Norepinephrine Dosing in Septic Shock

Initial Dosing and Administration

The American Heart Association recommends starting 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 a mean arterial pressure (MAP) target of 65 mmHg 1, 2
Administer norepinephrine through central venous access whenever possible to minimize the risk of tissue necrosis from extravasation, as recommended by the American College of Cardiology 1
Place an arterial catheter for continuous blood pressure monitoring as soon as practical, which is essential for all patients requiring vasopressors, according to the Society of Critical Care Medicine 1
Target a MAP ≥65 mmHg in most patients, though consider higher targets (70-75 mmHg) in those with chronic hypertension, as suggested by the American College of Cardiology 2

Add vasopressin at 0.03 units/minute when norepinephrine requirements remain elevated or reach 0.25-0.50 mcg/kg/min, as recommended by the Society of Critical Care Medicine 2
Vasopressin should never be used as monotherapy, but rather added to norepinephrine, according to the American College of Cardiology 2
Do not exceed 0.03-0.04 units/minute of vasopressin except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit, as warned by the Society of Critical Care Medicine 3, 4

Do not use dopamine except in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia, as it is associated with higher mortality and more arrhythmias compared to norepinephrine, according to the Society of Critical Care Medicine 2, 3
Never use low-dose dopamine for renal protection, as this is strongly discouraged and has no benefit, as stated by the American College of Cardiology 2, 3
Avoid phenylephrine except in specific circumstances, such as when norepinephrine causes serious arrhythmias or as salvage therapy when all other agents have failed, as recommended by the Society of Critical Care Medicine 3

Assess tissue perfusion markers beyond just MAP, including lactate clearance, urine output ≥0.5 mL/kg/hr, mental status, capillary refill, and skin temperature, as suggested by the Society of Critical Care Medicine 3, 4
Monitor for signs of excessive vasoconstriction, such as cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP, according to the American College of Cardiology 3

Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions, as warned by the American Heart Association 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, as recommended by the American College of Cardiology 1

The Critical Care Medicine guideline recommends starting norepinephrine at 0.05–0.10 µg kg⁻¹ min⁻¹ (≈3.5–7 µg min⁻¹ for a 70‑kg adult) after administering at least 30 mL kg⁻¹ of crystalloids within the first 3 hours of resuscitation. 5

Norepinephrine should be titrated until a mean arterial pressure (MAP) ≥ 65 mmHg is achieved in most patients, or MAP 70–85 mmHg in patients with pre‑existing chronic hypertension. 5

An arterial catheter for continuous blood‑pressure monitoring should be placed as soon as possible after vasopressor initiation. 5

Lactate clearance: obtain a baseline lactate level and repeat the measurement within 6 hours if the initial value is elevated. 5
Urine output: maintain a minimum of ≥ 0.5 mL kg⁻¹ h⁻¹ as an indicator of adequate renal perfusion. 5

When norepinephrine dose reaches 0.10–0.25 µg kg⁻¹ min⁻¹ (≈7–17.5 µg min⁻¹ for a 70‑kg adult) and MAP remains < 65 mmHg, add vasopressin at a fixed dose of 0.03 units min⁻¹. 5
Do not exceed 0.03–0.04 units min⁻¹ of vasopressin except as rescue therapy; higher doses are associated with cardiac, digital, and splanchnic ischemia without additional hemodynamic benefit. 5

If MAP is adequate (≥ 65 mmHg) but signs of tissue hypoperfusion persist (elevated lactate, low urine output, altered mental status), add dobutamine at 2.5–20 µg kg⁻¹ min⁻¹, especially when myocardial dysfunction is evident. 5

Dopamine should not be used as first‑line therapy in septic shock; it is associated with an absolute 11 % increase in mortality and a higher incidence of arrhythmias compared with norepinephrine. 5
Low‑dose dopamine for renal protection is strongly contraindicated (Grade 1A recommendation). 5