How to treat persistent hypotension?

Treatment of Persistent Hypotension

The treatment of persistent hypotension requires first identifying and eliminating reversible causes—particularly medications and volume depletion—then initiating targeted therapy based on the underlying etiology, with norepinephrine as first-line for distributive shock, inotropes for cardiogenic shock, and midodrine for chronic orthostatic hypotension. 1, 2

Initial Assessment and Reversible Causes

Confirm True Hypotension and Establish Symptom Correlation

• Measure blood pressure in both supine and standing positions to identify orthostatic hypotension (drop of ≥20 mmHg systolic and/or ≥10 mmHg diastolic within 3 minutes of standing). 1
• If orthostatic hypotension is not confirmed, use ambulatory blood pressure monitoring to identify hypotensive episodes that correlate with symptoms. 1
• Document neurological status and assess for signs of end-organ hypoperfusion including altered mental status, decreased urine output, rising lactate, and worsening acidosis. 1, 3

Systematically Review and Eliminate Causative Medications

Medications are the most common reversible cause of persistent hypotension and must be reviewed in every patient. 2

• Discontinue or reduce non-heart failure antihypertensive drugs including calcium channel blockers, centrally acting antihypertensive agents, and alpha-blockers. 1, 2
• Identify psychotropic medications (tricyclic antidepressants, phenothiazines, MAO inhibitors) that cause significant orthostatic hypotension. 2, 4
• Assess for excessive diuresis leading to volume contraction, which increases risk of hypotension with ACE inhibitors and vasodilators. 2
• Review NSAIDs and COX-2 inhibitors that may contribute to fluid retention or hypotension. 2

Address Volume Status

• Ensure adequate hydration and correct dehydration from diarrhea, fever, bleeding, or overtreatment with diuretics. 1, 2
• Adjust diuretics according to volume status, as overdiuresis may result in lower blood pressure. 1

Etiology-Specific Treatment Approaches

Distributive Shock (Sepsis, Pancreatitis)

Norepinephrine is the recommended initial vasoactive drug after appropriate fluid resuscitation in distributive shock. 1

• Initiate norepinephrine as first-line vasopressor after fluid resuscitation. 1
• If hypotension persists despite norepinephrine, add vasopressin (up to 0.03 units/min) to reduce norepinephrine requirements and possibly reduce need for renal replacement therapy. 1
• For persistent hypotension with evidence of myocardial depression and decreased perfusion, add dobutamine to norepinephrine or use epinephrine as a single agent. 1
• Reserve dopamine only for hypotensive patients with bradycardia or low risk for tachycardia. 1
• Use phenylephrine only as salvage therapy. 1
• Target mean arterial pressure of at least 65 mmHg, complemented by serial markers of perfusion (lactate, central venous oxygen saturation, urine output, skin perfusion, mental status). 1

Cardiogenic Shock

In cardiogenic shock, inotropes (dobutamine, dopamine, or phosphodiesterase III inhibitors) are first-line agents, with norepinephrine added for persistent hypotension with tachycardia. 1

• Use inotropes (dobutamine, dopamine, phosphodiesterase III inhibitors) as first-line agents in acute heart failure. 1
• Add norepinephrine in persistently hypotensive cardiogenic shock with tachycardia. 1
• Consider dopamine in patients with bradycardia. 1
• In afterload-dependent states (aortic stenosis, mitral stenosis), use phenylephrine or vasopressin. 1
• Continue vasopressor support with careful titration to maintain adequate tissue perfusion while avoiding excessive doses that worsen cardiac function. 3
• Perform serial echocardiographic assessments to monitor cardiac function and response to therapy. 3
• Consider temporary mechanical circulatory support for refractory cardiogenic shock despite optimal medical therapy. 3

Heart Failure with Reduced Ejection Fraction (HFrEF)

For persistent low blood pressure in asymptomatic or mildly symptomatic HFrEF patients with adequate perfusion, initiate SGLT2 inhibitors and mineralocorticoid receptor antagonists first, as they have the least effect on blood pressure but rapid beneficial effects. 1

Treatment-Naïve Patients:

• Start SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) as first drug class since they have minimal BP effect but rapid benefit. 1
• Subsequently add low-dose beta-blocker (if heart rate >70 bpm) or low-dose sacubitril/valsartan (50 mg twice daily or 25 mg twice daily for very low dose). 1
• If sacubitril/valsartan is poorly tolerated, use low-dose ACE inhibitor (or ARB if ACE inhibitors contraindicated). 1
• Prefer selective β₁ receptor blockers due to lesser BP-lowering effect than non-selective beta-blockers. 1
• If beta-blockers are not well tolerated hemodynamically, use ivabradine alone or with low-dose beta-blockers to facilitate titration. 1
• Up-titrate one drug at a time using small increments with close monitoring until highest tolerated or target dose is achieved. 1

Post-Procedural Hypotension (Carotid Artery Stenting)

For neurologically intact patients with persistent hypotension after carotid artery stenting, oral ephedrine (25-50 mg orally, 3-4 times daily) may be useful. 1

• Ensure adequate hydration and careful adjustment of antihypertensive medications before procedures. 1
• For persistent hypotension during procedures, use intravenous phenylephrine (1-10 mcg/kg/min) or dopamine (5-15 mcg/kg/min). 1
• For post-procedural persistent hypotension in neurologically intact patients, administer oral ephedrine 25-50 mg orally, 3-4 times daily. 1
• Provide additional in-hospital observation period for patients with persistent hypotension. 1

Chronic Orthostatic Hypotension

Midodrine is FDA-approved for symptomatic orthostatic hypotension and should be used only in patients whose lives are considerably impaired despite non-pharmacologic treatment. 5, 6, 7

Non-Pharmacologic Interventions (First-Line):

• Implement lifestyle modifications and physical countermaneuvers. 6, 7
• Use support stockings and fluid expansion. 5
• Prevent patient from becoming fully supine by sleeping with head of bed elevated to control supine hypertension. 5

Pharmacologic Treatment:

• Initiate midodrine 10 mg three times daily (with last dose not later than 6 PM to minimize nighttime supine hypertension) for patients with significant symptomatic impairment. 5
• Midodrine increases standing systolic blood pressure by approximately 15-30 mmHg at 1 hour after a 10 mg dose, with effects persisting 2-3 hours. 5
• Start with 2.5 mg in patients with renal impairment, as desglymidodrine is eliminated via kidneys. 5
• Consider fludrocortisone for volume expansion, either alone or combined with midodrine. 6, 7
• Continue midodrine only for patients who report significant symptomatic improvement. 5

Monitoring and Titration

Hemodynamic Targets

• Target mean arterial pressure of at least 65 mmHg in septic shock and distributive shock. 1
• In cardiogenic shock, individualize MAP goals to balance hypoperfusion risk against negative impact on cardiac output, myocardial oxygen consumption, and dysrhythmias. 1
• The goal of therapy in orthostatic hypotension is symptom relief and fall prevention, not arbitrary blood pressure values. 6, 7

Serial Assessment

• Monitor serial markers of systemic and organ perfusion: lactate, mixed or central venous oxygen saturations, urine output, skin perfusion, renal and liver function tests, mental status. 1
• Perform serial arterial blood gas analyses to monitor acid-base status in critically ill patients. 3
• Assess for signs of end-organ hypoperfusion including worsening acidosis, rising lactate levels, and decreased urine output. 3

Critical Pitfalls to Avoid

• Do not discontinue vasopressors too rapidly, as this can lead to hemodynamic collapse in cardiogenic shock. 3
• Avoid excessive fluid administration in patients with cardiomyopathy, as this worsens cardiac function. 3
• Do not allow excessive concern about mild hypotension or azotemia to lead to underutilization of necessary diuretics and persistent volume overload in heart failure. 2
• Monitor for supine hypertension with midodrine (BP >200 mmHg systolic); advise patients to avoid taking dose if supine for any length of time and take last daily dose 3-4 hours before bedtime. 5
• Avoid concomitant use of drugs that increase blood pressure (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine) with midodrine, or monitor blood pressure closely if unavoidable. 5
• Do not use MAO inhibitors or linezolid with midodrine. 5
• Recognize that polypharmacy is a common contributing factor, particularly in elderly patients. 2