How to administer 4mg of norepinephrine (noradrenaline)?

How to Administer 4mg Norepinephrine

Add 4 mg of norepinephrine to 250 mL of D5W to create a standard concentration of 16 μg/mL, then infuse through a central venous line starting at 0.5 mg/h (8-12 mcg/min), titrating every 4 hours by 0.5 mg/h increments up to 3 mg/h maximum, targeting a mean arterial pressure of 65 mmHg. 1, 2

Standard Preparation Protocol

• The FDA-approved dilution is 4 mg norepinephrine in 1,000 mL of 5% dextrose solution, yielding 4 μg/mL. 2
• The more concentrated preparation recommended by multiple guidelines is 4 mg in 250 mL D5W, creating 16 μg/mL concentration, which is easier to manage in fluid-restricted patients. 1
• Never dilute in saline alone—dextrose-containing solutions protect against oxidation and loss of potency. 2
• Do not mix with sodium bicarbonate or alkaline solutions, as norepinephrine is inactivated in alkaline environments. 1

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 with strict monitoring protocols—recent studies show extravasation rates of 2.3-7.6% with peripheral administration, but no cases of tissue necrosis requiring surgery when proper protocols are followed. 3, 4, 5
• Intraosseous administration is acceptable in emergency situations when neither central nor peripheral access is immediately available, particularly in pediatric septic shock after 40-60 mL/kg fluid resuscitation. 1

Initial Dosing and Titration

• Start at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min for a 70 kg adult). 1, 2
• The FDA label recommends starting with 2-3 mL/min of the 4 μg/mL solution (8-12 mcg/min), then adjusting to maintain blood pressure. 2
• Titrate by 0.5 mg/h increments every 4 hours as needed, up to maximum 3 mg/h. 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 1

Target Blood Pressure

• Target mean arterial pressure (MAP) of 65 mmHg for most patients with septic shock. 1
• Patients with chronic hypertension may require higher MAP targets (no more than 40 mmHg below their baseline systolic pressure). 2
• Titrate to both MAP and tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill. 1

Critical Pre-Administration Requirements

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation. 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues—do not delay for complete volume repletion. 1
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline for fluid resuscitation. 1

Escalation Strategy for Refractory Hypotension

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy. 1
• Do not increase vasopressin above 0.04 units/min—reserve higher doses for salvage therapy only. 1
• Consider adding epinephrine 0.1-0.5 mcg/kg/min if vasopressin addition is insufficient. 1
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction is present. 1

Monitoring Requirements

• Place arterial catheter as soon as practical for continuous blood pressure monitoring. 1
• Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output, elevated lactate. 1
• Assess tissue perfusion markers continuously: lactate levels, mental status, urine output, capillary refill. 1

Management of Extravasation

• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site to prevent tissue necrosis. 1
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride. 1
• Change infusion site immediately if swelling or skin paleness is detected. 3

Critical Pitfalls to Avoid

• Never use hydroxyethyl starch (HES) for fluid resuscitation with norepinephrine—it increases mortality (51% vs 43%, p=0.03) and renal injury. 1
• Do not use dopamine as first-line agent—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 1
• Avoid phenylephrine as first-line therapy—it may raise blood pressure while worsening tissue perfusion. 1
• Do not use low-dose dopamine for renal protection—it has no benefit. 1
• Never administer norepinephrine without addressing hypovolemia first, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 1

Pediatric Dosing Considerations

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect with typical range 0.1-1.0 mcg/kg/min. 1
• Maximum doses up to 5 mcg/kg/min may be necessary in some children. 1
• Use "Rule of 6" for simplified preparation: 0.6 × body weight (kg) = mg of norepinephrine diluted to 100 mL saline, then 1 mL/h delivers 0.1 mcg/kg/min. 1