What is the drug of choice in septic shock?

Drug of Choice in Septic Shock

Norepinephrine is the first-choice vasopressor for septic shock, with a strong recommendation (Grade 1B) from the Surviving Sepsis Campaign guidelines. 1

Initial Management Algorithm

Fluid Resuscitation First

• Administer at least 30 mL/kg of crystalloids in the first 3 hours before or concurrent with vasopressor initiation 1, 2
• Crystalloids are the fluid of choice (strong recommendation, moderate quality evidence) 1
• Do not delay norepinephrine if profound hypotension exists—early vasopressor administration improves cardiac output, microcirculation, and avoids fluid overload 3

Norepinephrine Administration

• Start norepinephrine as the first-line vasopressor immediately when hypotension persists after initial fluid resuscitation 1, 4
• Target mean arterial pressure (MAP) of 65 mmHg initially (Grade 1C) 1
• Administer through central venous access whenever possible 4, 2
• Place arterial catheter for continuous blood pressure monitoring as soon as practical 1, 4

Escalation Protocol for Refractory Hypotension

Second-Line Agent: Vasopressin

• Add vasopressin at 0.03 units/minute (not higher) when norepinephrine alone fails to achieve MAP target 1, 4, 2
• Vasopressin acts on V1 receptors (different pathway than norepinephrine's alpha-1 receptors), providing complementary vasoconstriction 2
• Never use vasopressin as monotherapy—it must be added to norepinephrine 1, 4
• Doses above 0.03-0.04 units/minute cause cardiac, digital, and splanchnic ischemia and should only be used for salvage therapy 1, 2

Third-Line Agent: Epinephrine

• Add epinephrine (0.05-2 mcg/kg/min) when additional vasopressor support is needed beyond norepinephrine plus vasopressin 1, 4, 5
• Epinephrine can be added to or potentially substituted for norepinephrine (Grade 2B) 1
• Consider epinephrine earlier if myocardial dysfunction is present with persistent hypoperfusion 1

Inotropic Support

• Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 1, 4, 2

Agents to Avoid

Dopamine

• Use dopamine ONLY in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia (Grade 2C) 1, 4
• Dopamine is associated with higher mortality and more arrhythmias compared to norepinephrine 4, 2, 6
• Never use low-dose dopamine for "renal protection"—this is strongly contraindicated (Grade 1A) 1, 2

Phenylephrine

• Phenylephrine is not recommended except in three specific circumstances (Grade 1C): 1, 4
  • Norepinephrine causes serious arrhythmias
  • Cardiac output is documented to be high with persistently low blood pressure
  • Salvage therapy when all other agents have failed
• Phenylephrine may raise blood pressure on the monitor while actually worsening tissue perfusion through excessive vasoconstriction 4

Critical Monitoring Requirements

• Monitor MAP continuously with arterial catheter 1, 4
• Assess tissue perfusion markers beyond blood pressure: lactate clearance, urine output, mental status, capillary refill, skin perfusion 1, 2
• Watch for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate despite adequate MAP 4

Common Pitfalls to Avoid

• Do not delay norepinephrine waiting for "complete" fluid resuscitation in profoundly hypotensive patients—early administration improves outcomes 3
• Do not escalate norepinephrine indefinitely—add vasopressin when norepinephrine requirements remain elevated 4, 2, 7
• Do not use vasopressin doses above 0.03-0.04 units/minute except as rescue therapy 1, 2
• Do not use dopamine as first-line therapy—it increases mortality compared to norepinephrine 4, 2, 6

Adjunctive Therapy for Refractory Shock

• Consider hydrocortisone 200 mg/day if hypotension remains refractory to vasopressors after adequate fluid resuscitation 4, 2
• Norepinephrine doses above 15 mcg/min (or approximately 0.2 mcg/kg/min in a 70 kg patient) indicate severe shock with mortality rates exceeding 80% 2