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