Department of Internal Medicine and Nephrology, University Hospital Maastricht, Maastricht, The Netherlands
Introduction
Intradialytic hypotension continues to be a leading problem, especially in the elderly and cardiovascularly compromised patient. This predominance can be explained by the fact that structural and functional abnormalities of the heart and blood vessels increase the sensitivity of the patient to changes in fluid status.
Intradialytic hypotension not only causes discomfort, but also increases mortality. According to recent data a low post-dialytic blood pressure was associated with a significantly increased risk for mortality [1]. Therefore prevention of intradialytic hypotension, especially in the elderly and vulnerable patient, remains an important challenge to the dialysis physician.
How to improve stability of blood volume?
The initiating factor in the pathogenesis of intradialytic hypotension is a decrease in blood volume. The decrease of blood volume is the consequence of the capillary Starling equilibrium, which determines the refilling rate. Many factors influence the refilling rate. As a result it is difficult to predict the changes of blood volume during dialysis. Recent developments allow continuous monitoring of relative changes in blood volume during dialysis [2]. The basis of these techniques is the continuous monitoring of (i) haematocrit, (ii) total protein, or (iii) haemoglobin from lysed erythrocytes from which the relative decrease in blood volume can be estimated [35]. The cardioregulatory reaction to changes in blood volume varies widely between dialysis patients. Blood volume monitoring may enable the physician to modify the dialysis treatment so that the maximal tolerated blood volume changes are not transgressed.
Based on repeated measurements in the same patient it has been suggested that intradialytic hypotension occurs once an absolute decrease in blood volume is exceeded which is specific for each individual patient [6,7]. A recent multicentre study examined the association between the relative decline in blood volume and symptomatic hypotension. In 72% of the patients the authors could identify an individual blood volume threshold, which varied by less than 4%. The majority of hypotensive periods occurred when this individually defined threshold was exceeded [8]. This study also documented, however, that the critical decrease of blood volume has to be determined empirically for each individual patient. It must also be stressed that in 30% of the patients a critical threshold could not be identified.
Ultrafiltration rate
One of the main determinants of the changes in blood volume is the ultrafiltration rate [9]. An earlier study documented that altering the ultrafiltration rate to a predetermined blood volume profile permitted to reduce the incidence of intradialytic symptoms [4,10]. To reach an equivalent volume compared to the standard treatment, the ultrafiltration rate was set high at the start of the dialysis and was then decreased during the treatment session. In this study the ultrafiltration rate was adjusted manually, a cumbersome procedure in daily practice. Moreover, patients who are prone to hypotensive episodes might be more sensitive to this treatment when higher ultrafiltration rates are needed to reach the dry weight. Problems may be avoided by selecting an empirically determined maximal ultrafiltration rate in hypotension-prone patients. This may differ for isolated ultrafiltration and haemodialysis respectively [11].
Not only the absolute blood volume, but also the rate of decrease in blood volume determine the preservation of blood volume and the risk of intradialytic hypotension. A high rate of blood volume decrease should therefore be prevented [12]. Of help would be a device which automatically adjusts the ultrafiltration profile to a predetermined volume without exceeding the empirically determined safe blood volume threshold, thus preventing an excessive rate of decrease in blood volume. Even with this approach it will be very difficult in some patients to achieve this goal unless one increases dialysis time.
Dialysate sodium
Another important factor affecting blood volume preservation is the dialysate sodium concentration. It has been shown that limiting the reduction in plasma osmolality during haemodialysis by selecting a higher sodium concentration of the dialysate improves haemodynamic stability. This is mediated through better blood volume preservation [13,14]. The disadvantage is that a higher dialysate sodium concentration increases the exchangeable sodium pool giving rise to increased interdialytic weight gain and hypertension [15]. It has been suggested that sodium profiling would be beneficial because it allows adjustment of the amount of transferred sodium so that sodium overload is avoided, thus reducing the incidence of intradialytic hypotension episodes [1620]. A sodium kinetic model device allows adjustment and control of the dialysate sodium concentration automatically in order to target a specific value for the patient's plasma water conductivity at the end of the dialysis session [21]. Although earlier studies yielded conflicting results regarding the benefit of sodium profiling, a recent study reported a significant decrease of the number of hypotensive episodes when this sodium kinetic model was used, although there were no relevant changes in sodium balance and interdialytic weight gain [22]. The clinical effect of an on-line sodium kinetic model is uncertain and currently under investigation. The optimal approach of individualizing and modeling the dialysate sodium concentration has not yet been established.
In some newer dialysis machines, options for continuous blood volume monitoring and sodium kinetic modelling have become standard. The combined use of blood volume and sodium kinetic monitoring may enable the clinician to adjust both the ultrafiltration rate and the dialysate sodium concentration in order to reach the target ultrafiltration volume within predetermined safe blood volume margins [23]. Probably, the development of closed loop systems in which these parameters can be automatically adjusted in order to achieve the desired pre-set values will greatly enhance the clinical utility of such devices.
How to improve (cardio)vascular reactivity?
In healthy individuals, a decline in blood volume of 25% is usually well tolerated. In contrast, in dialysis patients, hypotension occurs subsequent to a much smaller decrease of blood volume. This is the result not only of structural abnormalities of the cardiovascular system, but also of impaired vascular reactivity. It has been shown that the reaction of the resistance as well as the capacitance vessels is inadequate during a haemodialysis session [24]. This finding is of great clinical importance: both increased systemic vascular resistance and centralization of blood volume by venoconstriction determine the reaction of the circulation to fluid removal [25]. Especially the combination of a major decline in blood volume and insufficient translocation of blood from the capacitance vessels to the heart may lead to cardiac underfilling, activation of the sympatico-inhibitory cardiopressor reflex (Bezold-Jarish reflex), and sudden hypotension [26].
Thermal effects
There are very strong arguments for an important role of temperature in the pathogenesis of the impaired vascular response during dialysis. An increase in core temperature, as observed during a standard haemodialysis treatment (dialysate temperature 37.5°C), causes vasodilatation and impaired vascular response to a decrease in blood volume [27]. In contrast, the vascular response is normal during haemofiltration and isolated ultrafiltration. With both modalities the energy balance across the extracorporeal circuit is negative [28,29]. The importance of thermal effects was illustrated by recent studies. The authors showed that there were no longer any differences of vascular reactivity between haemodialysis and isolated ultrafiltration or haemofiltration respectively when energy transfer was identical [30].
The disadvantage is that a negative energy balance and a decrease in core temperature is uncomfortable for the patient. It may be sufficient, however, to prevent only the increase in core temperature during dialysis sessions [30,31]. New techniques enable the clinician to measure and model core temperature and energy transfer continuously during dialysis. They may be of great help in the prevention of intradialytic hypotension.
Practical guidelines
The incidence of episodes of intradialytic hypotension can often be reduced by relatively simple clinical manoeuvres [32]. The decline in blood volume can be reduced when the optimal dry weight is estimated by objective methods. The ultrafiltration rate should not be excessive and individualized for each patient. The optimal dialysate sodium concentration remains to be elucidated. High dialysate sodium concentrations may be disadvantageous. The selection of the dialysate sodium concentration should possibly be based on quantification of the sodium flux during hemodialysis. The standard dialysate temperature should be set at 35.5°C. When it is still necessary to improve vascular reactivity, decreasing the core temperature by adjusting the energy transfer over the extracorporeal system might have an additional, although minor, beneficial effect.
Conclusion
The key issues in the prevention of intradialytic hypotension are optimal blood volume preservation and improvement of cardiovascular response. In the future it may become possible to integrate blood volume monitoring, blood temperature monitoring, and sodium profiling, within a closed-loop biofeedback system, which automatically adjusts the ultrafiltration rate, the dialysate sodium concentration, and the dialysate temperature. Nevertheless, all these parameters will have to be determined individually and adapted to each patient. We therefore believe that the introduction of such automated devices can be of help in the prevention of intradialytic hypotension, but will never replace the individualized care of the patient by the physician.
Notes
Correspondence and offprint requests to: F. M. van der Sande, MD, PhD, Department of Internal Medicine and Nephrology, University Hospital Maastricht, P. Debeyelaan 25, PO Box 5800, NL-6202 AZ Maastricht, The Netherlands.
References