How should blood pressure be supported in septic shock, including fluid resuscitation, vasopressor selection and dosing, and adjunctive therapies?

Blood Pressure Support in Septic Shock

Initiate immediate fluid resuscitation with at least 30 mL/kg IV crystalloid within 3 hours, target MAP ≥65 mmHg with norepinephrine as first-line vasopressor if hypotension persists after adequate fluids, and add vasopressin 0.03 U/min as the second agent when additional support is needed. 1, 2

Immediate Fluid Resuscitation (First 3 Hours)

• Administer a minimum of 30 mL/kg of IV crystalloid (normal saline or balanced solution) within the first 3 hours of septic shock recognition. This is the cornerstone intervention and must begin immediately. 1, 2

• Give an initial 500 mL crystalloid bolus rapidly over 5–10 minutes to patients presenting with shock, monitoring for signs of fluid overload (jugular venous distension, worsening respiratory rate, declining oxygen saturation). 2

• Continue fluid administration beyond the initial 30 mL/kg bolus as long as hemodynamic improvement is observed. Use dynamic indices (pulse-pressure variation, stroke-volume variation) or static variables (arterial pressure, heart rate, urine output, mental status) to guide ongoing therapy. 1, 2

• Avoid hydroxyethyl starch formulations entirely—they increase acute kidney injury and mortality compared to crystalloids. 2

Fluid Resuscitation Caveats

• In patients with generalized peritonitis or at risk for abdominal compartment syndrome, exercise caution with aggressive fluid administration as excessive volume can worsen gut edema, raise intra-abdominal pressure, and precipitate respiratory compromise. 2

• For patients with chronic systolic heart failure (EF <40%), do not withhold the standard 30 mL/kg crystalloid bolus—evidence does not support restricting fluids in this population during septic shock. 3

Hemodynamic Targets (First 6 Hours)

• Target MAP ≥65 mmHg in most adults; this threshold prevents pressure-dependent organ hypoperfusion. 1, 2

• For patients with chronic hypertension, target a higher MAP of 70–85 mmHg because their autoregulatory curve is shifted rightward. 2

• Maintain urine output ≥0.5 mL/kg/hour as a bedside marker of adequate renal perfusion. 1, 2

• Target central venous pressure (CVP) of 8–12 mmHg (or 12–15 mmHg if mechanically ventilated) to guide fluid responsiveness. 1, 2

• Ensure central venous oxygen saturation (ScvO₂) ≥70% (or mixed venous O₂ saturation ≥65%) to confirm sufficient tissue oxygen delivery. 1, 2

• Keep capillary refill time <2 seconds with normal skin temperature, peripheral pulses, and mental status as additional perfusion endpoints. 2

Vasopressor Therapy

First-Line Agent: Norepinephrine

• Start norepinephrine when MAP remains <65 mmHg after adequate fluid resuscitation (i.e., after the initial 30 mL/kg crystalloid bolus). 1, 2, 4

• In severe shock with critically low diastolic pressure, initiate norepinephrine emergently even before completing fluid resuscitation. 2

• Initial norepinephrine dose: 0.05–0.1 µg/kg/min, titrated to maintain MAP ≥65 mmHg. 2, 3

• Peripheral administration through a 20-gauge or larger IV line is safe and acceptable initially to avoid delays while obtaining central venous access. 2, 4

• Norepinephrine is superior to dopamine—it reverses hypotension more effectively and causes fewer arrhythmias. 2, 3

Second-Line Agent: Vasopressin

• Add vasopressin 0.03 U/min to norepinephrine when additional MAP support is needed or to permit a lower norepinephrine dose. 1, 2, 3, 4

• Never use vasopressin as the sole initial vasopressor—it carries a higher risk of digital ischemia and should only be added to norepinephrine. 2, 3

Third-Line Agent: Epinephrine

• Add epinephrine if MAP targets are not achieved with norepinephrine plus vasopressin. 1, 2, 3, 4

Agents to Avoid

• Avoid dopamine as first-line therapy—it is associated with more arrhythmias and worse outcomes compared to norepinephrine. Reserve dopamine only for highly selected patients with bradycardia and low risk of tachyarrhythmias. 2, 5, 3

• Do not use low-dose dopamine for renal protection—evidence shows it is ineffective and contraindicated. 3

Inotropic Support

• Add dobutamine (2.5–20 µg/kg/min) when myocardial dysfunction with low cardiac output persists despite adequate MAP and volume status, particularly when ongoing tissue hypoperfusion is evident. 2, 5, 3

• This is especially important in patients with reduced ejection fraction heart failure who develop septic shock. 3

Lactate Monitoring as a Resuscitation Endpoint

• Measure serum lactate immediately at septic shock recognition. 1, 2

• Repeat lactate measurement within 6 hours after initial fluid resuscitation if initially elevated, and guide resuscitation toward lactate normalization as a marker of resolving tissue hypoperfusion. 1, 2

• Do not rely solely on MAP to assess adequacy of resuscitation—normal MAP can coexist with severe tissue hypoperfusion ("cold shock"). Serial lactate, urine output, mental status, and capillary refill must supplement MAP targets. 2

Adjunctive Therapies

Corticosteroids

• Do not use routine IV hydrocortisone in septic shock patients who achieve hemodynamic stability with fluids and vasopressors. 2

• Consider hydrocortisone 200 mg/day only if hemodynamic stability cannot be attained despite adequate fluid resuscitation and vasopressor therapy. 2, 4

Albumin

• Consider albumin supplementation when large volumes of crystalloids are required to maintain target MAP, particularly in patients with chronic heart failure. 3

Source Control

• Identify or exclude a specific anatomic infection source and perform definitive interventions (drainage, debridement, device removal) within 12 hours of septic shock onset—timely source control is as critical as antimicrobial therapy. 2

Monitoring Beyond Initial Resuscitation

• Place an arterial catheter promptly in any patient requiring vasopressor therapy to allow accurate continuous MAP monitoring. 3

• Reassess hemodynamics frequently using clinical examination (heart rate, blood pressure, respiratory rate, temperature, urine output, mental status) and available monitoring to evaluate response to treatment. 1, 2

Critical Pitfalls to Avoid

• Do not assume a universal MAP target of 65 mmHg applies to all patients—adjust upward for chronic hypertension or intra-abdominal hypertension, and consider lower targets in the very elderly. 2

• Do not substitute beta-blockers for adequate fluid resuscitation or appropriate vasopressor therapy—beta-blockers are not recommended in septic shock and are absolutely contraindicated when MAP <65 mmHg despite vasopressors. 5

• Do not prioritize heart rate targets over perfusion endpoints such as lactate clearance, urine output, mental status, and capillary refill—tachycardia may be a necessary compensatory response to maintain cardiac output. 5

• Do not delay vasopressor initiation in patients who remain hypotensive after the initial 30 mL/kg fluid bolus—waiting for additional fluid challenges when MAP remains <65 mmHg increases mortality. 2, 6