What is the recommended dosage of Noradrenaline (norepinephrine) for a critically ill patient in septic shock?

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 or 0.5 mg/h) via continuous IV infusion, targeting a mean arterial pressure of 65 mmHg. 1, 2

Critical Pre-Administration Requirements

• Administer at least 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to optimize cardiac output, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 1, 2

• In life-threatening hypotension (diastolic BP ≤40 mmHg or systolic <70 mmHg), start norepinephrine immediately as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion. 1, 3, 4

Administration Route and Monitoring

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis, though peripheral IV or intraosseous administration can be used temporarily if central access is unavailable or delayed. 1, 2

• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 1, 2, 5

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 1, 2

Standard Concentration and Titration

• Standard adult concentration: Add 4 mg of norepinephrine to 250 mL of D5W to yield 16 μg/mL. 2

• Titrate dose by 0.5 mg/h (approximately 8 mcg/min) every 4 hours as needed, up to a maximum of 3 mg/h. 2

• Target MAP of 65 mmHg for most patients, though patients with chronic hypertension may require higher targets (70-85 mmHg) to reduce need for renal replacement therapy. 1, 5

• Supplement blood pressure targets with assessment of tissue perfusion: lactate clearance, urine output >50 mL/h, mental status, capillary refill, and skin perfusion. 1, 2

Escalation Protocol for Refractory Hypotension

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists despite adequate fluid resuscitation:

• Add vasopressin 0.03 units/min (maximum 0.03-0.04 units/min) to raise MAP to target or decrease norepinephrine dosage—do not use vasopressin as monotherapy. 1, 5

• Alternatively, add epinephrine 0.1-0.5 mcg/kg/min when an additional agent is needed to maintain adequate blood pressure. 1, 5

• Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly when myocardial dysfunction is evident. 1, 5, 6

Agents to Avoid

• Do not use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine, and should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia. 1, 5

• Do not use low-dose dopamine for renal protection—this has no benefit and is strongly discouraged. 1, 5

• Do not use phenylephrine as first-line therapy except when: (a) norepinephrine causes serious arrhythmias, (b) cardiac output is documented to be high with persistently low blood pressure, or (c) as salvage therapy when other agents have failed. 1, 5

Pediatric Dosing

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect with a typical range of 0.1-1.0 mcg/kg/min; maximum doses up to 5 mcg/kg/min may be necessary in some children. 2

• "Rule of 6" for pediatric preparation: 0.6 × body weight (kg) = number of milligrams diluted to total 100 mL of saline; then 1 mL/h delivers 0.1 mcg/kg/min. 2

Extravasation Management

• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately to prevent tissue necrosis and sloughing. 2

• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride. 2

Common Pitfalls to Avoid

• Starting norepinephrine without adequate fluid resuscitation causes severe organ hypoperfusion through excessive vasoconstriction in hypovolemic patients. 1, 2

• Delaying norepinephrine in profound hypotension (diastolic BP ≤40 mmHg) unduly prolongs hypotension and organ hypoperfusion, as the response to volume expansion alone is inconstant, delayed, and transitory. 3, 4

• Escalating norepinephrine beyond 0.25 mcg/kg/min without adding vasopressin or epinephrine increases mortality risk—add second-line agents rather than continuing to escalate norepinephrine alone. 1, 5, 7

• Mixing norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line inactivates the medication. 2