Bioelectrical Impedance Analysis as a Bedside Tool to Estimate Volume of Distribution of Hydrophilic Antimicrobials in Critically Ill Patients

Study Overview
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Brief Summary
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Bioelectrical impedance analysis is studied as a bedside tool to estimate capillary leak in order to guide dosing of hydrophilic antimicrobials.

Detailed Description
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Abstract Background: Recent data suggest that antimicrobial pharmacokinetics (PK) like volume of distribution (Vd) or drug clearance (CL) is extremely altered in critically ill patients with sepsis or septic shock due to pathophysiological alterations (e.g. influence on fluid status). Bioelectrical impedance analysis (BIA) was recently introduced as a simple, non-invasive, bedside technique to assess hydration status. The primary aim of the present study was to explore the correlation between BIA parameters and Vd of hydrophilic antimicrobial agents in critically ill patients. Furthermore, the relationship between BIA measurements and clinical observations was evaluated. Methods: We performed a validation study in healthy volunteers in September 2015 that confirmed the reproducibility of BIA. Subsequently, a prospective observational study was carried out in eligible patients treat-ed with amoxicillin/clavulanic acid, meropenem, piperacillin/tazobactam or vancomycin, admitted at the in-tensive care unit (ICU) of the University Hospitals Leuven from October 2015 to March 2016. BIA measurement was performed on the same day as the collection of blood samples to calculate PK parameters of the administered antibiotic.

Official Title
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Bioelectrical Impedance Analysis as a Bedside Tool to Estimate Volume of Distribution of Hydrophilic Antimicrobials in Critically Ill Patients

Conditions
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Electric Impedance, Pharmacokinetics, Capillary Leak Syndrome

Intervention / Treatment
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* Drug: Monitor antibiotic exposure (PK profile)
* Device: Bioelectrical impedance analysis to measure body composition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to ICU ward Treated with one of the four studied antimicrobials Exclusion Criteria: <18 years Pregnant Do Not Resuscitate code 2 or 3 Renal replacement therapy ECMO Pacemaker/defibrillator Extended burns or dermatological ilness

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ICU patients on amoxicillin/clavulanic acid<br> | Drug: Monitor antibiotic exposure (PK profile)<br>* several plasma samples to measure drug exposure<br>Device: Bioelectrical impedance analysis to measure body composition<br>* non invasive analysis (electrodes) to measure extra- and intracellular, and total body water.<br>|
| ICU patients on piperacillin/tazobactam<br> | Drug: Monitor antibiotic exposure (PK profile)<br>* several plasma samples to measure drug exposure<br>Device: Bioelectrical impedance analysis to measure body composition<br>* non invasive analysis (electrodes) to measure extra- and intracellular, and total body water.<br>|
| ICU patients on meropenem<br> | Drug: Monitor antibiotic exposure (PK profile)<br>* several plasma samples to measure drug exposure<br>Device: Bioelectrical impedance analysis to measure body composition<br>* non invasive analysis (electrodes) to measure extra- and intracellular, and total body water.<br>|
| ICU patients on vancomycin<br> | Drug: Monitor antibiotic exposure (PK profile)<br>* several plasma samples to measure drug exposure<br>Device: Bioelectrical impedance analysis to measure body composition<br>* non invasive analysis (electrodes) to measure extra- and intracellular, and total body water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between BIA parameters and Vd of hydrophilic antimicrobial agents | Extracellular water (ECW), intracellular water, total body water (TBW), all expressed in liter, and ECW expressed as % of TBW will be correlated with Vd (L/kg) of vancomycin, meropenem, amoxicillin/clavulanic acid and piperacillin/tazobactam | 6-12 hours (= dosing interval) depending on the antimicrobial studied | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between BIA assessed hydration status and clinical observations | Hydration status measured by BIA (dehydrated, normohydrated, hyperhydrated) will be correlated with SOFA score and cumulative fluid balance (L) | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Distribution Volume, Antibiotics