What is the recommended initial dosage of noradrenaline (norepinephrine) for infusion in a patient in shock?

Noradrenaline Dosing for Shock

Start noradrenaline at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion, preferably through central venous access, while simultaneously ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus. 1

Initial Dosing Parameters

The recommended starting dose is 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult), titrated to achieve a mean arterial pressure (MAP) of 65 mmHg. 1 The American College of Critical Care Medicine supports this dosing range, which translates to approximately 0.5 mg/h when using standard concentration preparations 1.

Standard Concentration Preparation

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL 1
• Alternative concentration: Add 1 mg of norepinephrine to 100 mL of saline to create a 10 mcg/mL solution 1

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation—never start vasopressors in a hypovolemic patient. 1 This is a strong recommendation from the Surviving Sepsis Campaign guidelines, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1.

However, recent evidence suggests that in cases of profound, life-threatening hypotension (systolic BP <70 mmHg or diastolic BP ≤40 mmHg), norepinephrine should be started as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion 2, 3. The CENSER trial demonstrated that early norepinephrine administration significantly increased shock control rates by 6 hours (76.1% vs 48.4%, p<0.001) and reduced complications like cardiogenic pulmonary edema 3.

Administration Route and Monitoring

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1 If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring 1.

• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1

Titration Protocol

Increase dose by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h, targeting MAP ≥65 mmHg. 1 The target MAP should be individualized based on chronic hypertension status—patients with chronic hypertension may require higher targets, while younger normotensive patients may tolerate lower pressures 1.

Titration should be guided by:

• MAP ≥65 mmHg 1
• Normalization of capillary refill 1
• Age-appropriate heart rate 1
• Urine output >50 mL/h for at least 4 hours 1
• Lactate clearance ≥10% from baseline 1

Escalation Strategy for Refractory Hypotension

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03 units/min as second-line therapy rather than continuing to escalate norepinephrine alone. 1, 4 This recommendation is based on the VASST trial, which showed that patients requiring ≥15 mcg/min of norepinephrine had significantly elevated mortality 4.

Sequential escalation algorithm:

1. First-line: Norepinephrine 0.1-0.5 mcg/kg/min, titrate to MAP 65 mmHg 1
2. Second-line (at norepinephrine 0.25 mcg/kg/min): Add vasopressin 0.03 units/min 1, 4
3. Third-line: Add epinephrine 0.1-0.5 mcg/kg/min if hypotension persists 1
4. Inotropic support: Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with myocardial dysfunction 1

Research evidence supports adding vasopressin when baseline norepinephrine dose exceeds 0.38 mcg/kg/min, as this threshold predicts microcirculatory improvement with 53% probability (sensitivity 78%, specificity 77%) 5.

Special Populations

Obese Patients

Use total body weight for initial dosing calculations, but expect lower weight-based requirements. 6 A retrospective study showed obese patients required lower weight-based doses (0.09 vs 0.13 mcg/kg/min, p=0.006) but similar total doses (9 vs 8 mcg/min) compared to non-obese patients 6.

Pregnant Patients

Start at 0.02 mcg/kg/min with target MAP of 65 mmHg, and consider more restrictive initial fluid boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk. 1

Pediatric Patients

Start at 0.1 mcg/kg/min, titrating to desired clinical effect, with typical range of 0.1-1.0 mcg/kg/min. 1 Maximum doses up to 5 mcg/kg/min may be necessary in some children 1.

Critical Pitfalls to Avoid

Never use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 7, 4 Dopamine should only be used in highly selected patients with absolute bradycardia and low risk of tachyarrhythmias 4.

Do not use phenylephrine as first-line therapy—it may raise blood pressure while worsening tissue perfusion. 7, 4 Phenylephrine should be reserved for specific circumstances: norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy when other agents have failed 7, 4.

Never use low-dose dopamine for renal protection—this practice is strongly discouraged and has no benefit. 7, 4

Do not increase vasopressin above 0.03-0.04 units/min—higher doses are associated with cardiac, digital, and splanchnic ischemia. 7, 4 Reserve higher vasopressin doses only for salvage therapy when all other options have failed 4.

Extravasation Management

If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site to prevent tissue necrosis. 1 Pediatric dose is 0.1-0.2 mg/kg up to 10 mg 1.

Evidence Quality Considerations

The strongest evidence comes from the 2013 Surviving Sepsis Campaign guidelines 7 and the 2020 American Heart Association guidelines 7, both published in high-impact journals. The CENSER trial (2019) provides the highest quality prospective evidence supporting early norepinephrine administration 3, while the 1993 comparative study established norepinephrine's superiority over dopamine 8. The Praxis Medical Insights summaries 1, 4 synthesize recommendations from multiple guideline societies including the Society of Critical Care Medicine, American College of Critical Care Medicine, and Surviving Sepsis Campaign.