Reevaluation of Dry Weight: It is necessary to evaluate whether dry weight is set excessively low. Trial and error method by well-trained nephrologists is generally accepted. Blood volume marker such as ANP, BNP, or cGMP, bioimpedance analysis , and the measurement of inferior vena cava by ultrasound or echocardiograph have been reported helpful.

Restriction of Interdialytic Weight Gain: UF amount should not exceed 3 kg per session. If weight gain is more than this, education for water and diet uptake should be intensified targeting weight gain not exceeding 1 kg per day and/or not exceeding 2 kg for interdialytic period. To prevent excessive weight gain, salt restriction should be emphasized rather than water itself (Agarwal and Weir 2010).

Vascular refilling is an important physiological process to avoid hypovolemia during dialysis. Hypotension occurs if this process is inadequate. To achieve adequate vascular refilling, the rapidity of the osmolality change and that of water removal, i.e., UF rate, is most important. Recent dialysis machines can manipulate these two factors by adjusting dialysate sodium concentration and automatic control of ultrafiltration rate.

Sequential Dialysis (Isolated UF + Isovolemic Hemodialysis): Only ultrafiltration is performed for the initial 1 h without removing uremic molecules to keep the osmolality change minimally and to keep vascular volume. After then, hemodialysis is performed for the rest of the session to remove uremic molecules with minimal ultrafiltration . Usually 50% of target UF is achieved for the initial isolated UF time, and the rest is removed for the remaining 3 h of hemodialysis (Fig. 9.2).

Sodium Modeling: It is a method to maintain plasma osmolality, and thus to prevent hypotension by keeping dialysate sodium concentration higher than conventional HD (Zhou et al. 2006). Constant high sodium dialysis higher than 138 mmol/L frequently causes thirst and interdialytic weight gain. Sodium modeling dialysis is introduced to avoid these side effects. In sodium modeling dialysis, dialysate sodium concentration is initially high and decreased to normal or lower level linearly (linear sodium profiling) or stepwise (stepwise sodium profiling) to avoid patients’ hypernatremia after finish of dialysis (Fig. 9.3). In general, it has been regarded to be effective and easy method, but thirst, excessive interdialytic weight gain, and hypertension are still limitation (Song et al. 2002, 2005). Recently, UF profiling is used in combination with sodium profiling (so-called combined sodium and ultrafiltration profiling ) to maximize water removal and minimize hypovolemia (Fig. 9.4). Combination with cool temperature dialysis also is a convenient and effective option (K/DOQI 2005; van Der Sande et al. 2000).

Ultrafiltration Profiling: If vascular refilling rate does not match UF rate, blood volume will drop too early during the dialysis session. UF profiling is a method manipulating UF rate during the session to give the time for vascular refilling and to avoid intradialytic hypotension (Fig. 9.5). Reducing the UF rate sequentially or stepwise and keeping zero at the end of session is done to avoid the vascular refilling failure that usually occurs in the latter part of dialysis. Another method is the periodical stopping of UF, which gives enough time for vascular refilling.

Online Blood Volume Monitor and Automated Biofeedback-Controlled Dialysis: Online blood volume (BV) monitor can monitor real-time BV change. It is possible by measuring the hematocrit using optic or ultrasonic devices. Some recent dialysis machines are equipped with these devices, for example, Hemocontrol^® (Fig. 9.6) or BVM^® (Basile et al. 2001; Leypoldt and Lindsay 1999). Automated biofeedback-controlled dialysis system is a proprietary technology using “fuzzy logic” system (Mancini et al. 2007). These machines can automatically adjust dialysate conductivity, i.e., practically sodium concentration, and UF tracking on-line BV change (Deziel et al. 2007; Colì et al. 2011). This system appears to improve patients’ tolerability to dialysis, but data is inconsistent and still insufficient. Further work is needed before it can be routinely recommended for intradialytic hypotension-prone patients.

Antihypertensive agents taken before dialysis are a common cause of intradialytic hypotension . Careful evaluation of the association of the timing and dosing of antihypertensive drugs and inter-, pre-, and postdialytic blood pressure is required in intradialytic hypotension-prone patients. If the association is suspected, it should be considered to skip or reduce the dose of predialytic antihypertensive drugs. It also can be helpful to move the prescription time of antihypertensive drug to evening.

The food intake during dialysis increases the splanchnic blood flow . Consequently, the reduced blood flow in the core vasculatures may result in hypovolemia. Food intake should be refrained before and during the dialysis session in intradialytic hypotension-prone patients.

Acetate dialysate was a culprit causing frequently dialysis reaction and intradialytic hypotension . Although it is now rarely used, acetate may be present in a small quantity, approximately 3 mmol/L, in some bicarbonate-based dialysates. There have been some reports that acetate, even in small quantities, may cause intradialytic hypotension (Bolasco et al. 2011; Agarwal 2012).

When circulating blood volume is reduced, superficial vasculatures are constricted to redistribute blood flow to the core blood flow to compensate central hypovolemia by the sympathetic nervous system activation. During this process, core body temperature is elevated. In hypotension-prone patients, conventional dialysate temperature of 36–37 °C may elevate the core temperature too high to cause paradoxical superficial vasodilatation and hypotension (Fig. 9.7). Cool temperature dialysis with dialysate temperature of 34–36 °C is helpful to avoid intradialytic hypotension in these patients. A recent study suggested cool temperature hemodialysis also ameliorates subclinical myocardial ischemia (Selby et al. 2006). Recent biofeedback technology makes it possible to maintain patient’s body temperature constantly (isothermic hemodialysis) and to profile the temperature as needed (dialysate temperature profile). Some authors reported that it is most effective when sodium modeling is combined with cool temperature dialysis (K/DOQI 2005; van Der Sande et al. 2000).

Midodrine: Patients with advanced stage of diabetes, long-term uremia , and/or old age do not respond to other methods due to severe autonomic nervous system dysfunction. In these intractable patients, alpha-1 adrenergic agonist, midodrine, can be helpful at a dose of 10 mg orally 30 min before dialysis session. Midodrine is effectively cleared, and its half-life is reduced to 1.4 h by hemodialysis. Since it has specificity for alpha-1 receptor, cardiac or central nervous system effect is minimal. Common side effects are nausea , heartburn, piloerection, scalp itching or tingling, urinary urgency, headache, nervousness, and sleep disturbance. Long-term use has been associated with supine systolic hypertension in less than 10% of patients, which warrants cessation of therapy (Jankovic et al. 1993). The combination of cool dialysate and midodrine may be helpful to decrease intradialytic hypotension .

Sertraline: A selective serotonin reuptake inhibitor, sertraline, was originally used for idiopathic orthostatic hypotension and neurocardiogenic syncope. Administration of 50–100 mg a day for 4–6 weeks has been reported to improve autonomic function neurocardiogenic syncope. It has been reported that 4–6 weeks of therapy improves the hemodynamic parameters in patients with intradialytic hypotension (Dheenan et al. 1998; Yalcin et al. 2002, 2003). It can be considered for the patient showing clue of paradoxical sympathetic withdrawal, i.e., sudden decrease in blood pressure with bradycardia.

l -carnitine: Carnitine deficiency is associated with several metabolic defects, defined as dialysis-related carnitine disorders, including intradialytic hypotension (Bellinghieri et al. 2003). l-carnitine therapy at 20 mg/kg into the dialysis venous port with each session reduces frequency of intradialytic hypotension and muscle cramps (Ahmad et al. 1990; Riley et al. 1997). It is also effective in improving the quality of life in some patients. Mechanism of beneficial effect is not clear, but it could be due to improvement in vascular smooth muscle and cardiac muscle function.

Caffeine: Caffeine is an adenosine receptor antagonist. It may be helpful when the cause of intradialytic hypotension is increase of adenosine, an endogenous vasodilator, which is released due to anemia or organ ischemia.

Vasopressin: There is a report that the infusion of vasopressin infusion (0.3 mU/kg/min) reduces frequency of intradialytic hypotension and potentiates the removal of fluid although the subject number is too small to be conclusive (Santoro 2007).

It is important to check the presence of underlying heart diseases, such as congestive heart failure , arrhythmias , or ischemic heart disease. When it is found, appropriate treatment is mandatory. In particular, it is necessary to check for pericardial diseases.

According to K/DOQI guidelines , hemoglobin level should be maintained to 11–2 g/dL. It is an important and effective way to decrease vasodilation due to hypoxia . It also improves cardiovascular and myocardial function, and thus prevents hypotension.

High calcium dialysate (dialysate calcium concentration of 1.5 mmol/L) showed improvement of cardiac contractility and vasoconstriction in the patients with left ventricular ejection fraction of 40% or less or with NYHC III–IV heart failure as compared to low calcium dialysate (1.25 mmol/L) (Gabutti et al. 2009). Low magnesium dialysate (0.25 mmol/L) also may be helpful to improve heart function. The use of these dialysate can be considered for the patient with cardiac dysfunction. It should be made known that hypercalcemia may decrease bone turnover in some patients with the use of dialysate calcium of 1.5 mmol/L or more.

Nonspecific fatigue and malaise appear in about 33% of dialysis patients (Abuelo et al. 1993). Possible causes include reduced cardiac output, peripheral vascular diseases, depressed mood, poor conditioning, postdialytic hypoglycemia , hypokalemia , mild uremic encephalopathy, neuropathy, and uremic myopathy.

It tends to be more frequent with non-glucose or acetate dialysate and to be reduced with glucose-containing or bicarbonate dialysate. Complement activation or cytokine production by bioincompatibility of the dialyzer has also been thought to be related, but the exchange of cuprophan with polysulfone dialyzer failed to show symptom improvement in double-blind studies (Group BCDS 1991; Sklar et al. 1998). Carnitine deficiency also causes malaise. Supplementing of L-carnitine has shown improvement of well-being sensation (Lindsay et al. 2006).