How do I initiate a norepinephrine infusion for a patient with refractory hypotension (e.g., septic or cardiogenic shock), including line placement, preparation, dosing (0.05–0.1 µg/kg/min titrated to mean arterial pressure ≥65 mmHg), and monitoring?

How to Start a Norepinephrine Drip

Start norepinephrine at 0.02-0.05 mcg/kg/min (approximately 0.5 mg/h or 8-12 mcg/min in a 70 kg adult) via continuous IV infusion, preferably through central venous access, while simultaneously ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus, targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2, 3

Critical Pre-Administration Requirements

Address hypovolemia FIRST before starting norepinephrine by administering a minimum 30 mL/kg crystalloid bolus (approximately 2 liters in a 70 kg adult) within the first 3 hours, either before or concurrent with vasopressor initiation. 1, 3 Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure readings. 2

In cases of profound, life-threatening hypotension (systolic BP <70 mmHg or diastolic BP ≤40 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion. 2, 4, 5 Duration and depth of hypotension strongly worsen outcomes in septic shock. 5

Line Placement and Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 3 However, starting norepinephrine via a large peripheral vein in a shocked patient is safe until central access is established. 1 This is particularly important because the strongest barrier to norepinephrine administration is lack of central access, and delaying treatment while obtaining central access may prolong harmful hypotension. 6

Place an arterial catheter as soon as practical for continuous blood pressure monitoring. 2, 3, 4 Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 1, 2

Preparation and Concentration

Standard adult concentration: Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 mcg/mL. 2 Alternative concentration: Add 1 mg of norepinephrine to 100 mL of saline to create a 10 mcg/mL solution. 2

For pediatric patients, use the "Rule of 6": multiply 0.6 × body weight (kg) to get the number of milligrams, then dilute to 100 mL of saline; then 1 mL/h delivers 0.1 mcg/kg/min. 2

Initial Dosing

Adults: Start at 0.02-0.05 mcg/kg/min (approximately 0.5 mg/h or 8-12 mcg/min in a 70 kg adult). 1, 2, 3 Alternative starting range: 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult). 2, 4

Pediatric patients: Start at 0.1 mcg/kg/min, titrating to desired clinical effect, with a typical range of 0.1-1.0 mcg/kg/min. 1, 2 Maximum doses up to 5 mcg/kg/min may be necessary in some children. 2

Pregnant patients with sepsis: Start at 0.02 mcg/kg/min with more restrictive initial fluid boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk. 1

Target Blood Pressure and Titration

Target MAP of 65 mmHg for most patients with septic shock. 1, 2, 3 This represents the minimum threshold for adequate organ perfusion. 3

Titrate norepinephrine every 4 hours by 0.5 mg/h increments to a maximum of 3 mg/h. 2 Monitor not only MAP but also markers of tissue perfusion: lactate clearance, urine output >0.5 mL/kg/h, mental status, capillary refill ≤2 seconds, and skin perfusion. 1, 2, 3

Patients with chronic hypertension may require higher MAP targets of 70-75 mmHg to reduce the need for renal replacement therapy. 2, 3 However, targeting MAP of 85 mmHg does not improve renal function or mortality in most patients. 3

Monitoring Parameters

• Continuous arterial blood pressure via arterial catheter 2, 3
• Heart rate and rhythm continuously 1, 2
• Urine output hourly (target ≥0.5 mL/kg/h) 1, 2, 3
• Lactate levels every 2-4 hours during early resuscitation 2, 3
• Mental status and peripheral perfusion (capillary refill, extremity temperature) 1, 2
• Central venous pressure/oxygen saturation when available 1
• Signs of excessive vasoconstriction: cold extremities, decreased urine output, digital ischemia, rising lactate 2, 3

Escalation Strategy for Refractory Hypotension

When norepinephrine reaches 0.1-0.25 mcg/kg/min and hypotension persists:

1. Add vasopressin 0.03 units/min as second-line therapy rather than continuing to escalate norepinephrine alone. 1, 2, 3 Do not exceed 0.03-0.04 units/min for routine use; higher doses are reserved for salvage therapy only. 2, 3

2. Alternative: Add epinephrine 0.1-0.5 mcg/kg/min if vasopressin is unavailable. 2, 3

3. For persistent hypoperfusion despite adequate MAP and vasopressors: Add dobutamine 2.5-20 mcg/kg/min if there is evidence of myocardial dysfunction. 1, 2, 3

4. For refractory shock: Consider hydrocortisone 50 mg IV every 6 hours (or 200 mg/day continuous infusion) if shock persists despite high-dose vasopressors. 1, 2, 3

Management of Extravasation

If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of 0.9% sodium chloride intradermally at the site as soon as possible to prevent tissue necrosis. 2, 4 Pediatric dose: 0.1-0.2 mg/kg up to 10 mg. 2

Critical Pitfalls to Avoid

• Never delay norepinephrine while pursuing aggressive fluid resuscitation alone in severe hypotension (systolic <70 mmHg or diastolic ≤40 mmHg). 2, 5 Early administration of norepinephrine is beneficial to restore organ perfusion and avoid fluid overload. 7, 5

• Do not use dopamine as first-line therapy. It is associated with 11% higher absolute mortality and significantly more arrhythmias (53% risk reduction for supraventricular arrhythmias and 65% risk reduction for ventricular arrhythmias with norepinephrine vs. dopamine). 3

• Do not use low-dose dopamine for "renal protection"—it provides no benefit and is strongly discouraged. 2, 3

• Avoid phenylephrine as first-line therapy. It may raise blood pressure numbers while actually worsening tissue perfusion through pure alpha-agonism without cardiac support. 2, 3

• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions. 2, 4

• Avoid excessive fluid resuscitation. Norepinephrine increases mean systemic filling pressure and improves the fluid-induced increase in mean systemic filling pressure, potentially reducing the need for large fluid volumes. 5

Special Clinical Scenarios

Hepatorenal syndrome: Start norepinephrine at 0.5 mg/h, increasing every 4 hours by 0.5 mg/h to a maximum of 3 mg/h, with a goal to increase MAP by ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours. 2

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. 2, 3

Pediatric septic shock: Children commonly require 40-60 mL/kg in the first hour of fluid resuscitation. 1 Start norepinephrine at 0.1 mcg/kg/min for cold shock (poor perfusion with vasoconstriction). 1

Intraosseous administration: All intravenous medications including norepinephrine can be administered intraosseously with onset of action and drug levels comparable to venous administration. 3 Follow each medication with a saline flush to promote entry into central circulation. 3