What are the 2026 evidence‑based recommendations for the initial management of adult septic shock, including source control, antimicrobial timing, fluid resuscitation, vasopressor use, corticosteroids, lactate monitoring, and supportive care?

Septic Shock Management Guidelines 2026

The 2026 evidence-based approach to septic shock prioritizes norepinephrine as the mandatory first-line vasopressor after at least 30 mL/kg crystalloid resuscitation, targeting MAP ≥65 mmHg, with vasopressin added at 0.03 units/min when norepinephrine alone fails, and hydrocortisone 200 mg/day reserved only for refractory shock unresponsive to adequate fluids and vasopressors. 1, 2, 3

Initial Recognition and Hemodynamic Targets

Diagnostic Criteria for Septic Shock:

• Persistent hypotension (systolic BP <90 mmHg or MAP <65 mmHg) despite adequate fluid resuscitation (≥30 mL/kg crystalloid) 3
• Serum lactate >2 mmol/L requiring vasopressor infusion to maintain MAP ≥65 mmHg 4
• Clinical signs of tissue hypoperfusion: altered mental status, reduced capillary refill, skin mottling, or oliguria (≤0.5 mL/kg/h for ≥2 hours) 3

Resuscitation Targets:

• MAP ≥65 mmHg for most patients; consider 70–85 mmHg in chronic hypertension to reduce renal replacement therapy 1, 5
• Lactate clearance (repeat within 6 hours if elevated) 1
• Urine output ≥0.5 mL/kg/h 1, 3
• Mental status normalization and improved capillary refill 1, 5

Fluid Resuscitation Protocol

Initial Fluid Administration:

• Administer at least 30 mL/kg of crystalloid within the first 3 hours before or concurrent with vasopressor initiation 1, 3, 4
• Both balanced crystalloids and normal saline are acceptable options 5
• Continue fluid challenges while hemodynamic improvement is observed, using dynamic variables (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output) to guide further boluses 1

Monitoring Fluid Responsiveness:

• A positive response is defined as ≥10% increase in systolic or mean BP, ≥10% reduction in heart rate, improved mental status, peripheral perfusion, and/or diuresis 3
• Monitor for volume overload (pulmonary crackles) 3
• Once ARDS develops without tissue hypoperfusion, use a conservative fluid strategy 6

Vasopressor Management Algorithm

First-Line: Norepinephrine

• Norepinephrine is the mandatory first-choice vasopressor with Grade 1B recommendation, reducing 28-day mortality by 11% absolute risk reduction compared to dopamine 1
• Start at 0.02–0.05 µg/kg/min (approximately 5–10 µg/min for adults) via central venous access when possible 1
• Titrate to maintain MAP ≥65 mmHg with continuous arterial blood pressure monitoring via arterial catheter 1, 3
• Peripheral administration through 20-gauge or larger IV is safe and effective when central access is delayed 5

Second-Line: Vasopressin

• Add vasopressin at a fixed dose of 0.03 units/min when norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains <65 mmHg 1
• Vasopressin must always be added to norepinephrine, never used as monotherapy 1
• Do not exceed 0.03–0.04 units/min except as salvage therapy; higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit 1
• Vasopressin preferentially constricts the efferent arteriole, producing higher glomerular filtration and better urine output compared to norepinephrine alone 1

Third-Line: Epinephrine

• Add epinephrine starting at 0.05 µg/kg/min, titrating up to 0.3 µg/kg/min when MAP cannot be achieved with norepinephrine plus vasopressin 1, 5
• Epinephrine causes transient lactic acidosis through β₂-adrenergic stimulation of skeletal muscle, interfering with lactate clearance as a resuscitation endpoint 1

Inotropic Support: Dobutamine

• Add dobutamine 2.5–20 µg/kg/min when MAP is adequate (≥65 mmHg) but signs of tissue hypoperfusion persist (elevated lactate, low urine output, altered mental status), especially with myocardial dysfunction 1, 4, 5
• Dobutamine increases myocardial oxygen consumption and commonly causes tachycardia and arrhythmias, limiting dose escalation 1

Agents to Avoid

Dopamine:

• Strongly contraindicated as first-line therapy (Grade 1A); associated with 11% absolute increase in mortality and significantly more supraventricular (RR 0.47) and ventricular arrhythmias (RR 0.35) compared to norepinephrine 1
• Reserved only for highly selected patients with bradycardia and low arrhythmia risk 1
• Low-dose dopamine for renal protection is strongly discouraged (Grade 1A) 1

Phenylephrine:

• Not recommended except in three specific situations: (1) norepinephrine-induced serious arrhythmias, (2) documented high cardiac output with persistent hypotension, or (3) salvage therapy when all other agents have failed 1
• Pure α-agonist vasoconstriction can compromise microcirculatory flow and tissue perfusion despite raising blood pressure numbers 1

Corticosteroid Therapy

Indications for Hydrocortisone:

• Hydrocortisone 200 mg/day IV is recommended only for vasopressor-refractory septic shock: MAP remains <65 mmHg despite ≥30 mL/kg crystalloid and norepinephrine >0.1–0.2 µg/kg/min for >60 minutes 2, 3
• This is a conditional recommendation (Grade 2C) based on moderate-quality evidence 2

Dosing and Administration:

• 200 mg/day as continuous IV infusion (preferred) or 50 mg IV every 6 hours 2, 3
• Maintain full dose for at least 3 days before considering taper 2
• Begin taper only after vasopressors discontinued, tapering gradually over 6–14 days; abrupt cessation is contraindicated 2, 3

Evidence of Benefit:

• Accelerates shock reversal (hazard ratio ≈1.9 for earlier vasopressor discontinuation) and reduces total vasopressor requirements 2
• Mortality benefit demonstrated only in the most severely ill, refractory-shock population (53% vs 63% mortality in French Annane trial) 2
• No overall mortality benefit in CORTICUS trial, which enrolled less severely ill patients 2

Contraindications and Pitfalls:

• Do not use in sepsis without shock or when hemodynamic stability achieved with fluids and low-dose vasopressor 2, 3
• ACTH stimulation testing is not recommended (Grade 2B) 2, 3
• Do not add fludrocortisone; no improvement in outcomes demonstrated 2
• Avoid high-dose regimens (>400 mg/day); increased harm without added benefit 2
• Avoid etomidate for intubation in patients who may require hydrocortisone 2

Antimicrobial Therapy and Source Control

• Administer appropriate antibiotics as soon as possible; delays are associated with increased mortality 4, 5
• Evaluate and implement source control measures early 4

Mechanical Ventilation in Sepsis-Induced ARDS

When ARDS develops (PaO₂/FiO₂ <300):

• Target tidal volume of 6 mL/kg predicted body weight (strong recommendation, high-quality evidence) 6
• Upper limit goal for plateau pressures of 30 cm H₂O (strong recommendation, moderate-quality evidence) 6
• Use prone positioning for PaO₂/FiO₂ <150 (strong recommendation, moderate-quality evidence) 6
• Maintain head of bed elevated 30–45 degrees to prevent ventilator-associated pneumonia 6
• Use spontaneous breathing trials regularly for weaning (strong recommendation, high-quality evidence) 6

Monitoring and Escalation Strategy

Continuous Monitoring Requirements:

• Arterial catheter for continuous blood pressure monitoring as soon as practical 1, 3
• Measure blood pressure and heart rate every 5–15 minutes in patients receiving vasopressors 3
• Lactate every 2–4 hours during early resuscitation 1
• Urine output hourly (target ≥0.5 mL/kg/h) 1
• Mental status and peripheral perfusion (capillary refill, skin mottling) 1, 3

Refractory Shock Definition:

• Continued hemodynamic instability (MAP ≤65 mmHg, lactate ≥4 mmol/L, altered mental status) after adequate fluid loading (≥30 mL/kg), use of two vasopressors (with one as norepinephrine), and provision of antibiotics 7

Systematic Evaluation for Non-Responders:

• Source control adequacy 7
• Appropriate antimicrobial coverage 7
• Metabolic pathology (adrenal insufficiency, thyroid storm) 7
• Complications of resuscitation (abdominal compartment syndrome, respiratory failure) 7

Common Pitfalls to Avoid

• Do not delay norepinephrine while pursuing aggressive fluid resuscitation in severe hypotension; early vasopressor use is appropriate when diastolic BP is critically low 1, 3
• Avoid rapid boluses of sedatives in hemodynamically unstable patients 3
• Do not focus solely on MAP numbers; tissue perfusion markers (lactate, urine output, mental status) are equally critical 1
• Do not escalate vasopressin beyond 0.03–0.04 units/min; add epinephrine or dobutamine instead 1
• Monitor for extravasation with norepinephrine; infiltrate 5–10 mg phentolamine diluted in 10–15 mL saline immediately if it occurs 1