What is the recommended administration protocol for noradrenaline (norepinephrine) in an adult patient with no known allergies, experiencing hypotension due to shock?

Norepinephrine Administration in Shock

Preparation and Initial Dosing

Start norepinephrine at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion, targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2

Standard Concentration Preparation

• Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL 1
• Alternative concentration: 1 mg in 100 mL saline (10 mcg/mL) for specific scenarios 1

FDA-Approved Dosing Parameters

• Initial dose: 0.25-0.375 mL/min (8-12 mcg base/min) 3
• Average maintenance: 0.0625-0.125 mL/min (2-4 mcg base/min) 3
• Adjust flow rate to establish systolic BP of 80-100 mmHg sufficient to maintain circulation of vital organs 3

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus BEFORE or concurrent with norepinephrine initiation—never use vasopressors as a substitute for adequate volume resuscitation. 1, 2

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 2
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1
• Inadequate volume resuscitation causes severe organ hypoperfusion through excessive vasoconstriction despite "normal" blood pressure 1

Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 4

• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily 1
• Transition to central access as soon as practical for longer-term administration 1
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2, 4

Titration Protocol

Monitoring Frequency

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill 1, 2

Dose Escalation

• Increase dose by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h 1
• Target MAP ≥65 mmHg for most patients 1, 2, 4
• Consider higher MAP targets (70-75 mmHg) in patients with chronic hypertension 1, 2

Early Norepinephrine Consideration

Consider early norepinephrine administration (simultaneously with fluids) in patients with profound hypotension, particularly when diastolic BP ≤40 mmHg or diastolic shock index (HR/DBP) ≥3. 5

• Early administration increases shock control rates (76.1% vs 48.4% by 6 hours) and reduces fluid overload 6
• Norepinephrine rapidly increases and better stabilizes arterial pressure compared to fluids alone 5
• In septic shock specifically, norepinephrine improves renal blood flow despite typically causing renal vasoconstriction in other contexts 7

Escalation Strategy for Refractory Hypotension

Second-Line Vasopressor

Add vasopressin 0.03 units/min when norepinephrine reaches 0.1-0.25 mcg/kg/min and hypotension persists. 1, 2, 4

• Vasopressin should never be used as initial monotherapy—only as adjunct to norepinephrine 2, 4
• Do not increase vasopressin above 0.03-0.04 units/min; reserve higher doses for salvage therapy only 4
• Vasopressin spares conventional vasopressor use and improves renal function measures 8

Third-Line Options

• Add epinephrine 0.1-0.5 mcg/kg/min if norepinephrine plus vasopressin fail to achieve target MAP 1, 2
• Add dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP and vasopressors, particularly with myocardial dysfunction 1, 2, 4

Extravasation Management

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

• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 1
• Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate 1

Critical Pitfalls to Avoid

• Never use dopamine as first-line therapy—associated with higher mortality and more arrhythmias compared to norepinephrine 2, 4
• Never use low-dose dopamine for "renal protection"—provides no benefit and is strongly discouraged 1, 2, 4
• Avoid phenylephrine as first-line therapy—may raise blood pressure while worsening tissue perfusion 2, 4
• Do not mix with sodium bicarbonate or alkaline solutions—adrenergic agents are inactivated in alkaline solutions 1, 3
• Reduce infusion rate gradually when discontinuing—sudden cessation may result in marked hypotension 3

Special Considerations

Anaphylaxis

• Use norepinephrine only in cases not responding to epinephrine injections and volume resuscitation 1
• Infusion rate: 0.05-0.1 mcg/kg/min for persistent hypotension after 10 minutes despite epinephrine boluses 1

Pregnancy

• Start at 0.02 mcg/kg/min with target MAP 65 mmHg 2
• Consider more restrictive initial boluses (1-2L) due to lower colloid oncotic pressure and higher pulmonary edema risk 2