What is the recommended dose of norepinephrine for a critically ill adult with septic shock or severe hypotension?

Norepinephrine Dosing in Septic Shock

Start norepinephrine at 0.1–0.5 mcg/kg/min (approximately 7–35 mcg/min in a 70-kg adult) and titrate to achieve a mean arterial pressure (MAP) of 65 mmHg. 1

Initial Dosing and Administration

• Begin norepinephrine at 0.1–0.5 mcg/kg/min, which translates to approximately 7–35 mcg/min in a 70-kg patient, and titrate upward to achieve your MAP target. 1

• Administer through central venous access whenever possible to minimize the risk of tissue necrosis from extravasation. 1, 2

• Place an arterial catheter for continuous blood pressure monitoring as soon as practical—this is essential for all patients requiring vasopressors. 2

• Target a MAP ≥65 mmHg in most patients, though consider higher targets (70-75 mmHg) in those with chronic hypertension. 1, 2

Timing of Initiation

• Start norepinephrine early—as soon as hypotension persists after initial fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours), rather than waiting to complete all fluid administration. 2, 3, 4

• In patients with profound, life-threatening hypotension (systolic BP <80 mmHg or diastolic BP ≤40 mmHg), initiate norepinephrine simultaneously with fluid resuscitation rather than delaying. 3, 5

• Early norepinephrine administration (within 93 minutes vs 192 minutes) significantly increases shock control rates by 6 hours (76.1% vs 48.4%) and reduces complications like pulmonary edema and arrhythmias. 4

Escalation Strategy for Refractory Hypotension

When norepinephrine alone fails to achieve target MAP despite adequate fluid resuscitation, follow this algorithmic approach:

First Escalation: Add Vasopressin

• Add vasopressin at 0.03 units/minute (range 0.01-0.03 units/min) when norepinephrine requirements remain elevated or reach 0.25-0.50 mcg/kg/min. 1, 2, 6

• Vasopressin should never be used as monotherapy—it must be added to norepinephrine, not used alone. 1, 2

• Do not exceed 0.03-0.04 units/minute except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit. 2, 7

Second Escalation: Add Epinephrine

• If target MAP remains unachieved despite norepinephrine plus vasopressin, add epinephrine as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/min. 1, 2

• Epinephrine dosing typically starts at 0.1-0.5 mcg/kg/min and is titrated to effect. 1

Consider Dobutamine for Persistent Hypoperfusion

• Add dobutamine (2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident (elevated cardiac filling pressures, low cardiac output). 1, 2

Critical Agents to Avoid

• Do not use dopamine except in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 1, 2

• Never use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit. 1, 2

• Avoid phenylephrine except in specific circumstances: when norepinephrine causes serious arrhythmias, when cardiac output is documented to be high with persistently low blood pressure, or as salvage therapy when all other agents have failed. 2

Monitoring Beyond Blood Pressure

• Assess tissue perfusion markers beyond just MAP: lactate clearance, urine output ≥0.5 mL/kg/hr, mental status, capillary refill, and skin temperature. 2, 7

• Monitor for signs of excessive vasoconstriction: cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 2

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation waiting to complete entire fluid resuscitation if life-threatening hypotension is present—prolonged hypotension independently increases mortality. 8, 3, 5

• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions. 1

• If extravasation occurs, immediately infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site to prevent tissue necrosis and sloughing. 1

• Do not rely solely on norepinephrine dose thresholds for adding vasopressin—consider additional factors like obesity (negatively associated with vasopressin response), hyperlactatemia, and acidosis when deciding to add adjunctive therapy. 6