Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

Surviving sepsis campaign: international
guidelines for management of sepsis and septic
shock 2021

Screening and early treatment

Screening for patients with sepsis and septic shock

Recommendation

1. For hospitals and health systems, we recommend using a performance improvement programme for sepsis, including sepsis screening for acutely ill, high-risk patients and standard operating procedures for treatment

Strong recommendation, moderate quality of evidence for screening

Strong recommendation, very low-quality evidence for standard operating procedures

Recommendation
2. We recommend against using qSOFA compared to SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock
Strong recommendation, moderate-quality evidence

Recommendation
3. For adults suspected of having sepsis, we suggest measuring blood lactate
Weak recommendation, low-quality evidence

Initial resuscitation

Recommendations
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 intravenous (IV) crystalloid fluid should be given within the first 3 h of resuscitation Weak recommendation, low-quality evidence
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 recommendation, very low-quality evidence Remarks Dynamic parameters include response to a passive leg raise or a fluid bolus, using stroke volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV), or echocardiography, where available
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 recommendation, low-quality evidence Remarks During acute resuscitation, serum lactate level should be interpreted considering the clinical context and other causes of elevated lactate
8. For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion Weak recommendation, low-quality evidence

Mean arterial pressure

Recommendation
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 recommendation, moderate-quality evidence

Admission to intensive care

Recommendation
10. For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 h
Weak recommendation, low-quality evidence

Diagnosis of infection

Recommendation

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

Time to antibiotics

Recommendations
12. For adults with possible septic shock or a high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 h of recognition Strong recommendation, low quality of evidence (Septic shock) Strong recommendation, very low quality of evidence (Sepsis without shock)
13. For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus non-infectious causes of acute illness Best Practice Statement Remarks Rapid assessment includes history and clinical examination, tests for both infectious and non-infectious causes of acute illness and immediate treatment for acute conditions that can mimic sepsis. Whenever possible this should be completed within 3 h of presentation so that a decision can be made as to the likelihood of an infectious cause of the patient’s presentation and timely antimicrobial therapy provided if the likelihood of sepsis is thought to be high
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 h from the time when sepsis was first recognised Weak recommendation, very low 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 recommendation, very low quality of evidence

Biomarkers to start antibiotics

Recommendation
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 to clinical evaluation alone
Weak recommendation, very low quality of evidence

Antimicrobial choice

Recommendations
17. For adults with sepsis or septic shock at high risk of methicillin resistant staph aureus (MRSA), we recommend using empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage Best Practice statement
18. For adults with sepsis or septic shock at low risk of methicillin resistant staph aureus (MRSA), we suggest against using empiric antimicrobials with MRSA coverage, as compared with using antimicrobials without MRSA coverage Weak recommendation, low 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 recommendation, very low quality of evidence
20. For adults with sepsis or septic shock and low risk for MDR organisms, we suggest against using two Gram-negative agents for empiric treatment, as compared to one Gram-negative agent Weak recommendation, 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 recommendation, very low quality of evidence

Antifungal therapy

Recommendations
22. For adults with sepsis or septic shock at high risk of fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy Weak recommendation, low 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 recommendation, low quality of evidence

Antiviral therapy

Recommendation

24. We make no recommendation on the use of antiviral agents

Delivery of antibiotics

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 recommendation, moderate quality of evidence

Pharmacokinetics and pharmacodynamics

Recommendation
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

Source control

Recommendation
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

Recommendation
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

De-escalation of antibiotics

Recommendation
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 recommendation, very low quality of evidence

Duration of antibiotics

Recommendation
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 recommendation, very low quality of evidence

Biomarkers to discontinue antibiotics

Recommendation
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 recommendation, low quality of evidence

Haemodynamic management

Fluid management

Recommendations
32. For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation Strong recommendation, moderate quality of evidence
33. For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation Weak recommendation, low quality of evidence
34. For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids over using crystalloids alone Weak recommendation, moderate quality of evidence
35. For adults with sepsis or septic shock, we recommend against using starches for resuscitation Strong recommendation, high quality of evidence
36. For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation Weak recommendation, moderate quality

Vasoactive agents

Recommendations
37. For adults with septic shock, we recommend using norepinephrine as the first-line agent over other vasopressors. Strong recommendation Dopamine. High quality evidence Vasopressin. Moderate-quality evidence Epinephrine. Low-quality evidence Selepressin. Low-quality evidence Angiotensin II. Very low-quality evidence Remark In settings where norepinephrine is not available, epinephrine or dopamine can be used as an alternative, but we encourage efforts to improve the availability of norepinephrine. Special attention should be given to patients at risk for arrhythmias when using dopamine and epinephrine
38. For adults with septic shock on norepinephrine with inadequate MAP levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine Weak recommendation, moderate-quality evidence Remark In our practice, vasopressin is usually started when the dose of norepinephrine is in the range of 0.25–0.5 μg/kg/min
39. For adults with septic shock and inadequate MAP levels despite norepinephrine and vasopressin, we suggest adding epinephrine Weak recommendation, low-quality evidence
40. For adults with septic shock, we suggest against using terlipressin Weak recommendation, low quality of evidence

Inotropes

Recommendations
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 recommendation, 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 recommendation, low quality of evidence

Monitoring and intravenous access

Recommendations
43. For adults with septic shock, we suggest using invasive monitoring of arterial blood pressure over non-invasive monitoring, as soon as practical and if resources are available Weak recommendation, very low quality of evidence
44. For adults with septic shock, we suggest starting vasopressors peripherally to restore MAP rather than delaying initiation until a central venous access is secured Weak recommendation, very low quality of evidence Remark When using vasopressors peripherally, they should be administered only for a short period of time and in a vein in or proximal to the antecubital fossa

Fluid balance

Recommendation
45. There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 h of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after initial resuscitation
Remarks Fluid resuscitation should be given only if patients present with signs of hypoperfusion

Ventilation

Oxygen targets

Recommendation
46. There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure

High-flow nasal oxygen therapy

Recommendation
47. For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over non-invasive ventilation
Weak recommendation, low quality of evidence

Non-invasive ventilation

Recommendation
48. There is insufficient evidence to make a recommendation on the use of non-invasive ventilation in comparison to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure

Protective ventilation in acute respiratory distress syndrome (ARDS)

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 recommendation, high quality of evidence

Recommendation
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 recommendation, moderate quality of evidence

Recommendation
51. For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP Weak recommendation, moderate quality of evidence

Low tidal volume in non-ARDS respiratory failure

Recommendation
52. For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared to high tidal volume ventilation
Weak recommendation, low quality of evidence

Recruitment manoeuvres

Recommendations
53. For adults with sepsis-induced moderate-severe ARDS, we suggest using traditional recruitment maneuvers Weak recommendation, moderate quality of evidence
54. When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy Strong recommendation, moderate quality of evidence

Prone ventilation

Recommendation
55. For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for more than 12 h daily
Strong recommendation, moderate quality of evidence

Neuromuscular blocking agents

Recommendation
56. For adults with sepsis induced moderate-severe ARDS, we suggest using intermittent NMBA boluses, over NMBA continuous infusion
Weak recommendation, moderate quality of evidence

Extracorporeal membrane oxygenation (ECMO)

Recommendation
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 recommendation, low quality of evidence

Additional therapies

Corticosteroids

Recommendation
58. For adults with septic shock and an ongoing requirement for vasopressor therapy we suggest using IV corticosteroids Weak recommendation; moderate quality of evidence
Remark The typical corticosteroid used in adults with septic shock is IV hydrocortisone at a dose of 200 mg/day given as 50 mg intravenously every 6 h or as a continuous infusion. It is suggested that this is commenced at a dose of norepinephrine or epinephrine ≥ 0.25 mcg/kg/min at least 4 h after initiation

Blood Purification

Recommendations
59. For adults with sepsis or septic shock, we suggest against using polymyxin B haemoperfusion Weak recommendation; low quality of evidence
60. There is insufficient evidence to make a recommendation on the use of other blood purification techniques

Red blood cell (RBC) transfusion targets

Recommendation
61. For adults with sepsis or septic shock, we recommend using a restrictive (over liberal) transfusion strategy Strong recommendation; moderate quality of evidence
Remark A restrictive transfusion strategy typically includes a haemoglobin concentration transfusion trigger of 70 g/L; however, RBC transfusion should not be guided by haemoglobin concentration alone. Assessment of a patient’s overall clinical status and consideration of extenuating circumstances such as acute myocardial ischaemia, severe hypoxemia or acute haemorrhage is required

Immunoglobulins

Recommendation
62. For adults with sepsis or septic shock, we suggest against using intravenous immunoglobulins
Weak recommendation, low quality of evidence

Stress ulcer prophylaxis

Recommendation
63. For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding, we suggest using stress ulcer prophylaxis
Weak recommendation, moderate quality of evidence

Venous thromboembolism (VTE) prophylaxis

Recommendations
64. For adults with sepsis or septic shock, we recommend using pharmacologic VTE prophylaxis unless a contraindication to such therapy exists Strong recommendation, moderate quality of evidence
65. For adults with sepsis or septic shock, we recommend using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for VTE prophylaxis Strong recommendation, moderate quality of 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 recommendation, low quality of evidence

Renal replacement therapy

Recommendations
67. In adults with sepsis or septic shock and AKI who require renal replacement therapy, we suggest using either continuous or intermittent renal replacement therapy Weak recommendation, 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 recommendation, moderate quality of evidence

Glucose control

Recommendation
69. For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180 mg/dL (10 mmol/L) Strong recommendation; moderate quality of evidence
Remark Following initiation of an insulin therapy, a typical target blood glucose range is 144–180 mg/dL (8–10 mmol/L)

Vitamin C

Recommendation
70. For adults with sepsis or septic shock, we suggest against using IV vitamin C
Weak recommendation, low quality of evidence

Bicarbonate therapy

Recommendations
71. For adults with septic shock and hypoperfusion-induced lactic acidemia, we suggest against using sodium bicarbonate therapy to improve haemodynamics or to reduce vasopressor requirements Weak recommendation, low quality of evidence
72. For adults with septic shock, severe metabolic acidemia (pH ≤ 7.2) and AKI (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy Weak recommendation, low quality of evidence

Nutrition

Recommendation
73. For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 h) initiation of enteral nutrition
Weak recommendation; very low quality of evidence

Long-term outcomes and goals of care

Goals of care

Recommendations
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 h) over late [72] Weak recommendation, low-quality evidence
76. There is insufficient evidence to make a recommendation for any specific standardised criterion to trigger goals of care discussion

Palliative care

Recommendations
77. For adults with sepsis or septic shock, we recommend integrating principles of palliative care (which may include palliative care consultation based on clinician judgement) 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 recommendation, low-quality evidence

Peer support groups

Recommendation
79. For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral
Weak recommendation, very low quality of evidence

Transitions of care

Recommendations
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 recommendation, very low-quality evidence
81. There is insufficient evidence to make a recommendation for the use of any specific structured handoff tool over usual handoff processes

Screening for economic or social support

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

Sepsis education for patients and families

Recommendation
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 recommendation, very low-quality evidence

Shared decision making

Recommendation
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

Discharge planning

Recommendations
85. For adults with sepsis and septic shock and their families, we suggest using a critical care transition programme, compared to usual care, upon transfer to the floor Weak recommendation, very low-quality 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. There is insufficient evidence to make a recommendation on early post-hospital discharge follow-up compared to routine post-hospital discharge follow-up

Cognitive therapy

Recommendation
90. There is insufficient evidence to make a recommendation on early cognitive therapy for adult survivors of sepsis or septic shock

Post-discharge follow-up

Recommendations
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 programme if available Weak recommendation, very low-quality evidence
93. For adult survivors of sepsis or septic shock receiving mechanical ventilation for > 48 h or an ICU stay of > 72 h, we suggest referral to a post-hospital rehabilitation programme Weak recommendation, very low-quality evidence

Fuente: Intensive Care Med https://doi.org/10.1007/s00134-021-06506-y