What are the recommended initial doses and titration steps for norepinephrine, vasopressin, epinephrine, phenylephrine, and dopamine in an adult patient with a mean arterial pressure < 65 mmHg despite adequate fluid resuscitation?

Recommended Vasopressor Doses for Septic Shock

Norepinephrine is the mandatory first-line vasopressor, started at 0.02–0.05 µg/kg/min after administering at least 30 mL/kg crystalloid, with a target MAP ≥ 65 mmHg. 1

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Initial Fluid Resuscitation (Before Vasopressors)

• Administer a minimum of 30 mL/kg crystalloid within the first 3 hours before or concurrently with vasopressor initiation to correct hypovolemia. 2, 1
• In profound hypotension (SBP < 70 mmHg or critically low diastolic pressure), do not delay norepinephrine while pursuing aggressive fluid resuscitation—start vasopressors emergently as fluid resuscitation continues. 1
• For pregnant patients with sepsis, limit the initial bolus to 1–2 L due to higher pulmonary edema risk. 2

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Norepinephrine (First-Line Agent)

Starting Dose & Titration

• Initial dose: 0.02–0.05 µg/kg/min (approximately 0.5 mg/h or 8–12 µg/min for a 70 kg adult). 2, 1, 3
• Titrate in increments of 0.02–0.05 µg/kg/min every 5–10 minutes until MAP ≥ 65 mmHg is achieved. 1
• Maximum dose before adding second agent: 0.1–0.25 µg/kg/min. 1

Administration & Monitoring

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 3
• If central access is unavailable, a large-bore peripheral IV or intraosseous line may be used temporarily. 1, 4
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical. 1
• Monitor blood pressure and heart rate every 5–15 minutes during initial titration. 4, 3

Hemodynamic Target

• Target MAP ≥ 65 mmHg for most patients. 2, 1, 3
• In patients with chronic hypertension, consider a higher target of 70–85 mmHg to reduce renal replacement therapy risk. 1

Tissue Perfusion Markers (Beyond MAP)

• Assess lactate clearance (repeat every 2–4 hours if elevated). 2, 1
• Maintain urine output ≥ 0.5 mL/kg/h. 2, 1
• Monitor mental status, capillary refill ≤ 2 seconds, and skin perfusion. 2, 1

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Vasopressin (Second-Line Agent)

When to Add

• Add vasopressin when norepinephrine reaches 0.1–0.25 µg/kg/min and MAP remains < 65 mmHg despite adequate fluid resuscitation. 2, 1

Dosing

• Fixed dose: 0.03 units/min (do not titrate). 2, 1
• Maximum dose: 0.03–0.04 units/min; higher doses cause cardiac, digital, and splanchnic ischemia without additional hemodynamic benefit. 1
• Never use vasopressin as monotherapy—it must always be added to norepinephrine. 1

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Epinephrine (Third-Line Agent)

When to Add

• Add epinephrine when MAP cannot be achieved with norepinephrine plus vasopressin, or as an alternative to vasopressin if unavailable. 1

Dosing

• Starting dose: 0.05 µg/kg/min, titrating up to 0.3 µg/kg/min (approximately 3.5–21 µg/min for a 70 kg adult). 1

Important Cautions

• Epinephrine increases the risk of serious cardiac arrhythmias (65% risk reduction in ventricular arrhythmias with norepinephrine vs. epinephrine). 1
• Epinephrine causes transient lactic acidosis through β2-adrenergic stimulation, interfering with lactate clearance as a resuscitation endpoint. 1

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Phenylephrine (Rarely Used)

When to Consider

• Not recommended as first-line therapy; phenylephrine may raise blood pressure while worsening tissue perfusion. 1
• Use only in three specific scenarios: (1) norepinephrine-induced serious arrhythmias, (2) documented high cardiac output with persistent hypotension, or (3) salvage therapy after all other agents have failed. 1

Dosing

• No specific starting dose is provided in guidelines due to its limited role.

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Dopamine (Strongly Contraindicated as First-Line)

Evidence Against Use

• Dopamine is associated with an 11% absolute increase in mortality and significantly more arrhythmias compared to norepinephrine. 1, 4
• Low-dose dopamine for renal protection is strongly contraindicated (Grade 1A recommendation)—it provides no benefit. 1

Only Acceptable Indication

• Dopamine may be used only in highly selected patients with absolute or relative bradycardia and low arrhythmia risk. 1

Dosing (If Used)

• No specific starting dose is recommended due to its contraindication as first-line therapy.

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Dobutamine (For Persistent Hypoperfusion Despite Adequate MAP)

When to Add

• Add dobutamine when MAP is adequate (≥ 65 mmHg) but signs of tissue hypoperfusion persist (elevated lactate, low urine output, altered mental status), especially with evidence of myocardial dysfunction. 2, 1

Dosing

• Starting dose: 2.5 µg/kg/min, titrating up to 20 µg/kg/min based on response. 1
• Dose escalation is often limited by tachycardia, arrhythmias, or ischemia. 1

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Adjunctive Therapy: Hydrocortisone

When to Add

• For refractory shock requiring high-dose vasopressors after ≥ 4 hours of therapy. 2, 1

Dosing

• Hydrocortisone 200 mg/day IV (administered as 50 mg every 6 hours or continuous infusion). 2, 1

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Pediatric Dosing

Norepinephrine

• Starting dose: 0.1 µg/kg/min, titrating within a range of 0.1–1.0 µg/kg/min. 4, 3
• Maximum dose: up to 5 µg/kg/min in refractory cases. 4

Vasopressin

• Starting dose: 0.0002–0.0005 units/kg/min, titrating up to a maximum of 0.002 units/kg/min. 4

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Critical Pitfalls to Avoid

• Do not delay norepinephrine while pursuing excessive fluid resuscitation in profound hypotension. 1
• Do not focus solely on MAP—incorporate tissue perfusion markers (lactate, urine output, mental status) into decision-making. 2, 1
• Do not exceed vasopressin dosing beyond 0.03–0.04 units/min to avoid end-organ ischemia. 1
• Do not use dopamine for renal protection—it is contraindicated and delays appropriate therapy. 1
• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions, as this inactivates the drug. 1, 4
• If extravasation occurs, infiltrate phentolamine 5–10 mg diluted in 10–15 mL saline intradermally at the site immediately to prevent tissue necrosis. 4, 3