What is the role of intravenous (IV) noradrenaline (norepinephrine) in managing hypotension?

Norepinephrine is the First-Line Vasopressor for Hypotension in Septic Shock

Norepinephrine should be initiated as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg when hypotension persists after adequate fluid resuscitation (minimum 30 mL/kg crystalloid bolus). 1

Initial Resuscitation Strategy

Fluid Resuscitation First

• Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1, 2
• Use crystalloids (normal saline or balanced crystalloids like lactated Ringer's) as first-line fluid 1
• Avoid hydroxyethyl starch (HES) formulations entirely due to increased mortality (51% vs 43%, p=0.03) and renal injury 1, 2

Exception: Profound Life-Threatening Hypotension

• In severe hypotension (systolic BP <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues simultaneously, rather than waiting for complete volume repletion 2, 3
• Consider early norepinephrine when diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3, indicating severely depressed arterial tone 3

Norepinephrine Administration Protocol

Starting Dose and Titration

• Initiate at 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult or 0.5 mg/h) 1, 2
• Titrate every 4 hours by 0.5 mg/h increments to maximum 3 mg/h 2
• Target mean arterial pressure (MAP) of 65 mmHg initially 1, 2

Route of Administration

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2
• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring 2, 4
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 2

Monitoring Parameters

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1, 2
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill, skin color 1, 2
• Titrate to both MAP target AND markers of adequate tissue perfusion, not MAP alone 1, 2

Escalation Strategy for Refractory Hypotension

Second-Line Vasopressor

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min (do not exceed this dose) 1, 2
• Vasopressin should be added to norepinephrine to either raise MAP to target or decrease norepinephrine dose, but should not be used as the initial vasopressor 1

Third-Line Options

• Add epinephrine 0.1-0.5 mcg/kg/min when additional agent is needed to maintain adequate blood pressure 1, 2
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction is present (elevated cardiac filling pressures and low cardiac output) 1, 2

Critical Pitfalls to Avoid

Do NOT Use These as First-Line

• Dopamine is NOT recommended except in highly selected circumstances (absolute bradycardia with low risk of tachyarrhythmias), as it causes more tachycardia, arrhythmias, and higher mortality compared to norepinephrine 1, 2
• Phenylephrine should NOT be used as first-line therapy—reserve only for salvage therapy or when norepinephrine causes serious arrhythmias 1, 2
• Low-dose dopamine has no benefit for renal protection and should not be used 2

Extravasation Management

• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately to prevent tissue necrosis 1, 2
• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 2

Avoid Inadequate Volume Resuscitation

• Never start norepinephrine in a hypovolemic patient without concurrent fluid resuscitation, as vasoconstriction in hypovolemia causes severe organ hypoperfusion despite "normal" blood pressure 2, 3

Special Clinical Contexts

Timing Considerations

• Mortality is lowest when vasopressors are delayed by 1 hour and infused from hours 1-6 following onset of shock in patients receiving adequate fluid resuscitation 1
• However, in profound hypotension with low diastolic pressure, early administration (within first hour) may be beneficial to prevent prolonged hypotension 3

Alternative in Resource-Limited Settings

• In low- and middle-income countries where norepinephrine availability is limited, adrenaline (epinephrine) infusions are acceptable as the inotrope of choice, given equivalent efficacy to norepinephrine in septic shock 1

Pediatric Dosing

• Start at 0.1 mcg/kg/min, titrate to desired clinical effect 2
• Typical range: 0.1-1.0 mcg/kg/min; maximum doses up to 5 mcg/kg/min may be necessary 2

Why Norepinephrine is Superior

• More efficacious than dopamine for reversing hypotension in septic shock 1
• Rapidly increases and better stabilizes arterial pressure compared to fluids alone 3
• Increases mean systemic filling pressure by binding venous adrenergic receptors, transforming unstressed blood volume into stressed blood volume 3
• May improve end-organ perfusion and reduce fluid overload when started early 3
• Strong recommendation (1B) with moderate quality evidence from Surviving Sepsis Campaign guidelines 1