Temperature and Bicarbonate: Hemodynamic Effects During Dialysis (TURBO)

May 17, 2022 updated by: University of Aarhus

Hemodynamic Effects of Low vs. High Dialysate Temperature or Bicarbonate Concentration in Chronic Hemodialysis Patients

To elucidate the role of dialysate temperature and bicarbonate on hemodynamic parameters, plasma pH and electrolytes that potentially mediate this effect, the investigators wish to conduct a single-blinded, randomized, controlled, crossover study, specifically examining the effects of

  • A fixed low temperature dialysate of 35°C compared to a fixed dialysate temperature of 37°C.
  • A low dialysate bicarbonate concentration of 30 mmol/L compared to a high dialysate bicarbonate concentration of 38 mmol/L.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

Intradialytic hypotension (IDH) is a common complication of hemodialysis (HD) and is considered one of the most frequent complications with a prevalence between 10-12% depending on the definition of IDH (1). IDH has been associated with inefficient dialysis (2), vascular access thrombosis (3) and mortality (4,5).

Orthostatic hypotension (OH) is another common complication in HD with a prevalence around 42% in patients initiating HD treatment (6). OH is significantly associated with worse outcome in HD patients in terms of an increased two-year mortality (4) and increased risk of all-cause death (6).

Understanding the mechanisms underlying IDH and OH has the potential to optimize HD treatment, in order to minimize the occurrence of IDH and OH, potentially improving not only patient mortality and morbidity but also the everyday comfort of chronic HD patients when receiving dialysis treatment.

This study will investigate the hemodynamic effect of alterations in dialysate bicarbonate and dialysate temperature.

Dialysate temperature

Several clinical studies have examined the effect of low temperature dialysate (LTD) on IDH, but only few have examined the hemodynamic response in detail with intradialytic measurements of cardiac output (CO), central blood volume (CBV) and total peripheral resistance (TPR) (7-14). Generally, the studies confirm a blood pressure (BP) stabilizing effect of LTD, but diverse results are found on changes in CO, CBV and TPR. Some studies found greater increase in TPR during dialysis with LTD compared to a higher dialysate temperature (8,9,11,14). Other studies found that intradialytic CBV (7,12) and CO (12) improved considerably with LTD.

One previous study (14) examined OH in relation to use of LTD, but not with detailed intradialytic hemodynamic measurements. The study showed that both supine and upright mean arterial blood pressure (MAP) were significantly lower after dialysis with a dialysate temperature of 37°C compared to a dialysate temperature of 35°C. Furthermore, the increase in TPR was greater during dialysis with LTD.

Dialysate bicarbonate

Few studies have investigated the effect of dialysate bicarbonate (DB) concentration on intradialytic hemodynamics and results have been conflicting. Lower DB (from 32 to 26 mmol/L or a reduction of 6 mmol/L, respectively) was in two cross-over studies (15,16) shown to increase systolic BP (SBP) by approximately 5 mmHg, whereas a third study reported no significant effect on BP (17). One of these studies also found an increase in TPR with lower DB (16). IDH has been associated with lower DB in one of the previously mentioned cross-over studies (15), but this association was not found by Gabutti et al in 2005 (17) or in larger observational studies (17-19). Manipulation of DB inevitably affects plasma pH of the patient during dialysis. Thus, if pH decreases with DB-induced acidosis, hydrogen ions displace cations such as calcium from protein binding sites. DB-induced alkalosis on the other hand increases pH, which promotes increased protein binding, which decreases free cation levels. At the same time, intracellular sequestration of potassium at high pH levels has also been speculated to lower plasma potassium levels (20). Consequently, by changing DB a range of electrolytes including calcium are potentially affected which could impact neuromuscular function and thereby intradialytic hemodynamic parameters and the frequency of IDH and OH (17,21-26).

Hypotheses

Hemodialysis or hemodiafiltration (HdF) sessions with a decreased dialysate temperature (35°C vs. 37°C) or decreased DB concentration (30 mmol/L vs. 38 mmol/L) will have the following effects:

  • An increase in SBP, MAP and orthostatic blood pressure (OBP).
  • An increase in one or more of the following: Cardiac output (CO), total peripheral resistance (TPR), central blood volume (CBV), stroke volume (SV) and/or heart rate (HR).
  • A decrease in the frequency of IDH and OH.

Study participants

Participants will be recruited from the maintenance HD and HdF population associated with the Department of Renal Medicine at Aarhus University Hospital in Denmark. These include the Dialysis Clinic at Aarhus University Hospital as the main hub and satellite dialysis clinics in Randers and Horsens.

Power and sample size

Measurements from 30 randomly selected HD patients in our clinic yielded SD = 23 mmHg for the difference between within-treatment changes in SBP (non-standardized conditions). Assuming a lower SD due to standardized BP-measurements and strict in- and exclusion criteria an SD = 12 mmHg was used as a reasonable estimate. Sample size calculation with Stata/IC 16.1 (StataCorp, 4905 Lakeway Dr, College Station, TX 77845, USA) using analysis for a one-sample mean test (t-test), assuming a minimal detectable difference in means (mean difference between the two within-treatment changes in SBP) = 10 mmHg; SD = 12 mmHg; two-sided significance level (alpha) = 0.05; power=0.80 resulted in 14 participants. However, to account for dropout of two participants, a sample size of 16 was chosen.

Dialysis machines, filters, and dialysate composition

Dialysis console Fresenius 5008F (Fresenius Medical Care, Bad Homburg, Germany) and HD or HdF filters regularly used for treatment of the patient will be used in all dialysis sessions.

The standard dialysate prescribed for each individual patient will be used in all dialysis sessions thereby maintaining similar composition regarding electrolytes such as sodium, potassium, calcium, magnesium and chloride. Bicarbonate concentration will only be adjusted in the sessions investigating low (30 mmol/L) and high (38 mmol/L) DB concentration, respectively. Dialysate will be prepared on-line by the dialysis machine. Blood flow rate and dialysate flow rate will be kept as usual and will remain equal in all sessions regardless of intervention. Ultrafiltration rate will be kept constant and equal in the two dialysis sessions. The same applies for the volume of substitution fluid in HdF.

Orthostatic hypotension (OH)

OH is defined as a reduction in SBP of at least 20 mmHg or in DBP of at least 10 mmHg within 3 minutes of standing (27).

Intradialytic hypotension (IDH)

IDH is defined as a decrease in SBP ≥20 mmHg or a decrease in MAP ≥10 mmHg associated with clinical events/symptoms (e.g. muscle cramps, abdominal discomfort, nausea or vomiting, dizziness or fainting, restlessness or anxiety, yawning or signing) and/or need for intradialytic interventions (Trendelenburg positioning, fluid administration, reduction in ultrafiltration rate, reduction of blood flow rate) or dialysis treatment cessation (28).

Intradialytic measurements

Cardiac output (CO) will be obtained by a previously validated ultrasound dilution technique using Hemodialysis Monitor HD03, Flow-QC tubing sets, and clip-on flow/dilution sensors from Transonic Systems Inc., Ithaca, NY, USA (29-32). The ultrasound sensors will be positioned on the arterial and venous Flow-QC tubing set using standard ultrasound gel to secure good contact. Access recirculation in the AV-fistula can invalidate CO-measurements. A built-in recirculation protocol will be used to check for access recirculation using injection of 10 mL isotonic saline into the venous blood line prior to the first CO-measurement. If recirculation is detected the dialysis needles will most likely be reinserted. CO will be measured in duplicate by injecting a bolus of 30 mL 37°C isotonic saline into the venous blood line within 5 seconds. If results deviate more than 15% a third measurement will be done. The mean of the two closest recordings will serve as the result. With the Transonic device intradialytic hemodynamic parameters are obtained at 10, 70, 130, 190, and 230 minutes. Patients will be lying in a supine position with the head elevated 20 degrees. Before each CO measurement HR and BP will be measured. MAP, TPR, and SV are derived by the following equations:

MAP = diastolic BP + 1/3 x (systolic BP - diastolic BP)

CO = SV x HR = MAP/TPR

CBV is defined as the volume of blood in the heart, lungs and great vessels and is estimated with the Transonic device based on the CO measurement.

Blood samples and handling of biological material

Following the same time pattern as the Transonic measurements an arterial blood gas will be drawn from the arterial cannula.

Eleven blood samples will be taken from the arterial blood line via the AV-cannula used for dialysis treatment. Four of the samples will be regular blood samples of 3-4 mL, whereas 7 of the samples will be arterial blood gases of 1 mL. Thus, per session 22 mL blood per participant is collected which adds up to a total of 88 mL for the entire study period. The purpose of this is to determine several essential parameters:

  • Electrolytes such as calcium, magnesium, and potassium
  • Acid-base status: pH, standard bicarbonate, standard base excess
  • Hemoglobin, hematocrit
  • Urea for the determination of Kt/V and URR.
  • White cell count and C-reactive protein in the first blood sample in order to confirm the absence of infection

All blood samples will be transferred to the laboratory according to standard routine and analyzed according to current clinical standards at Department of Clinical Biochemistry, Aarhus University Hospital or local Department of Clinical Biochemistry normally servicing our satellite dialysis clinics in Randers and Horsens. Blood gas tests are analyzed using ABL blood gas analyzer (Radiometer, Radiometer Medical ApS, Brønshøj Denmark). All blood samples will be destroyed after analysis.

No samples will be stored in a biobank.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Region Midt
      • Aarhus, Region Midt, Denmark, 8200
        • Dialysis Clinic at Department of Renal Medicine, Aarhus University Hospital and affiliated dialysis clinics in Randers and Horsens

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Regular dialysis (HD or HDF) therapy for >3 months
  • Age >18 years
  • Stable and functional arteriovenous (AV)-fistula
  • Able to achieve a dialysis blood flow > 250 mL
  • Able to stand up for a minimum of 10 min
  • Able to undergo a 4 hour dialysis session without eating, drinking or sleeping
  • Proven cabable of cumulative ultrafiltration of 2% of end-dialytic weight (EDW)
  • Able to give informed consent to participation in the study
  • Hematocrit >30%
  • BMI >18 and <35

Exclusion Criteria:

  • Central venous catheter for HD or HDF
  • Recirculation in AV-fistula
  • Acute myocardial infarction within 3 months
  • Atrial fibrillation
  • Active malignant or infectious diseases
  • Cerebrovascular incident within 3 months
  • Pregnancy
  • Alcohol or drug abuse
  • History of interruptions during HD or untimely termination of HD treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low temperature
Dialysate temperature
Other: Low dialysate temperature
35°C
Active Comparator: High temperature
Dialysate temperature
Other: High dialysate temperature
37°C
Active Comparator: Low bicarbonate
Dialysate bicarbonate concentration
Other: Low dialysate bicarbonate concentration
30 mmol/L
Active Comparator: High bicarbonate
Dialysate bicarbonate concentration
Other: High dialysate bicarbonate concentration
38 mmol/L

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood pressure (BP)
Time Frame: 4 weeks
SBP (mmHg), Mean BP (mmHg) and Ortostatic BP (mmHg)
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intradialytic cardiac output
Time Frame: 4 weeks
CO (L/min)
4 weeks
Intradialytic total peripheral resistance
Time Frame: 4 weeks
TPR (mmHg/(L/min))
4 weeks
Intradialytic stroke volume
Time Frame: 4 weeks
SV (mL)
4 weeks
Intradialytic heart rate
Time Frame: 4 weeks
HR (beats/min)
4 weeks
Intradialytic central blood volume
Time Frame: 4 weeks
CBV (L)
4 weeks
Intradialytic mean arterial blood pressure
Time Frame: 4 weeks
MAP (mmHg)
4 weeks
Plasma calcium
Time Frame: 4 weeks
Calcium (mmol/L)
4 weeks
Plasma potassium
Time Frame: 4 weeks
Potassium (mmol/L)
4 weeks
Plasma magnesium
Time Frame: 4 weeks
Magnesium (mmol/L)
4 weeks
Intradialytic hypotension (IDH)
Time Frame: 4 weeks
IDH frequency (number of events)
4 weeks
Ortostatic hypotension (OH)
Time Frame: 4 weeks
OH frequency (number of events)
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Study Chair: Niels H Buus, Professor, Department of Renal Medicine, Aarhus University Hospital
  • Study Chair: Jens D Jensen, MD, PhD, Department of Renal Medicine, Aarhus University Hospital
  • Principal Investigator: Ina H Jørgensen, Student, Department of Renal Medicine, Aarhus University Hospital
  • Principal Investigator: Jonas SK Jensen, Student, Department of Renal Medicine, Aarhus University Hospital
  • Principal Investigator: Christian D Peters, MD, PhD, Department of Renal Medicine, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2021

Primary Completion (Actual)

December 20, 2021

Study Completion (Actual)

January 3, 2022

Study Registration Dates

First Submitted

August 26, 2021

First Submitted That Met QC Criteria

September 10, 2021

First Posted (Actual)

September 22, 2021

Study Record Updates

Last Update Posted (Actual)

May 18, 2022

Last Update Submitted That Met QC Criteria

May 17, 2022

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-06-21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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