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. 2019 Dec 31;7(4):155-169.
doi: 10.2478/jtim-2019-0031. eCollection 2019 Dec.

Pharmacokinetics and Pharmacodynamics of Anti-infective Agents during Continuous Veno-venous Hemofiltration in Critically Ill Patients: Lessons Learned from an Ancillary Study of the IVOIRE Trial

Dominique Breilh  1 , Patrick M Honore  2 , David De Bels  2 , Jason A Roberts  3 , Jean Baptiste Gordien  1 , Catherine Fleureau  4 , Antoine Dewitte  4 , Julien Coquin  4 , Hadrien Rozé  4 , Paul Perez  5 , Rachid Attou  2 , Sebastien Redant  2 , Luc Kugener  2 , Marie-Claude Saux  1 , Herbert D Spapen  6 , Alexandre Ouattara  4   7 , Olivier Joannes-Boyau  4 ; IVOIRE study group
Affiliations

Pharmacokinetics and Pharmacodynamics of Anti-infective Agents during Continuous Veno-venous Hemofiltration in Critically Ill Patients: Lessons Learned from an Ancillary Study of the IVOIRE Trial

Dominique Breilh et al. J Transl Int Med. .

Abstract

Background: Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients.

Methods: Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI). PK/PD parameters for all antimicrobial agents used in each patient were studied during five days.

Results: Antimicrobial treatment met efficacy targets for both percentage of time above the minimal inhibitory concentration and inhibitory quotient. A significant correlation was observed between the ultrafiltration flow and total systemic clearance (Spearman test: P < 0.005) and between CVVH clearance and drug elimination half-life (Spearman test: P < 0.005). All agents were easily filtered. Mean sieving coefficient ranged from 38.7% to 96.7%. Mean elimination half-life of all agents was significantly shorter during HV-CVVH (from 1.29 to 28.54 h) than during SV-CVVH (from 1.51 to 33.85 h) (P < 0.05).

Conclusions: This study confirms that CVVH influences the PK/PD behavior of most antimicrobial agents. Antimicrobial elimination was directly correlated with convection rate. Current antimicrobial dose recommendations will expose patients to underdosing and increase the risk for treatment failure and development of resistance. Dose recommendations are proposed for some major antibiotic and antifungal treatments in patients receiving at least 25 mL/kg/h CVVH.

Keywords: antibiotic dosage; antibiotics; continuous veno-venous hemofiltration; high volume hemofiltration; pharmacodynamics; pharmacokinetics; septic shock.

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Conflict of interest statement

Conflict of Interest The authors declare to have no competing interests.

Figures

Figure 1
Figure 1
Evolution of arterial plasma concentrations and effluent versus time for anti-infective agents in IVOIRE study during high volume CVVH (HD) and standard volume CVVH (BD)
Figure 1
Figure 1
Evolution of arterial plasma concentrations and effluent versus time for anti-infective agents in IVOIRE study during high volume CVVH (HD) and standard volume CVVH (BD)
See this image and copyright information in PMC

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