What is the 2nd line vasopressor agent for septic shock after noradrenaline (norepinephrine)?

Second-Line Vasopressor Agents for Septic Shock After Norepinephrine

Vasopressin is the recommended second-line vasopressor agent for septic shock after norepinephrine, with epinephrine as an alternative second-line option. 1

First-Line Management

• Norepinephrine is the established first-line vasopressor for septic shock with an initial target mean arterial pressure (MAP) of 65 mmHg 1, 2
• Adequate fluid resuscitation should precede or accompany vasopressor therapy 1
• Central venous access is required for vasopressor administration, and arterial catheter placement is recommended for all patients requiring vasopressors 2

Second-Line Vasopressor Options

Vasopressin

• Vasopressin (up to 0.03 U/min) is recommended as the preferred second-line agent to either raise MAP to target or decrease norepinephrine dosage 1, 2
• Standard dosing is 0.03 units/minute when added to norepinephrine, with a starting dose of 0.01 units/minute for septic shock 2, 3
• Vasopressin should not be used as the single initial vasopressor for septic shock 1
• Doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy when other vasopressors have failed to achieve target MAP 1
• Vasopressin causes vasoconstriction by binding to V1 receptors on vascular smooth muscle 3

Epinephrine

• Epinephrine is an alternative second-line agent that can be added to or potentially substituted for norepinephrine when additional vasopressor support is needed 1, 2
• Epinephrine achieves similar shock reversal as norepinephrine but may be associated with more metabolic and cardiac adverse effects 1, 4
• Consider epinephrine particularly in patients with refractory septic shock and myocardial dysfunction 4

Other Vasopressor Options

Dopamine

• Dopamine is not recommended as a second-line agent due to increased risk of arrhythmias 1, 5
• It should only be considered in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1
• The SOAP II trial demonstrated an increase in arrhythmic events with dopamine compared to norepinephrine 1

Phenylephrine

• Phenylephrine is not recommended in septic shock except in specific circumstances 1, 6:
  • When norepinephrine is associated with serious arrhythmias
  • When cardiac output is known to be high and blood pressure persistently low
  • As salvage therapy when other vasopressors have failed

Emerging Options

• Angiotensin II appears promising in severe septic shock, especially in patients with acute kidney injury requiring renal replacement therapy, but is not currently recommended due to limited evidence 4, 7
• Terlipressin and selepressin (synthetic analogs of vasopressin) are not currently recommended due to higher rates of digital ischemia 4, 7

Clinical Considerations

• Monitor for signs of adequate perfusion (lactate levels, urine output, mental status) when titrating vasopressors 2
• After target blood pressure has been maintained for 8 hours without catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated 3
• Consider adding dobutamine in patients with evidence of cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and norepinephrine 1

Potential Pitfalls

• Avoid excessive vasoconstriction which may compromise end-organ perfusion 7
• Do not use low-dose dopamine for renal protection as this practice is not supported by evidence 1
• Remember that drugs with positive chronotropic effects may be associated with higher risk of death compared to those without or with negative chronotropic effects 1