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
• The infection is most commonly by bacteria, but can also be by fungi, viruses, or parasites
• The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract
• Sepsis and septic shock are major healthcare problems, killing between one in three and one in six of those affected
• In-hospital mortality for septic shock is approximately 30-40%
• 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

	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.

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.

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)
• 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
• 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

• ≥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.

• Suspected infection with evidence of new organ dysfunction (SOFA increase ≥2), which may manifest as:
  • Hypotension
  • Altered mental status
  • Tachypnea
  • Oliguria
  • Coagulopathy
  • Elevated lactate
  • Hypoxia
  • Ileus

Septic shock

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

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

• Adrenal Insufficiency
• Salicylate Toxicity
• Anticholinergic Toxicity
• Neuroleptic Malignant Syndrome
• Malignant Hyperthermia
• Thyrotoxicosis

Shock

• Cardiogenic
  • Acute valvular Regurgitation/VSD
  • CHF
  • Dysrhythmia
  • ACS
  • Myocardial Contusion
  • Myocarditis
  • Drug toxicity (e.g. beta blocker, CCB, or bupropion OD)
• Obstructive
  • Air embolism
  • Aortic Stenosis
  • Cardiac Tamponade
  • PE
  • Tension pneumothorax
• Distributive
  • Adrenal crisis
  • Anaphylaxis
  • Neurogenic shock
  • Sepsis
  • Toxicologic
• Hypovolemic
  • Severe dehydration
  • Hemorrhagic shock (traumatic and non-traumatic)

Adrenal crisis

• Addison's disease
• Congenital adrenal hyperplasia
• Shock
• Sepsis
• Pituitary apoplexy
• Sheehan's syndrome

Evaluation

Work-Up

• CBC
• Urinalysis/Urine culture
• Blood culture (at least 2 sets, ideally before antibiotics but should not delay antibiotic administration)
• CXR
• Chem (BMP)
• LFTs
• Lipase
• VBG or ABG
• Lactate (re-measure within 2-4 hours if initially elevated)
• Coags
• Consider:
  • Procalcitonin (may help guide de-escalation of antibiotics; should not be used to withhold initial empiric antibiotics)
  • DIC panel (fibrinogen, D-dimer, FDP)
  • T&S
  • CT head and/or LP
  • TSH (thyroid storm)
  • Cosyntropin stim vs. random cortisol (adrenal insufficiency)
  • Pelvic exam (toxic shock syndrome, tampon)
  • Influenza and respiratory viral testing
  • CT Abd/Pelvis (abscess, other intra-abdominal source)
  • Spine imaging (epidural abscess, other)

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.

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:

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

• 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
• Perform daily reassessment for antimicrobial de-escalation

Source Control

• Identify and control the source of infection as soon as medically and logistically practical, ideally within 6-12 hours
• 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
  • 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)
• Use dynamic measures to guide ongoing fluid resuscitation (suggested over physical exam or static parameters alone):
  • 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
• Lactate-guided resuscitation: Suggest targeting a decrease in lactate (re-measure q2-4h) as a marker of tissue perfusion
• Increasing evidence that excessive fluid resuscitation can be harmful:
  • Positive fluid balance on day 3 of hospital admission independently associated with increasing mortality
  • Protocolized fluid administration (i.e. traditional Early Goal Directed Therapy) has no mortality benefit over usual care
  • High volume (5+ L) resuscitation associated with increased mortality
• 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

A central line and measurement of ScvO₂ is not required and does not impact mortality

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
• Target MAP ≥65 mmHg (SSC 2021 recommends an initial target of 65 mmHg over higher MAP targets)

Options:

• Norepinephrine 0.1-1 mcg/kg/min (typical start 5-20 mcg/min) IV drip
• Vasopressin 0.03 units/min (fixed dose) IV drip
  • SSC 2021 suggests adding vasopressin before epinephrine
  • May reduce the risk of atrial fibrillation compared to catecholamine-only regimens
• Epinephrine 1-20 mcg/min IV drip
• 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
• 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)
• The 2024 SCCM Focused Update further clarifies:
  • 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
• 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)
• Newer meta-analyses do not show an increased incidence of superinfections related to initiation of stress dose steroids
• 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

Esmolol

• One open-label, single-center RCT showing ~40% reduction in mortality when esmolol paired with norepinephrine infusion, with goal HR 80-95 BPM
• 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)

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

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

• MDCalc - SIRS, Sepsis, and Septic Shock Criteria
• MDCalc - qSOFA Score
• MDCalc - NEWS 2
• EMCrit Sepsis 3.0
• SSC 2021 Guidelines (Full Text)

See Also

• Initial Antibiotics in Sepsis (Main)
• Sepsis (Peds)
• EBQ:ProCESS Trial
• Quick Sequential (Sepsis Related) Organ Failure Assessment Score (qSOFA)
• Pneumonia (main)