medicine Collaborative Task Force [56] and Surviving Sepsis Campaign Guidelines 2021. [1]
Major New Recommendations in the 2012 Update
Emphasis was directed to (1) first-hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill of 2 seconds or less with specific evaluation after each bolus for signs of fluid overload, as well as first-hour antibiotic administration and (2) subsequent ICU hemodynamic support directed to goals of ScVO2 greater than 70% and cardiac index (CI) 3.3-6 L/min/m2 with appropriate antibiotic coverage and source control. [62]
Another major new recommendation in the 2012 update was that hemodynamic support of septic shock should be addressed at the institutional level rather than only at the practitioner level, with well-planned coordination between the family, community, prehospital, emergency department, hospital, and ICU settings. The 2012 guidelines recommend that each institution implement their own adopted or home-grown bundles that include the following:
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Recognition bundle containing a trigger tool for rapid identification of patients with suspected septic shock at that institution
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Resuscitation and stabilization bundle to drive adherence to consensus best practice at that institution
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Performance bundle to monitor, improve, and sustain adherence to that best practice
The 2016 Surviving Sepsis Campaign Guidelines
The 2016 guidelines [63, 64] give a detailed overview of initial resuscitation, screening, and diagnosis of sepsis. The management decisions concerning antibiotic therapy, fluid administration, source control, administration of pressors and steroids, blood products, anticoagulants, immunoglobulins, mechanical ventilation, sedation, analgesia, glucose control, blood purification, renal replacement therapy, bicarbonate, venous thromboembolism and stress ulcer prophylaxis, nutrition, and setting goals of care are addressed. The main differences between the 2012 and 2016 guidelines are discussed in detail in the cited reference. [65]
Unfortunately, a consensus could not be reached between some of the sponsoring organizations. A position paper issued by the IDSA does not endorse the Society of Critical Care Medicine/European Society of Intensive Care Medicine (SCCM/ESICM) 2016 Surviving Sepsis Campaign guidelines for the management of sepsis and septic shock, despite the IDSA's participation in the development of the guidelines. In particular, while the IDSA agrees that the SCCM/ESICM recommendations are life-saving for patients with septic shock, they may lead to overtreatment in those with milder variants of sepsis and sepsis syndromes. The IDSA does not endorse routine initiation of antibiotic therapy within one hour of suspecting sepsis nor administration of combination antibiotic therapy and a 7- to 10-day course of antibiotic therapy for all patients, regardless of presentation factors. The IDSA also notes unclear recommendations for removal of catheters when considered as the source of sepsis and for the role of procalcitonin when monitoring therapeutic response. [66]
As more research related to timing of therapy is completed, further guideline refinement is expected, and perhaps a consensus regarding the treatment approach can be achieved.
The 2021 Surviving Sepsis Campaign Guidelines
In 2021 after the Covid pandemic the guidelines for Sepsis have been changed significantly in terms of sepsis screening, diagnosis with qSOFA vs NEWS, MEWS or SIRS criteria, use of antibiotics, resuscitation including pressor support, IV fluids and use of steroids and blood purification techniques. Following is a tabulated list of changes from prior guidelines for a quick reference.
Table 1. Table of Current Recommendations and Changes From Previous 2016 Recommendations [1] (Open Table in a new window)
Recommendations 2021 | Recommendation Strength and Quality of Evidence | Changes From 2016 Recommendations |
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1. For hospitals and health systems, we recommend using a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment. | Strong; moderate-quality evidence (for screening) | Changed from Best practice statement |
“We recommend that hospitals and hospital systems have a performance improvement program for sepsis including sepsis screening for acutely ill, high-risk patients.” | ||
Strong; very low-quality evidence (for standard operating procedures) | ||
2. We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single-screening tool for sepsis or septic shock. | Strong; moderate-quality evidence | NEW |
3. For adults suspected of having sepsis, we suggest measuring blood lactate. | Weak; low quality of evidence | |
INITIAL RESUSCITATION | ||
4. Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately. | Best practice statement | |
5. For patients with sepsis induced hypoperfusion or septic shock we suggest that at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hr of resuscitation. | Weak; low quality of evidence | DOWNGRADE from Strong; low quality of evidence |
“We recommend that in the initial resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hr” | ||
6. For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation, over physical examination or static parameters alone. | Weak; very low quality of evidence | |
7. For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate. | Weak; low quality of evidence | |
8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. | Weak; low quality of evidence | NEW |
MEAN ARTERIAL PRESSURE | ||
9. For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets. | Strong; moderate-quality evidence | |
ADMISSION TO INTENSIVE CARE | ||
10. For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 hr. | Weak; low quality of evidence | |
INFECTION | ||
11. For adults with suspected sepsis or septic shock but unconfirmed infection, we recommend continuously re-evaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials if an alternative cause of illness is demonstrated or strongly suspected. | Best practice statement | |
12. For adults with possible septic shock or a high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 hr of recognition. | Strong; low quality of evidence (Septic shock) | CHANGED from previous: “We recommend that administration of intravenous antimicrobials should be initiated as soon as possible after recognition and within one hour for both a) septic shock and b) sepsis without shock” |
Strong; very low quality of evidence (Sepsis without shock) | ||
Strong recommendation; moderate quality of evidence | ||
13. For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus noninfectious causes of acute illness. | Best practice statement | |
14. For adults with possible sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for infection persists, the administration of antimicrobials within 3 hr from the time when sepsis was first recognized. | Weak; very low quality of evidence | NEW from previous: |
“We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock” | ||
Strong recommendation; moderate quality of evidence | ||
15. For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobials while continuing to closely monitor the patient. | Weak; very low quality of evidence | NEW from previous: |
“We recommend that administration of IV antimicrobials should be initiated as soon as possible after recognition and within 1 hr for both a) septic shock and b) sepsis without shock“ | ||
Strong recommendation; moderate quality of evidence | ||
16. For adults with suspected sepsis or septic shock, we suggest against using procalcitonin plus clinical evaluation to decide when to start antimicrobials, as compared with clinical evaluation alone. | Weak; very low quality of evidence | |
17. For adults with sepsis or septic shock at high risk for MRSA, we recommend using empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage. | Best practice statement | NEW from previous: |
“We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
Strong recommendation; moderate quality of evidence | ||
18. For adults with sepsis or septic shock at low risk for MRSA, we suggest against using empiric antimicrobials with MRSA coverage, as compared with using antimicrobials without MRSA coverage. | Weak; low quality of evidence | NEW from previous: |
“We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
Strong recommendation; moderate quality of evidence | ||
19. For adults with sepsis or septic shock and high risk for multidrug resistant (MDR) organisms, we suggest using two antimicrobials with gram-negative coverage for empiric treatment over one gram-negative agent. | Weak; very low quality of evidence | |
20. For adults with sepsis or septic shock and low risk for multidrug resistant (MDR) organisms, we suggest against using two gram-negative agents for empiric treatment, as compared to one gram-negative agent. | Weak; very low quality of evidence | |
21. For adults with sepsis or septic shock, we suggest against using double gram-negative coverage once the causative pathogen and the susceptibilities are known. | Weak; very low quality of evidence | |
22. For adults with sepsis or septic shock at high risk for fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy. | Weak; low quality of evidence | NEW from previous: |
“We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.” | ||
Strong recommendation; moderate quality of evidence | ||
23. For adults with sepsis or septic shock at low risk of fungal infection, we suggest against empiric use of antifungal therapy | Weak; low quality of evidence | NEW from previous: |
“We recommend empiric broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage.“ | ||
Strong recommendation; moderate quality of evidence | ||
24. We make no recommendation on the use of antiviral agents. | No recommendation | |
25. For adults with sepsis or septic shock, we suggest using prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion. | Weak; moderate-quality evidence | |
26. For adults with sepsis or septic shock, we recommend optimising dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic (PK/PD) principles and specific drug properties. | Best practice statement | |
27. For adults with sepsis or septic shock, we recommend rapidly identifying or excluding a specific anatomical diagnosis of infection that requires emergent source control and implementing any required source control intervention as soon as medically and logistically practical. | Best practice statement | |
28. For adults with sepsis or septic shock, we recommend prompt removal of intravascular access devices that are a possible source of sepsis or septic shock after other vascular access has been established. | Best practice statement | |
29. For adults with sepsis or septic shock, we suggest daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment for de-escalation. | Weak; very low quality of evidence | |
30. For adults with an initial diagnosis of sepsis or septic shock and adequate source control, we suggest using shorter over longer duration of antimicrobial therapy. | Weak; very low quality of evidence | |
31. For adults with an initial diagnosis of sepsis or septic shock and adequate source control where optimal duration of therapy is unclear, we suggest using procalcitonin AND clinical evaluation to decide when to discontinue antimicrobials over clinical evaluation alone. | Weak; low quality of evidence | |
HEMODYNAMIC MANAGEMENT | ||
32. For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation. | Strong; moderate-quality evidence | |
33. For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation. | Weak; low quality of evidence | CHANGED from weak recommendation; low quality of evidence. |
“We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock” | ||
34. For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids. | Weak; moderate-quality evidence | |
35. For adults with sepsis or septic shock, we recommend against using starches for resuscitation. | Strong; high-quality evidence | |
36. For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation. | Weak; moderate-quality evidence | UPGRADE from weak recommendation; low quality of evidence |
“We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock.” | ||
37. For adults with septic shock, we recommend using norepinephrine as the first-line agent over other vasopressors. | Strong | |
Dopamine. High-quality evidence | ||
Vasopressin. Moderate-quality evidence | ||
Epinephrine. Low quality of evidence | ||
Selepressin. Low quality of evidence | ||
Angiotensin II. Very low-quality evidence | ||
38. For adults with septic shock on norepinephrine with inadequate mean arterial pressure levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine. | Weak; moderate quality evidence | |
39. For adults with septic shock and inadequate mean arterial pressure levels despite norepinephrine and vasopressin, we suggest adding epinephrine. | Weak; low quality of evidence | |
40. For adults with septic shock, we suggest against using terlipressin. | Weak; low quality of evidence | |
41. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest either adding dobutamine to norepinephrine or using epinephrine alone. | Weak; low quality of evidence | |
42. For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest against using levosimendan. | Weak; low quality of evidence | NEW |
43. For adults with septic shock, we suggest invasive monitoring of arterial blood pressure over noninvasive monitoring, as soon as practical and if resources are available. | Weak; very low quality of evidence | |
44. For adults with septic shock, we suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying initiation until a central venous access is secured. | Weak; very low quality of evidence | NEW |
45. There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hr of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after the initial resuscitation. | No recommendation | NEW |
“We suggest using either balanced crystalloids or saline for fluid resuscitation of patients with sepsis or septic shock” | ||
Weak recommendation; low quality of evidence | ||
“We suggest using crystalloids over gelatins when resuscitating patients with sepsis or septic shock.” | ||
Weak recommendation; low quality of evidence | ||
VENTILATION | ||
46.There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure. | No recommendation | |
47. For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over noninvasive ventilation. | Weak; low quality of evidence | NEW |
48. There is insufficient evidence to make a recommendation on the use of noninvasive ventilation in comparison to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure. | No recommendation | |
49. For adults with sepsis-induced ARDS, we recommend using a low tidal volume ventilation strategy (6 mL/kg), over a high tidal volume strategy (> 10 mL/kg). | Strong; high-quality evidence | |
50. For adults with sepsis-induced severe ARDS, we recommend using an upper limit goal for plateau pressures of 30 cm H2O, over higher plateau pressures. | Strong; moderate-quality evidence | |
51. For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP. | Weak; moderate-quality evidence | |
52. For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared with high tidal volume ventilation. | Weak; low quality of evidence | |
53. For adults with sepsis-induced moderate-severe ARDS, we suggest using traditional recruitment maneuvers. | Weak; moderate-quality evidence | |
54. When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy. | Strong; moderate-quality evidence | |
55. For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for greater than 12 hr daily. | Strong; moderate-quality evidence | |
56. For adults with sepsis induced moderate-severe ARDS, we suggest using intermittent NMBA boluses, over NMBA continuous infusion. | Weak; moderate-quality evidence | |
57. For adults with sepsis-induced severe ARDS, we suggest using Veno-venous (VV) ECMO when conventional mechanical ventilation fails in experienced centers with the infrastructure in place to support its use. | Weak; low quality of evidence | NEW |
ADDITIONAL THERAPIES | ||
58. For adults with septic shock and an ongoing requirement for vasopressor therapy we suggest using IV corticosteroids. | Weak; moderate-quality evidence | UPGRADE from Weak recommendation , low quality of evidence |
“We suggest against using IV hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (see goals for Initial Resuscitation). If this is not achievable, we suggest IV hydrocortisone at a dose of 200 mg/day.” | ||
59. For adults with sepsis or septic shock we suggest against using polymyxin B hemoperfusion. | Weak; low quality of evidence | NEW from previous: “We make no recommendation regarding the use of blood purification techniques” |
60. There is insufficient evidence to make a recommendation on the use of other blood purification techniques. | No recommendation | |
61. For adults with sepsis or septic shock we recommend using a restrictive (over liberal) transfusion strategy. | Strong; moderate-quality evidence | |
62. For adults with sepsis or septic shock we suggest against using IV immunoglobulins. | Weak; low quality of evidence | |
63. For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding, we suggest using stress ulcer prophylaxis. | Weak; moderate-quality evidence | |
64. For adults with sepsis or septic shock, we recommend using pharmacologic venous thromboembolism (VTE) prophylaxis unless a contraindication to such therapy exists. | Strong; moderate-quality evidence | |
65. For adults with sepsis or septic shock, we recommend using low molecular weight heparin over unfractionated heparin for VTE prophylaxis | Strong; moderate-quality evidence | |
66. For adults with sepsis or septic shock, we suggest against using mechanical VTE prophylaxis, in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone. | Weak; low quality of evidence | |
67. In adults with sepsis or septic shock and AKI, we suggest using either continuous or intermittent renal replacement therapy. | Weak; low quality of evidence | |
68. In adults with sepsis or septic shock and AKI, with no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy. | Weak; moderate-quality evidence | |
69. For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180mg/dL (10 mmol/L). | Strong; moderate-quality evidence | |
70. For adults with sepsis or septic shock we suggest against using IV vitamin C. | Weak; low quality of evidence | NEW |
71. For adults with septic shock and hypoperfusion-induced lactic acidemia, we suggest against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements. | Weak; low quality of evidence | |
72. For adults with septic shock and severe metabolic acidemia (pH ≤ 7.2) and acute kidney injury (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy | Weak; low quality of evidence | |
73. For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 hr) initiation of enteral nutrition. | Weak; very low quality of evidence | |
LONG-TERM OUTCOMES AND GOALS OF CARE | ||
74. For adults with sepsis or septic shock, we recommend discussing goals of care and prognosis with patients and families over no such discussion. | Best practice statement | |
75. For adults with sepsis or septic shock, we suggest addressing goals of care early (within 72 hr) over late (72 hr or later). | Weak; low quality of evidence | |
76. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on any specific standardized criterion to trigger goals of care discussion. | No recommendation | |
77. For adults with sepsis or septic shock, we recommend that the principles of palliative care (which may include palliative care consultation based on clinician judgement) be integrated into the treatment plan, when appropriate, to address patient and family symptoms and suffering. | Best practice statement | |
78. For adults with sepsis or septic shock, we suggest against routine formal palliative care consultation for all patients over palliative care consultation based on clinician judgement. | Weak; low quality of evidence | |
79. For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral. | Weak; very low quality of evidence | |
80. For adults with sepsis or septic shock, we suggest using a handoff process of critically important information at transitions of care over no such handoff process. | Weak; very low quality of evidence | |
81. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on the use of any specific structured handoff tool over usual handoff processes. | No recommendation | |
82. For adults with sepsis or septic shock and their families, we recommend screening for economic and social support (including housing, nutritional, financial, and spiritual support), and make referrals where available to meet these needs. | Best practice statement | |
83. For adults with sepsis or septic shock and their families, we suggest offering written and verbal sepsis education (diagnosis, treatment, and post-ICU/post-sepsis syndrome) prior to hospital discharge and in the follow-up setting. | Weak; very low quality of evidence | |
84. For adults with sepsis or septic shock and their families, we recommend the clinical team provide the opportunity to participate in shared decision making in post-ICU and hospital discharge planning to ensure discharge plans are acceptable and feasible. | Best practice statement | |
85. For adults with sepsis and septic shock and their families, we suggest using a critical care transition program, compared with usual care, upon transfer to the floor. | Weak; very low quality of evidence | |
86. For adults with sepsis and septic shock, we recommend reconciling medications at both ICU and hospital discharge. | Best practice statement | |
87. For adult survivors of sepsis and septic shock and their families, we recommend including information about the ICU stay, sepsis and related diagnoses, treatments, and common impairments after sepsis in the written and verbal hospital discharge summary. | Best practice statement | |
88. For adults with sepsis or septic shock who developed new impairments, we recommend hospital discharge plans include follow-up with clinicians able to support and manage new and long-term sequelae. | Best practice statement | |
89. For adults with sepsis or septic shock and their families, there is insufficient evidence to make a recommendation on early post-hospital discharge follow-up compared with routine post-hospital discharge follow-up. | No recommendation | |
90. For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation for or against early cognitive therapy. | No recommendation | |
91. For adult survivors of sepsis or septic shock, we recommend assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge. | Best practice statement | |
92. For adult survivors of sepsis or septic shock, we suggest referral to a post-critical illness follow-up program if available. | Weak; very low quality of evidence | |
93. For adult survivors of sepsis or septic shock receiving mechanical ventilation for > 48hr or an ICU stay of > 72 hr, we suggest referral to a post-hospital rehabilitation program. | Weak; very low quality of evidence |
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A right lower quadrant abdominal wall abscess and enteric fistula are observed and confirmed by the presence of enteral contrast in the abdominal wall.