What are the guidelines for noradrenaline (norepinephrine) infusion in patients with hypotension?

Norepinephrine Infusion Guidelines

Start norepinephrine at 8-12 mcg/min (0.1-0.5 mcg/kg/min) via central venous access, targeting a mean arterial pressure of 65 mmHg, while simultaneously administering at least 30 mL/kg crystalloid bolus. 1, 2

Preparation and Concentration

• Standard concentration: Add 4 mg norepinephrine to 250 mL D5W to yield 16 mcg/mL 1
• Alternative concentration: 1 mg in 100 mL saline (10 mcg/mL) for specific scenarios 1
• Pediatric "Rule of 6": 0.6 × body weight (kg) = mg diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 1

Initial Dosing

• FDA-approved starting dose: 8-12 mcg/min (0.25-0.375 mL/min of standard concentration) 2
• Weight-based dosing: 0.1-0.5 mcg/kg/min (7-35 mcg/min in 70 kg adult) 1, 3
• Hepatorenal syndrome: Start at 0.5 mg/h, increase by 0.5 mg/h every 4 hours to maximum 3 mg/h 1, 4
• Pediatric dosing: Start at 0.1 mcg/kg/min, titrate to effect; typical range 0.1-1.0 mcg/kg/min, maximum up to 5 mcg/kg/min 1

Administration Route

• Central venous access is strongly preferred to prevent tissue necrosis from extravasation 1, 3, 2
• Peripheral IV or intraosseous access can be used temporarily if central access is unavailable or delayed 1
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1

Target Blood Pressure and Monitoring

• Primary target: Mean arterial pressure (MAP) ≥65 mmHg 1, 3, 4
• Individualize MAP target: Patients with chronic hypertension may require higher targets (e.g., 75-85 mmHg), while younger normotensive patients may tolerate lower pressures 1
• Monitor blood pressure every 5-15 minutes during initial titration 1, 4
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill, skin temperature 1, 4

Critical Pre-Administration Requirement

Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1, 5

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine as emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1
• Never use hydroxyethyl starch (HES) - strongly contraindicated due to increased mortality (51% vs 43%, p=0.03) 1

Titration Strategy

• Maintenance dose: 2-4 mcg/min (0.0625-0.125 mL/min) 2
• Increase dose by 0.5 mg/h every 4 hours as needed in hepatorenal syndrome 1, 4
• Typical range for septic shock: 0.1-2 mcg/kg/min 1
• Obese patients require lower weight-based doses but similar total doses compared to non-obese patients 6

Escalation for Refractory Hypotension

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

• Add vasopressin 0.03-0.04 units/min (do not exceed this dose; higher doses reserved for salvage therapy only) 1, 4, 7
• Consider adding epinephrine 0.1-0.5 mcg/kg/min as alternative second agent 1
• Add dobutamine up to 20 mcg/kg/min if persistent hypoperfusion exists despite adequate vasopressors, particularly with myocardial dysfunction 1
• Consider hydrocortisone 50 mg IV every 6 hours (or 200 mg continuous infusion) for refractory shock requiring high-dose vasopressors 4

Extravasation Management

If extravasation occurs, infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the site immediately to prevent tissue necrosis 1, 3, 2

• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL 0.9% sodium chloride 1

Weaning Protocol

• Reduce gradually by 25% of current dose every 30 minutes as tolerated to prevent rebound hypotension 3
• Sudden cessation may result in marked hypotension 2

Critical Pitfalls to Avoid

• Never use dopamine as first-line agent - associated with higher mortality and more arrhythmias compared to norepinephrine 1, 3
• Do not use low-dose dopamine for renal protection - no benefit and strongly discouraged 1
• Avoid phenylephrine as first-line therapy - may raise blood pressure while worsening tissue perfusion 1
• Do not mix with sodium bicarbonate or alkaline solutions - norepinephrine is inactivated in alkaline solutions 1
• Avoid inadequate volume resuscitation - vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1
• Higher doses >10 mcg/min associated with increased mortality - consider adding second vasopressor rather than escalating further 3

Special Populations

• Pregnant patients: Start at 0.02 mcg/kg/min, target MAP 65 mmHg; consider more restrictive initial boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk 1
• Patients on beta-blockers: Norepinephrine more effective than dopamine for hypotension; consider glucagon 1-5 mg IV over 5 min followed by infusion (5-15 mg/min) for refractory cardiovascular effects 8, 1
• Anaphylaxis: Use only in cases not responding to epinephrine injections and volume resuscitation 1

Monitoring for Adverse Effects

• Watch for arrhythmias, particularly at higher doses 3, 2
• Monitor for excessive vasoconstriction: cold extremities, decreased urine output, worsening lactate 1
• Assess for increased myocardial oxygen consumption in patients with ischemic heart disease 3
• While norepinephrine typically causes renal vasoconstriction, it may actually improve renal blood flow and urine output in septic shock 3