Dialysis fata morgana: can we finally successfully tackle intradialytic hypotension with plasma sodium biofeedback systems?

Abstract

In spite of all the progress made in dialysis treatment, in-tradialytic hypotension (IDH) is still one of the mostcommon complications of standard thrice-weekly haemo-dialysis (HD). It occurs in ∼20–30% of all dialysis ses-sions [1]. IDH is the clinical manifestation of a netreduction in the effective circulating plasma volume in ashort period of time, overwhelming normal compensatorymechanisms, including plasma refilling and reduction invenous capacity, due to the reduction in pressure trans-mission to veins [2]. The aetiology of IDH is multifactor-ial: autonomic dysfunction in uraemia, acute decrease inplasma osmolarity, reduction in vascular reactivity to va-sopressor agents and overproduction of vasodilators, anincorrectly estimated ‘dry weight’ resulting in a too highfiltration rate and overdosage of antihypertensive drugs—most often (but not necessarily) in addition to diabetes orcoexistence of cardiovascular diseases [3].Over many years, there has been a major effort to de-crease the frequency of IDH. Besides patient discomfort(one of the two most frequent complains in patient dialy-sis-related QOL questionnaires [4]), this quest has beenobjectively motivated by the serious cardiovascular com-plications associated with IDH. Indeed, recurrent episodesof IDH are associated with repetitive transient myocardialhypoperfusion; moreover, repetitive ischaemia and reperfu-sion induce myocardial fibrosis and ventricular dysfunc-tion, life-threatening arrhythmias and sudden cardiac death[5, 6]. After symptomatic IDH episodes, HD patients sufferoccult but significant myocardial injuries reflected byhigher serum levels of CK-MB and cTnT, observed even44 h after the end of the dialysis session [7]. RepetitiveIDH is also associated with cerebral ischaemia, and thedevelopment of lacunar and watershed infarcts withsubsequent atrophy of the frontal lobe of the brain [8].Moreover, IDH is an independent negative predictor oflong-term fistula outcomes [ 9, 10].Intra-dialytic hypotension is independently associatedwith higher mortality in HD patients, including reportsprovided by prospective cohort studies [11]. In 1244 HDpatients, a significant association was found between thelowest intradialysis systolic blood pressure (SBP) and2-year mortality (patients with intradialytic blood pressure(BP) values <110/92 showed a mortality rate ∼8% highercompared with the normotensive group) [12]. This highmortality rate may be explained by several mechanisms:first, IDH could be directly causal in increasing the risk ofdeath, independent of other classical risk factors, throughmyocardial ischaemia, ischaemic stroke or malignant ar-rhythmias triggered by the drop in BP during dialysis.Furthermore, IDH causes alterations in endothelial func-tion promoting the occurrence of arterial stiffness andother morbid events. Thirdly, as discussed, IDH mayresult in a lower dialysis dose delivered and therefore in ahigher chronic, toxic uraemic milieu. Alternatively, IDHmay be a marker for the presence of risk factors that in-crease the risk of mortality, such as diabetes, malnu-trition-inflammation syndrome or reduced cardiac reserveand performance. Of course, a combination of the abovepossibilities is the most plausible [11, 13].To reduce the frequency of IDH, several strategies havebeen developed. The EBPG (European Best Practice)guidelines on haemodynamic instability suggest a sequen-tial approach: dietary counselling, avoiding meals whileon dialysis, use of cool temperature dialysate and reas-sessment of dry weight [14]. Devices that monitor anindividual patient’s blood volume may be helpful, as maybe the use of longer dialysis times, through either pro-longed individual treatments or extra weekly dialysis ses-sions. Finally, the use of midodrine is a possibility and,for the most difficult patients, a transition to peritonealdialysis may be required [14].At the same time, a well-established body of evidenceindicates that either daily short-term, slow nocturnal HDor haemofiltration/haemodiafiltration are associated withimproved haemodynamic stability, when compared withthe standard thrice-weekly 3–4 h HD [15]. In a recentmulticentre, randomized, controlled trial, a significantreduction in the frequency of IDH was demonstrated, inpatients who were treated with pure (HF) or mixed (HDF)convection, compared with patients treated with standardlow-flux dialysis [16]. This beneficial effect was morepronounced in HDF (the adjusted relative risk reductionof IDH was 54% in comparison with low-flux dialysis).In contrast, HDF did not improve BP control or reducethe frequency of IDH episodes compared with high-fluxHD using cooled dialysate. In fact, the frequency of IDH