Citrate Pharmacokinetics in Critically Ill Liver Failure Patients Receiving CRRT

Study Overview
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Brief Summary
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Citrate has been proposed as anticoagulation of choice in continuous renal replacement therapy (CRRT). However, little is known about the pharmacokinetics (PKs) and metabolism of citrate in liver failure patients who require CRRT with regional citrate anticoagulation (RCA).

Detailed Description
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This study aimed to evaluate citrate PKs, metabolic complications, and clinical outcomes among critically ill acute liver failure (ALF) and acute on top chronic liver failure (ACLF) patients receiving CRRT.

Official Title
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Citrate Pharmacokinetics in Critically Ill Liver Failure Patients Receiving CRRT

Conditions
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Citrate Toxicity, Regional Citrate Anticoagulation, Liver Failure, Acute, Liver Failure, Acute on Chronic, Pharmacokinetic, Continuous Renal Replacement Therapy

Intervention / Treatment
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* Diagnostic Test: Pharmacokinetic study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill ALF or ACLF adult patients with AKI aged ≥ 18 y old Currently receiving CRRT. Exclusion Criteria: severe acidosis (pH < 7.1) or severe alkalosis (pH > 7.55) blood transfusion within 24 h prior to the study use of citrate-containing medications severe hypocalcemia (serum ionized calcium < 0.8 mmol/L) use of heparin as anticoagulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acute Liver Failure<br>Acute liver failure critically ill patients receiving CRRT | Diagnostic Test: Pharmacokinetic study<br>* Start CVVH session with isotonic citrate solution (13.3 mmol/L) as predilution, targeting citrate dose at 3 mmol/L Blood samples collection at pre-filter for citrate concentration, blood gas, electrolyte and ionized calcium and magnesium In addition, 10 minutes after the end of citrate infusion, blood samples were taken simultaneously from both pre-filter and post-filter to calculate citrate clearance by filter<br>|
| Experimental: Acute on top Chronic Liver Failure<br>Acute on top chronic liver failure critically ill patients receiving CRRT | Diagnostic Test: Pharmacokinetic study<br>* Start CVVH session with isotonic citrate solution (13.3 mmol/L) as predilution, targeting citrate dose at 3 mmol/L Blood samples collection at pre-filter for citrate concentration, blood gas, electrolyte and ionized calcium and magnesium In addition, 10 minutes after the end of citrate infusion, blood samples were taken simultaneously from both pre-filter and post-filter to calculate citrate clearance by filter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Citrate clearance | Citrate clearance by body | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Citrate accumulation | Number of total calcium to ionized calcium ratio > 2.5 with acidosis with hypocalcemia | 4 hours | 
| Tmax | Time to maximum concentration of citrate at 2 hours | 2 hours | 
| Area under the time curve | Area under the plasma concentration-time curve of citrate | 4 hours | 
| Change of systemic ionized calcium | Change in systemic ionized calcium in arterial blood gas during study | 4 hours | 
| Change of ionized magnesium | Change in systemic ionized magnesium in arterial blood gas during study | 4 hours | 
| Change of bicarbonate | Change of bicarbonate in arterial blood gas during study | 4 hours | 
| Ratio of total calcium to systemic ionized calcium | Number of patients with total calcium to systemic ionized calcium > 2.5 with or without metabolic acidosis | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Regional citrate anticoagulation, Liver failure, Pharmacokinetics, Cirrhosis, CRRT