How is the dose of noradrenaline (norepinephrine) calculated?

Norepinephrine Dose Calculation

Norepinephrine should be initiated at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion, titrated every 4 hours by 0.5 mg/h increments to a maximum of 3 mg/h, targeting a mean arterial pressure of 65 mmHg. 1, 2

Standard Preparation and Concentration

The FDA-approved standard concentration is 4 mg of norepinephrine base added to 250 mL of D5W, yielding 16 mcg/mL. 3, 2

• Alternative concentration: 1 mg in 100 mL saline creates a 10 mcg/mL solution, sometimes used in specific scenarios like anaphylaxis 2
• The FDA label specifies initial dosing of 0.25-0.375 mL/min (8-12 mcg base/min), with average maintenance of 0.0625-0.125 mL/min (2-4 mcg base/min) 3

Weight-Based vs. Non-Weight-Based Dosing

Use actual body weight for dose calculations in mcg/kg/min, but recognize that obese patients require lower weight-based doses while achieving similar hemodynamic effects. 4

• Standard weight-based range: 0.1-0.5 mcg/kg/min initially, titrating up to maximum 3 mg/h 1, 2
• For a 70 kg adult: starting dose is 7-35 mcg/min 2
• Obese patients (BMI ≥30) require approximately 0.09 mcg/kg/min at 60 minutes versus 0.13 mcg/kg/min in non-obese patients, but similar absolute doses (9 vs 8 mcg/min) 4

Dose Titration Algorithm

Start at 0.5 mg/h, increase by 0.5 mg/h every 4 hours as needed, targeting MAP ≥65 mmHg and adequate tissue perfusion markers. 1, 2

Initial Phase:

• Begin at 0.5 mg/h (8-12 mcg/min) 1, 2
• Monitor blood pressure every 5-15 minutes during initial titration 2
• Assess tissue perfusion: lactate clearance, urine output >50 mL/h for 4 hours, mental status, capillary refill 1, 2

Escalation Strategy:

• Increase by 0.5 mg/h every 4 hours if MAP remains <65 mmHg 1, 2
• Maximum dose: 3 mg/h 1, 2
• When reaching 0.25 mcg/kg/min with persistent hypotension, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 2

Dose Severity Classification:

• Low dose: <0.2 mcg/kg/min (hospital mortality ~14%) 5
• Intermediate dose: 0.2-0.4 mcg/kg/min (hospital mortality ~26%) 5
• High dose: >0.4 mcg/kg/min (hospital mortality ~40%) 5

Administration Route and Monitoring

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 3

• If central access unavailable, peripheral IV can be used temporarily with strict monitoring 2
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 2
• The FDA warns that extravasation can cause local necrosis due to vasoconstrictive action 3

Extravasation Management:

• Infiltrate 10-15 mL saline containing 5-10 mg phentolamine into affected area immediately 3, 2
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 2

Critical Pre-Administration Requirements

Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation—vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 2

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 2
• In severe hypotension (systolic <70 mmHg), start norepinephrine as emergency measure while fluid resuscitation continues 2
• Never use hydroxyethyl starch (HES) with norepinephrine due to increased mortality (51% vs 43%, p=0.03) 2

Target Blood Pressure Parameters

Target MAP of 65 mmHg for most patients, but individualize based on chronic hypertension status and tissue perfusion markers. 1, 2

• Patients with chronic hypertension may require higher MAP targets 2
• Younger normotensive patients may tolerate lower pressures 2
• Titrate to both MAP and tissue perfusion markers, not MAP alone 2

Pediatric Dosing Considerations

Pediatric starting dose: 0.1 mcg/kg/min, titrating to effect with typical range 0.1-1.0 mcg/kg/min; maximum doses up to 5 mcg/kg/min may be necessary. 2

"Rule of 6" for Pediatric Preparation:

• Multiply 0.6 × body weight (kg) = number of milligrams 2
• Dilute to 100 mL saline 2
• Then 1 mL/h delivers 0.1 mcg/kg/min 2

Common Pitfalls to Avoid

Do not start norepinephrine without adequate fluid resuscitation—this is the most critical error leading to organ hypoperfusion. 2

• Never mix with sodium bicarbonate or alkaline solutions in IV line (causes inactivation) 2, 3
• Do not use dopamine as first-line agent (associated with higher mortality and arrhythmias) 2
• Avoid abrupt discontinuation—taper gradually to prevent rebound hypotension 3
• Do not use low-dose dopamine for "renal protection" (no benefit, strongly discouraged) 2
• Monitor for ischemic complications: cold extremities, decreased urine output, arrhythmias 1, 3

Special Clinical Scenarios

Hepatorenal Syndrome:

• Start at 0.5 mg/h, increase every 4 hours by 0.5 mg/h to maximum 3 mg/h 1
• Goal: increase MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1
• Administer with albumin 1 g/kg day 1, then 20-40 g daily 1

Septic Shock:

• Norepinephrine is mandatory first-choice vasopressor (strong recommendation, moderate quality evidence) 2
• Target MAP 65 mmHg with normalization of capillary refill and age-appropriate heart rate 2
• Add vasopressin 0.03 units/min when norepinephrine reaches 0.25 mcg/kg/min with persistent hypotension 2

Pregnant Patients:

• Start at 0.02 mcg/kg/min with target MAP 65 mmHg 2
• Consider more restrictive initial fluid boluses (1-2 L) due to lower colloid oncotic pressure and higher pulmonary edema risk 2
• Add vasopressin 0.04 units/min for refractory shock with fetal monitoring when appropriate 2