Critical Care Explorations (Jul 2024)

Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study

  • Nicolas Deye, MD, PhD,
  • Amelie Le Gouge, MSc,
  • Bruno François, MD,
  • Camille Chenevier-Gobeaux, MD, PhD,
  • Thomas Daix, MD,
  • Hamid Merdji, MD, PhD,
  • Alain Cariou, MD, PhD,
  • Pierre-François Dequin, MD, PhD,
  • Christophe Guitton, MD,
  • Bruno Mégarbane, MD, PhD,
  • Jacques Callebert, PharmD, PhD,
  • Bruno Giraudeau, PhD,
  • Alexandre Mebazaa, MD, PhD,
  • Nicolas Vodovar, PhD,
  • for the Clinical Research in Intensive Care and Sepsis-TRIal Group for Global Evaluation and Research in SEPsis (TRIGGERSEP) Network and the ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) Study Group,
  • Arnaud Desachy,
  • Christophe Cracco,
  • Laurence Robin,
  • Marie Anne Fally,
  • David Schnell,
  • Olivier Baudin,
  • Charles Lafon,
  • Philippe Petua,
  • Stéphane Rouleau,
  • Cyrille Nowak,
  • Gaétan Plantefeve,
  • Hervé Mentec,
  • Olivier Pajot,
  • Damien Contou,
  • Jo-Anna Tirolien,
  • Constance Vuillard,
  • Cécile Zylberfajn,
  • Nadile Ali,
  • Dieudonne Kilendo,
  • Olivia Chauvel,
  • Elias Karam,
  • Pascal Chevallier,
  • Dorothée Ducoux,
  • Fabrice Raymond,
  • Christophe Gellis,
  • Jean-Pierre Quenot,
  • Thérèse Devaux,
  • Audrey Large,
  • Sébastien Mortreux,
  • Pierre-Emmanuel Charles,
  • Sébastien Prin,
  • Jean-Baptiste Roudaut,
  • Pascal Andreu,
  • Auguste Dargent,
  • Nora Perrot,
  • Audrey Massard,
  • Solenne Villot,
  • Corinne Pernot,
  • Bruno Francois,
  • Thomas Daix,
  • Philippe Vignon,
  • Nicolas Pichon,
  • Celine Gonzalez,
  • Nicolas Rodier,
  • Jean François Mary,
  • Ludmila Baudrillart,
  • Christine Vallejo,
  • Emmanuelle Begot,
  • Claire Mancia,
  • Michelle Nouaille,
  • Cécile Duchiron,
  • Sandrine Naturel,
  • Marie-Anne De Vinzellles,
  • Hélène Beacco,
  • Thierry Boulain,
  • Chantal Brossard,
  • Armelle Mathonnet,
  • Dalila Benzekri-Lefevre,
  • Anne Bretagnol,
  • Isabelle Runge,
  • François Barbier,
  • Grégoire Muller,
  • Mai-Anh Nay,
  • Julie Rossi,
  • Lucie Muller,
  • Sophie Tollec,
  • Alain Cariou,
  • Nathalie Marin,
  • Camille Chenevier-Gobeaux,
  • Michel Arnaout,
  • Omar Ben Hadj Salem,
  • Wulfran Bougouin,
  • Simon Bourcier,
  • Benoit Champigneulle,
  • Matthieu Jamme,
  • Alexis Ferre,
  • Guillaume Geri,
  • Frédéric Pene,
  • Julien Charpentier,
  • Jean-Daniel Chiche,
  • Lucie Guillemet,
  • Jean-Paul Mira,
  • Marine Paul,
  • Nicolas Deye,
  • Bruno Megarbane,
  • Alexandre Mebazaa,
  • Isabelle Malissin,
  • Sebastian Voicu,
  • Nicolas Vodovar,
  • Jacques Callebert,
  • Claire Pernin,
  • Lydia Suarez,
  • Philippe Manivet,
  • Dominique Vodovar,
  • Anthony Checinski,
  • Lamia Kerdjana,
  • Pierre Garcon,
  • Antoine Goury,
  • Catherine Fauvaux,
  • Salamata Agne,
  • Nahima Gueblaoui,
  • Aude Jacob,
  • Loic Chimot,
  • Catherine Huchet,
  • Nadège Lacoste,
  • Pierre-Henri Dessalles,
  • Mélanie Saint-Leger,
  • Yannick Monseau,
  • Marie Heil,
  • Ferhat Meziani,
  • Hamid Merdji,
  • DrKhoury,
  • Samir Chenaf,
  • Christine Kummerlen,
  • Yannick Rabouel,
  • Hayat Allam,
  • Anne Hutt-Clauss,
  • Alexandra Monnier,
  • Pierre-François Dequin,
  • Christine Mabilat,
  • Emmanuelle Rouve,
  • Charlotte Salmon-Gandonnière,
  • Denis Garot,
  • Youen Jouan,
  • Stephan Ehrmann,
  • Antoine Guillon,
  • Laetitia Bodet–Contentin,
  • Emmanuelle Mercier,
  • Julie Mankikian,
  • Stéphane Legriel,
  • MrSébastien Cavelot,
  • Christophe Guitton,
  • Charlotte Garret,
  • Cédric Bretonniere,
  • Laurent Nicolat,
  • Noëlle Brule,
  • Olivier Zambon

DOI
https://doi.org/10.1097/CCE.0000000000001104
Journal volume & issue
Vol. 6, no. 7
p. e1104

Abstract

Read online

IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.