Norepinephrine 16mg in 250cc PNSS: Concentration and Titration
Concentration Calculation
The concentration is 64 mcg/mL (16mg ÷ 250mL = 0.064 mg/mL = 64 mcg/mL). 1, 2
However, this is NOT the standard concentration recommended by guidelines. The standard adult concentration is 16 mcg/mL (4mg in 250mL D5W), not 64 mcg/mL. 1, 2, 3 Your preparation is 4 times more concentrated than standard, which increases the risk of dosing errors and makes titration less precise.
Initial Dosing
Start at 8-12 mcg/min (0.1-0.5 mcg/kg/min in a 70kg adult) via central venous access, targeting a mean arterial pressure of 65 mmHg. 1, 2, 3
With your 64 mcg/mL concentration:
- Initial rate: 7.5-11 mL/h (delivers 8-12 mcg/min)
- This translates to approximately 0.5-0.75 mg/h using your preparation 1
Critical Pre-Administration Requirements
Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation. 1, 2 Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline. 1 In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion. 1
Administration Route
Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 4, 2, 3 If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring, but transition to central access as soon as practical. 5, 1
Titration Protocol
Monitor blood pressure every 5-15 minutes during initial titration. 1, 2 Titrate to achieve:
- Target MAP ≥65 mmHg for most patients 5, 1, 4, 2
- In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below pre-existing systolic pressure 3
- Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill 1, 2
Maintenance dose typically 2-4 mcg/min (approximately 2-4 mL/h with your concentration). 2, 3
Escalation Strategy for Refractory Hypotension
When norepinephrine reaches 0.25 mcg/kg/min (approximately 17.5 mcg/min or 16 mL/h with your concentration) and hypotension persists:
- Add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 5, 1, 2
- If persistent hypoperfusion despite adequate vasopressors, add dobutamine 2.5-20 mcg/kg/min for myocardial dysfunction 5, 1
- Do NOT add dopamine - it is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 4, 6
- Avoid phenylephrine as first-line - it may raise blood pressure while worsening tissue perfusion 1
Monitoring Requirements
- Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 4
- Monitor for arrhythmias (especially tachyarrhythmias, which can occur even at low doses) 2, 7, 6
- Assess for excessive vasoconstriction: cold extremities, decreased urine output 1
- Monitor lactate levels (norepinephrine may cause transient lactate increase, which is not clinically relevant) 1
Extravasation Management
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, 4, 2
Critical Pitfalls to Avoid
- Never use norepinephrine without adequate volume resuscitation - vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1
- Do not mix with sodium bicarbonate or alkaline solutions - adrenergic agents are inactivated in alkaline solutions 1
- Avoid doses >0.5 mcg/kg/min (35 mcg/min in 70kg adult) - mortality risk increases significantly above this threshold 8
- Monitor closely for arrhythmias - DA causes significantly more arrhythmias (19.4%) than NE (3.4%) in septic shock 6
Weaning Protocol
Decrease norepinephrine dose by 25% of current dose every 30 minutes as tolerated when hemodynamic stability is achieved. 4