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Hank Park

Hypotension is a big problem!

• Hypotension during dialysis treatment is an unresolved issue.

• Delivery of an adequate dose of dialysis is essential to improve the prognosis of dialysis patients

• Low blood pressure during the hemodialysis procedure is expected to occur more frequently in patients with comorbidities because it compels a limit to dialysis time and dialysis efficacy.

- van der Zee S, Thompson A, Zimmerman R, et al: Vasopressin administration facilitates fluid removal during hemodialysis. - Davenport A: Intradialytic complications during hemodialysis.- Imai E, Fujii M, KohnoY, et al: Adenosine A1 receptor antagonist improves intradialytic hypotension.

IDH (Intradialytic Hypotension)• Definition: A fall in SBP by at least 20mmHg or SBP < 100mmHG

• Cause: Decline Cardiac Function and Systemic Vascular Resistance (SVR) during removed solute : A rapid reduction in Plasma osmolality: High Interdialytic weight gain: Anemia: Autonomic neuropathy: Decrease pressor response to Vasopressor agents: LV Hypertrophy & Decrease cardiac preload: Decrease cardiac reserve: Increase arterial stiffness: Impaired venous compliance: Meal: Use of low sodium/ Increase magnesium dialysate: Anti-hypertension medication before HD: Excessive release of vasodilators (Not Adrenomedullin and Adenosine): Imbalance in the synthesis of vasoconstrictors (Endothelin & Vasopressin)

Intradialytic Hypotension (IDH) mechanism?

Patient factors

Cardiac disease - Systolic dysfunction - Diastolic dysfunction

Arrhythmias Pericardial disease Autonomic neuropathy Dietary excess Interdialytic weight gain Food ingestion in dialysis Antihypertensive agents Anemia (< Hb 7.0g/dL)

Dialysis procedure factors

Ultrafiltration, solute removal Thermal amplication Sympathetic failure

- Increased adenosine - Increased nitric oxide

Dialysate composition Low sodium (<138mEq/L) Low calcium High magnesium Acetate

IDH ---> Hypertension

• Mechanism of therapy for intradialytic hypotension are of great interest (van der Zee. S et al.)

• Increase in adenosine generation during hemodialysis may cause vasodilation and decrease in cardiac output, which results in systemic hypotension (Imai. E et al.)

• Removal of excess extracellular fluid -> symptomatic decreases in arterial pressure -> intradialytichypotension -> chronically volume-expanded -> Chronic Hypertension (van der Zee. S et al.)

Solution?

Routine management of IDH

Target dry weight Diet fluid counseling Medication adjustment Correct anemia High sodium dialysate Sodium modeling

Individualized therapy of IDH

High calcium dialysate Low-magenesium dialysate Carnitine Sertraline Cool dialysate Midodrine (A vasopressor /antihypotensive agent)

How to increase BP?Farese S. et al. Am J Kidney Dis. 2008.

• TEMS : Transcutaneous muscle simulation , PCMs : Passive cycling movement

• For each patient, each procedure was performed only once weekly and never on the same weekday.

Patient Characteristics

TEMS & PCMs during dialysis show significant results in raising BP

Increased Cardiac Output!

• Heart rate was unchanged during both treatment (TEMS & PCM) modalities.

• Therefore, the observed increase in blood pressure can only be explained by an increase in either peripheral resistance or cardiac output.

• For TEMS and active exercise, decreased vascular resistance has been described. Miller BF et al. Phys Ther 80:53-60, 2000

• Thus, increased cardiac output is a more likely explanation for the increase in blood pressure, a contention supported because increased central blood and preload volume positively alter cardiac output. Hanft LM et al. Cardiovasc Res 77:627-636, 2008

• There is an evidence that electrical muscle stimulation increases venous backflow from the musculature. Clarke Moloney M et al. Eur J Vasc Endovasc Surg 31:300-305, 2006

Efficiency? Urea & Phosphate!

• Longer observation periods with more patients are needed to assess potential benefits of TEMS and PCMs on hypotensive episodes during dialysis sessions

Several Studies about Passive Training

• Passive movement of the lower leg has been found to result in an approximate three-fold increase in muscle blood flow, and stretch of the muscle tissue without an alteration in either EMG activity or muscle oxygen uptake. (Krustrup et al. 2004)

• Vascular endothelial growth factor (VEGF) is probably one of the most important factor for endothelial activation, proliferation and migration.

• The passive movement model induced an enhanced level of muscle interstitial VEGF protein and an increased endothelial cell proliferative effect of muscle interstitial fluid from the muscle as well as a higher expression of endothelial nitric oxide synthase (eNOS) mRNA in the muscle. (Hellsten et al. 2008, Am J PhysiolRegul Integr Comp Physiol)

Capillarization and presence of proliferating endothelial cells in skeletal muscle before and after passive training of the leg

• B. Hoier et al. J Physiol 588.19 (2010) pp 3833–3845

Relationship with CVD ?

• Farese et al. (Am J Kidney Dis): Blood flow in the Femoral Artery increased up to 40% with TEMS and PCMs (unpublished): Increased Cardiac Output by electrical muscle stimulation increases venous backflow from the musculature (Increased venous return)

• Future direction: ABI (Ankle Brachial Index) : BP Function between Ankle and Brachial: FMD : specific to Femoral Arterial function: Heart Rate Variability : Autonomic dysfunction: Cardiac Function : Mitral Inflow Conventional Doppler, Mitral Annular Velocity Tissue Doppler

Thank you