Surviving Sepsis Campaign 2021: Updates Are InErica E. Remer, MD, FACEP, CCDS Editor’s Note: While Dr Remer normally talks to us about CDI, she is an Emergency Medicine physician so the treatment of sepsis is second in her heart after the coding and clinical validation of the diagnosis of sepsis. She took the time to summarize the new guidelines on sepsis for ACPA members. Take the time to read it and then ensure your facility is going with the guidelines. Surviving Sepsis Campaign (SSC) updated their guidelines last week (early October 2021), and they were simultaneously published in Critical Care Medicine and Intensive Care Medicine (Surviving sepsis campaign 2021) . The definition of sepsis is still expressed as “life-threatening organ dysfunction due to dysregulated host response to infection.” The update is of the treatment of sepsis and septic shock, and the revisions are based on research studies available since the previous iteration in 2016.
Some of the revisions seem semantic and do not seem to impart significant changes to the recommendations or protocols. I strongly suggest anyone interested in sepsis should review Table 1 which lays out the table of current recommendations and changes from the previous 2016 recommendations. The rationales for the changes and recommendations follow in the narrative of the SSC 2021 article. I am summarizing the current recommendations for the approach to sepsis and septic shock in adults in this article. They use the word “recommend” for strong recommendations and “suggest” for weak recommendations, so I will, too.
They moved the screening section up to the top of the recommendations. They recommend the use of a performance improvement program for sepsis, including sepsis screening for acutely ill, high-risk patients and standardizing treatment. Acknowledging some inconsistency, a 50-study meta-analysis seemed to demonstrate that PI programs were associated with better adherence to sepsis bundles with a reduction in mortality. Surprisingly, they note that the specifics of the program were not as important as its existence and focus on screening and treatment. I interpret this to mean that just the rigor of attending to the potential for sepsis and following a standard protocol improved outcomes, although Dr. Edward Hu had a different take (you’ll have to ask Eddie for his opinion!).
SSC 2021 notes that “a variety of clinical variables and tools are used for sepsis screening,” including systemic inflammatory response syndrome (SIRS) criteria, vital signs, Sequential Organ Failure Assessment Score (SOFA) or qSOFA, and other predictive scores. They postulate that machine learning may improve performance of screening tools. qSOFA is not recommended as a sole screening tool. Although there is variation in sensitivity and specificity of sepsis screening tools, there is agreement that it is important to identify “sepsis early for timely intervention.”
There is a weak recommendation (i.e., suggestion) to use lactate level as an adjunctive but not diagnostic test to modify the pretest probability of suspected sepsis in patients. Later on in the paper, they note that “serum lactate is an important biomarker of tissue hypoxia and dysfunction but is not a direct measure of tissue perfusion.”
In terms of initial resuscitation, SSC makes a “best practice statement” that “sepsis and septic shock are medical emergencies, and we recommend that treatment and resuscitation begin immediately.” The administration of at least 30 mL/kg of crystalloids in the case of sepsis-induced hypoperfusion or septic shock has been downgraded to a suggestion. They note this recommendation is from observational studies, and there have been no prospective interventional studies investigating what precise volume is optimal. They note that failure to receive 30 mL/kg within 3 hours of sepsis onset is associated with worse outcomes, even if a patient has comorbidities which might constitute a risk to assertive fluid resuscitation. Interestingly, SEP-1, the CMS sepsis bundle, as of January 1, 2022, will allow dispensation to patients who are deemed at risk of fluid overload (e.g., heart failure, renal failure) and permit a smaller volume of fluid resuscitation.
Tools to provide guidance of resuscitation with weak recommendations/suggestions include dynamic measures (e.g., passive leg raising combined with cardiac output measurement and actions to effect increases in stroke volume), lactate levels, and new in 2021, assessment of capillary refill time. SSC 2021 continues to recommend a target mean arterial pressure (MAP) of 65 mmHg.
There is an increase in mortality reported in multiple studies when there is a delay in transferring a patient to the intensive care unit (ICU) from the emergency department. SSC 2021 responds by recommending patients who require ICU admission be admitted within 6 hours. From the emergency physician perspective, it is our intention to get patients to the unit as soon as we humanly can get the patient out of our department! Perhaps this directive will be helpful in facilitating that.
There are some subtle changes and new emphasis in the Infection section. There seems to be more recognition that all that appears to be sepsis may not turn out to be and that continuous reassessment is indicated. If a noninfectious cause is determined for clinical presentation, antibiotics are to be discontinued. If there is a low likelihood of infection, antibiotics may be deferred while rapidly investigating and closely monitoring.
Patients with possible septic shock or a high likelihood of sepsis should receive antimicrobials “immediately, ideally within 1 hr of recognition,” and the empiric broad-spectrum therapy should cover all likely organisms, even potentially resistant bacteria, fungi or viruses as clinically indicated. Sustained double gram-negative coverage is discouraged except in patients for whom there seems to be no other choice, to minimize undesirable side effects and complications. After a loading dose of beta-lactam antibiotics when appropriate, prolonged infusion (as opposed to conventional bolus therapy) is recommended if the necessary equipment is available.
There does not seem to be substantive change in source control from 2016. The recommendation is to determine if there is an infection amenable to source control measures (e.g., drainage, debridement, explantation of an infected device), and to promptly remove intravascular access devices that could represent sources for sepsis, unless impractical. Medical therapy instead of source control when indicated is not advised.
To minimize adverse effects, de-escalation, targeting, and discontinuation of antibiotics is recommended. The suggestion is to assess daily rather than having a fixed duration of course. The shortest effective course of therapy is less costly and has fewer undesirable effects. Procalcitonin is suggested as an adjunct to decide when to discontinue antibiotics, when available.
Crystalloids are the clear fluid of choice, being least expensive and widely available. Balanced solutions are suggested over normal saline, which is new since 2016. Albumin can be included for large volume resuscitation. Hydroxyethyl starch (HES) and gelatin are discouraged.
For septic shock, norepinephrine is the clear front-runner for vasopressor choice. If the MAP is not responding, in their experience, once the norepinephrine dose is in the range of 0.25-0.5 μg/kg/min, the suggestion is to add vasopressin. If that doesn’t do the trick, they recommend epinephrine. For patients with septic shock and cardiac dysfunction, an inotrope such as dobutamine is suggested. Invasive monitoring and central access is suggested. New to 2021, if central venous access is not immediately feasible, peripheral vasopressor administration is suggested. With ongoing requirement for vasopressor therapy, IV corticosteroids are suggested.
No recommendations were made as to whether restrictive or liberal fluid management is preferable in the first 24 hours following the initial fluid bolus.
They felt there was insufficient evidence to make a recommendation (or even a suggestion!) regarding conservative oxygen therapy. If high-flow nasal oxygen (HFNC) therapy is possible in the setting, it is suggested as preferable to non-invasive ventilation (NIV) [new suggestion since 2016], but the patients must be closely monitored to see if intubation becomes necessary. No recommendation as to use of NIV as opposed to full-fledged invasive ventilation was made. There is a recommendation to use lung-protective low tidal volume ventilation (6 mL/kg) as opposed to high tidal volume (>10 mL/kg) in sepsis-induced acute respiratory distress syndrome (ARDS), and it is suggested in patients without ARDS. Higher positive end expiratory pressure (PEEP) is suggested especially for adults with moderate to severe ARDS. Prone positioning was recommended for moderate-severe ARDS. Neuromuscular blockade is suggested to be administered intermittently as opposed to by continuous infusion and should be utilized with adequate patient sedation and analgesia. Venovenous extracorporeal membrane oxygenation (ECMO) is suggested in severe ARDS when conventional mechanical ventilation fails if the facility can provide it [new since 2016 – I bet COVID-19 helped facilitate this recommendation].
Additional strategies: Restrictive transfusion strategy at 7 g/dL is recommended over liberal threshold (i.e., 10 g/dL). IV immunoglobulin is discouraged. Stress ulcer prophylaxis is suggested in patients who have risk factors for GI bleeding. Venous thromboembolism (VE) prophylaxis is recommended, and low molecular weight heparin (LMWH) is recommended over unfractionated heparin (UFH). Mechanical VTE prophylaxis is not felt to confer any additional benefits over pharmacologic.
This next one is kind of funny to me: If there is no definitive indication for renal replacement therapy (RRT), don’t use it. However, if a patient does require RRT, the panel does not have a preference for continuous or intermittent.
If a patient is hyperglycemic (> 180 mg/dL), the recommendation is to initiate insulin therapy with a typical targe range of 144-180 mg/dL. Skip the vitamin C [new since 2016]. Only use sodium bicarbonate for severe metabolic acidemia (pH ≤ 7.2) and AKI. Enteral feeding is suggested early (within 72 hours) for those who can tolerate it.
The consensus panel recognizes that there is wide variation in ICU and post-ICU management of heterogeneous critically ill patients, but they feel there are overarching best practice concepts for goals of care. There is no recommendation for specific criteria to initial a goals of life discussion, and there are many factors to take into consideration, such as premorbid condition, prognosis, response to therapy, and receptiveness of family to have the discussion. However, it is felt that having a quality of life discussion is recommended. Formal palliative care consultation is recommended when appropriate but not as a routine practice.
Peer support groups for survivors are suggested. Competent transition of care is suggested, but there was no specific structured format or tool for hand-off. Screening for need and referral for economic and social support is recommended. Sepsis education including common impairments such as post-intensive care/post-sepsis syndrome is suggested prior to discharge. Shared decision making in discharge planning is recommended. Medications should be reconciled (this needs to be a recommendation?!). Discharge summary and patient information should include details of the ICU stay and sepsis.
The final recommendations/suggestions deal with post-discharge. Although on their radar, they claimed insufficient evidence to make a recommendation on early cognitive therapy for adult survivors of sepsis/septic shock. They recommend some mechanism to assess and follow-up for post-discharge physical, cognitive, and emotional problems stemming from the admission. They suggest referral to a post-critical illness program if available and rehabilitation as needed.
I think it is really helpful for these authoritative pundits to review the medical literature for us and condense it into actionable items. There may be some changes that your facility’s sepsis protocol should undergo as a result of this publication. If you are interested in the studies they reviewed and the data, read the whole article. If not, I hope this summary will be helpful to you!
Dr. Remer is the founder and president of Erica Remer, MD, Inc., icd10md.com.
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