Plasma CO2 Removal Due to CRRT and Its Influence on Indirect Calorimetry

Study Overview
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Brief Summary
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The aim of the present study is to assess the metabolic impact of Continuous Renal Replacement Therapy and overview the obstacles and important factors compromising the use of Indirect Calorimetry in CRRT and suggest a model to overcome these issues.

Detailed Description
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Acute kidney injury (AKI) complicates a critical illness from 13% up to 78%, needing renal replacement therapy (RRT) up to10 % of all patients in the intensive care unit (ICU). Both intermittent (IRRT) and continuous renal replacement therapy (CRRT) are used. The advantage of the latter is that it has lesser influence on hemodynamics and is better tolerated in critical ill patients. Another complication during their stay is the inability to feed themselves. Nutrition is a cornerstone in the care for the critical ill and should be started within 3 days of admission to the intensive care unit. To optimize a nutritional prescription, protein and energy targets need to be defined. Predicting formulae based on anthropometric measures and other parameters can be used to calculate the caloric need but indirect calorimetry (IC) remains the gold standard. Caloric need can be derived from Energy expenditure which is calculated with the Weir's equation using carbon dioxide (CO2) production (VCO2) and oxygen (O2) consumption (VO2). Therefore, it is underestimated if CO2 is lost through other means than the normal respiratory route. Hence one of the contra-indications of IC is CRRT. The totalCO2 (tCO2) travels through the vascular structures within the red blood cells or inside plasma. There, most of the content has 3 different forms: as physically dissolved CO2, bicarbonate, and carbamino compounds. These compounds are in equilibrium with each other. During RRT, a potential loss of CO2 and its different forms may occur due to ultrafiltration in the dialysate. No large trials were conducted trying to quantify this loss nor identifying the determining factors which can be used to predict this loss. Indeed, one author even found a gain in tCO2 of the blood during dialysis with acetate. Trisodiumcitrate is used as an anticoagulant during CRRT. It is a weak base and due to pH change may alter the equilibrium of the Henderson-Hasselbalch equation and thus influence the balance between CO2 and HCO3- and its extraction through CRRT. Although indirect calorimetry in the intensive care unit has been evaluated during CRRT, the loss of tCO2was not considered. The investigators explored the possibility to predict and easily calculate this CO2 exchange so IC can be used during CRRT.

Official Title
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MEtabolic Consequences of Continuous Renal Replacement Therapy and Impact on Indirect cAlorimetry Study

Conditions
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Continuous Renal Replacement Therapy, CO2 Removal, Nutrition Poor, Acute Renal Failure

Intervention / Treatment
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* Diagnostic Test: blood gas analysis under citrate predilution
* Device: filter replacement
* Device: IC
* Drug: NaCl predilution
* Diagnostic Test: blood gas analysis under NaCl predilution
* Drug: double ultrafiltration
* Diagnostic Test: blood gas analysis under citrate predilution and double ultrafiltration rate
* Dietary Supplement: pause and restart nutritional therapy
* Diagnostic Test: evolution of vitamin and trace elements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AKI requiring CRRT Patient on CRRT who's filter you want to change Expected stable patient during the test ( +- 2h) evaluated at discretion of physician : No alteration in medication Stable respiratory settings where no change in conditions is expected. If possible, controlled mode ventilation is preferred. Expected stable pH and lactate no intervention will be made on patient (transport/washing/physiotherapy/…) no alterations on settings of CRRT is expected to be made. Maximal respiratory settings: max FiO2: 60% / max inspiratory plateau pressure 30 mmHg/max tidal volumes 8ml/kg pH between 7,30-7,50, lactate levels <2,0 starting settings CRRT with citrate: Blood pump flow: 150 ml/min Predilution ( citrate): 1500-2300ml/h Dialysate dose: 25-40 ml/kg/h ultrafiltration: 0-300 ml /h Substitution: NaCl 300-800 ml/h or B22: 400-2000 ml/h Exclusion Criteria: Pregnancy / lactation Contra-indications for the use of indirect calorimetry as stated by the AARC (FiO2>60%, chest tubes) Severe hemodynamic or ventilator instability. CRRT modalities unusual to daily clinical ICU practice

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: all patients<br>Classic CRRT with citrate predilution | Diagnostic Test: blood gas analysis under citrate predilution<br>* blood gas analysis of blood on different sample points and dialysis fluid<br>Device: filter replacement<br>* Using local protocol: stop and disconnect CRRT, replace filter and reconnect and restart CRRT.<br>Device: IC<br>* monitor patients during the whole study period with indirect calorimetry<br>Drug: NaCl predilution<br>* Replace citrate predilution with NaCl<br>Diagnostic Test: blood gas analysis under NaCl predilution<br>* repeat blood gas analysis of blood on different sample points and dialysis fluid<br>Drug: double ultrafiltration<br>* double the ultrafiltration fluid by augmenting post dilution fluid and keeping ultrafiltration at the same rate.<br>Diagnostic Test: blood gas analysis under citrate predilution and double ultrafiltration rate<br>* repeat blood gas analysis of blood on different sample points and dialysis fluid<br>Dietary Supplement: pause and restart nutritional therapy<br>* pause parenteral and enteral nutrition before indirect calorimetry is performed. and restart after first blood analysis for vitamine status<br>Diagnostic Test: evolution of vitamin and trace elements<br>* blood analysis for vitamin and trace elements. Perform this blood analysis after restart of CRRT but before restart of nutritional therapy, 30 minutes after restart of nutritional therapy and 24h after restart of nutritional therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in CO2 flow and O2 flow on different sample points of CRRT | CO2 flow and O2 flow ( ml/min) will be compared between the different sample points on CRRT with and without citrate. CO2 flow and O2 flow is calculated by multiplying fluid flow ( ml/min) on different sample points of CRRT with CO2 content or O2 content of fluid on respective sample points during CRRT with and without Citrate. | 2hours | 
| REE change due to CRRT | REE ( Kcal) will be measured during the whole procedure using IC. REE will be measured during CRRT. citrate wil be replaced by NaCl 0,9% fluid and REE will be measured. After this, CRRT will be stopped and REE will be measured. The difference in REE during CRRT with and without citrate and without CRRT will be calculated and compared. REE is calculated using the weir equation and VO2, VCO2. VO2 and VCO2 is calculated using FiO2, FeO2, FiCO2, FeCO2 and VE. | 2hours | 
| does change in CO2 flow and O2 flow on different sample points of CRRT correlate with VCO2 and VO2 change due to CRRT with or without citrate | VCO2 and VO2 change due to CRRT and due to citrate will be correlated with change in CO2 and O2 flow of fluids passing through CRRT with or without citrate. | 2 hours | 
| Are vitamins and trace elements sufficiently supplemented with standard nutritional therapy during CRRT | blood analysis for concentrations of Vitamin A, B1, B6, B9, B12, C, D, E ; trace elements selenium, zinc, copper, chrome; and cholesterol and triglyceride | 24hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VCO2 and VO2 change due to CRRT with or without citrate | VCO2 and VO2 ( ml/min) will be measured during the whole procedure using IC. VCO2 and VO2 will be measured during CRRT with citrate. citrate wil be replaced by NaCl 0,9% fluid and VCO2 and VO2 will be measured. After this, CRRT will be stopped and VCO2 and VO2 will be measured. The difference in VCO2 and VO2 during CRRT with or without citrate and without CRRT will be calculated and compared. VO2 and VCO2 is calculated using FiO2, FeO2, FiCO2, FeCO2 and VE. | 2 hours | 
| FiO2, FeO2, FiCO2 and FeCO2 change due to CRRT with or without citrate | FiO2, FeO2, FiCO2 and FeCO2 ( %) will be measured during the whole procedure using IC. FiO2, FeO2, FiCO2 and FeCO2 will be measured during CRRT with citrate. citrate wil be replace by NaCl0,9% fluid and FiO2, FeO2, FiCO2 and FeCO2 will be measured. After this CRRT will be stopped and FiO2, FeO2, FiCO2 and FeCO2 will be measured. The difference in FiO2, FeO2, FiCO2 and FeCO2 during CRRT with or without citrate and without CRRT will be calculated. | 2hours | 
| VE change due to CRRT with or without citrate | VE( ml/min) will be measured during the whole procedure using IC. VE will be measured during CRRT with citrate. citrate wil be replace by NaCl0,9% fluid and VE will be measured. After this CRRT will be stopped and VE will be measured. The difference in VE during CRRT with or without citrate and without CRRT will be calculated. | 2hours | 
| change in CO2 and O2 content of fluid passing through CRRT | using blood gas analyser, CO2 content and O2content ( mmol/L)of fluid on different sample points in extracorporeal circuit of CRRT with or without citrate will be analysed and compared. | 2hours | 
| change in bicarbonate content of fluid passing through CRRT | using blood gas analyser, bicarbonate ( mmol/L) of fluid on different sample points in extracorporeal circuit of CRRT with or without citrate will be analysed and compared. | 2hours | 
| change in pH change of fluid passing through CRRT | using blood gas analyser, pH of fluid on different sample points in extracorporeal circuit of CRRT with or without citrate will be analysed and compared | 2hours | 
| change in pCO2 and pO2 change of fluid passing through CRRT | using blood gas analyser, pCO2 and pO2 (mmHg) of fluid on different sample points in extracorporeal circuit of CRRT with or without citrate will be analysed and compared. | 2hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calorimetry, Indirect, respiratory dialysis