Sepsis (main)

This page is for adult patients. For pediatric patients, see: Sepsis (peds)

Background

  • Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection[1]
  • The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites[2]
  • The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract[3]
  • Sepsis and septic shock are major healthcare problems, killing between one in three and one in six of those affected[4]
  • In-hospital mortality for septic shock is approximately 30-40%[4]
  • Positive cultures are not obligatory in the diagnosis of sepsis
  • Pneumonia, intra-abdominal infections, and pyelonephritis are the most common primary causes

Sepsis-3 Definitions (2016)

In 2016 new definitions were adopted for the evaluation and diagnosis of Sepsis and Septic Shock[5]

Old Definition Sepsis-3 Definition (2016)
Sepsis 2 SIRS criteria + suspected infection Life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as:
  • Suspected/documented infection PLUS
  • Increase in SOFA score by ≥2 points
Severe Sepsis Sepsis + organ dysfunction:
  • SBP <90, or
  • MAP <65, or
  • Lactate >2, or
  • INR >1.5, or
  • Bili >2, or
  • Urine output <0.5 mL/kg/hr, or
  • Creatinine >2.0, or
  • Platelets <100, or
  • SpO₂ <90%
 No longer a category (subsumed into "sepsis," which now requires organ dysfunction by definition)
Septic Shock Sepsis + hypotension after adequate fluid resuscitation Sepsis PLUS:
  • Vasopressors needed to maintain MAP ≥65 AND
  • Lactate >2 mmol/L (>18 mg/dL) despite adequate volume resuscitation

qSOFA (Bedside Screening Tool)

The qSOFA was proposed as a bedside screening tool to identify patients outside the ICU who may have sepsis. It is not the definition of sepsis.[5]

SSC 2021 recommends against using qSOFA as a single screening tool for sepsis or septic shock, as it has poor sensitivity; however, it may prompt further workup when positive.[4]

qSOFA Score

Quick Sequential (Sepsis Related) Organ Failure Assessment Score

  • Respiratory rate of 22/min or greater (+1 Point)
  • Altered mentation (+1 Point)
  • Systolic blood pressure of 100 mm Hg or less (+1 Point)
  • qSOFA ≥2 should prompt:
    • Consideration of possible sepsis
    • Initiation of workup (cultures, lactate, imaging)
    • Assessment for organ dysfunction (formal SOFA score)
  • A qSOFA <2 does not rule out sepsis

SOFA Score

  • The SOFA score is the formal tool for identifying organ dysfunction in sepsis (increase of ≥2 points = sepsis)[1]
  • Generally used in the ICU; can stratify mortality based on initial score and subsequent changes
  • Baseline SOFA score assumed to be 0 in patients without known pre-existing organ dysfunction

MEDS Score

  • The Mortality in Emergency Department Sepsis (MEDS) prediction rule is a proposed method to risk stratify ED patients with sepsis
  • Has not gained widespread clinical adoption

NEWS 2 Score

  • National Early Warning Score (NEWS) 2 determines degree of illness in non-pregnant patients ≥16 years old[6]
  • Used by the UK NHS to identify acutely ill patients, including those with sepsis
  • Not reliable in spinal cord injury patients due to disturbance of autonomic responses
  • Combination of:
    • Respiratory rate
    • Presence of hypercapnic respiratory failure
    • Presence of supplemental O₂
    • Temperature
    • SBP
    • Pulse rate
    • Consciousness (AVPU scale)
  • See below for MDCalc link

Systemic Inflammatory Response Syndrome (SIRS) Criteria

  • Still acceptable to use in ED depending on local protocol
  • Misses up to 1/8 very septic ICU patients[7]


  • ≥2 of 4 criteria must be present:
  1. Temperature >38°C (100.4F) or <36°C (96.9F)
  2. HR >90 BPM
  3. RR >20 breaths/minute or PaCO2 <32 mmHg
  4. WBC count >12,000/mm3, <4,000/mm3, or >10% bands/immature forms

Clinical Features

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to infection.[1]

Septic shock

Patients with sepsis and both of the following despite adequate volume resuscitation:[1]

  1. Vasopressor requirement to maintain a mean arterial pressure ≥65 mm Hg AND
  2. Serum lactate level >2 mmol/L (>18 mg/dL)

Differential Diagnosis

Shock

Adrenal crisis

Evaluation

Work-Up

Management

Hour-1 Bundle

Time zero is the time of triage in the emergency department or the earliest documentation of sepsis-consistent elements. Sepsis and septic shock are medical emergencies; treatment and resuscitation should begin immediately.[4]

The Hour-1 Bundle should be viewed as a quality improvement target. Ideally all interventions begin in the first hour, though they may not all be completed within that time:

  1. Measure lactate level (re-measure within 2-4 hours if initial lactate >2 mmol/L)
  2. Obtain blood cultures prior to administration of antibiotics (but do not delay antibiotics to obtain cultures)
  3. Administer broad-spectrum antibiotics (see timing below)
  4. Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
  5. Apply vasopressors if patient is hypotensive during or after fluid resuscitation to maintain MAP ≥65 mmHg

Antibiotic Timing (SSC 2021)

Timing is stratified by presence of shock and likelihood of infection:[4]

Clinical Scenario Antibiotic Timing
Septic shock or high likelihood of sepsis Immediately, ideally within 1 hour of recognition (strong recommendation)
Possible sepsis without shock Rapid assessment of infectious vs. non-infectious causes; within 3 hours if concern for infection persists (weak recommendation)
Alternative non-infectious diagnosis identified Reassess; discontinue empiric antibiotics if infection is not confirmed[4]
  • See Initial Antibiotics in Sepsis (Main) for regimen selection
  • Initial choice dependent on suspected source, local antibiogram, and severity of illness
  • Prolonged (extended/continuous) infusions of beta-lactam antibiotics are suggested for maintenance therapy over conventional bolus infusions[4]
  • Perform daily reassessment for antimicrobial de-escalation[4]

Source Control

  • Identify and control the source of infection as soon as medically and logistically practical, ideally within 6-12 hours[4]
  • Remove any infected lines or devices
  • Drain abscesses
  • Consult surgery or other specialists if indicated (e.g. for appendicitis, cholangitis, necrotizing fasciitis, etc.)
  • Prolonged efforts at medical stabilization should not delay source control in severely ill patients

Circulation Management

IVF

  • SSC 2021 suggests (downgraded from recommends in 2016) initial 30 mL/kg crystalloid for sepsis-induced hypoperfusion or septic shock, to be given within the first 3 hours[4]
    • This is a starting point; some patients will need more, some less
    • Reassess after each bolus — do not reflexively give the full 30 mL/kg without clinical reassessment
  • Balanced crystalloids (e.g. Lactated Ringer's) are suggested over 0.9% normal saline (weak recommendation)[4]
  • Use dynamic measures to guide ongoing fluid resuscitation (suggested over physical exam or static parameters alone):[4]
    • Passive leg raise with assessment of stroke volume/cardiac output
    • Fluid challenge with reassessment of hemodynamic response
    • Stroke volume variation, pulse pressure variation
    • Bedside cardiovascular ultrasound (IVC ultrasound)
  • Capillary refill time can be used to guide resuscitation as an adjunct to other measures[4]
  • Lactate-guided resuscitation: Suggest targeting a decrease in lactate (re-measure q2-4h) as a marker of tissue perfusion[4]
  • Increasing evidence that excessive fluid resuscitation can be harmful:
    • Positive fluid balance on day 3 of hospital admission independently associated with increasing mortality[8]
    • Protocolized fluid administration (i.e. traditional Early Goal Directed Therapy) has no mortality benefit over usual care[9][10]
    • High volume (5+ L) resuscitation associated with increased mortality[11]
  • Consider assessing diastolic dysfunction via echo in CHF patients in whom IVC ultrasound is not reliable
  • CVP targets (>8 cmH₂O non-intubated, >12 cmH₂O intubated) are no longer recommended as resuscitation endpoints[4]

A central line and measurement of ScvO₂ is not required and does not impact mortality[12][13][14]

Pressors

  • Indicated if MAP <65 despite initial fluid resuscitation, or if fluid resuscitation is contraindicated/unlikely to be sufficient
  • Vasopressors may be started peripherally while central access is being obtained — do not delay initiation to place a central line[4]
  • Target MAP ≥65 mmHg (SSC 2021 recommends an initial target of 65 mmHg over higher MAP targets)[4]

Options:

  • Norepinephrine 0.1-1 mcg/kg/min (typical start 5-20 mcg/min) IV drip [15][4]
  • Vasopressin 0.03 units/min (fixed dose) IV drip[4]
    • SSC 2021 suggests adding vasopressin before epinephrine
    • May reduce the risk of atrial fibrillation compared to catecholamine-only regimens[16]
  • Epinephrine 1-20 mcg/min IV drip[4]
  • Dopamine — should be used hesitantly and only in highly selected patients (e.g. patients with low risk of tachyarrhythmias and absolute or relative bradycardia)
    • Do not use low-dose dopamine for renal protection
    • Dopamine may have increased mortality rates compared to other vasopressors, especially in the pediatric septic patient[17]
  • Phenylephrine — should not be used for treating septic shock except if:
    • Norepinephrine is associated with serious arrhythmias
    • Cardiac output is known to be high and blood pressure persistently low
    • As salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve MAP target
  • Methylene blue — consideration for septic shock refractory to catecholaminergic pressors (limited evidence)

Inotropes

  • Dobutamine 2-20 mcg/kg/min IV drip may be added if:
    • Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
    • Ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate MAP
    • Note: Beta-2 agonism causes vasodilation; therefore needs to be used in conjunction with vasopressors

Steroids

  • SSC 2021 suggests IV corticosteroids for adults with septic shock and an ongoing requirement for vasopressor therapy (weak recommendation)[4]
  • The 2024 SCCM Focused Update further clarifies:[18]
    • Suggests corticosteroids for adults with septic shock (conditional recommendation, low certainty)
    • Recommends against high-dose/short-duration corticosteroids (>400 mg/day hydrocortisone equivalent for <3 days) (strong recommendation, moderate certainty)
  • Dosing: Hydrocortisone 50 mg IV q6h (200 mg/day) IV
  • Do not administer steroids for treatment of sepsis in the absence of shock
  • Stress dose steroids are associated with faster time to shock resolution and faster ICU discharge[19]
  • While stress dose steroids shorten recovery time, they have not been consistently shown to decrease overall mortality (though meta-analyses suggest a possible small benefit)[18]
  • Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids[20]
  • Addition of fludrocortisone likely unnecessary as hydrocortisone has both glucocorticoid and mineralocorticoid effects
  • ACTH cosyntropin testing is likely unreliable in critically ill patients and should not guide the decision to give steroids
  • Steroids are associated with adverse effects including hyperglycemia, hypernatremia, and neuromuscular weakness; weigh risks and benefits[21]

Esmolol

  • One open-label, single-center RCT showing ~40% reduction in mortality when esmolol paired with norepinephrine infusion, with goal HR 80-95 BPM[22]
  • All patients were fluid resuscitated, intubated, given hydrocortisone 300 mg/day
  • Not standard of care — will require further multi-center RCTs to confirm findings; this result has not been replicated

Blood Products

RBCs

  • Only transfuse RBCs when hemoglobin decreases to <7.0 g/dL (target 7.0–9.0 g/dL in adults)[4]

Erythropoietin

  • Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis

Platelets

  • In severe sepsis, administer platelets prophylactically when counts are <10,000/mm³ (10 × 10⁹/L) in the absence of apparent bleeding
  • If <20,000/mm³ (20 × 10⁹/L) and significant risk of bleeding, then administer platelets
  • <50,000/mm³ (50 × 10⁹/L) if there is active bleeding, planned surgery, or other procedures

Disposition

  • Admit, likely to step-down or ICU
  • SSC 2021 suggests admitting patients with sepsis or septic shock who require ICU care within 6 hours of identification[4]

Calculators

qSOFA Score

qSOFA (Quick SOFA) Score
Criteria No (0) Yes (+1)
Altered mental status (GCS <15) 0 1
Respiratory rate ≥22 breaths/min 0 1
Systolic BP ≤100 mmHg 0 1
qSOFA Score 0   / 3
Interpretation
0–1 Low Risk — Not high risk for in-hospital mortality. Continue standard evaluation.
≥2 High Risk — Associated with ≥10% in-hospital mortality. Consider ICU-level care, lactate, blood cultures, and broad-spectrum antibiotics.
References
  • Singer M et al. Sepsis-3 Definitions. JAMA. 2016;315(8):801-810. PMID 26903338.
  • Seymour CW et al. Assessment of clinical criteria for sepsis. JAMA. 2016;315(8):762-774. PMID 26903335.

SIRS Criteria

SIRS Criteria
Criteria No (0) Yes (+1)
Temperature >38°C (100.4°F) or <36°C (96.8°F) 1
Heart rate >90 bpm 1
Respiratory rate >20 breaths/min or PaCO₂ <32 mmHg 1
WBC >12,000/mm³ or <4,000/mm³ or >10% bands 1
SIRS Criteria Met / 4
Interpretation
0–1 SIRS criteria NOT met — Fewer than 2 criteria present.
≥2 SIRS criteria MET — If infection is suspected or confirmed, meets criteria for sepsis (per Sepsis-1/2 definition). Note: Sepsis-3 uses qSOFA/SOFA criteria instead.
References
  • Bone RC et al. Definitions for sepsis and organ failure. Chest. 1992;101:1644-1655. PMID 1303622.
  • Kaukonen KM et al. SIRS criteria in defining severe sepsis. N Engl J Med. 2015;372:1629-1638. PMID 25776936.


SOFA Score

Sequential Organ Failure Assessment (SOFA) Score
Organ System 0 1 2 3 4
Respiration (PaO₂/FiO₂) 1 ≥400 <400 <300 <200 + vent <100 + vent
Coagulation (Platelets ×10³/µL) 1 ≥150 <150 <100 <50 <20
Liver (Bilirubin mg/dL) 1 <1.2 1.2–1.9 2.0–5.9 6.0–11.9 >12
Cardiovascular 1 MAP≥70 MAP<70 Dopa ≤5 Dopa>5/Epi≤0.1 Dopa>15/Epi>0.1
CNS (GCS) 1 15 13–14 10–12 6–9 <6
Renal (Cr mg/dL or UO) 1 <1.2 1.2–1.9 2.0–3.4 3.5–4.9/<500mL/d >5.0/<200mL/d
SOFA Score / 24
Interpretation — ICU Mortality
0–6 <10% mortality
7–9 15–20% mortality
10–12 40–50% mortality
13–14 50–60% mortality
≥15 >80% mortality. SOFA ≥2 = organ dysfunction (Sepsis-3 definition).
References
  • Vincent JL, et al. The SOFA score to describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707-710. PMID 8844239.
  • Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. PMID 26903338.

External Links

See Also

References

  1. ↑ 1.0 1.1 1.2 1.3 Singer, Mervyn et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
  2. ↑ Jui, Jonathan (2011). "Ch. 146: Septic Shock". In Tintinalli, Judith E.; Stapczynski, J. Stephan; Ma, O. John; Cline, David M. et al. Tintinalli's Emergency Medicine: A Comprehensive Study Guide (7th ed.). New York: McGraw-Hill. pp. 1003–14.
  3. ↑ Munford, Robert S.; Suffredini, Anthony F. (2014). "Ch. 75: Sepsis, Severe Sepsis and Septic Shock". In Bennett, John E.; Dolin, Raphael; Blaser, Martin J.. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (8th ed.). Philadelphia: Elsevier Health Sciences. pp. 914–34.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 4.20 4.21 4.22 4.23 Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49(11):e1063-e1143.
  5. ↑ 5.0 5.1 Seymour C. Assessment of Clinical Criteria for Sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774. doi:10.1001/jama.2016.0288.
  6. ↑ Royal College of Physicians. National Early Warning Score (NEWS) 2: Standardising the assessment of acute-illness severity in the NHS. Updated report of a working party. London: RCP, 2017.
  7. ↑ Kaukonen KM, Bailey M, Bellomo R. Systemic Inflammatory Response Syndrome Criteria for Severe Sepsis. The New England journal of medicine. 373(9):881. 2015.
  8. ↑ Sakr Y et al. Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit. Critical care medicine. 45(3):386-394, Mar 2017.
  9. ↑ Yealy DM, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93. DOI: 10.1056/NEJMoa1401602
  10. ↑ Mouncey PR, et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015;372:1301-11. DOI: 10.1056/NEJMoa1500896
  11. ↑ Marik PE, et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med (2017) 43:625–632 DOI 10.1007/s00134-016-4675-y
  12. ↑ ProCESS Investigators, Yealy DM, Kellum JA, Juang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370(18):1683-1693. Full Text
  13. ↑ The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371:1496-1506.
  14. ↑ Mouncey PR, Osborn TM, Power GS, et al for the ProMISe trial investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015:DOI: 10.1056/NEJMoa1500896.
  15. ↑ EBQ:SOAP II Trial
  16. ↑ McIntyre WF, Um KJ, Alhazzani W, et al. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock. JAMA. 2018;319(18):1889.
  17. ↑ Ventura AM, Shieh HH, Bousso A, et al. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015;43:2292-302.
  18. ↑ 18.0 18.1 Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia. Crit Care Med. 2024;52(5):e219-e233.
  19. ↑ Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018;378(9):797-808.
  20. ↑ Sligl WI, Milner DA Jr, Sundar S, Mphatswe W, Majumdar SR. Safety and efficacy of corticosteroids for the treatment of septic shock: A systematic review and meta-analysis. Clin Infect Dis. 2009 Jul 1;49(1):93-101.
  21. ↑ Pitre T, Drover K, Chaudhuri D, et al. Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis. Crit Care Explor. 2024;6(1):e1000.
  22. ↑ Andrea Morelli et al. Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial. JAMA. 2013;310(16):1683-1691.
This page is issued from WikEM. The text is available under an unknown license unless otherwise noted. Additional terms may apply for the media files.