What is the initial dose and management strategy for a patient on a norepinephrine (vasopressor) drip?

Norepinephrine Drip: Initial Dosing and Management

Initial Dose and Preparation

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 (MAP) of 65 mmHg. 1

Standard 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 of norepinephrine to 100 mL of saline to create a 10 mcg/mL solution 1

Pediatric Dosing

• Start at 0.1 mcg/kg/min and titrate to 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
• Use the "Rule of 6": multiply 0.6 × body weight (kg) = number of milligrams, then dilute to 100 mL of saline; 1 mL/h delivers 0.1 mcg/kg/min 1

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation—vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 1, 2

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In profound, life-threatening hypotension (systolic BP <70-80 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1, 3
• Early norepinephrine administration (within 93 minutes vs 192 minutes) significantly increases shock control by 6 hours (76.1% vs 48.4%, p<0.001) and reduces cardiogenic pulmonary edema (14.4% vs 27.7%, p=0.004) 4

Administration Route

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

• If central access is unavailable or delayed, peripheral IV administration can be used temporarily at low doses (<0.2 mcg/kg/min) for less than 24 hours using large-bore (18-20 gauge) catheters in the antecubital fossa 1, 5
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2

Titration Protocol

Target MAP of 65 mmHg for most patients, monitoring blood pressure and heart rate every 5-15 minutes during initial titration. 1, 2

• Increase dose by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h 1
• Titrate to perfusion markers beyond just MAP: capillary refill, urine output >50 mL/h, lactate clearance, and mental status 1
• Patients with chronic hypertension may require higher MAP targets, while younger normotensive patients may tolerate lower pressures 1

Dose Severity Classification

• Low dose: <0.2 mcg/kg/min (hospital mortality 14.0%) 6
• Intermediate dose: 0.2-0.4 mcg/kg/min (hospital mortality 26.4%) 6
• High dose: >0.4 mcg/kg/min (hospital mortality 40.2%) 6

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, 2

• Alternative: Add epinephrine 0.1-0.5 mcg/kg/min if vasopressin is unavailable 1, 2
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min, particularly with myocardial dysfunction 1, 2
• Do NOT increase vasopressin above 0.03-0.04 units/min—reserve higher doses for salvage therapy only 2

Monitoring and Safety

Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 1

• Monitor for potential side effects including hypertension, arrhythmias, and tissue ischemia 1
• Check IV site every 2 hours for signs of infiltration 5
• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline at the site immediately to prevent tissue necrosis 1
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 1

Critical Pitfalls to Avoid

Do NOT use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 1, 2

• Do NOT use low-dose dopamine for renal protection—it has no benefit and is strongly discouraged 1, 2
• Do NOT use phenylephrine as first-line therapy—it may raise blood pressure while worsening tissue perfusion through excessive vasoconstriction 2
• Do NOT mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line—adrenergic agents are inactivated in alkaline solutions 1
• Do NOT delay norepinephrine initiation in profound hypotension (diastolic BP ≤40 mmHg or diastolic shock index ≥3) waiting to complete entire fluid resuscitation 3

Special Clinical Scenarios

Anaphylaxis

• Use norepinephrine only in cases not responding to epinephrine injections and volume resuscitation 1
• Add norepinephrine infusion (0.05-0.1 mcg/kg/min) for persistent hypotension after 10 minutes despite epinephrine boluses 7

Hepatorenal Syndrome

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

Pregnancy

• 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