What are the causes and treatment options for persistent hypotension?

Causes of Persistent Hypotension

Medications are the most common reversible cause of persistent hypotension and must be systematically reviewed first, followed by assessment of cardiac dysfunction, volume depletion, and distributive shock states. 1

Medication-Related Causes (Most Common and Reversible)

• Antihypertensive agents including diuretics, ACE inhibitors, ARBs, vasodilators, and centrally acting agents are the primary culprits 1
• Excessive diuresis leading to volume contraction significantly increases hypotension risk, particularly when combined with ACE inhibitors or vasodilators 1
• Psychotropic medications (tricyclic antidepressants, phenothiazines, monoamine oxidase inhibitors) cause significant orthostatic hypotension 1
• NSAIDs and COX-2 inhibitors can paradoxically contribute to hypotension by blocking diuretic effects and causing fluid retention 1
• Polypharmacy is a frequently missed contributing factor, especially in elderly patients 1, 2

Cardiovascular Causes

• Volume depletion from dehydration, bleeding, or excessive diuresis is a critical reversible cause requiring immediate assessment 1, 3
• Heart failure with reduced ejection fraction (HFrEF) causes decreased cardiac output leading to hypotension 1
• Cardiogenic shock is defined as systolic BP <90 mmHg for >30 minutes despite adequate volume with signs of hypoperfusion (oliguria, cold peripheries, altered mental status, lactate >2 mmol/L, metabolic acidosis, SvO2 <65%) 3, 1
• Myocardial ischemia or acute myocardial infarction reduces cardiac output 3
• Cardiac arrhythmias (particularly rapid atrial fibrillation) impair cardiac output and require rate control 3
• Aortic dissection is a life-threatening cause that must be excluded 3

Distributive Shock States

• Septic shock is characterized by vasoplegia with variable cardiac output (low, normal, or high), shunting, and decreased oxygen extraction 1
• Myocardial depression commonly occurs in septic shock despite the distributive nature 1
• Anaphylaxis causes relative hypovolaemia requiring aggressive fluid therapy, with hypotension resulting from vasodilation and capillary leak 3
• Pancreatitis and other inflammatory states cause distributive shock through systemic inflammatory response 1

Drug Toxicity (Specific Overdoses)

• Calcium channel blocker toxicity causes both myocardial depression and vasodilation 1
• Beta-blocker toxicity causes bradycardia and decreased contractility 1
• Tricyclic antidepressant overdose causes sodium channel blockade leading to hypotension 1
• Cocaine toxicity causes coronary vasospasm and myocardial dysfunction 1

Endocrine Causes

• Adrenal insufficiency (primary or secondary) causes hypotension with hyponatremia and hyperkalemia 4
• Isolated hypoaldosteronism (primary with hyperreninism or secondary with hyporeninism) presents with hypotension and electrolyte abnormalities 4
• Diabetic dysautonomia causes autonomic dysfunction leading to orthostatic hypotension 4
• Pheochromocytoma can paradoxically cause hypotension, especially during surgical removal without adequate alpha-blockade preparation 4

Neurogenic Causes

• Autonomic neuropathies from diabetes, peripheral autonomic impairment (Bradbury-Eggleston syndrome), or central autonomic impairment (Shy-Drager syndrome) 5
• Dopamine-beta-hydroxylase deficiency causes absence of norepinephrine with dopamine accumulation 5
• Baroreceptor dysfunction causes wide blood pressure swings unrelated to posture 5
• Paroxysmal parasympathetic activation from cough, micturition, or carotid sinus pressure 5

Critical Pitfalls to Avoid

• Failure to recognize polypharmacy as a contributing factor, particularly in elderly patients, is the most common oversight 1, 2
• Excessive concern about mild hypotension can lead to underutilization of necessary diuretics in heart failure patients, perpetuating volume overload 1
• Missing hypovolemia as a cause of pulseless electrical activity in cardiac arrest situations 3
• Delayed recognition that persistent hypotension (systolic BP <50 mmHg) requires cardiac compressions 3

---

Treatment of Persistent Hypotension

Immediately discontinue or reduce causative medications, correct volume depletion with normal saline, and initiate norepinephrine as the first-line vasopressor after adequate fluid resuscitation in distributive shock, while using inotropes (dobutamine) for cardiogenic causes. 2, 6

Immediate Assessment and Reversible Causes

• Measure blood pressure in both supine and standing positions to identify orthostatic hypotension (drop ≥20 mmHg systolic and/or ≥10 mmHg diastolic within 3 minutes) 2
• Document neurological status and assess for end-organ hypoperfusion: altered mental status, decreased urine output (<0.5 mL/kg/hr), rising lactate (>2 mmol/L), worsening metabolic acidosis, and cold peripheries 2, 3
• Discontinue or reduce non-essential antihypertensive drugs including calcium channel blockers, centrally acting agents, and alpha-blockers immediately 2
• Review and stop psychotropic medications contributing to hypotension 1

Volume Resuscitation (First-Line Treatment)

• Administer fluid challenge with normal saline or Ringer's lactate >200 mL over 15-30 minutes as first-line treatment if no signs of overt fluid overload 3
• Correction of hypovolemia and optimization of cardiac output are the most important initial priorities 3
• In anaphylaxis, aggressive fluid therapy is required due to relative hypovolaemia from capillary leak 3
• Avoid excessive fluid administration in patients with cardiomyopathy as this worsens cardiac function 2

Vasopressor and Inotrope Selection (Etiology-Specific)

For Distributive Shock (Sepsis, Anaphylaxis)

• Norepinephrine is the initial vasoactive drug after appropriate fluid resuscitation 2, 6
• Target mean arterial pressure of at least 65 mmHg 2
• Alternative vasopressors (vasopressin, metaraminol, phenylephrine) may be considered for refractory hypotension 3

For Cardiogenic Shock and Heart Failure

• Inotropes (dobutamine, dopamine, or phosphodiesterase III inhibitors) are first-line agents 2
• Add norepinephrine for persistent hypotension with tachycardia 2
• Fluid challenge should be attempted first if no overt fluid overload 3

For Acute Ischemic Stroke with Hypotension

• Volume replacement with normal saline is the primary intervention 3
• Correct cardiac arrhythmias (slow ventricular response to rapid atrial fibrillation) 3
• If ineffective, use dopamine (5-15 mcg/kg/min) as the vasopressor of choice 3

For Refractory Anaphylaxis

• Double the initial bolus dose of epinephrine after 10 minutes of inadequate response 3
• Start epinephrine infusion after a total of three bolus doses 3
• Give IV glucagon 1-2 mg to patients taking beta-adrenergic receptor blockers 3
• Consider extracorporeal life support if skills and equipment are available 3

Monitoring and Titration

• Monitor serial markers of perfusion: lactate, mixed or central venous oxygen saturations (target SvO2 ≥65%), urine output, skin perfusion, renal and liver function, mental status 2, 3
• Invasive arterial line monitoring is needed in cardiogenic shock 3
• Echocardiography assists management by assessing ventricular function, filling, and vasodilation 3
• Consider end-tidal CO2 monitoring: values <3 kPa (20 mm Hg) suggest inadequate cardiac output and may warrant cardiac compressions after excluding airway/ventilation problems 3

Specific Clinical Scenarios

Post-Carotid Endarterectomy Hypotension

• Ensure adequate hydration and review perioperative antihypertensive medications 7
• For persistent hypotension after fluid resuscitation, initiate IV phenylephrine (1-10 mcg/kg/min) or dopamine (5-15 mcg/kg/min) 7
• Maintain systolic BP below 180 mmHg to prevent hyperperfusion syndrome while avoiding excessive hypotension 7

Cardiac Arrest with Hypotension

• Initiate cardiac compressions when systolic arterial BP is <50 mm Hg 3
• Assume relative hypovolaemia requiring aggressive fluid therapy 3

Critical Pitfalls to Avoid

• Never discontinue vasopressors too rapidly as this causes hemodynamic collapse in cardiogenic shock 2
• Do not abruptly stop beta blockers or clonidine perioperatively as this causes rebound hypertension 7
• Avoid excessive fluid in cardiomyopathy patients 2
• Do not use sublingual nifedipine for blood pressure management due to unpredictable rapid absorption and precipitous decline 3
• Recognize that systolic hypotension and oliguria are late signs of shock; earlier signs include decreased pulse pressure, decreased urine sodium, increased urine osmolarity, tachypnea, and tachycardia 8