What is the initial drip rate for a norepinephrine (vasopressor) infusion in a critically ill patient with hypotension?

Norepinephrine Initial Drip Rate for Critically Ill Hypotensive Patients

Start norepinephrine at 0.1-0.5 mcg/kg/min (equivalent to 8-12 mcg/min or 2-3 mL/hour of standard concentration in a 70 kg adult), targeting a mean arterial pressure of 65 mmHg, while simultaneously administering at least 30 mL/kg crystalloid bolus. 1, 2, 3

Standard Preparation and Concentration

• Add 4 mg of norepinephrine to 250 mL of 5% dextrose to create a concentration of 16 mcg/mL - this is the FDA-approved standard dilution that protects against oxidation 1, 2
• Alternative concentration: 1 mg in 100 mL saline (10 mcg/mL) can be used in specific scenarios requiring less fluid volume 2, 4
• Do not use saline solution alone as the primary diluent - dextrose-containing solutions are required to prevent significant potency loss 1

Initial Dosing Protocol

• Begin at 0.1-0.5 mcg/kg/min, which translates to 7-35 mcg/min in a 70 kg adult 1, 2, 4
• Using standard concentration (16 mcg/mL at 60 mL/hour): this delivers approximately 2-3 mL/min or 8-12 mcg/min 1, 2
• In profound, life-threatening hypotension (systolic <70 mmHg or diastolic ≤40 mmHg), start norepinephrine immediately as an emergency measure while continuing fluid resuscitation rather than waiting for complete volume repletion 3, 5, 2

Critical Pre-Administration Requirement

• Administer minimum 30 mL/kg crystalloid bolus BEFORE or simultaneously with norepinephrine initiation - this is a strong recommendation with moderate quality evidence 3, 2, 6
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 6
• In severe shock, do not delay norepinephrine while attempting to complete full fluid resuscitation, as prolonged hypotension worsens outcomes 5, 3

Administration Route

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 3, 2, 4
• If central access unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring 3, 2
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 2, 6

Target Blood Pressure and Titration

• Initial target: MAP ≥65 mmHg for most patients with septic shock 3, 2, 6, 4
• In previously hypertensive patients, consider higher targets (70-75 mmHg) but do not elevate more than 40 mmHg below pre-existing systolic pressure 3, 1, 6
• Monitor blood pressure every 5-15 minutes during initial titration 2, 4
• Titrate dose every 4 hours as needed, increasing by 0.5 mg/hour increments 2, 4

Maintenance and Maximum Dosing

• Typical maintenance range: 0.5-1 mL/min (2-4 mcg base/min) of standard dilution 1
• Common dosing range in septic shock: 0.1-2 mcg/kg/min 2
• Maximum doses up to 3 mg/hour may be necessary in refractory cases, though occult hypovolemia should always be suspected at high doses 1, 2, 4

Escalation Strategy for Refractory Hypotension

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min rather than continuing to escalate norepinephrine alone 3, 2, 6, 4
• Do not increase vasopressin above 0.03-0.04 units/min except as salvage therapy 2, 6
• Consider adding epinephrine 0.1-0.5 mcg/kg/min if vasopressin plus norepinephrine insufficient 3, 2
• Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with myocardial dysfunction 2, 6

Monitoring Tissue Perfusion

• Supplement blood pressure targets with assessment of: lactate clearance, urine output >50 mL/hour, mental status, capillary refill time, and skin perfusion 3, 2, 4
• Target normalization of capillary refill and age-appropriate heart rate in septic shock 2

Management of Extravasation

• If extravasation occurs, immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline at the site to prevent tissue necrosis 3, 2, 4
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 2

Critical Pitfalls to Avoid

• Never use dopamine as first-line agent - it is associated with higher mortality and more arrhythmias compared to norepinephrine 3, 2, 6
• Do not use phenylephrine as first-line therapy - it may raise blood pressure while worsening tissue perfusion through excessive vasoconstriction 2, 6
• Do not mix with sodium bicarbonate or other alkaline solutions in the IV line - adrenergic agents are inactivated in alkaline solutions 3, 4
• Avoid relying solely on fluids to restore blood pressure in profound hypotension, as this unduly prolongs hypotension and organ hypoperfusion 5
• Do not use low-dose dopamine for "renal protection" - it provides no benefit 2, 6

Special Populations

Pediatric Dosing

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect 2, 4
• Typical range: 0.1-1.0 mcg/kg/min, with maximum doses up to 5 mcg/kg/min in exceptional circumstances 2
• "Rule of 6" for simplified preparation: 0.6 × body weight (kg) = mg to dilute to 100 mL saline; then 1 mL/hour delivers 0.1 mcg/kg/min 2

Pregnant Patients

• Start at 0.02 mcg/kg/min with target MAP of 65 mmHg 6
• Consider more restrictive initial fluid boluses (1-2 L) due to lower colloid oncotic pressure and higher pulmonary edema risk 6