**2. Intradialytic hypotension**

The causes of IDH are multifactorial. On one side, a number of patient-related conditions can promote blood pressure (BP) fall during HD: age, comorbidities such as diabetes and cardiomyopathy, anemia, large interdialytic weight gain (IDWG), use of anti-hypertensive

Automated Blood Volume Regulation During Hemodialysis 29

Relative blood volume (RBV) is the term used to describe « the blood volume at any time as a percentage of the blood volume at the commencement of treatment » (Nesrallah et al., 2008). Most of the non-invasive devices extrapolate the RBV change from the variation of the hemoconcentration of a blood element. The basic premise of this calculation is that if the blood component remains constant throughout the HD session (i.e., the numerator), the variation of its concentration is necessarily due to the change in the blood volume (i.e., the denominator). The various devices available vary in the blood element they measure (i.e., red blood cells, hematocrit, total protein concentration) and in the method used to measure

One caveat of these techniques is that they are based on the assumption that uniform mixing of the measured blood element and plasma occurs throughout the whole circulation (Dasselaar et al., 2007a). Venous (or systemic) hematocrit (Hctsys) is usually higher than whole-body hematocrit (Hctw), due to the dynamic reduction of hematocrit in the microcirculation during blood flow through capillaries and venules. This is expressed as the F-cell ratio, Hctw/Hctsys. However, during UF, it was shown that the F-cell ratio rises as a result of the compliance of the microcirculation and fluid transfer to the macrocirculation. Therefore, the equations on which the inference of the blood volume change during HD is

In a study from Dasselaar et al. (2007a), the blood volume reduction estimated by three commonly used devices (Crit-line®, Hemoscan® and BVM®, see below) was compared to a standard laboratory-derived Hb relative blood volume measurement during two HD sessions. It was shown that all three devices systematically overestimate the RBV reduction at modest RBV change, and underestimate the real fall in blood volume at higher RBV

In addition, RBV monitoring also assumes that red blood cell mass or plasma protein density remains constant throughout the length of the session, which may not be true if

While hypovolemia is clearly a major determinant in the pathogenesis of IDH, the link between blood volume reduction and appearance of arterial hypotension is still a matter of debate. Recent studies have been unable to find a linear relationship between RBV and blood pressure, and a specific threshold to which hypotension will certainly occur does not seem to exist, even in an individual patient. This is probably because of variations, for each treatment, in the patient's ability to activate cardio-vascular compensatory mechanisms, in

In fact, in many trials where blood volume (BV) biofeedback was effective in reducing the occurrence of IDH, there was no difference in the final RBV reached by either the standard treatment or the BV-controlled treatment. According to some authors, it is possible that RBV reduction *per se* is not the main risk factor for development of IDH. Rather, the excessive fluctuations of BV and the form of the RBV slope during HD may contribute more to hemodynamic instability (Andrulli et al., 2002). Indeed, the slope of the RBV curve with BV regulation device is different from that produced by standard HD (Franssen et al, 2006). The initial phase is usually steeper (meaning higher UF rate), which is rendered possible and tolerable because of higher initial interstitial pressures and better plasma refilling rate. The second phase is characterized by a reduced UF rate, which in turn make the RBV more

hemolysis or blood leak happens, or when a blood transfusion is given.

**3.3 Relation between relative blood volume and intradialytic hypotension**

order to offset BP reductions induced by a wide range of hypovolemic states.

stable and the patient less prone to IDH in this vulnerable period.

it (i.e., optical absorbance, ultrasound, etc.).

based may not be always valid (Mitra et al., 2004).

decline.

medication, etc. On the other hand, factors associated with the dialysis prescription itself can also contribute to hemodynamic instability: short HD sessions, high ultrafiltration rate, high dialysate temperature, low dialysate sodium concentration, inflammation caused by membrane activation, etc. As a consequence, various interventions aimed at modulating these parameters have been proposed to ameliorate the vascular tolerance to ultrafiltration (UF), but with variable efficacy and limited benefits.

On a physiological basis, IDH can be viewed as the inability of the cardio-vascular system to respond adequately to the reduction of blood volume. Cardio-vascular reactivity involves reflex activation of the sympathetic system, with appropriate tachycardia and arterial and venous vasoconstriction in response to cardiac underfilling and hypovolemia. These compensatory mechanisms are altered in some patients, which put them at risk of developing IDH. However, these are difficult to assess and to modify. Comprehensive study of blood volume regulation during HD can help understand IDH susceptibility of individual patients.
