INDIVIDUALISED DIALYSATE SODIUM PRESCRIPTION IN PATIENTS WITH INTRADIALYTIC HYPERTENSION

Introduction:

With the increasing prevalence of non-communicable medical problems such as Diabetes Mellitus, Hypertension and Arthrosclerosis, prevalence of chronic kidney disease (CKD) is also increasing around the world.  At present time, patients with CKD undergo renal replacement therapy (RRT) such as hemodialysis, peritoneal dialysis and renal transplant surgery. Although these treatment measures can improve patients’ mortality, morbidity and quality of life, renal replacement therapy itself can be associated with some adverse reactions, including intradialytic hypertension in HD patients. The common cause of death in CKD patients is cardiovascular diseases which is associated with long standing hypertension and left ventricular hypertrophy. Various studies found that intradialytic hypertension was associated with increased mortality and hospitalization. Long standing intradialytic hypertension leads to hypertension which is difficult to treat and it may lead to structural damage to the heart such as left ventricular hypertrophy. Some studies found that Intradialytic hypertension was linked with patients’ interdiaytic weight gain, sodium and water retention, sympathetic overactivity, endothelium receptor abnormality and renin-angiontension-aldosterone system activation. Adjusting dialysate sodium concentration based on patients’ blood sodium level can lower patients’ sodium retention thereby decrease blood pressure. In Myanmar, number of hemodialysis patients is increasing dramatically together with rising CKD population. It is needed to identify the distribution of intradalytic hypertension among dialysis population. To achieve better blood pressure control among dialysis patients, non-pharmacological measures like managing fluid overload and sodium retention are important apart from pharmacological measures. Using dialysate sodium concentration higher than plasma could contribute to an increase in the interdialytic fluid ingestion thereby leading to increase blood pressure resulting in intradialytic hypertension. Adjusting dialysate sodium concentration based on patients’ pre-dialysis serum sodium concentration is one of the management options for intradialytic hypertension. Therefore, it is needed to find out the effectiveness of individualized dialysate sodium prescriptions among patients with intradialytic hypertension.

Methods:

This study was a hospital based interventional study. All CKD patients treating with maintenance hemodialysis meeting inclusion criteria at No (1) Defense Services General Hospital were included. Inclusion Criteria 1. Age of 18 years and above 2. CKD patients treating with maintenance haemodialysis at least 2 times per week for more than 1 month. 3. CKD patients treating with maintenance haemodialysis with Pre and Post- dialysis MAP difference>15mmHg at least 3 heamodialysis sessions in 6 consecutive haemodiaysis sessions. Exclusion Criteria 1. Patients with life threatening arrhythmia. 2. Patients with GCS less than 7. 3. Patients with pregnancy. 4. Patients with known case of malignant diseases.

Results:

To study the effects of individualized intradialytic sodium prescription, total of 204 dialysis patients from Dialysis Center, Nephrology Department, No (1), Defence Services General Hospital (1000 Bedded) were accessed. (It was studied from October 2016 to September 2018). A total of 57 patients on regular haemodialysis met the inclusion criteria and the definition of intradialytic hypertension. Three patients dropped out (1-death, 1-lost follow up and 1-withdrown) Thus, fifty-four patients were analysed at the end of the study. Among 204 CKD patients treating with maintenance hemodialysis, 57 patients (27.94%) met definition of intradialytic hypertension. Among 204 CKD patients treating with maintenance hemodialysis, 57 patients (27.94%) met definition of intradialytic hypertension. 

Regarding the age distribution, the majority were 41 to 60 years. Only 25% of cases were over 60 years. The mean age was 54.11 year and youngest age was 34 and the eldest was 72 year. 

Out of 54 patients, 31 patients (57.4 %) were female and 23 patients (42.6 %) were male. It represents male/female ratio of 1.35. Thirty patients (56% of study population) had hypertension, while 20 patients (37%) had diabetes mellitus. 

Three patients (5%) had glomerulonephritis and 1 patient (2%) had history of obstructive uropathy previously. 

Majority of patients (40.7%) in this study were taking two antihypertensive medications while 5.6% of study population were treated with combining four antihypertensive medications. Eight patients (14.8%) were taking only one antihypertensive medication. 21 patients (38.9 % of study population) were taking three drugs for hypertension. The most commonly used anti-hypertensive drug was calcium blocker (98.1%). It was followed by alpha blocker (33.3%) and diuretics (20.4%). The lowest number of patients took ARB (5.6%). Only 13% of study population were on methyl dopa. During study period, dosages of anti-hypertensive medication were not restricted and can be modified according to their clinical status and response. Ten patients (18% of patients) were needed to increase their dosage of anti-hypertensive medications whereas dosages of 2 patients (4 %) were reduced. Most of the patients (78%) were remained in same dosage of drugs during study period. During study period, adding or omitting of anti-hypertensive medications were not restricted and can be modified according to their clinical status and response. Six patients (11%) required new anti-hypertensive medications or adding dose whereas  only one patient (2 %) could reduce the medication. Most of the patients (87%) were remained in same dosage of drugs. 

Pre-HD/Post-HD sodium was measured 1st HD, 6th HD and 12th along standard phase. During individualized phase, pre-HD sodium was measure before HD in every HD sessions. Regarding post-HD, it was taken 1st HD, 6th HD and 12th HD sessions. The pre-HD blood was drawn prior to connection of the blood lines (arterial tubing) to the vascular access and after removal of the saline and anti-clotting agent. In patients with tunneled catheter, blood was drawn from arterial port of catheter. Initial 10 ml of blood from arterial port was discarded as it may mix with anti-coagulant or saline. After that, new 3 ml syringe was used to take blood sample from tunneled catheter. Regarding post-HD sample, blood was drawn after completion of the HD treatment and prior to commencing the rinse-back procedure. Blood was drawn with 3 ml syringe from sampling port after stopping the blood pump or reducing blood flow to 100 mL/min for 15 seconds. During standard phase, the range of pre-HD serum sodium value varied from 128 mmol/L to 145 mmol/L. 

The mean pre-HD serum sodium value was 136.15  mmol/L. In  individualized phase, the mean pre-HD serum sodium value was  lower than standard phase and it was 134.93 mmol/L. The minimum  value was 129 mmol/L and maximum  was 143 mmol/L. Its maximum value was even lower than the  standard phase. During standard phase, pre-HD serum sodium and post-HD serum sodium were compared using paired-t test, and it was significantly increased after HD, confirming that there was increased sodium retention after HD. (p= 0.002) Regarding post HD value, in standard phase, the mean post-HD serum sodium value was 137.37 mmol/L. The range of post HD serum sodium value varied from 133 mmol/L to 143 mmol/L. In individualized phase, the mean post-HD serum sodium value was lower than standard phase and it was 132.05 mmol/L. The minimum value was 127 mmol/L and maximum was 140 mmol/L. Both minimum and  maximum  value were  lower than that of  standard phase. In individualized phase, pre-HD serum sodium and post-HD serum sodium were compared using paired student T test, and it was significantly decreased after HD, confirming that individualized dialysate sodium prescription can reduce sodium retention after HD. (p=<0.001) During standard phase, individualized dialysate sodium prescription was set to default. As usual, it was set to 140 mmol/L for dialysate sodium prescription. During individualized phase, dialysate sodium prescriptioin was given according to patients’ pre-dialysis serum sodium level. It was calculated by using Donnan’s coefficient, by multiplying serum sodium concentration with Donnan’s coefficient 0.95. In present study, the minimal prescribed dialysate sodium value which can be set in HD machine was 130 mmol/L. If it was adjusted below 130 mmol/L, dialysate conductivity would be too reduced. The normal value of dialysis conductivity was  Therefore, if patients’ serum sodium value was less than 135 mmol/L, or calculated dialysate sodium value was less than 130 mmol/L, dialysate sodium value was set to 130 mmol/L. Mean value of dialysate sodium prescription was 130.67 mmol/L. Dialysate sodium was adjusted from 130 mmol/L  which is the lowest prescribed value, to 136 mmol/L, the highest prescribed value. 

Pre-HD and post-HD blood pressure were recorded each dialysis session in both phase of study. Pre HD blood pressure was measured prior to needle insertion in those with functioning AV fistula or prior to connection with catheter in those having tunneled catheter/temporary catheter. The blood pressure, pulse rate, oxygen saturation were monitored hourly during HD. Mean blood pressure of patients for each dialysis session was also calculated. Pre and post BP changes were also analyzed by paired student-T test.  In standard phase, the mean pre-HD SBP and post-HD SBP were 151.35 mmHg and 175.10 mmHg respectively. Thus, the post HD systolic blood pressure was significantly higher than that of pre HD. ( p =<0.001 ) The possible reasons were rapid same as intradialytic hypertension, rapid infusion of saline after HD, dialysate sodium concentration, usage of dialyzable anti-hypertensive medications, ESA dosing, skipping morning dose of anti-hypertensive medications and anxiety during dialysis. In individualized phase, the mean pre-HD SBP and post-HD SBP were 145.68 mmHg and 150.48 mmHg respectively. After adjusting individual dialysate sodium concentration according to prior serum sodium level, their post HD systolic blood pressure was still significantly higher than that of pre HD. (p =0.008). However, it was lower than that of standard phase. Regarding the highest systolic blood pressure, it was 220 mmHg in both pre and post state in first phase. After handling the dialysate, it was 182 mmHg and 173 mmHg respectively. Thus, the systolic pressure measurement were significantly lower than that of standard phase. Pre-HD and post-HD blood pressure were recorded each dialysis session in both phase of study. Pre HD blood pressure was measured prior to needle insertion in those with functioning AV fistula or prior to connection with catheter in those having tunneled catheter/temporary catheter. The blood pressure, pulse rate, oxygen saturation were monitored hourly during HD. Mean blood pressure of patients for each dialysis session was also calculated. Pre and post BP changes were also analyzed by paired student-T test. In standard phase, the mean pre-HD DBP and post-HD DBP  were 84.29  mmHg and 92.38 mmHg respectively. Thus, the post HD diastolic blood pressure was significantly higher than that of pre HD. ( p = <0.001 ) The possible reasons were  the same  as that of systolic pressure. The compliance of vessels may play a role too. In individualized phase, the mean  pre-HD DBP and post-HD DBP were 85.10  mmHg and 83.13  mmHg respectively. Although individual dialysate sodium concentration according to prior serum sodium level was adjusted, their post HD diastolic blood pressure was not significantly changed. ( p = 0.004 ). Although, the mean pre-HD DBP  in both phase were the same  in both phases, that of   post-HD DBP  was different significantly. It may be due to changes in dialysate sodium concentration . During standard phase of study, mean pre-HD MAP and post-HD MAP were 106.64 mmHg and 119.87 mmHg respectively. The lowest pre-HD MAP was 73 mmHg in both pre-HD and post-HD measurement. The highest pre-HD BP was 153 mmHg whereas 157 mmHg in post-HD BP measurement. During individualized phase of study, mean pre-HD SBP and post-HD SBP were 105.30 mmHg and 105.51 mmHg respectively. The lowest pre-HD SBP was 77 mmHg and the highest pre-HD BP was 147 mmHg whereas 82 mmHg lowest and 147 mmHg highest in post-HD BP measurement. Regarding mean arterial pressure, it was significantly higher in standard phase, from pre-HD to post-HD. (p= <0.001)  However, it was the same in individualized phase pre-HD to post-HD, and significant changes was not observed. (p=0.822) 

IDWG was 2.52 kg and 2.12 kg in standard phase and individualized phase respectively. The lowest IDWG was 1 kg in both pre-HD and post-HD measurement, the highest IDWG was also 1 kg and 5 kg respectively in standard phase and indivualized phase. The inter-dialytic weight gain was lower in individualized phase. (p=<0.001) Patients’ SBP were recorded and compared using paired sample t-test for each HD session. 

After comparing  the blood pressure of each HD session for  the standard  and  individualized phase, pre-HD SBPs were significantly reduced in individualized phase (p value = <0.001). However, those of early HD session (HD 1, HD 2, HD 3, HD 4 and HD 6) in standard phase were not significantly changed. Post-HD SBPs were reduced in all HD sessions during individualized phase. (p value = <0.001) Patients’ DBP were recorded and compared using paired sample t-test for each HD session. After comparing each HD session for standard and individualized phase, pre-HD DBP changes were not significant. However, post-HD DBPs were reduced significantly in all HD sessions during individualized phase. (p value = <0.001) The MAP was recorded and compared using paired sample t-test for each HD session. After comparing each HD session for standard and individualized phase, pre-HD MAP changes were less significance except 8th HD session and 12th HD session. There was significant reduction in MAP of Post-HD in all HD sessions during individualized phase. (p value = <0.001)

Patients’ IDWGs were recorded and compared using paired sample t-test for each HD session. After comparing each HD session for standard and individualized phase, IDWG were reduced in individualized phase and significant (p value = <0.001) except 2nd HD session. 

 MAP difference is the difference between post-HD MAP and pre-HD MAP. In standard phase mean MAP difference is 13.24 mmHg but it dropped to 0.21 mmHg in individualized phase. The lowest MAP difference in standard phase was -2.22 mmHg while highest was 28.47 mmHg. In individualized phase, minimum value of MAP difference was -18.33 mmHg and the maximum value was 18.89 mmHg. In standard phase, only 60% (30/54) of cases had minimum variation in MAP. In individualized phase, more than 95% (53/54)  of patients had the least change in MAP. It showed that dialysate sodium handling based on initial serum sodium had significant impact on MAP. 

Serum sodium level, SBP, DBP, MAP and IDWG were recorded both pre and post-HD during study period. SBP difference, DBP difference and MAP difference were calculated. All variables were compared between standard phase and individualized phase, using paired sample T-test. Pre-HD serum Sodium value in standard phase was 136.15± 3.46 mmol/L whereas it was 134.93±2.96 mmol/L in individualized phase. Post-HD serum sodium  value was 137.37±2.37 mmol/L and 132.05±2.63 mmol/L in standard phase and individualized phase respectively. It was clear that both pre-HD and post-HD serum sodium values were reduced in individualized phase significantly. (p =  <0.001) Pre-HD SBP in standard phase was 151.35±15.53 mmHg and it was 145.68±13.44 mmHg in individualized phase. Post-HD SBP was 175.10±15.42 mmHg and 150.48±12.63 mmHg in standard phase and individualized respectively. It can be seen that both pre-HD and post-HD SBP were reduced in individualized phase significantly. (p =  <0.001)             Pre-HD DBP was 84.29±11.34 mmHg in standard phase and 85.10±6.76 mmHg in individualized phase. Post-HD DBP was 92.38±11.37 mmHg and 83.13±6.05 mmHg in standard phase and individualized phase respectively. Pre-HD DBP was slightly increased in individualized phase and it was not statistically significant. (p= 0.48). However, post-HD DBP was reduced in individualized phase significantly. (p =  <0.001) Pre-HD MAP was 106.64±10.92 mmHg in standard phase and 105.30±7.63 mmHg in individualized phase. Post-HD MAP was 119.87±10.99 mmHg and 105.51±6.90 mmHg in standard phase and individualized phase respectively. Pre-HD MAP was slightly increased in individualized phase and it was not statistically significant. (p= 0.21). Nevertheless, post-HD MAP was reduced in individualized phase significantly. (p =  <0.001) SBP difference was the difference between post-HD SBP and pre-HD SBP. Mean SBP difference in standard phase was 23.75 ±13.71 mmHg whereas 4.80 ±12.69 mmHg in individualized phase. Thus, SBP difference was significantly reduced in individualized phase of the study. (p = <0.001) DBP difference was the difference between post-HD DBP and pre-HD DBP. The mean DBP difference in standard phase was 8.08 ±4.87 mmHg whereas it was      -1.97 ±4.77 mmHg in individualized phase. So, DBP difference was reduced significantly in individualized phase of the study. (p = <0.001) MAP difference was the difference between post-HD MAP and pre-HD MAP, The mean MAP difference in standard phase was 13.23±6.62 mmHg whereas 0.21±6.81 mmHg in individualized phase. The MAP difference dropped in individualized phase of the study. (p = <0.001) IDWG was the amount of weight gain during inter-dialytic period. IDWG was calculated by subtracting post-HD body weight after last HD, from pre-HD body weight of current HD. IDWG was significantly reduced in individualized phase of the study. (p = <0.001) 

Regarding adverse reactions during HD were recording during study period. Common adverse effects were categorized into dizziness, cramps and intradialytic hypotension. Patients who were experienced during HD at any phase, or any times, it was counted and recorded. During standard phase of study, dizziness occurred in 24 patients (44.4%), cramps occurred in 3 patients (5.6%) and 27 patients were free of adverse effects. During individualized phase, 16 patients (29.6%) had dizziness, 3 patients had cramps (5.6%) and 2 patients had intradialytic hypotension (3.7%) while 33 patients (61.1%) were not suffered from any adverse reaction during HD. These adverse reactions were compared using Pearson Chi-Square test, although more patients were found to be free of adverse effects and reduced population of dizziness in individualized phase, patients with intradialytic hypotension were observed during individualized phase. There was no significant reduction of adverse effects in individualized phase. (p= 0.078)

Conclusions:

In conclusion, paradoxical raise in BP after HD also termed as intradialytic hypertension is common in daily practice. ESRD is the complex syndrome which is associated with adverse cardiovascular outcomes. Most of the ESRD patients being treated with hemodialysis have history of hypertension resulting target organ damage including left ventricular hypertrophy. Being suffered from intradialytic hypertension, especially increase in SBP post-HD, there is increased risk of mortality and hospitalization rate. To counteract intradialytic hypertension, not only the pharmacological measures, but also non pharmacological measures like reducing dialysate sodium according to patients’ serum sodium or individualized dialysate sodium prescription was found to have a certain role in managing.             ESRD patients are unable to maintain sodium balance naturally thus HD is the major route to maintain sodium balance especially in those without residual renal function. During HD, patients’ blood is exposed to dialysate solution leading to diffusive and convective shifts of electrolytes. Normally, sodium concentration in standard dialysate solution is set to 138 mmol/L to140 mmol/L by default in machine. This amount of concentration is usually higher than patients’ serum sodium concentration and not fit for every patient, resulting sodium retention thereby inadequate fluid removal or fluid re-accumulation. Although those changes are subtle, the amount of sodium and fluid retention can result in increased BP gradually, and raised post-HD BP. According to various researches, increasing interdialytic weight gain and sodium retention is taking part as one of the culprits for intradialytic hypertension. Based on the results of present study, individualized dialysate sodium prescription can be observed as simple and useful measure to prevent intradialytic hypertension. The data indicate that individualized dialysate sodium prescription can act as adjuvant measure to lower not only occurrence of intradialytic hypertension but also interdialytic BP by lowering pre-HD BP. It can also help to reduce inter dialytic weight gain thereby better fluid management. The present study suggests that individualized dialysis sodium prescription in consecutive HD sessions is one of the particular measures in managing intradialytic blood pressure as well as hypertension in HD patients. Although it is difficult to practice individualized dialysate sodium prescription in routine HD, prescribing the lower amount of dialysate sodium close to patients’ serum sodium can have a certain role in managing intradialytic hypertension. 

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.