Patients Undergoing Continuous Venovenous Hemodiafiltration: Effects of Increased Blood Flow

December 14, 2023 updated by: Hospital Israelita Albert Einstein

Evaluation of Filters Useful Life, Metabolic Control, Electrolyte Profile and Acid-base Balance During Regional Anticoagulation With 4% Trisodium Citrate in Patients Undergoing CVVHDF: Effects of Increased Blood Flow

Acute Kidney Injure (AKI) is a syndrome with high incidence and prevalence in Intensive Care Units (ICU). It is estimated that 50% of the in the sector present AKI at some point and 10 to 15% require renal replacement therapy (RRT). Although studies do not show the superiority of continuous methods, the most severely ill patients are directed to this type of RRT. A disadvantage of continuous therapies is the need for anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture).

On the one hand, ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter clotting. There is no consensus on what would be the optimal blood flow (Qb) in continuous dialysis, especially when regional citrate anticoagulation (RCA) is used. Theoretically, a higher flow rate would prevent stasis in the system and decrease the risk of filter clotting. Studies show conflicting results. Increasing Qb from 150 to 250 mL/min showed that circuit life and the chance of coagulation were similar. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow. Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter. Therefore, the higher the convection rate, the higher the blood flow should be to keep the FF in the optimal range. Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing the blood flow, the citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could cause its overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when its maximum metabolizing capacity is not reached and there is an excess of citrate infusion relative to the buffering requirement. Thus, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients undergoing continuous venovenous hemodiafiltration (CVVHDF), regional citrate anticoagulation during blood flow augmentation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Acute kidney injury (AKI) is a clinical syndrome with a high incidence and prevalence in Intensive care units (ICU). It is estimated that 50% of ICU patients have AKI at some point.

About 10-15% of these individuals require renal replacement therapy (RRT). Although studies have not conclusively shown the superiority of continuous methods, the most severe patients are usually referred for this type of therapy.

The main indications for continuous therapies are hemodynamic instability, cardiogenic shock, severe respiratory insufficiency, risk situations for brain edema, hypercatabolism, need for strict volume control, acute liver disease and major sodium disturbances. One of the main disadvantages of continuous therapies is the necessity of anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture). On the one hand, the lack or ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter coagulation. On the other hand, excessive use of anticoagulants, especially heparin, is associated with bleeding and increased transfusions.

In this scenario, regional anticoagulation with citrate (RCA) has become the method of choice in the different modalities of continuous dialysis. When compared to heparin, the use of regional citrate anticoagulation is associated with less bleeding and transfusion need and longer life of the extracorporeal system. It also seems to decrease endothelial activation, neutrophil degranulation and activation of the complement system.

The anticoagulate property of citrate is based on its binding to calcium (Ca). Citrate quenches Ca in the extracorporeal system, an essential cofactor in several steps of coagulation. Optimal anticoagulation is achieved when ionic Ca concentration in the extracorporeal circuit is maintained between 0.25 and 0.35 mmol/L. This is usually achieved with a citrate level in the circuit around 4mmol/L of blood. Depending on the modality chosen and other factors, up to 60% of the citrate-Ca complex is eliminated during passage through the filter (molecular weigh of 298 Daltons and partition coefficient of 1.0). The rest is metabolized in the Krebs cycle mainly in the liver, kidneys and skeletal muscles. Each mol of trisodium citrate causes 3 moles of bicarbonate thus correctly, partially or completely, the metabolic acidosis resulting from renal failure. Ca and sodium (Na) are released into the systemic circulation. Trisodium citrate also increases the strong ion difference due to the high sodium concentration in the solution, thus increasing the buffering capacity. In parallel it is necessary the Ca replacement to maintain normal calcemia. The citrate also quenches magnesium, which can lead to a disturbance of this electrolyte.

There is no consensus on what the optimal blood flow (Qb) would be in continuous dialysis, especially when using regional citrate anticoagulation. Theoretically, a higher blood flow would prevent stasis in the system and thus decrease the risk of filter coagulation. Studies show conflicting results. For example, one study evaluated increasing Qb from 150 to 250 mL/min and showed that circuit useful life and the chance of coagulation of the extracorporeal system were similar between the two groups. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultra-filtrated flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher the convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range.

Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing blood flow, citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could lead to citrate overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when the maximum capacity of citrate metabolization is not reached and there is an excess of citrate infusion relative to the buffering requirement. The total Ca/systemic ionic Ca ration remains normal, below 2.5. The oversupply of citrate can be easily corrected by decreasing the bicarbonate concentration of the dialysate, increasing the dialysate dose or decreasing the citrate infusion.

Therefore, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients with AKI undergoing continuous venovenous hemodiafiltration (CVVHDF), regional anticoagulation with citrate during increased blood flow.

Hypothesis: Increasing blood flow during continuous venovenous hemodiafiltration prevents stasis in the system and thus reduces the risk of filter coagulation. Blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range. Therefore, it is expected that higher blood flow (250 mL/min) will reduce the FF and concomitantly prolong the life of the filter.

Study Type

Interventional

Enrollment (Estimated)

27

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 Contact

Study Contact Backup

  • Name: Hospital I Albert Einstein
  • Phone Number: +551121513729
  • Email: cep@einstein.br

Study Locations

  • Brazil
      • São Paulo, Brazil
        • Recruiting
        • Hospital Israelite Albert Einstein
        • Contact:
        • Principal Investigator:
          • Marcelino Durão Junior

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

Description

The inclusion criteria will be:

  • Age greater than 18 years.
  • Weight ≥ 50 Kg.
  • Agreeing to participate in the study (TCLE duly elucidated and signed by the patient or family member/guardian).
  • Admitted to the hospital ICU.
  • Acute Kidney Injury in need of RRT and indication (according to the evaluation of the assistant nephrologist) of continuous therapy.

Exclusion criteria will be:

  • Age < 18 years.
  • Weight < 50 Kg.
  • Refusal to participate in the study (absence of informed consent).
  • Patient with chronic kidney disease on dialysis

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Qb150

This group will be exposed to continuous venovenous therapy with a blood flow of 150ml/min; already standardized by the institution; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency.

Both groups will have a "wash out" of 6 hours before crossing the arms of the work.
Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
Patients will be exposed to continuous venovenous renal therapy with distinct blood flows in 2 periods, to be defined by draw. The control group will have a flow of 150ml/min and the intervention group 250ml/min. Therapy is intended for a period of 72 hours (maximum defined by the manufacturer); with a 6-hour "washout" and, after that, the arm is changed to be exposed to the other blood flow.
Active Comparator: Qb 250

This group will be exposed to continuous venovenous therapy with a blood flow of 250ml/min; experimental group to evaluate increased blood flow and filter durability; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency.

Both groups will have a "wash out" of 6 hours before crossing the arms of the work.
Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
Patients will be exposed to continuous venovenous renal therapy with distinct blood flows in 2 periods, to be defined by draw. The control group will have a flow of 150ml/min and the intervention group 250ml/min. Therapy is intended for a period of 72 hours (maximum defined by the manufacturer); with a 6-hour "washout" and, after that, the arm is changed to be exposed to the other blood flow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Analyze filter/system useful life
Time Frame: 72 hours per filter
Evaluate the duration of the continuous hemodiafiltration filter according to changes in blood flow
72 hours per filter

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Examine the system pressures
Time Frame: 72 hours per filter
Assess changes in system pressures during the 2 blood flows (transmembrane pressure, filter pressure and access pressure)
72 hours per filter
Mortality of the cohort
Time Frame: 30, 60 and 90 days
Assess the overall mortality of the cohort in 30, 60 and 90 days
30, 60 and 90 days
Assess filtration fraction variation
Time Frame: 72 hours per filter
Assess filtration fraction variation during the 2 blood flows
72 hours per filter
Electrolytic control - Potassium
Time Frame: 72 hours per filter (dosage every 12 hours according to protocol)
Assess changes in potassium (changes from baseline)
72 hours per filter (dosage every 12 hours according to protocol)
Electrolytic control - Sodium
Time Frame: 72 hours per filter (dosage every 12 hours according to protocol)
Assess changes in sodium (changes from baseline)
72 hours per filter (dosage every 12 hours according to protocol)
Acid-base balance - blood pH
Time Frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Assess changes in blood pH during the 2 blood flows (changes from baseline)
72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - sodium bicarbonate
Time Frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Assess changes in sodium bicarbonate during the 2 blood flows (changes from baseline)
72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - base excess
Time Frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Assess changes in base excess during the 2 blood flows (changes from baseline)
72 hours per filter (venous blood gas analysis every 12 hours)

Collaborators and Investigators

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

Sponsor

Hospital Israelita Albert Einstein

Investigators

  • Principal Investigator: Lucas T Avila Neto, Hospital Israelita Albert Einstein

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)

January 9, 2023

Primary Completion (Estimated)

January 31, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

March 14, 2023

First Submitted That Met QC Criteria

March 30, 2023

First Posted (Actual)

April 3, 2023

Study Record Updates

Last Update Posted (Actual)

December 15, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRRT-QbTrial

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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