Evidence map›Paper›PMID 34683408›Full record

ArticleMicroorganisms2021

Voriconazole Pharmacokinetics Are Not Altered in Critically Ill Patients with Acute-on-Chronic Liver Failure and Continuous Renal Replacement Therapy: An Observational Study.

Jörn Grensemann, Christoph Pfaffendorf, Sebastian G Wicha, Christina König, Kevin Roedl, Dominik Jarczak, Stefanie Iwersen-Bergmann, Carolin Manthey, Stefan Kluge, Valentin Fuhrmann

Open access · goldAbstract read
In one paragraph

Article in Microorganisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. The impact ofFrontiers in pharmacology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Jörn GrensemannDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.ORCID 0000-0002-3341-669X
Christoph PfaffendorfDepartment of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany.
Sebastian G WichaDepartment of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, 20146 Hamburg, Germany.
Christina KönigDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.ORCID 0000-0002-3354-3496
Kevin RoedlDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.ORCID 0000-0002-0721-9027
Dominik JarczakDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.ORCID 0000-0003-0480-2089
Stefanie Iwersen-BergmannDepartment of Legal Medicine, University Medical Center Hamburg-Eppendorf, Butenfeld 34, 22529 Hamburg, Germany.
Carolin MantheyFirst Department of Internal Medicine and Gastroenterology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.ORCID 0000-0002-9806-4197
Stefan KlugeDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Valentin FuhrmannDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Universität Hamburg · DE

Funding

Damp Stiftung 2017-20
6 · The paper itself

Abstract

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5-3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6-104) and V2 106L (65-166) with a body clearance of 4.7L/h (2.87-7.81) and RRT clearance of 1.46L/h (1.29-1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.

Indexed as

antifungal therapyintensive careMonte-Carlo simulationpopulation pharmacokineticsprobability of target attainmenttarget attainmentvolume of distribution

Identifiers

PMID34683408
PMCPMC8538714
OpenAlexW3202722236

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.