Causes of Persistent Hypotension

Medication-Related Causes

Medications are the most common reversible cause of persistent hypotension and should be systematically reviewed in every patient. 1, 2

Antihypertensive agents including diuretics (especially at high doses), ACE inhibitors, ARBs, vasodilators, and centrally acting agents are frequent culprits 1, 3, 2
Excessive diuresis leading to volume contraction increases risk of hypotension with ACE inhibitors and vasodilators 1
Psychotropic medications including tricyclic antidepressants, phenothiazines, and monoamine oxidase inhibitors cause significant orthostatic hypotension 1, 3, 2
Antiparkinsonian medications and dopamine agonists commonly produce hypotension 3, 2
Cardiovascular drugs including nitrates, antianginals, and antiarrhythmics 3, 2
NSAIDs and COX-2 inhibitors can block diuretic effects and contribute to fluid retention or hypotension 1
Alcohol consumption, both acute and chronic, leads to orthostatic hypotension 3

Autonomic failure represents a major category of persistent hypotension, particularly in elderly patients and those with chronic diseases. 4, 5

Neurodegenerative disorders including Parkinson's disease, multiple system atrophy (Shy-Drager syndrome), and pure autonomic failure (Bradbury-Eggleston syndrome) 3, 4, 5
Diabetic autonomic neuropathy is a common cause, particularly in patients with long-standing diabetes 3, 6, 4
Rare genetic defects such as dopamine-beta-hydroxylase deficiency causing absence of norepinephrine 4
Baroreceptor dysfunction causing wide blood pressure swings unrelated to posture 4

Adrenal insufficiency must be considered in any patient with persistent hypotension, especially when accompanied by electrolyte abnormalities. 6

Primary adrenal failure from various etiologies including congenital 21-hydroxylase deficiency with salt loss, presenting with hyperreninism 6
Secondary adrenal insufficiency from hypopituitarism with hyporeninism 6
Isolated hypoaldosteronism (primary with hyperreninism or secondary with hyporeninism) typically presents with hyponatremia and hyperkalemia 6
Pseudohypoaldosteronism from congenital or acquired resistance to aldosterone 6
Pheochromocytoma rarely presents with hypotension, particularly during surgical removal without adequate calcium channel blocker preparation 6
Carcinoid syndrome with flushing and hypotensive crises 6

Cardiac dysfunction and volume depletion are critical reversible causes requiring immediate assessment. 1, 3, 7

Heart failure with reduced ejection fraction (HFrEF) causing decreased cardiac output 1, 3, 7
Cardiogenic shock defined as systolic BP <90 mmHg for >30 minutes despite adequate volume with signs of hypoperfusion (oliguria, altered mentation, cool extremities, elevated lactate) 7
Myocardial depression common in septic shock 1
Volume depletion from dehydration, bleeding, or excessive diuresis 3, 7
Mitral valve prolapse associated with idiopathic sympathetic orthostatic hypotension 4

Aging causes progressive deterioration in blood pressure regulation mechanisms, making elderly patients particularly vulnerable. 3, 8

Baroreceptor sensitivity decline at approximately 1% per year after age 40 3
Reduced cardiac compliance and arterial stiffness contributing to blood pressure variability 3
Cumulative effects of age and hypertension-related alterations in blood pressure regulation 8

Volume depletion from various sources must be identified and corrected before attributing hypotension to other causes. 1, 7, 6

Inadequate fluid intake or dehydration 3, 8
Enteric losses from total colectomy with ileostomy 6
Renal losses from interstitial nephropathy, Bartter syndrome, or Gitelman syndrome with hyperreninism-hyperaldosteronism 6
Excessive diuretic use leading to volume contraction 1

Specific triggers can precipitate hypotensive episodes through parasympathetic activation. 4

Paroxysmal parasympathetic activation from cough, micturition, or carotid sinus pressure 4
Prolonged bed rest or deconditioning 3
Postprandial hypotension particularly in elderly patients 8

In septic and distributive shock, hypotension results from vasoplegia with variable cardiac output. 1

Septic shock with vasoplegia, shunting, decreased oxygen extraction, and low, normal, or high cardiac output 1
Pancreatitis and other inflammatory states 1

Specific drug overdoses require targeted management approaches. 1

Calcium channel blocker toxicity causing myocardial depression and vasodilation 1
Beta-blocker toxicity causing bradycardia and decreased contractility 1
Tricyclic antidepressant overdose with sodium channel blockade 1
Cocaine toxicity with coronary vasospasm 1

Excessive concern about mild hypotension or azotemia can lead to underutilization of necessary diuretics and persistent volume overload, which limits efficacy of other heart failure medications 1
Failure to recognize polypharmacy as a contributing factor, particularly in elderly patients 3, 8
Not measuring orthostatic vital signs at different times of day and after meals or medications 8
Overlooking endocrine causes when electrolyte abnormalities (hyponatremia, hyperkalemia) are present 6