Evidence map›Paper›PMID 38169065›Full record

SynthesisClinical pharmacokinetics2024

Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass.

Audrick Gibert, Julien Lanoiselée, Isabelle Gouin-Thibault, Adeline Pontis, Kasra Azarnoush, Andranik Petrosyan, Nathalie Grand, Serge Molliex, Jérome Morel, Laurent Gergelé and 5 more

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Audrick GibertINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France. audrick.gibert@gmail.com.ORCID 0000-0002-8928-7057
Julien LanoiseléeINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.
Isabelle Gouin-ThibaultLaboratory of Hematology, Pontchaillou, University Hospital of Rennes, University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, Rennes, France.
Adeline PontisLaboratory of Hematology, Pontchaillou, University Hospital of Rennes, University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, Rennes, France.
Kasra AzarnoushService de Chirurgie Cardiaque, CHU de Saint-Etienne, Saint-Etienne, France.
Andranik PetrosyanService de Chirurgie Cardiaque, CHU de Saint-Etienne, Saint-Etienne, France.
Nathalie GrandDépartement d'Anesthésie-Réanimation, CHU de Saint-Etienne, Saint-Etienne, France.
Serge MolliexDépartement d'Anesthésie-Réanimation, CHU de Saint-Etienne, Saint-Etienne, France.
Jérome MorelDépartement d'Anesthésie-Réanimation, CHU de Saint-Etienne, Saint-Etienne, France.
Laurent GergeléDépartement d'Anesthésie-Réanimation, CHU de Saint-Etienne, Saint-Etienne, France.
Sophie HodinINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.
Valérie BinINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.
Robin ChauxINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.
Xavier DelavenneINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.
Edouard OllierINSERM, U1059, Dysfonction Vasculaire et Hémostase, 20 Rue Camelinat, 42000, Saint-Étienne, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUnfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies.

methodsAn individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered.

resultsActivities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates.

conclusionsThe population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation.

Indexed as

Cardiopulmonary BypassHeparinAnticoagulantsBayes TheoremBody WeightFibrinogenHumansObservational Studies as TopicAnticoagulantsFibrinogenHeparin

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.