Can 5mg of Lisinopril (Angiotensin-Converting Enzyme inhibitor) cause hypotension leading to circulatory shock?

Can 5 mg of Lisinopril Cause Circulatory Shock?

Yes, 5 mg of lisinopril can cause circulatory shock, particularly in high-risk patients with volume depletion, heart failure with low systolic blood pressure, or those on high-dose diuretics, though this is uncommon. 1

Risk Factors for Lisinopril-Induced Hypotension and Shock

The FDA label explicitly warns that lisinopril can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. 1 Patients at highest risk include those with:

• Heart failure with systolic blood pressure below 100 mmHg 1
• Severe volume and/or salt depletion of any etiology 1
• High-dose diuretic therapy 1
• Renal dialysis 1
• Ischemic heart disease or cerebrovascular disease 1
• Hyponatremia 1

Clinical Evidence of Shock from Low-Dose ACE Inhibitors

A case report documented refractory circulatory shock after a single dose of lisinopril (Zestril) in a 42-year-old woman with acute myocardial infarction. 2 Right heart catheterization revealed markedly decreased systemic vascular resistance with preserved cardiac index—a distributive shock pattern. 2 The shock was refractory to fluid resuscitation and norepinephrine, requiring angiotensin II infusion for resolution. 2

In the GISSI-3 trial of acute MI patients, those receiving lisinopril had a significantly higher incidence of persistent hypotension (systolic blood pressure <90 mmHg for more than 1 hour) compared to controls: 9.0% versus 3.7%. 1 This occurred despite protocol exclusions for baseline hypotension (systolic <100 mmHg), severe heart failure, cardiogenic shock, and renal dysfunction. 1

Mechanism of ACE Inhibitor-Induced Shock

ACE inhibitors block angiotensin II formation, which is critical for maintaining systemic vascular resistance in certain physiologic states. 2 In patients whose blood pressure depends heavily on renin-angiotensin system activity—such as those with renal artery stenosis, chronic kidney disease, severe heart failure, post-MI, or volume depletion—even low doses can precipitate acute circulatory collapse. 1

Management Protocol for Suspected Lisinopril-Induced Shock

Immediate Actions:

• Discontinue lisinopril immediately 1
• Initiate aggressive volume resuscitation with crystalloid 2
• Start norepinephrine as first-line vasopressor if hypotension persists after fluid resuscitation 3
• Consider angiotensin II (if available) for refractory shock unresponsive to norepinephrine, as this directly replaces the depleted substrate 2

Monitoring Requirements:

• Continuous arterial blood pressure monitoring via arterial catheter 3
• Serial assessment of renal function and urine output 1
• Right heart catheterization may be needed to differentiate distributive from cardiogenic shock 2

Critical Pitfalls to Avoid

Do not assume hypotension from ACE inhibitors is always volume-responsive. The case report demonstrates that even repeated fluid challenges may fail when systemic vascular resistance is profoundly decreased due to angiotensin II depletion. 2

Do not use phenylephrine as first-line therapy. While it raises blood pressure numbers, it can compromise microcirculatory flow and tissue perfusion. 3 Norepinephrine is preferred because it maintains cardiac output while increasing systemic vascular resistance. 3

Do not restart ACE inhibitors in patients who develop shock. The FDA label states that lisinopril should be started "under very close medical supervision" in high-risk patients and followed closely for the first two weeks. 1 Patients who develop shock should be considered to have an absolute contraindication to rechallenge.

Prevention Strategy

In high-risk patients (those meeting criteria above), the FDA recommends:

• Starting lisinopril at 2.5 mg rather than 5 mg 1
• Very close medical supervision during initiation 1
• Close follow-up for the first two weeks of treatment 1
• Avoiding use in hemodynamically unstable patients after acute MI 1

The incidence of first-dose hypotensive episodes in hypertensive patients with normal renal function is only 0.6%, but increases to 6.7% in those with impaired renal function. 4 In elderly patients, lisinopril was generally well-tolerated with no postural hypotension observed, though one patient was withdrawn due to adverse effects. 5