What are the recommended vasopressor agents and dosing regimens for adult patients with hypotension or shock?

Vasopressor Agents and Dosing in Adult Hypotension and Shock

First-Line Vasopressor: Norepinephrine

Norepinephrine is the mandatory first-choice vasopressor for all forms of shock, including septic, cardiogenic, and vasodilatory shock. 1, 2, 3

Initial Dosing and Administration

• Start at 0.02–0.05 mcg/kg/min (approximately 0.5 mg/h or 8–12 mcg/min for a 70 kg adult) via continuous IV infusion 1, 2, 3
• Standard concentration: Add 4 mg norepinephrine to 250 mL D5W to yield 16 mcg/mL 2
• Target MAP ≥ 65 mmHg for most patients; increase to 70–85 mmHg in chronic hypertension 1, 2, 3
• Titrate in increments every 10–15 minutes based on hemodynamic response 1, 2
• Typical dosing range: 0.1–2 mcg/kg/min, though higher doses may be required in refractory shock 1, 2

Critical Pre-Administration Requirements

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to prevent severe organ hypoperfusion from vasoconstriction in hypovolemic patients 1, 2, 3
• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2, 3
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2, 3

Extravasation Management

• If extravasation occurs, infiltrate phentolamine 5–10 mg diluted in 10–15 mL saline intradermally at the site immediately to prevent tissue death 2
• Pediatric dose: 0.1–0.2 mg/kg up to 10 mg 2

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Second-Line Vasopressor: Vasopressin

Add vasopressin at 0.03 units/min (fixed dose) when norepinephrine reaches 0.1–0.25 mcg/kg/min and MAP remains < 65 mmHg. 1, 4

Dosing Parameters

• Septic shock: Start at 0.01 units/min, titrate by 0.005 units/min every 10–15 minutes to maximum 0.03–0.04 units/min 1, 4
• Post-cardiotomy shock: 0.03–0.1 units/min 1, 4
• Never use as monotherapy—must be added to norepinephrine 1, 4
• Do not exceed 0.03–0.04 units/min except as salvage therapy; higher doses cause cardiac, digital, and splanchnic ischemia without additional hemodynamic benefit 1, 4

Preparation

• Dilute 20 units/mL vial with normal saline or D5W to either 0.1 units/mL or 1 unit/mL 4
• Discard unused diluted solution after 18 hours at room temperature or 24 hours refrigerated 4

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Third-Line Vasopressor: Epinephrine

Add epinephrine when norepinephrine plus vasopressin fail to achieve target MAP, particularly when myocardial dysfunction is present. 1, 5

Dosing Parameters

• Start at 0.05 mcg/kg/min, titrate in increments of 0.05–0.2 mcg/kg/min every 10–15 minutes 1, 5
• Maximum dose: 0.3–2 mcg/kg/min (approximately 21 mcg/min for a 70 kg patient) 1, 5
• Preparation: Dilute 1 mg in 1,000 mL of D5W to produce 1 mcg/mL concentration 5
• Wean incrementally over 12–24 hours after hemodynamic stabilization 5

Important Considerations

• Epinephrine increases myocardial oxygen consumption more than norepinephrine and causes transient lactic acidosis through β2-adrenergic stimulation 1
• Higher risk of cardiac arrhythmias, particularly when combined with other sympathomimetics 1
• Use cautiously in patients with ischemic heart disease 1

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Phenylephrine (Limited Role)

Phenylephrine is NOT recommended as first-line therapy and should be avoided except in three specific circumstances. 1, 6

Indications (Very Limited)

1. Norepinephrine causes serious arrhythmias 1, 6
2. Documented high cardiac output with persistent hypotension 1, 6
3. Salvage therapy when all other agents have failed 1, 6

Dosing (If Used)

• Perioperative setting: 50–250 mcg IV bolus; most common initial dose is 50–100 mcg 6
• Continuous infusion: 0.5–1.4 mcg/kg/min for perioperative use 6
• Septic shock: 0.5–6 mcg/kg/min (no bolus); doses above 6 mcg/kg/min show no incremental benefit 6
• Preparation: Dilute 10 mg in 500 mL D5W or NS to yield 20 mcg/mL 6

Why Avoid Phenylephrine

• Pure α-agonist causes reflex bradycardia and may reduce cardiac output despite raising blood pressure 1
• Can compromise microcirculatory flow and tissue perfusion while raising MAP on the monitor 1

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Inotropic Support: Dobutamine

Add dobutamine when MAP is adequate (≥ 65 mmHg) but signs of tissue hypoperfusion persist, particularly with myocardial dysfunction. 1, 3

Dosing Parameters

• Start at 2.5 mcg/kg/min, titrate up to 20 mcg/kg/min based on response 1, 3
• Double the dose every 15 minutes according to response, limited by tachycardia, arrhythmias, or ischemia 1

Indications

• Low cardiac output with ScvO₂ < 70% despite adequate MAP and fluid resuscitation 1, 3
• Elevated filling pressures with low cardiac output 1, 3
• Persistent hypoperfusion (elevated lactate, low urine output, altered mental status) despite adequate vasopressor support 1, 3

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Agents to AVOID

Dopamine

Dopamine should NOT be used as first-line therapy—it is associated with an 11% absolute increase in mortality and significantly more arrhythmias compared to norepinephrine. 1, 2, 3

• Only acceptable indication: Highly selected patients with bradycardia and low arrhythmia risk 1
• Low-dose dopamine for "renal protection" is strongly contraindicated (Grade 1A)—it provides no benefit 1, 2, 3

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Monitoring Beyond MAP Targets

MAP ≥ 65 mmHg alone is insufficient—assess tissue perfusion markers every 2–4 hours: 1, 2, 3

• Lactate clearance: Obtain baseline and repeat within 6 hours if elevated 1, 3
• Urine output: Maintain ≥ 0.5 mL/kg/h 1, 3
• Mental status: Assess for altered mentation 1, 3
• Skin perfusion and capillary refill: Monitor for peripheral hypoperfusion 1, 3

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Sequential Escalation Algorithm

1. Norepinephrine alone at 0.02–0.05 mcg/kg/min, titrate to MAP ≥ 65 mmHg 1, 2, 3
2. When norepinephrine reaches 0.1–0.25 mcg/kg/min and MAP remains < 65 mmHg, add vasopressin 0.03 units/min 1, 4
3. If MAP still inadequate, add epinephrine 0.05 mcg/kg/min, titrate up to 0.3–2 mcg/kg/min 1, 5
4. If MAP adequate but hypoperfusion persists, add dobutamine 2.5–20 mcg/kg/min 1, 3
5. For refractory shock after ≥ 4 hours of high-dose vasopressors, consider hydrocortisone 200 mg/day IV 1

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Special Populations

Chronic Hypertension

• Target MAP 70–85 mmHg instead of 65 mmHg to reduce need for renal replacement therapy 1, 2

Obstetric Patients

• Start norepinephrine at 0.02 mcg/kg/min after 1–2 L fluid bolus 1
• Consider more restrictive initial fluid boluses due to lower colloid oncotic pressure and higher pulmonary edema risk 2

Pediatric Patients

• Norepinephrine: Start at 0.1 mcg/kg/min, typical range 0.1–1.0 mcg/kg/min, maximum up to 5 mcg/kg/min 2
• Vasopressin: 0.0002–0.002 units/kg/min 2