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

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03410771
• Other study ID #: mp05488
• Status: Completed
• Phase: N/A
• First received: January 8, 2018
• Last updated: January 26, 2018
• Start date: October 1, 2015
• Est. completion date: June 1, 2016

Study information

• Verified date: January 2018
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: June 1, 2016
• Est. primary completion date: March 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Capillary Leak Syndrome
• Critical Illness
• Electric Impedance
• Pharmacokinetics

Intervention

Drug:
• Monitor antibiotic exposure (PK profile)
several plasma samples to measure drug exposure

Device:
• Bioelectrical impedance analysis to measure body composition
non invasive analysis (electrodes) to measure extra- and intracellular, and total body water.

Locations

Country	Name	City	State
Belgium	UZLeuven	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven	Katholieke Universiteit Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (8)

Balik M, Sedivy J, Waldauf P, Kolar M, Smejkalova V, Pachl J. Can bioimpedance determine the volume of distribution of antibiotics in sepsis? Anaesth Intensive Care. 2005 Jun;33(3):345-50. — View Citation

Basso F, Berdin G, Virzì GM, Mason G, Piccinni P, Day S, Cruz DN, Wjewodzka M, Giuliani A, Brendolan A, Ronco C. Fluid management in the intensive care unit: bioelectrical impedance vector analysis as a tool to assess hydration status and optimal fluid balance in critically ill patients. Blood Purif. 2013;36(3-4):192-9. doi: 10.1159/000356366. Epub 2013 Dec 20. — View Citation

Dewitte A, Carles P, Joannès-Boyau O, Fleureau C, Roze H, Combe C, Ouattara A. Bioelectrical impedance spectroscopy to estimate fluid balance in critically ill patients. J Clin Monit Comput. 2016 Apr;30(2):227-33. doi: 10.1007/s10877-015-9706-7. Epub 2015 May 29. — View Citation

Jones SL, Tanaka A, Eastwood GM, Young H, Peck L, Bellomo R, Mårtensson J. Bioelectrical impedance vector analysis in critically ill patients: a prospective, clinician-blinded investigation. Crit Care. 2015 Aug 12;19:290. doi: 10.1186/s13054-015-1009-3. — View Citation

Lee YH, Lee JD, Kang DR, Hong J, Lee JM. Bioelectrical impedance analysis values as markers to predict severity in critically ill patients. J Crit Care. 2017 Aug;40:103-107. doi: 10.1016/j.jcrc.2017.03.013. Epub 2017 Mar 22. — View Citation

Malbrain ML, Huygh J, Dabrowski W, De Waele JJ, Staelens A, Wauters J. The use of bio-electrical impedance analysis (BIA) to guide fluid management, resuscitation and deresuscitation in critically ill patients: a bench-to-bedside review. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):381-91. doi: 10.5603/AIT.2014.0061. Review. — View Citation

Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, Hope WW, Farkas A, Neely MN, Schentag JJ, Drusano G, Frey OR, Theuretzbacher U, Kuti JL; International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014 Jun;14(6):498-509. doi: 10.1016/S1473-3099(14)70036-2. Epub 2014 Apr 24. Review. — View Citation

Samoni S, Vigo V, Reséndiz LI, Villa G, De Rosa S, Nalesso F, Ferrari F, Meola M, Brendolan A, Malacarne P, Forfori F, Bonato R, Donadio C, Ronco C. Impact of hyperhydration on the mortality risk in critically ill patients admitted in intensive care units: comparison between bioelectrical impedance vector analysis and cumulative fluid balance recording. Crit Care. 2016 Apr 8;20:95. doi: 10.1186/s13054-016-1269-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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