Why is it not recommended to give Lisinopril (Angiotensin-Converting Enzyme inhibitor) to a patient on Levophed (Norepinephrine, a vasopressor)?

Why Lisinopril Should Not Be Given to Patients on Levophed (Norepinephrine)

Lisinopril should not be administered to patients on norepinephrine (Levophed) due to the high risk of profound hypotension that could lead to cardiovascular collapse, organ hypoperfusion, and increased mortality.

Pathophysiological Interaction

The contraindication between Lisinopril and norepinephrine stems from their opposing mechanisms of action:

1. Norepinephrine (Levophed) is a potent vasopressor that:

   • Acts primarily as a strong alpha-1 receptor agonist with moderate beta-1 activity 1
   • Increases systemic vascular resistance (SVR) and mean arterial pressure (MAP)
   • Is indicated in cardiogenic shock when other treatments fail to restore adequate blood pressure 2

2. Lisinopril is an ACE inhibitor that:

   • Reduces angiotensin II production, leading to vasodilation
   • Decreases aldosterone secretion, potentially causing electrolyte imbalances
   • Lowers blood pressure through multiple mechanisms 3, 4

Clinical Consequences of Co-administration

When these medications are used together, several dangerous clinical scenarios can develop:

1. Hemodynamic Instability

• ACE inhibitors like Lisinopril can severely undermine the vasopressor effects of norepinephrine
• This antagonistic interaction can lead to refractory hypotension and shock 2

2. Compromised Organ Perfusion

• The resulting hypotension can cause inadequate perfusion to vital organs
• Particularly concerning for patients already in shock states requiring vasopressor support 2

3. Renal Function Deterioration

• Both medications affect renal blood flow through different mechanisms
• Patients on norepinephrine often have compromised renal function that can be worsened by Lisinopril 2

Guideline Recommendations

The European Society of Cardiology guidelines specifically state:

• "Treatment with an ACEI should not be initiated in hypotensive patients who are at immediate risk of cardiogenic shock. Such patients should first receive other forms of treatment for their HF and then be re-evaluated for ACE inhibition once stability has been achieved." 2

• "Vasopressors (norepinephrine) are not recommended as first-line agents and are only indicated in cardiogenic shock when the combination of an inotropic agent and fluid challenge fails to restore SBP >90 mmHg, with inadequate organ perfusion." 2

Special Considerations

Blood Pressure Thresholds

• ACE inhibitors should be used with caution in patients with systolic blood pressure less than 80 mmHg 2
• Patients requiring norepinephrine typically have significant hypotension (systolic BP ≤70 mmHg) 1

Sequence of Therapy

• If a patient on chronic Lisinopril develops shock requiring norepinephrine, the ACE inhibitor should be temporarily withheld
• For patients stabilized on norepinephrine, Lisinopril should only be considered after:
  1. Vasopressors have been weaned
  2. Hemodynamic stability has been achieved
  3. Adequate organ perfusion has been restored 2

Management Algorithm

1. For patients in shock requiring norepinephrine:

   • Hold all ACE inhibitors including Lisinopril
   • Focus on stabilizing blood pressure with vasopressors
   • Ensure adequate fluid resuscitation

2. After shock resolution:

   • Gradually wean norepinephrine
   • Wait at least 24 hours after complete vasopressor discontinuation
   • Reassess hemodynamic stability before considering reintroduction of ACE inhibitors

3. When reintroducing ACE inhibitors:

   • Start at the lowest possible dose (e.g., Lisinopril 2.5 mg)
   • Monitor blood pressure closely for at least 4 hours after first dose
   • Titrate slowly with frequent reassessment of hemodynamic parameters

Conclusion

The simultaneous use of Lisinopril and norepinephrine creates a dangerous pharmacological conflict that can compromise hemodynamic stability and increase mortality. Clinical guidelines clearly recommend against initiating ACE inhibitor therapy in hypotensive patients, particularly those requiring vasopressor support.