Mathematical investigation of some physiological factors involved in hemodialysis hypotension

A previously developed mathematical model is used to investigate the role of some hemodynamic, regulatory, and osmotic factors in the development of symptomatic hypotension during hemodialysis. Sensitivity analysis of the model parameters suggests that a decrease in atrial pressure, with a consequent fall in cardiac output (Frank-Starling mechanism), is the primary hemodynamic perturbation induced by ultrafiltration. Also, during the first hours of a hemodialysis session, the sympathetic mechanism working on systemic resistance is the main factor responsible for arterial pressure maintenance, and the physiological response is probably characterized by a prevalence of the cardiopulmonary over the arterial baroreflex control. During this period, a decrease in plasma osmolarity, caused mainly by urea removal, may contribute to the reduction of vascular refilling. During the last hours of the session, the arterial pressure level is also significantly affected by other factors that influence vascular refilling and mean circulatory filling pressure (systemic compliance; action of feedback mechanisms working on venous unstressed volume; plasma oncotic pressure; and, especially, capillary wall permeability and interstitial space elastance). Simulation of hemodialysis with different modalities emphasizes the importance of avoiding high ultrafiltration rates and of maintaining the sodium concentration in the dialysate close to the sodium concentration of the extracellular fluid to limit the risk of symptomatic hypotension. Higher values of sodium in the dialysate are, however, associated with poor sodium removal from the extracellular pool with risks of interdialytic morbidity. In the future, the model may be used to optimize the ultrafiltration rate and sodium profile in the dialysate according to individual patient prescriptions.