What is the recommended use of noradrenaline (norepinephrine) in a critically ill adult patient with severe hypotension or septic shock, particularly those with a history of cardiovascular disease, diabetes, or immunocompromised status?

Norepinephrine in Critically Ill Adults with Severe Hypotension or Septic Shock

Norepinephrine is the mandatory first-line vasopressor for critically ill adults with severe hypotension or septic shock, regardless of cardiovascular disease, diabetes, or immunocompromised status. 1

Initial Administration Protocol

Start norepinephrine at 0.1–0.5 mcg/kg/min (approximately 7–35 mcg/min in a 70-kg patient) as soon as hypotension persists after initiating fluid resuscitation—do not delay for complete fluid administration if life-threatening hypotension (systolic BP <80 mmHg) is present. 2, 3

Critical Pre-Administration Requirements

• Administer a minimum of 30 mL/kg crystalloid fluid resuscitation in the first 3 hours, concurrent with vasopressor initiation if needed 1
• Establish central venous access whenever possible to minimize tissue necrosis risk from extravasation 2, 4
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical—this is mandatory for all patients requiring vasopressors 1, 2

Target Blood Pressure

• Target mean arterial pressure (MAP) ≥65 mmHg in most patients 1, 2
• Consider higher MAP targets of 70-75 mmHg in patients with chronic hypertension 1, 2

Why Norepinephrine Over Other Agents

Norepinephrine provides an 11% absolute mortality reduction compared to dopamine and causes significantly fewer arrhythmias. 1 The Society of Critical Care Medicine gives it a Grade 1B (strong) recommendation based on superior survival data. 1

• Norepinephrine rapidly increases and better stabilizes arterial pressure compared to fluid resuscitation alone 3, 5
• It transforms unstressed blood volume into stressed blood volume by binding venous adrenergic receptors, increasing mean systemic filling pressure 3
• Early administration reduces fluid overload and improves microcirculation 3, 5
• Profound and prolonged hypotension independently increases mortality—relying solely on fluids may unduly prolong organ hypoperfusion 3, 5

Special Populations: Cardiovascular Disease, Diabetes, Immunocompromised

Norepinephrine remains the first-line agent in patients with cardiovascular disease, though it requires cautious monitoring. 1

• In patients with congestive heart failure, norepinephrine may increase myocardial oxygen requirements but this does not contraindicate its use 1
• Consider adding dobutamine (2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP, particularly when myocardial dysfunction is evident 1, 2
• In sepsis specifically, norepinephrine improves renal blood flow and urine output despite typically causing renal vasoconstriction in other contexts 1
• Continue chronic beta-blockers unless acute hemodynamic decompensation or cardiogenic shock is present 1

No specific contraindications exist for diabetes or immunocompromised status—standard norepinephrine protocols apply. 4

Escalation Strategy for Refractory Hypotension

Add vasopressin at 0.03 units/minute when norepinephrine requirements reach 0.25-0.50 mcg/kg/min or remain elevated despite adequate dosing. 1, 2

Vasopressin Addition Protocol

• Start vasopressin at 0.01 units/minute and titrate by 0.005 units/minute every 10-15 minutes to maximum 0.03 units/minute 1
• Never use vasopressin as monotherapy—it must be added to norepinephrine, not used alone 1, 6
• Do not exceed 0.03-0.04 units/minute except as salvage therapy—higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit 1, 6, 2

Third-Line Options

• Add epinephrine (0.05-2 mcg/kg/min) if norepinephrine plus vasopressin fail to achieve target MAP 1
• Add dobutamine (up to 20 mcg/kg/min) for persistent hypoperfusion despite adequate MAP and vasopressor therapy, particularly with myocardial dysfunction 1, 6
• Consider low-dose corticosteroids (hydrocortisone 200 mg/day IV) for refractory shock 1

Critical Agents to Avoid

Never use dopamine as first-line therapy—it is associated with higher mortality and significantly more arrhythmias compared to norepinephrine. 1, 2

• Dopamine should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1
• Never use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit 1, 6, 2
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is documented high with persistent hypotension, or as salvage therapy 1, 2
• Phenylephrine may raise blood pressure numbers while actually worsening tissue perfusion through excessive vasoconstriction 1

Monitoring Beyond Blood Pressure

Assess tissue perfusion markers beyond MAP alone—blood pressure numbers do not guarantee adequate organ perfusion. 1, 2

• Monitor lactate clearance, urine output ≥0.5 mL/kg/hr, mental status, capillary refill, and skin temperature 1, 2
• Watch for signs of excessive vasoconstriction: cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 1, 2
• Perform continuous cardiac monitoring in patients with underlying heart disease or arrhythmias 4

Critical Safety Considerations

Extravasation Management

• Check infusion site frequently for free flow and monitor for signs of extravasation 4
• If extravasation occurs, immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the site to prevent tissue necrosis 2, 4
• Sympathetic blockade with phentolamine causes immediate hyperemic changes if infiltrated within 12 hours 4

Drug Interactions and Contraindications

• Do not mix norepinephrine with sodium bicarbonate or alkaline solutions—adrenergic agents are inactivated in alkaline solutions 2
• Use cautiously in patients taking MAO inhibitors, tricyclic antidepressants, or other sympathomimetic agents due to additive effects 4
• Cyclopropane and halothane anesthetics increase cardiac autonomic irritability 4
• Norepinephrine contains sodium metabisulfite, which may cause allergic reactions in susceptible individuals, particularly asthmatics 4

Discontinuation Protocol

• Never abruptly stop norepinephrine—sudden cessation causes marked hypotension 4
• Gradually reduce infusion rate while expanding blood volume with intravenous fluids 4
• Ensure MAP ≥65 mmHg is sustained for at least 2-4 hours before weaning 6
• When weaning combination therapy, reduce norepinephrine first by 0.01-0.02 mcg/kg/min every 15-30 minutes while maintaining vasopressin at 0.03 units/min 6
• Withdraw vasopressin only after weaning norepinephrine to avoid hemodynamic instability 6

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation waiting to complete entire fluid resuscitation if life-threatening hypotension is present 6, 3
• Avoid hypovolemia before initiating norepinephrine—administration to hypovolemic patients causes severe peripheral vasoconstriction, decreased renal perfusion, tissue hypoxia, and lactic acidosis despite "normal" blood pressure 4
• Do not use norepinephrine in patients with mesenteric or peripheral vascular thrombosis—this increases ischemia and extends infarction area 4
• Monitor for gangrene of extremities in patients with occlusive vascular disease or those receiving prolonged/high-dose infusions 4