What is the dosage calculation for norepinephrine in an adult patient?

Norepinephrine Dosage Calculation for Adults

For adult patients with hypotension or septic shock, start norepinephrine at 0.5 mg/hour (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

Standard Preparation and Concentration

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL 1
• Alternative concentration: Add 1 mg norepinephrine to 100 mL saline for a 10 μg/mL solution, sometimes used in anaphylaxis scenarios 1

Initial Dosing Parameters

Weight-Based Dosing

• Start at 0.1-0.5 mcg/kg/min (equivalent to 7-35 mcg/min in a 70 kg adult) 1, 2
• Alternative starting point: 0.02 mcg/kg/min per American College of Cardiology recommendations 1

Non-Weight-Based Dosing

• Start at 0.5 mg/hour, titrate by 0.5 mg/hour increments every 4 hours to maximum of 3 mg/hour 1, 3
• This approach is particularly useful in obese patients, as they require similar total doses but lower weight-based doses compared to non-obese patients 4

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In profound, life-threatening hypotension (systolic <70 mmHg or diastolic ≤40 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1, 5

Administration Route

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2
• If central access unavailable: peripheral IV or intraosseous administration can be used temporarily with strict monitoring 1
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1

Target Blood Pressure and Titration

Primary Target

• Mean arterial pressure (MAP) of 65 mmHg for most patients with septic shock 1, 3, 2
• Patients with chronic hypertension may require higher MAP targets, while younger normotensive patients may tolerate lower pressures 1

Monitoring Parameters

• 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, capillary refill 1, 3
• Goal: increase MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1, 3

Dose Escalation Strategy

When to Add Second Vasopressor

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy 1, 3

• Alternative: Add epinephrine 0.1-0.5 mcg/kg/min if vasopressin unavailable 1
• Do NOT increase vasopressin above 0.03-0.04 units/min; reserve higher doses for salvage therapy only 1

Dose Severity Classification

Based on validated cutoffs, norepinephrine doses can be categorized as: 6

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

Special Clinical Scenarios

Anaphylaxis (Refractory to Epinephrine)

• Use norepinephrine infusion at 0.05-0.1 mcg/kg/min for persistent hypotension after 10 minutes despite epinephrine boluses and volume resuscitation 7, 1
• Alternative preparation: 1 mg in 100 mL saline administered at 30-100 mL/h 1

Hepatorenal Syndrome

• Start at 0.5 mg/hour, increase every 4 hours by 0.5 mg/hour to maximum 3 mg/hour 1
• Goal: increase MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1

Pregnant Patients with Sepsis

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

Critical Pitfalls to Avoid

Do NOT Use These Alternatives First-Line

• Dopamine: Associated with higher mortality and more arrhythmias compared to norepinephrine 1, 2
• Phenylephrine: May raise blood pressure while worsening tissue perfusion 1
• Low-dose dopamine for "renal protection": No benefit, strongly discouraged 1

Extravasation Management

• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline intradermally at the site immediately 1, 2
• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 1

Drug Incompatibilities

• Do NOT mix with sodium bicarbonate or other alkaline solutions in the IV line, as norepinephrine is inactivated in alkaline solutions 1

Weaning Strategy

Once hemodynamic stability achieved: 3

• Decrease norepinephrine dose by 25% of current dose every 30 minutes as tolerated 2
• Continue fluid resuscitation as needed while weaning 3
• Prioritize weaning vasopressors when adequate tissue perfusion is restored 3

Pediatric Dosing Considerations

• Start at 0.1 mcg/kg/min, titrate to desired clinical effect 1, 3
• Typical range: 0.1-1.0 mcg/kg/min; maximum doses up to 5 mcg/kg/min may be necessary 1
• "Rule of 6" for simplified preparation: 0.6 × body weight (kg) = number of milligrams diluted to 100 mL saline; then 1 mL/hour delivers 0.1 mcg/kg/min 1