Guideline sources The following summarized guidelines for the evaluation and management of sepsis and septic shock are prepared by our editorial team based on guidelines from the European Association of Urology (EAU 2022), the French Society of Emergency Medicine (SFMU/SFAR 2022), the Surviving Sepsis Campaign (SSC 2021; 2017), the European Society of Intensive Care Medicine (ESICM 2020), and the British Medical Journal (BMJ 2018). 1 2 3 4 5 6 7 7 8 9 9 10 Definition Sepsis and septic shock are syndromes characterized by dysregulated systemic inflammation and end organ dysfunction caused by an underlying infectious process. 7 Epidemiology https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 1/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway The most common infectious pathogens responsible for the development of sepsis are S. aureus (20.5%), Pseudomonas species (19.9%), fungi (19%), E. coli (16.0%), Klebsiella species (12.7%), and Acinetobacter (9%). 7 Pathophysiology In hospitalized adult patients, the incidence of sepsis is estimated at 6.0%. 8 Disease course In patients with sepsis, continued activation of immune cells in response to an infection result in a dysregulated inflammatory response. The coagulation system is closely tied to the inflammatory response, with cross talk between the two systems. These pathophysiological changes cause the clinical manifestations of organ dysfunction, which may progress to multiple organ failure, and death. 9 9 Prognosis and risk of recurrence The overall mortality associated with sepsis, severe sepsis, and septic shock is 10-20%, 20-50%, and 40-80%, respectively. 10 Pathway Calculator Calculator Sepsis and septic shock Investigation and management Pediatric SIRS, sepsis, and septi Quick Seq Guidelines 1. Screening and diagnosis Screening tools: do not use qSOFA compared to SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock. D 2. Diagnostic investigations Hemodynamic assessment: obtain further hemodynamic assessment (such as assessment of cardiac function) to determine the type of shock, if the clinical examination does not lead to a clear diagnosis. E Lactate levels: consider measuring blood lactate in adult patients with suspected sepsis. C Microbiologic cultures: obtain appropriate microbiologic cultures, including blood cultures, before starting antimicrobial therapy in patients with suspected sepsis or septic shock, if it does not substantially delay the initiation of antimicrobials. E https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 2/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway 3. Respiratory support High-flow nasal oxygen therapy: consider administering high-flow nasal oxygen over noninvasive ventilation in adult patients with sepsis-induced hypoxemic respiratory failure. C Mechanical ventilation: Use a low tidal volume ventilation strategy (6 mL/kg) in adult patients with sepsis-induced ARDS. A Show 9 more Minimize continuous or intermittent sedation in mechanically ventilated sepsis patients, and target specific titration endpoints. E Extracorporeal membrane oxygenation: consider performing veno-venous extracorporeal oxygenation in adult patients with sepsis-induced severe ARDS in experienced centers with the infrastructure in place to support its use, if conventional mechanical ventilation fails. C 4. Medical management Timing for ICU admission: consider admitting adult patients with sepsis or septic shock to the ICU within 6 hours, if ICU admission is required. C Goals of care: discuss goals of care and prognosis with patients with sepsis or septic shock and their families. E Show 2 more Fluid resuscitation (indications): initiate treatment and resuscitation in patients with sepsis and septic shock immediately. E Show 5 more Updated evidence: CLOVERS In adult patients within 4 hours of a suspected or confirmed infection and sepsis-induced hypotension, restrictive fluid strategy was not superior to liberal fluid strategy with respect to death from any causes before discharge home at day 90. National Heart et al. N Engl J Med. 2023 Feb 9. Fluid resuscitation, choice of fluids: As per SFMU/SFAR 2022 guidelines, administer balanced crystalloids rather than 0.9% saline for fluid resuscitation to reduce mortality and/or occurrence of adverse renal events in patients with sepsis or septic shock. B Show 2 more As per SSC 2021 guidelines, administer crystalloids as first-line fluid for resuscitation in adult patients with sepsis or septic shock. B Consider administering balanced crystalloids instead of https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 3/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway normal saline for resuscitation. B Show 3 more Landmark trials: ALBIOS In patients with severe sepsis, albumin was not superior to crystalloids with respect to death at 28 days. Caironi P et al. N Engl J Med. 2014 Apr 10. Vasopressors: use norepinephrine as the first-line vasopressor in adult patients with septic shock. E Show 3 more Landmark trials: VASST In patients who had septic shock and were receiving a minimum of 5 g of norepinephrine per minute, vasopressin was not superior to norepinephrine with respect to death at day 28. Russell JA et al. N Engl J Med. 2008 Feb 28. Inotropes: Consider adding dobutamine to norepinephrine or administering epinephrine alone in adult patients with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial BP. C Avoid using levosimendan in adult patients with septic shock and cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial BP. D Intravenous corticosteroids: As per SSC 2021 guidelines, consider administering IV corticosteroids in adult patients with septic shock and an ongoing requirement for vasopressor therapy. E Landmark trials: ADRENAL In patients with septic shock undergoing mechanical ventilation, hydrocortisone was not superior to placebo with respect to death at 90 days. Venkatesh B et al. N Engl J Med. 2018 Mar 1. As per BMJ 2018 guidelines, consider administering corticosteroids in adult and pediatric patients with sepsis, with or without shock. C https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 4/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway Landmark trials: Annane Trial In patients with septic shock and relative adrenal insufficiency, hydrocortisone and fludrocortisone were superior to placebo with respect to death. Annane D et al. JAMA. 2002 Aug 21. Antimicrobial therapy (indications): initiate antimicrobials immediately, ideally within 1 hour of recognition, in adult patients with possible septic shock B or a high likelihood for sepsis. E Show 5 more Antimicrobial therapy (choice of antibiotic agent): initiate empiric antimicrobials with MRSA coverage in adult patients with sepsis or septic shock at high risk of MRSA. E Show 6 more Antimicrobial therapy (choice of antifungal agent): Consider initiating empiric antifungal therapy in adult patients with sepsis or septic shock at high risk of fungal infection. C Avoid initiating empiric use of antifungal therapy in adult patients with sepsis or septic shock at low risk of fungal infection. D Updated evidence: CandiSep In adult patients with sepsis at high risk for invasive Candida infection, (1,3)- -D-glucan guidance was not superior to standard care with respect to death at day 28. Frank Bloos et al. Intensive Care Med. 2022 Jul. Antimicrobial therapy (de-escalation): obtain daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment for de-escalation in adult patients with sepsis or septic shock. B Show 2 more Anticoagulants: Avoid using antithrombin for the treatment of sepsis and septic shock. D Insufficient evidence to assess the risks and benefits of thrombomodulin or heparin for the treatment of sepsis and septic shock. I Intravenous immunoglobulin: avoid administering IVIGs in patients with sepsis or septic shock. D Management of hyperglycemia: initiate insulin therapy in adult patients with sepsis or septic shock at a glucose level of 180 mg/dL (10 mmol/L). E Management of acidosis: Avoid initiating sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements in adult patients with septic shock and hypoperfusion-induced lactic acidemia. D https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 5/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway Consider initiating sodium bicarbonate therapy in adult patients with septic shock, severe metabolic acidemia (pH 7.2) and AKI (AKIN score 2 or 3). C Palliative care: Integrate principles of palliative care (including palliative care consultation based on clinician judgment) into the treatment plan of adult patients with sepsis or septic shock, when appropriate, to address patient and family symptoms and suffering. E Avoid offering routine formal palliative care consultation in all adult patients with sepsis or septic shock. D 5. Inpatient care Monitoring of mean arterial pressure: set mean arterial pressure of 65 mmHg as an initial target in adult patients with septic shock on vasopressors. B Show 2 more 6. Nonpharmacologic interventions Enteral nutrition: consider initiating early enteral feeding rather than a complete fast or only IV glucose in critically ill patients with sepsis or septic shock able to be fed enterally. C Show 2 more Parenteral nutrition: Avoid initiating early parenteral nutrition alone or parenteral nutrition in combination with enteral feedings in critically ill patients with sepsis or septic shock able to be fed enterally. D Avoid initiating parenteral nutrition alone or in combination with enteral feeds over the first 7 days in critically ill patients with sepsis or septic shock, if early enteral feeding is not feasible. D Nutritional supplements: avoid the use of omega-3 fatty acids as an immune supplement in critically ill patients with sepsis or septic shock. D Intravenous vitamin C: avoid administering IV vitamin C in adult patients with sepsis or septic shock. D Updated evidence: LOVIT In adult patients with sepsis receiving vasopressor therapy in the ICU, vitamin C was inferior to placebo with respect to the composite of death or persistent organ dysfunction at day 28. Fran ois Lamontagne et al. N Engl J Med. 2022 Jun 23. 7. Therapeutic procedures https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 6/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway Red blood cell transfusion: As per SSC 2021 guidelines, use a restrictive (over liberal) transfusion strategy in adult patients with sepsis or septic shock. E As per ESICM 2020 guidelines, consider setting a restrictive transfusion threshold (7 g/dL) in critically ill adult patients with sepsis and septic shock. C Hemoperfusion: Avoid performing polymyxin B hemoperfusion in adult patients with sepsis or septic shock. D Insufficient evidence to recommend for or against other blood purification techniques. I Renal replacement therapy: Consider initiating either continuous or intermittent RRT in adult patients with sepsis or septic shock and AKI requiring RRT. C Avoid initiating RRT in adult patients with sepsis or septic shock and AKI, with no definitive indications for RRT. D 8. Surgical interventions Source control: Identify rapidly or exclude a specific anatomical diagnosis of infection requiring emergent source control and implement any required source control intervention as soon as medically and logistically practical in adult patients with sepsis or septic shock. E Remove intravascular access devices promptly that are possible source of sepsis or septic shock in adult patients with sepsis or septic shock, after other vascular access has been established. E 9. Specific circumstances Patients with urosepsis: use the qSOFA score to identify patients with potential sepsis. A Show 5 more 10. Preventative measures Thromboprophylaxis: administer pharmacologic VTE prophylaxis with LMWH rather than UFH in adult patients with sepsis or septic shock, if not contraindicated. B Show 2 more Stress ulcer prophylaxis: consider administering stress ulcer prophylaxis in adult patients with sepsis or septic shock and having risk factors for gastrointestinal bleeding. C 11. Follow-up and surveillance https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 7/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway Transition of care: consider undertaking a handoff process of critically important information at transitions of care of adult patients with sepsis or septic shock. E Show 2 more Hospital discharge: consider providing adult patients with sepsis or septic shock and their families with written and verbal sepsis education (diagnosis, treatment, and post-ICU/post-sepsis syndrome) before hospital discharge and in the follow-up setting. E Show 5 more Referral for peer support programs: consider referring adult survivors of sepsis or septic shock and their families to peer support groups. C Referral for socioeconomic support: screen adult patients with sepsis or septic shock and their families for economic and social support (including housing, nutritional, financial, and spiritual support), and refer where available to meet these needs. E Follow-up: insufficient evidence to recommend for or against early post-hospital discharge follow- up compared to routine post hospital discharge follow up. Show 3 more 12. Quality improvement Screening programs: implement performance improvement programs for sepsis in hospitals and health systems, including sepsis screening for acutely ill, high-risk patients B and standard operating procedures for treatment. E Likelihood Ratios Pertinent positives The following findings increase the probability of sepsis and septic shock in adults. 1 11 Finding LR+ Value Positive SIRS criteria ( 2/4) 3.4 Increased serum procalcitonin 2.4 Positive qSOFA criteria ( 2/3) 2.17 Pertinent negatives The following findings decrease the probability of sepsis and septic shock in adults. 1 11 Finding LR- Value serum procalcitonin not increased 0.4 Negative SIRS criteria (< 2/4) 0.46 Negative qSOFA criteria (< 2/3) 0.54 https://web.pathway.md/diseases/recQx8pU4iIPt8Ecs 8/10 6/24/23, 3:06 PM Sepsis and septic shock Pathway References 1. G. Bonkat, R. Bartoletti, F. Bruy re et al. EAU Guidelines on Urological Infections. EAU. 2022. Open 2. Lamontagne F, Rochwerg B, Lytvyn L et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. Open 3. Laura Evans, Andrew Rhodes, Waleed Alhazzani et al. 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