HEmoFiltration With Citric Acid Anticoagulation (HEFCAA)

Evaluation of Safety and Efficacy of a Regional Anticoagulation Protocol for Continuous Renal Replacement Therapies.

Prospective observational study of all consecutive cardio-vascular surgical patients treated with post-dilution hemofiltration with regional citrate anticoagulation as first-choice anticoagulation method. The filter life-span was assessed in the context of postoperative cardiac surgical antithrombotic prophylaxis. Reasons for termination of hemofiltration sessions were assessed. The second aim of this study was to assess the influence ACD-A based anticoagulation protocol on acid-base and ion homeostasis in cardiac surgical patients with acute renal failure.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Renal Replacement Therapy; Acute Kidney Failure; Hemofiltration
• Intervention / Treatment: Procedure: Hemofiltration with regional citrate anticoagulation

Detailed Description

All consecutive cardio-vascular surgery patients treated with post-dilution hemofiltration with regional citrate anticoagulation (HF RCA) from August 2015 through November 2017 were included to prospective audit. Indication to hemofiltration treatment was based on clinical assessment of patients renal function and clinical status by attending physician and conformed conventional indications to renal replacement therapy (RRT) in intensive care unit (ICU). Severe chronic liver disease or acute liver injury with INR > 2 and refractory shock with lactate increasing above 8 mmol/L were considered as contraindication to RCA.

Initially set blood flow was 5 times higher than filtrate flow, which makes filtration fraction of 20%. To reduce the risk of metabolic alkalosis, ACD-A citrate solution was proposed instead of most commonly used trisodium citrate solution, and relatively low target citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35 ml/kg/hour down to 25 ml/kg/hour which should reduce bicarbonate synthesis by 25%. If metabolic alkalosis persisted, the second step involved reduction of blood flow from initial 5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.

In order to avoid hypomagnesemia resulting from magnesium binding to citrate, and its removal with ultrafiltrate not balanced with magnesium content in replacement fluid, the original protocol was modified by connecting magnesium sulfate solution 2g/50 ml 0.9% NaCl at the flow 1 mL/hour.

All sessions stopped due to patients death before 48 hours of HF treatment were excluded from the analysis. Similarly, all cases where hemofiltration session was stopped before 48 hours of treatment due to organizational reasons, recovery of renal function, change of therapy, and when patients were treated with heparin infusion due to surgical indications were excluded from further circuit survival analysis.

Blood gas parameters together with pH, bicarbonate concentration, Na, Cl, K, Ca, hemoglobin concentration, hematocrit, lactate, and anion gap were analyzed every 6 hours. Post filter ionized calcium concentration was not assessed. Serum phosphate, magnesium and total calcium was assessed every 24 hours during hemofiltration treatment with RCA.

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

Study Locations

• Poland
  • Polska
    • Gdańsk, Polska, Poland, 80-516
      • Romuald Lango

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All consecutive cardio-vascular surgery patients treated with post-dilution hemofiltration with regional citrate anticoagulation from August 2015 through November 2017

Description

Inclusion Criteria:

• cardiac and vascular surgery patients treated with continuous hemofiltration with regional citrate anticoagulation

Exclusion Criteria:

• severe chronic liver disease, acute liver injury with INR > 2, and refractory shock with lactate increasing above 8 mmol/L

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

HF RCA; Cardiovascular surgery patients treated with hemofiltration with regional citrate anticoagulation

Procedure: Hemofiltration with regional citrate anticoagulation; To reduce risk of metabolic alkalosis during hemofiltration treatment, ACD-A citrate solution was proposed instead of most commonly used trisodium citrate solution and relatively low target citrate concentration (2.8 mmol/L) was adopted. In case of pH increase above 7.5 or bicarbonate concentration above 40 mmol/L filtrate flow was decreased from initial 35 ml/kg/hour down to 25 ml/kg/hour which reduced bicarbonate delivery by 25%. If metabolic alkalosis persisted, the second step involved reduction of blood flow from initial 5 times down to 4 times filtrate flow, which reduced citrate flow by the same factor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemofiltration circuit survival time	in hours	up to 120 hours from the beginning of hemofiltration session
Incidence of metabolic alkalosis	Arterial blood pH>7.5 or BE > 40 mmol/L	From the beginning of hemofiltration session until 6 hours after its end
Incidence of hypernatremia and hyponatremia	Incidence of hypernatremia> 150 mmol/L and hyponatremia < 130 mmol/L in arterial blood sample	From the beginning of hemofiltration session until 6 hours after its end

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of citrate accumulation	Incidence of total to ionized calcium ratio > 2,5 in arterial blood sample	From the beginning of hemofiltration session until 24 hours after its end

Collaborators and Investigators

• Sponsor: Medical University of Gdansk

Publications and helpful links

General Publications

• Kirwan CJ, Hutchison R, Ghabina S, Schwarze S, Beane A, Ramsay S, Thompson E, Prowle JR. Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution. Blood Purif. 2016;42(4):349-355. doi: 10.1159/000452755. Epub 2016 Nov 19. Erratum In: Blood Purif. 2017;43(1-3):144.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2015
• Primary Completion (Actual): November 10, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 8, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 11, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: NKBBN/539/2016-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD are to be shared with other researcher

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No