What is the recommended first-line pressor for sepsis-induced hypotension?

First-Line Vasopressor for Sepsis-Induced Hypotension

Norepinephrine is the mandatory first-choice vasopressor for sepsis-induced hypotension, initiated after or concurrent with fluid resuscitation (minimum 30 mL/kg crystalloid), targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2

Initial Management Protocol

Fluid Resuscitation Requirements

• Administer at least 30 mL/kg of crystalloid fluid in the first 3 hours before or simultaneously with vasopressor initiation 1, 2
• However, in life-threatening hypotension (particularly when diastolic blood pressure is critically low), start norepinephrine as an emergency measure while continuing fluid resuscitation rather than delaying for complete volume repletion 1

Norepinephrine Administration

• Preferred route: Central venous access to minimize extravasation risk and tissue necrosis 1, 2, 3
• Alternative route: Peripheral IV or intraosseous access can be used temporarily if central access is unavailable or delayed 2, 3
• Starting dose: 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult) 2, 3
• Target MAP: 65 mmHg initially for most patients 1, 2

Monitoring Requirements

• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2, 3
• Assess tissue perfusion markers: lactate clearance, urine output, mental status, capillary refill, skin perfusion 1, 2

Management of Refractory Hypotension

Second-Line Vasopressor Addition

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

• Add vasopressin at 0.03 units/min (maximum 0.03-0.04 units/min) to raise MAP or decrease norepinephrine requirements 1, 2
• Vasopressin should NEVER be used as monotherapy—it must always be added to norepinephrine 1, 2
• Doses above 0.03-0.04 units/min are reserved for salvage therapy only due to risk of digital and splanchnic ischemia 1, 2

Alternative Second-Line Options

• Epinephrine (0.05-2 mcg/kg/min) can be added to or substituted for norepinephrine when additional vasopressor support is needed 1, 4
• Dobutamine (up to 20 mcg/kg/min) should be added if persistent hypoperfusion exists despite adequate vasopressors, particularly with evidence of myocardial dysfunction 1, 2

Critical Agents to Avoid

Dopamine

• Use ONLY in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 2
• Dopamine is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 2
• Never use low-dose dopamine for renal protection—this is strongly discouraged with no demonstrated benefit 1, 2

Phenylephrine

• NOT recommended except in specific circumstances: 1, 2
  • 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 numbers while actually worsening tissue perfusion through excessive vasoconstriction 2

Common Pitfalls to Avoid

• Don't delay norepinephrine waiting for complete fluid resuscitation in life-threatening hypotension—start early as an emergency measure 1
• Don't rely solely on MAP—supplement with tissue perfusion markers (lactate, urine output, mental status) to guide therapy 1, 2
• Don't use vasopressin as initial monotherapy—it must be added to norepinephrine, not used alone 1, 2
• Don't escalate vasopressin beyond 0.03-0.04 units/min—add epinephrine instead if additional support is needed 1, 2
• Don't use dopamine as first-line—the evidence clearly favors norepinephrine for mortality and arrhythmia outcomes 1, 2

MAP Target Individualization

While 65 mmHg is the standard initial target, consider higher targets in: 1, 2

• Patients with chronic hypertension or atherosclerosis
• Elderly patients with known vascular disease

Conversely, younger previously normotensive patients may tolerate lower MAP targets adequately 1