What is the best approach to manage hemodialysis-associated hypotension?

Pathogenesis of Hemodialysis-Associated Hypotension

Primary Pathophysiologic Mechanisms

Hemodialysis-associated hypotension results from two fundamental mechanisms: insufficient intravascular volume to support the ultrafiltration rate and inadequate cardiovascular compensatory responses to volume removal. 1

Volume Depletion and Plasma Refill Dynamics

• Excessive ultrafiltration creates a mismatch between the rate of fluid removal from the intravascular space and the rate of plasma refill from the interstitial compartment, leading to intravascular volume depletion 1
• Ultrafiltration rates as low as 6 mL/h/kg are associated with higher mortality risk, suggesting that even modest rates can exceed the body's compensatory capacity in vulnerable patients 1
• The relationship between ultrafiltration volume and rate directly determines hemodynamic stability—higher volumes removed over shorter treatment times exponentially increase hypotension risk 1

Impaired Cardiovascular Compensation

• Inadequate peripheral vasoconstriction fails to maintain blood pressure during volume removal, often related to autonomic dysfunction in chronic kidney disease patients 1
• Reduced cardiac output response, particularly in patients with underlying cardiovascular disease or cardiomyopathy, prevents adequate compensation for decreased preload 1
• The Bezold-Jarisch reflex (cardiodepressor response) can be activated during rapid ultrafiltration, causing paradoxical vasodilation and bradycardia 1

Contributing Pathophysiologic Factors

Dialysate-Related Mechanisms

• Acetate-containing dialysate inappropriately decreases total vascular resistance, increases venous pooling, and increases myocardial oxygen consumption, all contributing to hypotension 1
• Higher dialysate temperatures (37°C) promote peripheral vasodilation and reduce sympathetic tone, whereas lower temperatures (34-35°C) increase peripheral vasoconstriction through enhanced sympathetic activity 1
• Rapid sodium removal with low dialysate sodium concentrations can impair vascular refilling and osmotic support of the intravascular compartment, though the optimal dialysate sodium concentration remains controversial 1

Neurohormonal and Autonomic Dysfunction

• Chronic kidney disease patients exhibit impaired neurohormonal responses to intravascular volume loss, including blunted activation of the renin-angiotensin-aldosterone system and sympathetic nervous system 1
• Autonomic insufficiency is considered a primary contributing cause of hemodialysis hypotension, preventing appropriate vasoconstriction and heart rate responses 2

Medication-Induced Mechanisms

• Antihypertensive medications taken before dialysis sessions exacerbate hypotension by preventing compensatory vasoconstriction and cardiac responses 1, 3
• Dialyzable antihypertensive agents (such as metoprolol) may be removed during treatment, but their acute presence during ultrafiltration contributes to hemodynamic instability 3

Nutritional and Metabolic Factors

• Food intake immediately before or during hemodialysis causes splanchnic vasodilation and decreased peripheral vascular resistance, redirecting blood flow away from the peripheral circulation 1, 4
• Anemia reduces oxygen-carrying capacity and may impair cardiovascular compensation, though correction to hemoglobin 11 g/dL can reduce hypotension incidence 1

End-Organ Ischemia Cascade

• Recurrent intradialytic hypotension creates a cascade of end-organ ischemia affecting the heart, brain, liver, gut, and kidneys 1
• This ischemic injury contributes to increased morbidity and mortality, though the direct causal relationship between isolated hypotensive episodes and outcomes remains incompletely defined 1
• Protracted hypotension during hemodialysis may exaggerate urea rebound, compromising dialysis adequacy 1

Critical Pathophysiologic Pitfalls

• Dry weight set too low is the most common cause of persistent hypotension—patients become chronically hypovolemic, triggering compensatory mechanisms including increased thirst and paradoxically higher interdialytic weight gains 1, 3
• The assumption that hypotension always indicates adequate volume removal is incorrect; hypotension may signal excessive ultrafiltration below true dry weight 3
• Rare causes such as secondary adrenal insufficiency can present as intradialytic hypotension and should be considered when standard interventions fail 5