How to manage intradialytic hypotension in patients with end-stage renal disease (ESRD) and multiple comorbidities?

Management of Intradialytic Hypotension

Prioritize non-pharmacologic interventions first—specifically reducing ultrafiltration rate below 6 mL/h/kg by extending dialysis time to minimum 4 hours or increasing frequency to three times weekly—before considering any medications, as this addresses the fundamental pathophysiology and improves mortality outcomes. 1, 2

Immediate Interventions During Hypotensive Episodes

When intradialytic hypotension occurs acutely, implement the following sequence:

• Stop or reduce ultrafiltration immediately to prevent further blood pressure decline and end-organ ischemia 2
• Place patient in Trendelenburg position to improve venous return 2
• Administer supplemental oxygen to improve tissue oxygenation and reduce symptoms 2
• Avoid routine saline boluses for every hypotensive episode, as this perpetuates volume overload and creates a vicious cycle 2

Dialysis Prescription Modifications (Primary Strategy)

Ultrafiltration Rate Management

The ultrafiltration rate is the single most critical modifiable factor:

• Target ultrafiltration rates below 6 mL/h/kg, as rates exceeding this threshold are associated with higher mortality risk and increased hypotension 1, 2, 3
• Achieve lower ultrafiltration rates through two mechanisms: extending treatment time or increasing treatment frequency 1
• Extend treatment time to minimum 4 hours per session to slow ultrafiltration rate below the critical 6 mL/h/kg threshold 2
• Increase from twice to three times weekly dialysis sessions to reduce the volume requiring removal per session and prevent recurrent hypotension 2

Target Weight Reassessment

A critical but often overlooked intervention:

• Reassess target weight if hypotension persists, as hypotension frequently indicates the target weight is set too low 1, 2
• Gradually probe the target weight upward over 4-12 weeks without inducing hypotension 2
• Recognize that residual urine output may lead to underestimation of true dry weight, making the target potentially too low 2
• Balance the narrow therapeutic window between volume depletion (causing hypotension and loss of residual kidney function) and volume overload (causing hypertension and cardiovascular complications) 1

Dialysate Modifications

Technical adjustments that improve hemodynamic stability:

• Lower dialysate temperature to 0.5°C below body temperature (typically 35-36°C) to promote peripheral vasoconstriction and improve hemodynamic stability 1, 3
• Consider dialysate sodium concentration carefully: lower dialysate sodium reduces interdialytic weight gain but may increase intradialytic hypotension risk 1
• Avoid acetate-containing dialysate when possible, as it decreases vascular resistance and increases venous pooling 3, 4

Antihypertensive Medication Management

Medication Review and Adjustment

Critical evaluation of existing medications:

• Review all antihypertensive medications and consider reducing or withholding doses, particularly in patients with four or more concurrent antihypertensives that prevent compensatory vasoconstriction 2
• Consider drug dialyzability patterns: avoid nondialyzable medications (propranolol, carvedilol) in patients with frequent intradialytic hypotension, as they may worsen hemodynamic instability 1
• Time antihypertensive administration individualized to interdialytic blood pressure patterns and frequency of intradialytic hypotension 1
• Note that carvedilol specifically blunts compensatory tachycardia and cardiac output increases needed during volume removal 2

Evidence on Withholding Medications

• The effectiveness of routinely withholding antihypertensive agents before dialysis remains uncertain and is under investigation in ongoing trials 1
• Make decisions based on individual intradialytic blood pressure patterns rather than blanket protocols 1

Pharmacologic Interventions for Hypotension

Use medications only after optimizing dialysis prescription and volume management, as the evidence base is weak and observational data suggest potential harm. 1

Midodrine (Most Studied Agent)

• Midodrine improves nadir systolic blood pressure by an average of 13 mm Hg (95% CI: 9-18 mm Hg) and reduces hypotensive symptoms 1
• Administer 5-10 mg orally 30 minutes before each hemodialysis session based on clinical trials 5, 6
• Efficacy maintained over 5-8 months of continuous use without adverse effects in clinical studies 5
• Critical caveat: Observational data found midodrine use associated with significantly higher risks of cardiovascular events, all-cause hospitalization, and mortality when matched for baseline blood pressure 1
• FDA labeling notes increased responsiveness to vasopressors in ESRD patients undergoing hemodialysis, suggesting lower doses may be appropriate 7
• Monitor for bradycardia, supine hypertension, and urinary retention 8

Alternative Pharmacologic Options

Other agents with limited evidence:

• Arginine-vasopressin, sertraline, droxidopa, amezinium metilsulfate, fludrocortisone, and carnitine have been studied 1
• All have weak evidence bases with small, short-duration studies and no clinical endpoint data 1
• Midodrine remains most widely used despite limited availability outside the United States 1

Long-Term Prevention Strategies

Interdialytic Weight Gain Control

• Limit sodium intake to <5.8 g/day to reduce thirst and interdialytic weight gain 2
• Restrict interdialytic weight gain to <3% of body weight between sessions to prevent volume overload requiring aggressive ultrafiltration 2
• Continue loop diuretics in patients with residual kidney function, as observational data shows association with lower interdialytic weight gain and lower intradialytic hypotension rates 1

Anemia Management

• Maintain hemoglobin at 11 g/dL to improve oxygen-carrying capacity and cardiovascular compensation during ultrafiltration 2

Residual Kidney Function Preservation

• Avoid intradialytic hypotension itself, as repeated episodes accelerate loss of residual kidney function 1
• Consider RAS blockers (ACE inhibitors/ARBs) which may preserve residual kidney function, especially in peritoneal dialysis patients 1
• Avoid nephrotoxins and maintain adequate perfusion pressure 1

Special Population: Chronically Hypotensive Patients

For patients with persistent hypotension despite standard interventions:

• Increase dialysis time as the primary strategy for chronically hypotensive patients 1, 2
• Consider transition to peritoneal dialysis, as these patients may tolerate PD better than hemodialysis due to slower, continuous ultrafiltration 1, 2
• Reduce ultrafiltration volume by adjusting peritoneal dialysis solutions (using less hypertonic glucose or changing icodextrin to conventional 1.5% glucose) 1
• Liberalize salt intake cautiously in selected patients 1

Critical Pitfalls to Avoid

• Never continue twice-weekly dialysis in hypotension-prone patients, as this forces dangerously high ultrafiltration rates exceeding 6 mL/h/kg and inadequate solute clearance 2
• Avoid routine saline administration for every hypotensive episode, as this perpetuates volume overload and creates a cycle requiring higher ultrafiltration rates 2
• Do not ignore cardiovascular assessment in high-risk patients with strong cardiac history who develop recurrent intradialytic hypotension 4
• Recognize that repeated intradialytic hypotension creates a cascade of end-organ ischemia affecting heart, brain, liver, gut, and kidneys, contributing to increased mortality 3
• Avoid food intake immediately before or during hemodialysis, as it causes splanchnic vasodilation and decreased peripheral vascular resistance 3

Monitoring and Quality Assurance

• Track the percentage of patients experiencing intradialytic hypotension and those presenting with systolic blood pressure <110 mm Hg as a quality assurance initiative 4
• Implement clinical training sessions on intradialytic hypotension risk recognition and appropriate treatment within the dialysis unit 4
• Recognize that intradialytic hypotension occurs in approximately 25% of all hemodialysis sessions and is associated with vascular access thrombosis, inadequate dialysis dose, and mortality 9