What is the up and down titration protocol for norepinephrine in a critically ill adult patient?

Norepinephrine Titration Protocol

Up-Titration (Escalation)

Increase norepinephrine by 25% of the current dose every 5-15 minutes until target mean arterial pressure (MAP) of 65 mmHg is achieved, monitoring blood pressure continuously during initial titration. 1

Initial Starting Dose

• Begin at 8-12 mcg/min (0.5-0.75 mg/h with standard 16 mcg/mL concentration) via central venous access 1
• Alternative starting range: 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult) 1, 2

Escalation Increments

• Increase by 0.5 mg/h every 4 hours as needed for hepatorenal syndrome or similar contexts 2
• Monitor blood pressure every 5-15 minutes during active titration 1, 2
• Assess tissue perfusion markers including lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1, 2

Maximum Dosing Thresholds

• When norepinephrine reaches 0.25 mcg/kg/min (approximately 17.5 mcg/min in 70 kg patient), add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 1, 3
• Maximum recommended dose: 3 mg/h (50 mcg/min) 2
• Doses above 15 mcg/min indicate severe shock and warrant addition of second vasopressor 3

Critical Pre-Escalation Requirements

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1, 3
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine immediately while fluid resuscitation continues 1

Down-Titration (Weaning)

Decrease norepinephrine dose by 25% of current dose every 30 minutes as tolerated when hemodynamic stability is achieved. 1

Weaning Criteria

• Sustained MAP ≥65 mmHg for at least 2-4 hours 1
• Improving tissue perfusion markers: declining lactate, adequate urine output, normal mental status 1
• Resolution of underlying shock etiology 4

Weaning Protocol

• Reduce dose by 25% every 30 minutes 1
• Monitor blood pressure every 15 minutes during active weaning 1
• If MAP drops below 60 mmHg, return to previous dose and reassess in 1-2 hours 1

Monitoring During Weaning

• Place arterial catheter for continuous blood pressure monitoring 1, 3
• Watch for signs of inadequate perfusion: rising lactate, decreased urine output, altered mental status 1
• Assess for rebound hypotension after each dose reduction 1

Critical Monitoring Requirements

Continuous Monitoring

• Arterial catheter placement as soon as practical for continuous blood pressure monitoring 1, 3
• Monitor for arrhythmias, especially tachyarrhythmias, which can occur even at low doses 1
• Assess for excessive vasoconstriction: cold extremities, decreased urine output, rising lactate 1

Extravasation Management

• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline intradermally at the site to prevent tissue necrosis 1, 2
• Central venous access strongly preferred to minimize this risk 1, 2

Common Pitfalls to Avoid

• Never use norepinephrine without adequate volume resuscitation—vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1, 2
• Do not mix with sodium bicarbonate or alkaline solutions—adrenergic agents are inactivated in alkaline solutions 1, 2
• Do not escalate norepinephrine beyond 0.25 mcg/kg/min without adding vasopressin—higher doses alone are associated with increased mortality 1, 3
• Avoid abrupt discontinuation—gradual weaning prevents rebound hypotension 1