Potassium in Haemodialysis Fluids and Haemodynamics

Haemodialysis Clinical Trial

Official title: Haemodynamic Consequences of Changing Potassium Concentrations in Haemodialysis Fluids

Status Completed

Clinical Trial Summary

In a study published in 1995 in the American Journal of Kidney Diseases, Dolson et al demonstrated that a rapid decrease of serum potassium concentrations during haemodialysis would produce a significant increase in systolic blood pressure at the end of the session, even though there were no clear effects on intra-dialytic blood pressure. The authors defined this post-dialysis blood pressure behaviour as "rebound hypertension". Paradoxically, in animal models, other than in the context of end-stage renal disease, potassium is a vasodilator. Considering that the removal of potassium during the haemodialysis session could be theoretically modulated in profiles (as with sodium and bicarbonate), it was deemed suitable to delve deeper into this argument by studying, in detail, the (non invasive) hemodynamic repercussions of changes in the potassium concentration of the dialysate. Not being able to linearly modify the concentration, we decided to divide the dialysis session in 3 tertiles, randomising the patients to all possible dialysate sequences containing the usual concentration of potassium or two cut-off points at +1 and -1 mmol/l. Haemodynamic measurements were performed using a finger beat-to-beat monitor.

Clinical Trial Description

INTRODUCTION:

Potassium is the most abundant cation in the body (35-40 mmol/kg in haemodialysis patients [1]), although only 2% of the pool is located extracellularly [2]. Whereas, on a short-term basis, serum potassium is regulated by the shift of potassium between the intracellular and the extracellular compartment by insulin, cathecolamines, acid-base balance, and osmolarity; kidneys are responsible for long-term potassium homeostasis [2]. Patients with end-stage renal disease are at high risk of hyperkalaemia [3-6], which may present itself as generalised weakness, paralysis, and cardiac arrhythmia [2]. Recovering potassium homeostasis is thus an important objective of dialysis. Still, considering that its location is mainly intracellular, which connects to the pharmacological concept of great distribution volume, its removal during a haemodialysis session is quantitatively modest (between 40 and 80 mmol corresponding to 1-2% of total body potassium) [1]. As a consequence, even if, in order to be suitable, potassium removal during dialysis should be equal to the amount accumulated during the inter-dialytic phase, in clinical practice the potassium concentration in the dialysate is usually adjusted with the suboptimal goal of avoiding pre-dialysis hyperkalaemia [7].

The importance of the body content and serum concentration of potassium to control blood pressure remains controversial. Epidemiological data suggest a role for potassium depletion as a co-factor in the development and severity of hypertension, while dietary potassium inversely correlates with blood pressure [8-10]. In animal models, an acute increase in serum potassium concentration produces vasodilatation mediated by the vascular endothelium; the opposite effect is observed if it decreases [11,12]. In haemodialysis, the extent of the difference between serum potassium and the potassium concentration in the dialysis fluid is directly correlated to an increase in blood pressure at the end of the dialysis session, producing what has been named "rebound hypertension" [1]. In this same study no significant changes in blood pressure were found during the dialysis.

In haemodialysis the nephrologists are faced with sudden changes in blood pressure and haemodynamic fragility phases that have a multi-factorial origin; ultrafiltration, decrease in osmolarity with imbalance and correction of metabolic acidosis play a predominant role [13-19]. Despite this, and thanks to some artifices, with particular reference to calcium concentration in the dialysate [15], dialysate temperature [20] and ultrafiltration and sodium concentration profiles [18,21-24], pressure stability is guaranteed as a general rule. Some electrolytes, particularly sodium and bicarbonate, can be modulated in profiles with the purpose of better respecting the gap in osmolarity or concentration that is established during the haemodialysis session, but their haemodynamic effect still remains controversial [20,22,24].

Serum potassium is an electrolyte whose concentration - in order to guarantee a negative balance - varies rapidly and significantly during dialysis, frequently resulting in going from pre-dialysis hyperpotassaemia to intra-dialysis hypopotassaemia. As mentioned above, in Dolson's study [1], differences in dialyses blood pressure were not found between the groups treated with dialysates containing 1, 2 or 3 mmol/l of potassium, but at the end of the dialyses those patients treated with the lower potassium concentrations showed what was called a "rebound hypertension".

With the purpose of better characterising this phenomenon, we redesigned the study dividing the dialysis session into 3 phases (in fact, clinical practice suggests that the haemodynamic pattern at the beginning, intermediate and final phases of the dialysis are not the same) and programming for each a more or less sharp drop in serum potassium concentration, respecting in the meantime the need to remove the amount of potassium that usually keeps the patient in steady-state. Using a crossover research model, we divide the dialysis session in 3 tertiles where the potassium concentration in the dialysate was modulated between the usual concentration for the study subject and two cut-off points at +1 e -1 mmol/l respectively. To complete the information provided by blood pressure, haemodynamics were measured in a non-invasive manner using a finger beat-to-beat monitor.

The primary end point was the difference in haemodynamic parameters between the extremes in potassium concentration of the dialysate, while the incidence of hypotension during dialysis was considered a secondary end point.

METHODS:

Twenty-four chronic haemodialysis patients (13 male and 11 female) were enrolled in the study. Each patient was dialysed for 3 to 4 hours and 30 minutes three times a week and was clinically stable and without intercurrent illnesses. Using a single blind crossover design, patients were randomised in the six dialysate potassium sequences of the study. Each dialysis session was divided into three equal parts (tertiles): during one part the potassium concentration of the dialysate was the same as the one usually prescribed to the patient, whereas during the other two parts it was either increased or reduced by 1 mmol/L. The 6 different permutations were repeated twice, so that each patient underwent 12 dialysis sessions during the study (see Table 1 for sequence details).

The haemodialyses were performed using a 4008 H machine, equipped with a cartridge of bicarbonate Bibag©, and a high flux single use polysulfone membrane, all from Fresenius Medical Care (Bad Homburg, Germany). The prescribed dialyser effective surface area, dialysis fluid conductibility, dialysate temperature and composition (with the exception of potassium concentration), effective blood flow, and dry weight were recorded at the enrolment in the study and were then left unchanged. The medications of the patients were also left unchanged. Serum potassium and patient weight were measured at the beginning and at the end of each dialysis session. Blood samples were taken from the arterial limb of the shunt.

Kt/V was used to quantify haemodialysis adequacy and was calculated using a second generation single-pool Daugirdas formula (Kt/V = -ln(R-0.03) + [(4-3.5 x R) x (UF/W)], where R = post-dialysis BUN/pre-dialysis BUN, UF = net ultrafiltration, W = weight, K= dialyzer clearance of urea, t= dialysis time, and V= patient's total body water.

The incidence of hypotension episodes (defined as a systolic blood pressure < 90 mmHg) was recorded.

Systolic and diastolic blood pressures, heart rate, stroke volumes (integrated mean of the flow waveform between the current upstroke and the dicrotic notch) and total peripheral resistances (ratio of mean arterial pressure to stroke volume multiplied by heart rate) were evaluated at the beginning of the session and then every 30 minutes using a Finometer© finger beat-to-beat monitor (Finapres Medical Systems BV, Arnhem, The Netherlands). Finometer© measures finger blood pressure noninvasively on a beat-to-beat basis and gives waveform measurements similar to intra-arterial recordings.

Mean blood pressure (BPmean) was calculated using the following formula:

BPmean=(BPsyst+2BPdias)/3, where BPsyst and BPdias are systolic and diastolic blood pressure, respectively.

The fluid loss as a function of the time was considered to be constant during the dialysis session and was recorded as total ultrafiltration.

Statistical analyses were performed using the SAS System (Statistical Analysis System). Comparisons between body weight, potassium concentration and haemodynamic parameters were done first with an ANOVA and followed, if significant by a paired t-test performed between the mean values obtained in each patient with each modality. To improve the probability of showing significant differences, the haemodynamic parameters within the tertiles were compared against the dialysate potassium concentration cut-off points (-1 vs. +1 mmol/l). Percentages were compared using a Fisher Exact test. In all cases, a P ≤ 0.05 was considered statistically significant; P was expressed as ns (not significant) and as significant (P ≤0.05).

REFERENCES:

See Citations ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Haemodialysis

• NCT number: NCT01224314
• Study type: Interventional
• Source: Ospedale Regionale di Locarno
• Status: Completed
• Phase: N/A
• Start date: September 2007
• Completion date: December 2007