Surviving Sepsis Campaign: Management of Sepsis and Septic Shock 2021

Publication Date: October 2, 2021
Last Updated: March 14, 2022

Screening and early treatment

For hospitals and health systems, we recommend using a performance improvement programme for sepsis, including sepsis screening for acutely ill, high-risk patients (S, M)
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For hospitals and health systems, we recommend using a performance improvement programme for sepsis, including standard operating procedures for treatment (S, VL)
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We recommend against using qSOFA compared to SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock (S, M)
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For adults suspected of having sepsis, we suggest measuring blood lactate (C, L)
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Initial resuscitation

Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately (U, U)
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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 (C, L)
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For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation, over physical examination or static parameters alone (C, VL)
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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 (C, L)
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For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion (C, L)
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Mean arterial pressure

For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets (S, M)
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Admission to intensive care

For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 h (C, L)
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Diagnosis of infection

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 (U, U)
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Time to antibiotics

For adults with high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 h of recognition (S, VL)
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For adults with possible septic shock, we recommend administering antimicrobials immediately, ideally within 1 h of recognition

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For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus non-infectious causes of acute illness (U, U)
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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 (C, VL)
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For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobials while continuing to closely monitor the patient (C, VL)
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Biomarkers to start antibiotics

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 (C, VL)
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Antimicrobial choice

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 (U, U)
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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 (C, L)
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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 (C, VL)
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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 (C, VL)
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For adults with sepsis or septic shock, we suggest against using double gram-negative coverage once the causative pathogen and the susceptibilities are known (C, VL)
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Antifungal therapy

For adults with sepsis or septic shock at high risk of fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy (C, L)
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For adults with sepsis or septic shock at low risk of fungal infection, we suggest against empiric use of antifungal therapy (C, L)
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Antiviral therapy

We make no recommendation on the use of antiviral agents (U, U)
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Delivery of antibiotics

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 (C, M)
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Pharmacokinetics and pharmacodynamics

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 (U, U)
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Source control

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 (U, U)
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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 (U, U)
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De-escalation of antibiotics

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 (C, VL)
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Duration of antibiotics

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 (C, VL)
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Biomarkers to discontinue antibiotics

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 (C, L)
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Haemodynamic management

Fluid management

For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation (S, M)
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For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation (C, L)
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For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids over using crystalloids alone (C, M)
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For adults with sepsis or septic shock, we recommend against using starches for resuscitation (S, H)
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For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation (C, M)
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Vasoactive agents

For adults with septic shock, we recommend using norepinephrine as the first-line agent over
dopamine (S, H)
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vasopressin (S, M)
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epinephrine (S, L)
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selepressin (S, L)
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angiotensin II (S, VL)
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
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For adults with septic shock on norepinephrine with inadequate MAP levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine (C, M)
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For adults with septic shock and inadequate MAP levels despite norepinephrine and vasopressin, we suggest adding epinephrine (C, L)
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For adults with septic shock, we suggest against using terlipressin (C, L)
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Inotropes

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 (C, L)
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For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest against using levosimendan (C, L)
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Monitoring and intravenous access

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 (C, VL)
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For adults with septic shock, we suggest starting vasopressors peripherally to restore MAP rather than delaying initiation until a central venous access is secured (C, VL)
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Fluid balance

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 (U, U)
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Ventilation

Oxygen targets

There is insufficient evidence to make a recommendation on the use of conservative oxygen targets in adults with sepsis-induced hypoxemic respiratory failure (U, U)
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High-flow nasal oxygen therapy

For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high flow nasal oxygen over non-invasive ventilation (C, L)
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Non-invasive ventilation

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 (U, U)
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Protective ventilation in acute respiratory distress syndrome (ARDS)

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) (S, H)
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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 (S, M)
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For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP (C, M)
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Low tidal volume in non-ARDS respiratory failure

For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared to high tidal volume ventilation (C, L)
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Recruitment manoeuvres

For adults with sepsis-induced moderate-severe ARDS, we suggest using traditional recruitment maneuvers (C, M)
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When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy (S, M)
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Prone ventilation

For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for more than 12 h daily (S, M)
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Neuromuscular blocking agents

For adults with sepsis induced moderate-severe ARDS, we suggest using intermittent NMBA boluses, over NMBA continuous infusion (C, M)
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Extracorporeal membrane oxygenation (ECMO)

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 (C, L)
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Additional Therapies

Corticosteroids

For adults with septic shock and an ongoing requirement for vasopressor therapy we suggest using IV corticosteroids (C, M)
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Blood Purification

For adults with sepsis or septic shock, we suggest against using polymyxin B haemoperfusion (C, L)
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There is insufficient evidence to make a recommendation on the use of other blood purification techniques (U, U)
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Red blood cell (RBC) transfusion targets

For adults with sepsis or septic shock, we recommend using a restrictive (over liberal) transfusion strategy (S, M)
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Immunoglobulins

For adults with sepsis or septic shock, we suggest against using intravenous immunoglobulins (C, L)
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Stress ulcer prophylaxis

For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding, we suggest using stress ulcer prophylaxis (C, M)
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Venous thromboembolism (VTE) prophylaxis

For adults with sepsis or septic shock, we recommend using pharmacologic VTE prophylaxis unless a contraindication to such therapy exists (S, M)
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For adults with sepsis or septic shock, we recommend using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for VTE prophylaxis (S, M)
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For adults with sepsis or septic shock, we suggest against using mechanical VTE prophylaxis in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone (C, L)
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Renal replacement therapy

In adults with sepsis or septic shock and AKI who require renal replacement therapy, we suggest using either continuous or intermittent renal replacement therapy (C, L)
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In adults with sepsis or septic shock and AKI, with no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy (C, M)
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Glucose control

For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180 mg/dL (10 mmol/L) (S, M)
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Vitamin C

For adults with sepsis or septic shock, we suggest against using IV vitamin C (C, L)
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Bicarbonate therapy

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 (C, L)
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For adults with septic shock, severe metabolic acidemia (pH ≤ 7.2) and AKI (AKIN score 2 or 3), we suggest using sodium bicarbonate therapy (C, L)
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Nutrition

For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 h) initiation of enteral nutrition (C, VL)
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Long-term outcomes and goals of care

Goals of care

For adults with sepsis or septic shock, we recommend discussing goals of care and prognosis with patients and families over no such discussion (U, U)
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For adults with sepsis or septic shock, we suggest addressing goals of care early (within 72 h) over late (C, L)
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There is insufficient evidence to make a recommendation for any specific standardised criterion to trigger goals of care discussion (U, U)
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Palliative care

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 (U, U)
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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 (C, L)
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Peer support groups

For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral (C, VL)
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Transitions of care

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 (C, VL)
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There is insufficient evidence to make a recommendation for the use of any specific structured handoff tool over usual handoff processes (U, U)
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Screening for economic or social support

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 (U, U)
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Sepsis education for patients and families

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 (C, VL)
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Shared decision making

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 (U, U)
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Discharge planning

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 (C, VL)
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For adults with sepsis and septic shock, we recommend reconciling medications at both ICU and hospital discharge (U, U)
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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 (U, U)
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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 (U, U)
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There is insufficient evidence to make a recommendation on early post-hospital discharge follow-up compared to routine post-hospital discharge follow-up (U, U)
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Cognitive therapy

There is insufficient evidence to make a recommendation on early cognitive therapy for adult survivors of sepsis or septic shock (U, U)
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Post-discharge follow-up

For adult survivors of sepsis or septic shock, we recommend assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge (U, U)
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For adult survivors of sepsis or septic shock, we suggest referral to a post-critical illness follow-up programme if available (C, VL)
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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 (C, VL)
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Recommendation Grading

Overview

Title

Surviving Sepsis Campaign: Management of Sepsis and Septic Shock 2021

Authoring Organization

Publication Month/Year

October 2, 2021

Last Updated Month/Year

February 8, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Target Patient Population

Adult patients experiencing sepsis or septic shock in the hospital setting

Target Provider Population

Clinician caring for adult patients with sepsis or septic shock in the hospital setting

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Emergency care, Hospital

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management

Diseases/Conditions (MeSH)

D018805 - Sepsis, D012772 - Shock, Septic

Keywords

sepsis, septic shock, hospital

Source Citation

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Møller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. PMID: 34599691; PMCID: PMC8486643.