Children in Cardiac Intensive Care Requiring Surgery for Congenital Heart Disease
Conditions
Keywords
Cefazolin, Cardiac surgery, Mediastinitis, Microdialysis
Brief summary
Postoperative mediastinitis is an important cause of postoperative morbidity in children. The main objective of this study is to describe the distribution of cefazolin, using as surgical antibiotic prophylaxis, in the mediastinal compartment in children after cardiac surgery for congenital heart disease. The investigators aims to build a population pharmacokinetic model of cefazolin using plasma and tissue concentrations in order to optimize and individualize cefazolin dosing regimens. Cefazolin tissue pharmacokinetics will use a microdialysis procedure.
Detailed description
Children with congenital heart disease are very fragile during the postoperative period and at risk of life-threatening mediastinitis due to various factors: post-extracorporeal circulation inflammation, frequent organ failure, possible delayed thorax closure. These patients are at risk of unpredictable pharmacokinetics alteration and inter-individual variability of the drug tissue: significant fluid intake, drug metabolism and elimination functions alteration, extracorporeal circulation. The effective prevention of postoperative mediastinitis in this population is therefore a major issue and challenge. Studying the distribution of cefazolin in the mediastinum and identifying the factors of inter-individual variability would improve the prevention of this pathology by optimizing the dosing. During cardiac surgery, a microdialysis probe is placed by the surgeon in the mediastinum. The outgoing fluid will be collected every 30 minutes to every 2 hours, for approximately 28 hours. Six plasma samples will be drawn over these 28 hours to measure plasma concentrations. The probe's recovery will then be calculated and the probe will be removed up to 36 hours after insertion.
Interventions
PROCEDUREMicrodialysis probe placement
Microdialysis probe is placed at the end of cardiac surgery in mediastinum and used during 36 hours for tissue samples until withdrawal.
PROCEDUREMicrodialysis and Plasma samples
26 Cefazolin Free tissue concentrations 6 total plasma concentrations
Sponsors
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
* Child aged over 6 months and under 6 years * Hospitalized in pediatric cardiac intensive care after cardiac surgery for congenital heart disease. * Selected congenital heart diseases: ventricular septal defect auricular septal defect, pulmonary stenosis, tetralogy of Fallot * Surgery with median sternotomy and intraoperative cardiopulmonary bypass * Intraoperative antibiotic prophylaxis with cefazolin * Patient affiliated with a social security plan or eligible * whose two parents or legal guardians have accepted and signed the study consent
Exclusion criteria
* Emergency cardiac surgery * Patient already enrolled in the study * Patient who has previously undergone cardiac surgery * Patient with haemostasis disorders or immune deficiency * Patient with bacterial colonization indicating antibiotic prophylaxis other than cefazolin * Participation in another interventional research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total clearance | 36 hours | Pharmacokinetics of cefazolin total clearance in children after cardiac surgery and inter-individual variability. |
| Distribution volume | 36 hours | Pharmacokinetics of cefazolin distribution volume in children after cardiac surgery and inter-individual variability. |
| Inter-compartmental clearance | 36 hours | Pharmacokinetics of cefazolin inter-compartmental clearance in children after cardiac surgery and inter-individual variability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monte Carlo simulations and dosing optimization | 36 hours | Monte Carlo simulations performed using the model with SimulX (version 2024R1) and R (version 4.4.2) softwares. Probability of attainment of PK/PD target (100 % ƒT \> 4xCMI) with simulated dosing regimens No patient data is required for this step. |
| post-operative mediastinitis occurrence | Month 1 | Assess the relationship between tissue exposure and clinical outcome: occurrence of post-operative mediastinitis |
Countries
France
Contacts
Primary ContactNoemie De Cacqueray, MD
Backup ContactGael Plastow
Outcome results
None listed