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Surviving Sepsis Campaign Guidelines 2021

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Published: 10/4/2021

Critical Care Medicine: October 4, 2021

Surviving Sepsis Campaign Guidelines 2021

Citation: Critical Care Medicine: October 4, 2021

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International Guidelines for Management of Sepsis and Septic Shock 2021

Updated global adult sepsis guidelines, released in October 2021 by the Surviving Sepsis Campaign (SSC), place an increased emphasis on improving the care of sepsis patients after they are discharged from the intensive care unit (ICU) and represent greater geographic and gender diversity than previous versions.

The new guidelines specifically address the challenges of treating patients experiencing the long-term effects of sepsis. Patients often experience lengthy ICU stays and then face a long, complicated road to recovery. In addition to physical rehabilitation challenges, patients and their families are often uncertain how to coordinate care that promotes recovery and matches their goals of care.
 
To address these issues, the guidelines recommend involving patients and their families in goals-of-care discussions and hospital discharge plans, which should include early and ongoing follow-up with clinicians to support and manage long-term effects and assessment of physical, cognitive, and emotional issues after discharge.

Guideline Type: Clinical

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Category: Quality and Patient Safety, Sepsis,

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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.
Quality of evidence: Moderate for screening and very low for standard operating procedures.

We recommend against using qSOFA compared with SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock.
Quality of evidence: Moderate

For adults suspected of having sepsis, we suggest measuring blood lactate.
Quality of evidence: Low

Sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately.

For patients with sepsis-induced hypoperfusion or septic shock, we suggest that at least 30 mL/kg of IV crystalloid fluid be given within the first 3 hours of resuscitation.
Quality of evidence: Low

For adults with sepsis or septic shock, we suggest using dynamic measures to guide fluid resuscitation over physical examination or static parameters alone.
Quality of evidence: Very low

For adults with sepsis or septic shock, we suggest guiding resuscitation to decrease serum lactate in patients with elevated lactate levels over not using serum lactate.
Quality of evidence: Low

For adults with septic shock, we suggest using capillary refill time to guide resuscitation as an adjunct to other measures of perfusion.
Quality of evidence: Low

For adults with septic shock on vasopressors, we recommend an initial target mean arterial pressure (MAP) of 65 mm Hg over higher MAP targets.
Quality of evidence: Moderate

For adults with sepsis or septic shock who require ICU admission, we suggest admitting the patients to the ICU within 6 hours.
Quality of evidence: Low

For adults with suspected sepsis or septic shock but unconfirmed infection, we recommend continuously reevaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials if an alternative cause of illness is demonstrated or strongly suspected.

For adults with possible septic shock or a high likelihood for sepsis, we recommend administering antimicrobials immediately, ideally within 1 hour of recognition.
Quality of evidence: Low

For adults with possible sepsis without shock, we recommend rapid assessment of the likelihood of infectious versus noninfectious causes of acute illness.

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 hours from the time when sepsis was first recognized.
Quality of evidence: Very low

For adults with a low likelihood of infection and without shock, we suggest deferring antimicrobials while continuing to closely monitoring the patient.
Quality of evidence: Very low

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.
Quality of evidence: Very low

For adults with sepsis or septic shock at high risk of MRSA, we recommend using empiric antimicrobials with MRSA coverage over using antimicrobials without MRSA coverage.

For adults with sepsis or septic shock at low risk of MRSA, we suggest against using empiric antimicrobials with MRSA coverage, as compared with using antimicrobials without MRSA coverage.
Quality of evidence: Low

For adults with sepsis or septic shock and low risk for multidrug-resistant (MDR) organisms, we suggest against using 2 gram-negative agents for empiric treatment, as compared to 1 gram-negative agent.
Quality of evidence: Very low

For adults with sepsis or septic shock and high risk for multidrug-resistant (MDR) organisms, we suggest using 2 antimicrobials with gram-negative coverage for empiric treatment over 1 gram-negative agent.
Quality of evidence: Very low

For adults with sepsis or septic shock, we suggest against using double gram-negative coverage once the causative pathogen and the susceptibilities are known.
Quality of evidence: Very low

For adults with sepsis or septic shock at high risk of fungal infection, we suggest using empiric antifungal therapy over no antifungal therapy.
Quality of evidence: Low

For adults with sepsis or septic shock at low risk of fungal infection, we suggest against empiric use of antifungal therapy.
Quality of evidence: Low

We make no recommendation on the use of antiviral agents.

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.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we recommend optimizing dosing strategies of antimicrobials based on accepted pharmacokinetic/pharmacodynamic principles and specific drug properties.

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.

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.
Quality of evidence: Very low

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.
Quality of evidence: Very low

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.
​Quality of evidence: Low

For adults with sepsis or septic shock, we recommend using crystalloids as first-line fluid for resuscitation.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we suggest using balanced crystalloids instead of normal saline for resuscitation.
Quality of evidence: Very low

For adults with sepsis or septic shock, we suggest using albumin in patients who received large volumes of crystalloids.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we recommend against using starches for resuscitation.
Quality of evidence: High

For adults with sepsis and septic shock, we suggest against using gelatin for resuscitation.
Quality of evidence: Moderate

For adults with septic shock, we recommend using norepinephrine as the first-line agent over other vasopressors.
Quality of evidence:
Dopamine: High
Vasopressin: Moderate
Epinephrine: Low
Selepressin: Low
Angiotensin 2: Very low

For adults with septic shock on norepinephrine with inadequate mean arterial pressure levels, we suggest adding vasopressin instead of escalating the dose of norepinephrine.
Quality of evidence: Moderate

For adults with septic shock and inadequate mean arterial pressure levels despite norepinephrine and vasopressin, we suggest adding epinephrine.
Quality of evidence: Low

For adults with septic shock, we suggest against using terlipressin.
Quality of evidence: Low

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.
Quality of evidence: Low

For adults with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure, we suggest against using levosimendan.
Quality of evidence: Low

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.
Quality of evidence: Very low

For adults with septic shock, we suggest starting vasopressors peripherally to restore mean arterial pressure rather than delaying initiation until central venous access is secured.
Quality of evidence: Very low

There is insufficient evidence to make a recommendation on the use of restrictive versus liberal fluid strategies in the first 24 hours of resuscitation in patients with sepsis and septic shock who still have signs of hypoperfusion and volume depletion after the initial resuscitation.

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

For adults with sepsis-induced hypoxemic respiratory failure, we suggest the use of high-flow nasal oxygen over noninvasive ventilation.
Quality of evidence: Low

There is insufficient evidence to make a recommendation on the use of noninvasive ventilation compared to invasive ventilation for adults with sepsis-induced hypoxemic respiratory failure.

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).
Quality of evidence: High

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.
Quality of evidence: Moderate

For adults with moderate to severe sepsis-induced ARDS, we suggest using higher PEEP over lower PEEP.
Quality of evidence: Moderate

For adults with sepsis-induced respiratory failure (without ARDS), we suggest using low tidal volume as compared with high tidal volume ventilation.
Quality of evidence: Low

For adults with sepsis-induced severe ARDS, we suggest using traditional recruitment maneuvers.
Quality of evidence: Moderate

When using recruitment maneuvers, we recommend against using incremental PEEP titration/strategy.
Quality of evidence: Moderate

For adults with sepsis-induced moderate-severe ARDS, we recommend using prone ventilation for greater than 12 hours daily.
Quality of evidence: Moderate

For adults with sepsis-induced moderate to severe ARDS, we suggest using intermittent NMBA boluses over NMBA continuous infusion.
Quality of evidence: Moderate

For adults with sepsis-induced severe ARDS, we suggest using venovenous ECMO when conventional mechanical ventilation fails in experienced centers with the infrastructure in place to support its use.
Quality of evidence: Low

For adults with septic shock and an ongoing requirement for vasopressor therapy, we suggest using IV corticosteroids.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we suggest against using polymyxin B hemoperfusion.
Quality of evidence: Low

There is insufficient evidence to make a recommendation on the use of other blood purification techniques.

For adults with sepsis or septic shock, we recommend using a restrictive transfusion strategy over a liberal transfusion strategy.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we suggest against using IV immunoglobulin.
Quality of evidence: Low

For adults with sepsis or septic shock and risk factors for gastrointestinal bleeding, we suggest using stress ulcer prophylaxis.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we recommend using pharmacologic venous thromboembolism prophylaxis unless a contraindication to such therapy exists.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we recommend using low-molecular-weight heparin.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we suggest against using mechanical venous thromboembolism prophylaxis in addition to pharmacologic prophylaxis, over pharmacologic prophylaxis alone.
Quality of evidence: Low

In adults with sepsis or septic shock and acute kidney injury, we suggest using either continuous or intermittent renal replacement therapy.
Quality of evidence: Low

In adults with sepsis or septic shock and acute kidney injury with no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy.
Quality of evidence: Moderate

For adults with sepsis or septic shock, we recommend initiating insulin therapy at a glucose level of ≥ 180mg/dL (10mmol/L).
Quality of evidence: Moderate

For adults with sepsis or septic shock, we suggest against using IV vitamin C.
Quality of evidence: Low

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.
Quality of evidence: Low

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.
Quality of evidence: Low

For adult patients with sepsis or septic shock who can be fed enterally, we suggest early (within 72 hours) initiation of enteral nutrition.
Quality of evidence: Very low

For adults with sepsis or septic shock, we recommend discussing goals of care and prognosis with patients and families over no such discussion.

For adults with sepsis or septic shock, we suggest addressing goals of care early (within 72 hours) over late (72 hours or later).
Quality of evidence: Low

For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation on any specific standardized criterion to trigger a goals-of-care discussion.

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.

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.
Quality of evidence: Low

For adult survivors of sepsis or septic shock and their families, we suggest referral to peer support groups over no such referral.
Quality of evidence: Very low

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.
Quality of evidence: Very low

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.

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 making referrals where available to meet these needs.

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.
Quality of evidence: Very low

For adults with sepsis or septic shock and their families, we recommend that the clinical team provide the opportunity to participate in shared decision-making in post-ICU and hospital discharge planning to ensure that discharge plans are acceptable and feasible.

For adults with sepsis and septic shock and their families, we suggest using a critical care transition program, compared with usual care, on transfer to the ward.
Quality of evidence: Very low

For adults with sepsis and septic shock, we recommend reconciling medications at both ICU and hospital discharge.

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.

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.

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.

For adults with sepsis or septic shock, there is insufficient evidence to make a recommendation for or against early cognitive therapy.

For adult survivors of sepsis or septic shock, we recommend assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge.

For adult survivors of sepsis or septic shock, we suggest referral to a post-critical illness follow-up program if available.

For adult survivors of sepsis or septic shock receiving mechanical ventilation for more than 48 hours or an ICU stay of more than 72 hours, we suggest referral to a post-hospital rehabilitation program.

A complete list of the guidelines authors and contributors is available within the published manuscript.