Risk factors for early suspected ventilator-associated pneumonia in severe thoracic blunt trauma patient: A French national cohort study

Gary Duclos; Victor Vidal; Noemie Resseguier; Mathieu Boutonnet; Thomas Botrel; Gerard Audibert; Manon Séguret; Vincent Legros; Caroline Jeantrelle; Anh Dao Phan; Olivier Langeron; Elisabeth Gaertner; Jean-Luc Hanouz; Thomas Clavier; Véronique Ramonda; Fanny Bounes; Paër-selim Abback; Mathieu Willig; Julien Pottecher; Marc Leone; for Traumabase® Group

doi:10.1371/journal.pone.0324120

. 2025 May 27;20(5):e0324120. doi: 10.1371/journal.pone.0324120

Risk factors for early suspected ventilator-associated pneumonia in severe thoracic blunt trauma patient: A French national cohort study

Gary Duclos ^1,^*, Victor Vidal ¹, Noemie Resseguier ^2,³, Mathieu Boutonnet ⁴, Thomas Botrel ⁵, Gerard Audibert ⁶, Manon Séguret ⁷, Vincent Legros ⁸, Caroline Jeantrelle ⁹, Anh Dao Phan ¹⁰, Olivier Langeron ¹¹, Elisabeth Gaertner ¹², Jean-Luc Hanouz ¹³, Thomas Clavier ¹⁴, Véronique Ramonda ¹⁵, Fanny Bounes ¹⁶, Paër-selim Abback ¹⁷, Mathieu Willig ¹⁸, Julien Pottecher ¹⁹, Marc Leone ²⁰; for Traumabase® Group

Editor: Jean Baptiste Lascarrou²¹

¹Service d’anesthésie et de réanimation traumatologique, Assistance – Publique Hôpitaux de Marseille, Hôpital Nord, France Aix- Marseille Université, Marseille, France

²Service d’Épidémiologie et d’Économie de la Santé, AP-HM, France Aix- Marseille Université, Marseille, France

³CEReSS-Health Services and Quality of Research, Aix-Marseille University, Marseille, France

⁴Service de réanimation, Hôpital d’Instruction des Armées Percy, Service de santé des Armées, Clamart, France

⁵Anaesthesia and Intensive Care Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

⁶Department of Anesthesiology and Surgical Intensive Care, CHRU-Nancy, Université de Lorraine, Nancy, France

⁷Service d’Anesthésie-Réanimation Chirurgicale, Hôpital Bicêtre, Université Paris-Saclay, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France

⁸Department of Anesthesiology and Critical Care, Reims University Hospital, Hôpital Robert Debré - CHU de Reims, Rue Koenig, Reims, France

⁹Department of Anesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP.Nord, Paris, France

¹⁰Department of Anesthesiology and Critical Care Medicine, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France

¹¹Department of Anesthesia and Intensive Care, Henri Mondor University Hospital, Assistance Publique - Hôpitaux de Paris (APHP), University Paris-Est Créteil (UPEC), Paris, France

¹²Hôpital Louis Pasteur, Service d’Anesthésie-Réanimation Pôle 2, 39 Avenue de la Liberté, Colmar, France

¹³Department of Anesthesiology and Critical Care Medicine, Caen University Hospital, Avenue de la cote de Nacre, Caen, France

¹⁴Department of Anesthesiology, Critical Care and Perioperative Medicine, Surgical Intensive Care Unit, Rouen University Hospital, Rouen, France

¹⁵Department of Anesthesiology and Critical Care, University Toulouse 3-Paul-Sabatier, University Hospital of Toulouse, Hôpital Pierre-Paul Riquet, CHU Toulouse-Purpan, Toulouse, France

¹⁶Anesthesiology and Intensive Care Department CHU Toulouse, Toulouse, France

¹⁷Department of Anesthesiology and Critical Care Medicine, CHU Tours, Tours University Hospital, Tours, France

¹⁸Anaesthesiology and Critical Care Department, Dijon Bourgogne University Hospital, Dijon, France

¹⁹Department of Anaesthesiology, Critical Care and Perioperative Medicine, Fédération de Médecine Translationnelle de Strasbourg, ER, Strasbourg University Hospital, Strasbourg, France

²⁰Service d’anesthésie et de réanimation traumatologique, Assistance – Publique Hôpitaux de Marseille, Hôpital Nord, Marseille, France Aix- Marseille Université, Marseille, France

²¹CHU Nantes, FRANCE

^✉

* E-mail: Gary.duclos@ap-hm.fr

Competing Interests: The authors have declared that no competing interests exist.

Roles

Gary Duclos: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Writing – original draft

Victor Vidal: Data curation

Noemie Resseguier: Formal analysis, Methodology

Mathieu Boutonnet: Validation, Writing – review & editing

Thomas Botrel: Validation, Writing – review & editing

Gerard Audibert: Validation, Writing – review & editing

Manon Séguret: Validation, Writing – review & editing

Vincent Legros: Validation, Writing – review & editing

Caroline Jeantrelle: Data curation, Project administration, Validation, Writing – review & editing

Anh Dao Phan: Resources, Validation, Writing – review & editing

Olivier Langeron: Validation, Writing – review & editing

Elisabeth Gaertner: Validation, Writing – review & editing

Jean-Luc Hanouz: Resources, Validation, Writing – review & editing

Thomas Clavier: Validation, Writing – review & editing

Véronique Ramonda: Data curation, Project administration, Resources, Visualization, Writing – review & editing

Fanny Bounes: Validation, Writing – review & editing

Paër-selim Abback: Data curation, Methodology, Project administration, Validation, Writing – review & editing

Mathieu Willig: Validation, Writing – review & editing

Julien Pottecher: Project administration, Resources, Validation, Writing – review & editing

Marc Leone: Project administration, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing

Jean Baptiste Lascarrou: Editor

PMCID: PMC12112400 PMID: 40424409

Abstract

Background

Ventilator-associated pneumonia (VAP) is the most common infection in severely injured patients requiring mechanical ventilation. Chest trauma has been identified as a significant risk factor for VAP. This study aimed to describe the risk factors for early VAP in patients with severe blunt thoracic trauma admitted to the intensive care unit (ICU) and receiving mechanical ventilation.

Materials and Methods

A retrospective cohort study was conducted using data from a national registry including data from 17 French trauma centers during a period of seven years. The study included patients with severe blunt thoracic trauma requiring invasive mechanical ventilation. Data analysis focused on identifying independent risk factors for early suspected VAP (occurring within 48 hours to 5 days after ICU admission) using two models of logistic regression.

Results

From 31700 patients screened 712 patients were analyzed. Early suspected VAP occurred in 192 (27%) patients. The study identified several independent risk factors associated with early suspected VAP in patients with severe blunt thoracic trauma: male gender (OR= 2.77, 95%CI: 1.68–4.77, p < 0.001), ASA score >1 (OR= 1.64, 95%CI: 1.08–2.50, p = 0.019), injury severity score (ISS) >15 (OR=3.15, 95%CI: 1.13–11.99, p = 0.025), initial Glasgow Coma Scale (GCS) score <9 (OR=2.71, 95%CI: 1.88–3.96, p < 0.001), absolute thoracic abbreviated injury scale (AIS) (OR=1.51, 95%CI: 1.14–1.99, p = 0.003), and the number of packed red blood cells (PRBCs) transfused within the first 24 hours (OR=1.04, 95%CI: 1.00–1.08, p = 0.027). Prehospital antibiotic administration was identified as a protective factor (OR=0.54, 95%CI: 0.29–0.94, p = 0.028).

Conclusion

In patients with severe blunt chest trauma receiving invasive mechanical ventilation, male gender, ASA score, ISS > 15, GCS < 9, thoracic AIS and number of PRBCs transfused were independent risk factors for early suspected VAP. Prehospital antibiotic therapy was a protective factor, suggesting potential strategies for VAP prevention.

Background

Ventilator-associated pneumonia (VAP) is the commonest healthcare-associated infections in severely injured patients receiving mechanical ventilation [1]. In 2020, a retrospective study including a heterogeneous population of 1403 severely injured patients highlighted that the risk for VAP increased with age, the need for massive transfusion and the presence of facial, spinal, and sternal injuries [2]. A multicenter study identified chest injuries as an independent risk factor for VAP in patients with severe traumatic brain injuries [3]. To date, only one Dutch large retrospective study assessed the risk of pneumonia among 1162 patients with severe thoracic trauma (defined by an abbreviated injury scale (AIS) of thoracic region of 2 or more). [4] The incidence of pneumonia was 27.5% and the risk factors were age, male gender, and duration of mechanical ventilation, while severity criteria scores and comorbidities were not associated with this risk [4]. However, this study included heterogeneous patients: patients with and without tracheal intubation and those with blunt and penetrating injuries were indifferently included. Moreover, confounding factors such as coma or admission under invasive mechanical ventilation were not considered [4].

Our study aimed to describe risk factors for suspected VAP occurring within the first five days after intensive care unit (ICU) admission in a homogeneous, highly characterized population of patients with severe blunt thoracic trauma requiring mechanical ventilation.

Materials and methods

Study design

We conducted a retrospective cohort study using prospectively collected data recorded in the French trauma registry Traumabase® [5,6]. The registry has obtained authorization from the Comité national informatique et libertée (CNIL) and is registered under number 911461. This study was approved by a Research Ethics Committee and is registered under the IRB number 00006477. We included patients from 17 centers contributing to the Traumabase® and agreeing to participate. The study period covers from January 2014 to December 2021.The conduct of this study followed the STrengthening the Reporting of OBservational studies (STROBE) recommendations [7].

Inclusion and exclusion criteria

Inclusion occurred with three criteria present: 1) Primary admission to trauma resuscitation room, 2) blunt thoracic trauma defined by an AIS > 2 and 3) early invasive mechanical ventilation initiated in the prehospital setting or trauma resuscitation room for at least five days.

Excluded patients were those under 18 years old, with any kind of penetrating trauma and those who had a cardiac arrest before hospital admission. To minimize the exposure bias, the patients who died within the first 5 days after ICU admission were also excluded. Suspected pneumonia declare before day 2 and after day 5 were by instanced not included.

Outcome

The diagnosis of suspected VAP was based on international guidelines [8–10]. It was suspected in case of systemic infection (fever (>38°C) or hypothermia (<36°C) or leukocytosis (≥12,000 cells/mm³) or leukopenia (≤4000 cells/mm³)), a worsening of gas exchange and a new onset or progressive infiltrate at the chest X-ray. To improve the consistency of this diagnosis, Physician investigators in each center were asked to declare the presence of an episode of pneumonia in the registry according to international criteria and antibiotic treatment. As no microbiological documentation was available in the data base we have chosen to qualify the diagnosis of VAP as suspected.

Early suspected VAP was considered if the patient developed pneumonia after 48 hours of initiation of mechanical ventilation and before the end of the 5^th day after ICU admission [10]. In case of missing data on this information, the patient was excluded from the analysis.

Definitions of analyzed variables

The following quantitative variables were considered for analysis: age, weight, height, body mass index (BMI), American Society of Anesthesiologists (ASA) score, initial Glasgow coma scale (GCS) score, and initial motor GCS score. Pre-hospital data were vital signs on scene (systolic and diastolic blood pressure, heart rate, transcutaneous oxygen saturation), and their worst values during transport, initial point-of-care hemoglobin, volumes of infused crystalloids, administered blood products, and maximal flow of catecholamine infused. Hospital data included vital signs at the trauma bay admission (systolic and diastolic blood pressure, heart rate, transcutaneous oxygen saturation, respiratory rate, expired carbon dioxide (CO₂), body temperature), laboratory values, pH, arterial PaO₂ and PaCO₂, lactatemia, hemoglobin, platelet, prothrombin time, fibrinogen, creatinine, bicarbonate, troponin, alcohol), simplified acute physiology score (SAPS), sequential organ failure assessment (SOFA) score and detail of each of its components, lowest PaO₂:FiO₂ ratio, number of intubation, duration of mechanical ventilation, day of first pneumonia, overall and critical care length of hospital stay (in days). The intra-hospital mortality rate was assessed at day 30.

We collected pre-hospital parameters and treatments including use of catecholamine, decompression of tension pneumothorax, transfusion and type of transfused blood product in the first 24 hours (including the number of packed red blood cells (PRBCs), fresh frozen plasma (FFP) and concentrate of platelets (CP)) and use of pre-hospital antibiotic therapy without precision.

The following variables were also collected in the first 24 hours of admission in the trauma bay: chest drainage, transfusion, massive transfusion defined by transfusion of more than 10 PRBCs units in the first 24 hours, surgery within the first 24 hours.

During the ICU stay, the following variables were collected: ICU mortality, withdrawal or withholding of life-sustaining therapy decision, use of invasive mechanical ventilation, use of tracheostomy, acute respiratory distress syndrome (ARDS), sepsis, septic shock, thoracic or abdominal surgery, and date of the first pneumonia.

For each patient, an injury severity score (ISS) and AIS code of traumatic injury was computed by each center [11,12]. For the need of this study, the ISS codes corresponding to hemothorax, unilateral or bilateral lung contusions, and rib flail were extracted and analyzed.

Statistical Analysis

Statistical analysis was conducted with R version 4.0.5 (R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria). Two groups were defined: a group with early suspected VAP and a group without early suspected VAP. Quantitative variables were described as means and standard deviations (SD) or medians and 1st-3rd quartiles depending on their distribution. Univariate analyses were conducted to identify factors associated with the occurrence of early suspected VAP. Comparisons between the two groups were made using a Student’s t-test when the conditions were met or a non-parametric Mann-Whitney test when they were not. Qualitative values were described as numbers (percentage) and compared between the two groups using a chi-square test for qualitative variables when the conditions were met or a non-parametric Fisher’s test otherwise. A multivariate logistic regression model was established including potential confounding risk factors. Potential risk factors were selected a priori based on literature data. No selection based on statistical criteria was then performed. Adjusted odds ratios (OR) were estimated, along with their 95% confidence intervals (CI).

To increase the sensitivity of the analysis and avoid variable redundancy, two multivariate models were run to identify factors independently associated with the risk of early suspected VAP.

The first model included variables such as age, male gender, ASA score >1, absolute thoracic AIS value (3, 4 or 5), abdominal AIS > 2, pre-hospital antibiotic administration, presence of spinal cord injury with neurological deficit, massive transfusion, and GCS score <9 at initial management.
The second model included variables such as age, male gender, ASA score >1, ISS > 15, pre-hospital antibiotic administration, presence of spinal cord injury with neurological deficit, number of PRBCs transfused in the first 24 hours, GCS score <9 at initial management, presence of hemothorax, presence of a rib fail, and presence of lung contusion.

Multivariate regression models were checked for non-multicollinearity by estimating variance inflation factors and for goodness-of-fit by using Hosmer-Lemeshow test. Patients with missing data regarding one item included in the models were excluded of the analysis.

Results

Patient characteristics

During the study period, 31700 patients were registered in the Traumabase®. We screened 2037 chest trauma patients from 17 centers responding to the inclusion criteria. A cohort of 712 patients was included in our analysis after application of non-inclusion criteria (Fig 1: flow chart). The mean (SD) age was 39 (17) years, 569 (80%) patients were males, and the mean ISS was 31 (11). Two hundred fifty-one (35%) patients developed an infection during ICU stay, including 187 (26%) patients who developed early suspected VAP. The day-30 mortality was 8%. Main characteristics of patients included in the analysis are resumed in Table 1.

Table 1. Descriptive statistics and univariate analyses comparing the early VAP and no early VAP groups.

Quantitative variables are expressed in medians and interquartile ranges (25-75) or in means ± standard deviations depending on their distribution.

Variable	Sample size (n)	Total population (n = 712)	Suspected early VAP (n = 187)	Control group (n = 525)	p
Age (years)	712	39 ± 17	39 ± 17	38 ± 17	0.402
Male gender (%)	711	569 (80%)	166 (89%)	403 (77%)	<0.001
BMI value	611	25 ± 4	25 ± 5	25 ± 4	0.314
ASA score	697	1.6 ± 1.2	1.7 ±1.2	1.6 ± 1.1	0.200
ASA score >1	697	243 (35%)	77 (42%)	166 (32%)	0.021
Initial Glasgow scale <9	704	367 (52%)	128 (68%)	239 (46%)	<0.001
Initial Glasgow scale value	704	8.9 ± 4.4	7.3 ± 4.1	9.4 ±4.3	<0.001
Initial Glasgow motor scale value	660	4.1 ± 2.0	3.4 ± 2.0	4.4 ±1.9	<0.001
Initial SBP (mmHg)	670	122 ± 30	124 ± 33	122 ± 29	0.494
Intial DBP (mmHg)	669	74 ± 20	73 ± 21	74 ± 20	0.596
Initial HR (mmHg)	672	101 ± 28	104 ± 29	100 ± 27	0.119
Initial SpO2 (mmHg)	712	95 ± 6	93 ± 8	96 ± 5	0.003
SOFA Respiratory value	687	1.8 ± 1.3	2.4 ± 1.3	1.6 ± 1.3	<0.001
SOFA Coagulation value	683	0.60 ± 0.84	0.68 ±0.89	0.57 ± 0.82	0.127
SOFA Cardiovascular value	686	3.0 ± 1.5	3.6 ± 1.1	2.8 ± 1.6	<0.001
SOFA Central nervous system value	686	2.0 ± 1.5	2.5 ± 1.5	1.8 ± 1.5	<0.001
SOFA liver value	666	0.23 ± 0.56	0.35 ± 0.66	0.18 ±0.51	<0.001
SOFA Renal function value	683	0.30 ± 0.59	0.39 ± 0.63	0.27 ± 0.58	0.0193
Total SOFA score	709	8.3 ± 3.5	10.3 ± 3.0	7.6 ± 3.4	<0.001
ISS >15 (%)	712	673 (95%)	184 (98%)	489 (93%)	0.007
ISS value	712	31 ± 11	37 ± 11	28 ± 10	<0.001
AIS Head value	712	2.6 ± 1.8	3.5 ±1.5	2.2 ± 1.7	<0.001
AIS Face value	712	0.77 ± 1.05	0.87 ± 1.10	0.73 ± 1.03	0.107
AIS Thorax value	712	3.5 ± 0.6	3.6 ± 0.7	3.4 ± 0.6	<0.001
AIS Abdomen value	712	1.2 ± 1.5	1.4 ± 1.5	1.2 ± 1.4	0.037
AIS Abdomen >2 (%)	712	146 (21%)	49 (26%)	97 (18%)	0.025
SAPSII Score	709	45 ± 16	53 ± 14	42 ± 16	<0.001
PRBC unit transfused in 24h	712	2.1 ± 5.0	2.9 ± 6.4	1.8 ± 4.4	0.011
FFP units transfused in 24h	712	1.6 ± 4.1	2.5 ± 5.3	1.3 ± 3.4	<0.001
Platelet unit transfused in 24h	712	0.30 ± 1.41	0.49 ± 1.48	0.23 ± 1.39	0.030
Massive transfusion (%)	712	45 (6%)	18 (10%)	27 (5%)	0.031
Flail chest (%)	712	74 (10%)	26 (14%)	48 (9%)	0.067
Pulmonary contusion (uni or bilateral) (%)	712	184 (26%)	58 (31%)	126 (24%)	0.060
Hemothorax (%)	712	179 (25%)	59 (32%)	120 (23%)	0.019
Spinal cord injury with ND (%)	712	40 (6%)	14 (7%)	26 (5%)	0.196
Chest drainage (%)	712	83 (12%)	34 (18%)	49 (9%)	0.001
Thoracic surgery (%)	712	24 (3%)	7 (4%)	17 (3%)	0.742
Rib fixation surgery (%)	712	8 (1%)	3 (2%)	5 (1%)	0.439
Abdominal surgery (%)	164	26 (16%)	4 (11%)	22 (17%)	0.340
Prehospital antibiotic administration (%)	712	91 (13%)	16 (9%)	75 (14%)	0.044
Sepsis during ICU stay (%)	712	251 (35%)	187 (100%)	64 (12%)	<0.001
Abdominal sepsis (%)	712	29 (4%)	22 (12%)	7 (1%)	<0.001
Urinary sepsis (%)	712	27 (4%)	14 (7%)	13 (2%)	0.002
Neuro-meningeal sepsis (%)	712	5 (<1%)	2 (1%)	3 (<1%)	0.611
Device-related sepsis (%)	712	71 (10%)	51 (27%)	20 (4%)	<0.001
Sepsis related to surgical site infection (%)	712	50 (7%)	16 (9%)	34 (6%)	0.339
Septic shock during icu stay (%)	712	60 (8%)	49 (26%)	11 (2%)	<0.001
Days of mechanical ventilation	685	6 [2 ; 19]	26 [20 ; 38]	3 [1 ; 7]	<0.001
Tracheotomy (%)	693	148 (21%)	95 (51%)	53 (10%)	<0.001
ARDS (%)	712	142 (20%)	82 (44%)	60 (11%)	<0.001
ICU LOS (days)	712	13 [6 ; 29]	39 [27 ; 51]	9 [5 ; 15]	<0.001
Hospital LOS (days)	658	28 [13 ; 48]	50 [36 ; 71]	19 [11 ; 36]	<0.001
Death in critical care	712	71 (10%)	27 (14%)	44 (8%)	0.018
30-day mortality	712	52 (8%)	10 (5%)	42 (8%)	0.186

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BMI: Body Mass Index; ASA: American society of anesthesiologists; SBP: Systolic blood pressure, DBP: diastolic blood pressure; SpO2: Pulse oximetry Oxygen saturation; SOFA: Sequential organ failure assessment score; ISS:Injury Severity score, AIS: Abbreviated Injury Scale; SAPSII: Simplified acute physiology score; PRBC 24h: number of packed red blood cells administered in the first 24hours; FFP 24h: number of fresh frozen plasma administered in the first 24hours; Platelet unit 24h: number of platelet unit administered in the first 24hours; Spinal cord injury with ND: Spinal cord injury with neurological deficit; ARDS: acute respiratory distress syndrome; ICU: intensive care unit; LOS: length of stay.

Univariate analyses

The patients with early suspected VAP were more frequently males, had higher ISS, SOFA score, and SAPS II, and did not receive prehospital antibiotic therapy (Table 1). They received a longer duration of invasive mechanical ventilation and developed more commonly ARDS and septic shock (Table 1). No difference was found for mortality rate at day 30 between the patients with early suspected VAP and those with no early suspected VAP (Table 1).

Multivariate analyses

Results from the two multivariable models are summarized in Table 2. Twenty-five patients were excluded because of missing data on at least one of the variables included in the models. In brief, male gender, ASA score and initial GCS score < 9 were independent factors associated with early suspected VAP in both models (Table 2). Conversely, prehospital administration of antibiotic was the only protective factor (Table 2). The ISS, the absolute thoracic AIS value, the number of PRBCs transfused in the first 24 hours were significantly associated with early suspected VAP (Table 2). No significant association were found with age, rib fractures, hemothorax, contusion, abdominal AIS > 2, and spinal injury with neurologic deficit (Table 2). Variance inflation factors were low for each model (Table 2).

Table 2. Multivariate analysis for prediction of VAP occurrence.

Model 1 (n = 688)	OR	Inf CI	Sup CI	p-value	VIF
Age (years)	1.00	0.99	1.01	0.941	1.35
Male gender	2.77	1.68	4.77	< 0.001	1.03
ASA score > 1	1.64	1.08	2.50	0.019	1.32
AIS Abdomen > 2	1.55	0.99	2.39	0.053	1.09
Absolute thoracic AIS value	1.51	1.14	1.99	0.003	1.10
Prehospital antibiotic administration	0.54	0.29	0.94	0.028	1.02
Spinal cord lesion with neurologic deficit	1.51	0.70	3.12	0.283	1.09
Massive transfusion	1.80	0.90	3.55	0.096	1.09
Initial GCS score < 9	2.71	1.88	3.96	< 0.001	1.04
Model 2 (n = 688)
Age (years)	1.00	0.99	1.01	0.949	1.38
Male gender	2.72	1.65	4.66	< 0.001	1.03
ASA > 1	1.71	1.13	2.59	0.011	1.30
ISS > 15	3.15	1.13	11.99	0.025	1.02
Prehospital antibiotic administration	0.51	0.27	0.90	0.018	1.03
Lung contusion	1.23	0.82	1.84	0.321	1.08
Flail chest	1.24	0.70	2.15	0.451	1.06
Hemothorax	1.40	0.93	2.10	0.105	1.07
Spinal cord lesion with neurologic deficit	1.81	0.87	3.66	0.112	1.04
Number of transfused PRBCs in the first 24 h	1.04	1.00	1.08	0.027	1.11
Initial GCS score < 9	2.57	1.79	3.74	< 0.001	1.03

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ASA: American society of anesthesiology; AIS: Abbreviated injury score; GCS: Glasgow coma scale; ISS: injury severity score; VAP: Ventilator associated pneumonia; VIF: Variance Inflation Factor PRBCs: packed red blood cells

Discussion

In our cohort, independent risk factors associated with early suspected VAP in patients with severe blunt thoracic trauma receiving invasive mechanical ventilation were male gender, ASA score >1, ISS > 15, absolute thoracic AIS value, initial GCS score < 9 and number of transfused PRBCs in the first 24 hours. Prehospital administration of antibiotic therapy was an independent protective factor. To our knowledge, this is the first study reporting risk factors for early suspected VAP in a homogeneous population of blunt thoracic trauma patients receiving invasive mechanical ventilation.

To date, Wutzler et al. in one of the largest multicentric retrospective cohort study (n = 1162) in this question, identified age, male gender, inhalation of gastric content, and duration of invasive mechanical ventilation as independent risk factors for pneumonia [4]. Unlike this study, we considered GCS score < 9 rather than inhalation. Indeed, a GCS score < 9 represents a risk factor for inhalation and this can be easily identified, unlike with reported pre-hospital inhalation [13–15]. In this study, severity scores such as ISS or thoracic AIS did not appear as independent risk factors in contrast to our study and others [2,15,16]. In fact, the most severe patients could have died before the onset of pneumonia, thus inducing a non-exposure bias. Furthermore, the heterogeneity of patients (blunt and penetrating trauma and patients with and without invasive mechanical ventilation) and the heterogeneity of the type of pneumonia probably explains this divergence.

Our findings showed that an initial GCS score < 9 was an independent risk factor associated with early suspected VAP. This association was previously described in the literature. In a single-center study of 221 severely thoracic trauma patients (ISS > 16 and thoracic AIS > 2), Michelet et al. found that the GCS score and the Head AIS were associated with pneumonia occurring within the first 72 hours [16]. The Head AIS was also an independent risk factor associated with pneumonia in another study assessing risk factors for pneumonia in 571 severely trauma patients receiving initial invasive mechanical ventilation [15]. The largest study describing risk factors for pneumonia in traumatic brain injury patients receiving invasive mechanical ventilation was performed by Robba et al.[3]. This retrospective multicenter cohort study from the CENTER-TBI study data included 962 patients with traumatic brain injury receiving invasive mechanical ventilation for more than 48 hours and staying in the ICU for more than 72 hours [3]. A GCS score < 9 and the motor component of GCS score were associated with VAP in univariate analyses, although the multivariate analysis did not confirm this finding [3]. In this cohort, the presence of associated chest trauma was as an independent risk factor for VAP with a hazard ratio of 1.40 [CI95%: 1.03–1.90] [3]. Thus, severe thoracic associated with severe traumatic brain injury was associated with high rates of pneumonia.

The results of our study did not confirm massive transfusion as a risk factor associated with suspected VAP (OR = 1.80 [CI95%: 0.90; 3.55]). However, the number of PRBCs was associated with early suspected VAP in one of the multivariate analysis models (OR = 1.04 [CI95%: 1.00–1.08]; p = 0.03). In our cohort, the lack of association between massive transfusion and the occurrence of early suspected VAP could be explained by the exclusion of patients not surviving within the first five days who were the most susceptible to be massively transfused. Furthermore the study was not designed for this specific end-point and may lack power. Nevertheless, blood product transfusion was frequently described as being associated with an increased risk of pneumonia. Bochicchio et al., in a cohort of 766 ICU trauma patients receiving more than 48 hours of invasive mechanical ventilation, identified blood product transfusion as an independent risk factor associated with pneumonia, regardless of the type of blood product transfused [17]. Torrance et al., in a study including 112 ICU trauma patients mechanically ventilated, measured a set of biomarkers including interleukin-10 (IL-10), Foxp3, TNF alpha, and interferon gamma [18]. They found an association between blood transfusion within the first 24 h and increased serum levels of IL-10 reflecting an immunosuppressive response, which could explain the increased risk for VAP due to an immunosuppression associated with blood transfusion [18].

Male gender and ASA score were associated with more suspected VAP in our cohort such as severity of thoracic injury and general severity of the trauma. These findings are in line with previous studies on the topic. In a prospective study Michet et al. described an association between thoracic AIS and increase risk of pneumonia [16]. Indeed, on two larges epidemiologic cohorts male gender, preexisting disease where associated with an increasing risk of sepsis [19,20]. Severity of trauma was also associated with a six-fold to 16-fold increase incidence of sepsis for moderate (ISS 15–29) and severe injury (ISS > 29) compared with mild injury defined as an ISS < 15 [19].

Finally, we found that prehospital antibiotic therapy was a protective factor associated with a decreased rate of early suspected VAP. This finding confirmed those reported in previous studies [21]. In guidelines, use of prehospital antibiotic therapy in justified by open bone fractures infection prevention [22]. This practice seems to be associated with less early suspected VAP occurrence for patients with risk factors. In trauma patients with severe traumatic brain injury receiving invasive mechanical ventilation, Robba et al. highlighted that the administration of antibiotic prophylaxis was a protective factor associated with a decreased risk for pneumonia (hazard ratio (HR) of 0.69 [95%CI: 0.50–0.96]) [3]. Recently Dahyot-Fizelier et al., in a randomized clinical trial including 345 patients with severe traumatic brain injury requiring mechanical ventilation, showed that one single dose of ceftriaxone reduced the occurrence of early VAP (HR 0·60 [95% CI 0·38–0·95], p = 0·030) [23]. This result offer opportunities for further studies on the prevention or early VAP in the context of trauma.

Our study has some limitations. First, the diagnosis of VAP is declarative, which could introduce a level of variability between centers. However, our data were collected from French ICUs in which the diagnosis of VAP was based on our national guidelines and reflected a pragmatic approach [8,10]. Nevertheless we qualified the diagnosis of VAP as suspected because no microbiological documentation was reported in the data base. The choice of our first outcome may be matter of debate. In our study, we focused on early suspected VAP (occurring from 48 h to day 5 after ICU admission). This choice reduced the number of patients but avoided a potential confounding bias in the early phase due to premature deaths. Indeed, pneumonia remains a difficult diagnosis and therefore could be misdiagnosed in patients with pulmonary contusions or in inhalation context at the initial phase, i.e., in the first 48 h. Finally, we excluded a large number of patients due to missing data, which is inherent to the study design. Despite these exclusions, our study represents, to our knowledge, the largest cohort of severely blunt chest trauma patients admitted to ICU and receiving invasive mechanical ventilation. Finally, logistic regression identified pre-hospital antibiotics therapy as a protective factor, this result is in line with recent finding as describe above but the database was not able to provide information about the duration of the antibiotic therapy after admission. This bias may affect the interpretation of the finding.

Conclusion

In conclusion, in patients with severe blunt chest trauma patients receiving invasive mechanical ventilation, male gender, ASA score >1, ISS > 15, initial GCS score < 9, absolute thoracic AIS value, and the number of PRBCs transfused were independent risk factors associated with early suspected VAP. Administration of pre-hospital antibiotic therapy could be an independent protective factor for early suspected VAP. This point may lead to future studies in VAP prevention in the trauma context.

Supporting information

S1 File. STROBE Statement—Checklist of items that should be included in reports of case-control studies.

(DOC)

pone.0324120.s001.doc^{(99.5KB, doc)}

S1 Table. Descriptive statistics and univariate analysis comparing the suspected VAP and non-suspected VAP group. Quantitative variables are expressed in medians and interquartile ranges (25-75) or in means ± standard deviations depending on their distribution.

(DOC)

pone.0324120.s002.docx^{(26.4KB, docx)}

Data Availability

Data cannot be shared because of french legislation . Data are available from the Comité informatique et liberté Institutional Data Access for researchers who meet the criteria for access to confidential data on reasonable request to contact@traumabase.eu

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. 2025 May 27;20(5):e0324120. doi: 10.1371/journal.pone.0324120.r001

Author response to Decision Letter 0

22 Nov 2024

PLoS One. doi: 10.1371/journal.pone.0324120.r002

Decision Letter 0

Jean Baptiste Lascarrou

14 Jan 2025

Dear Dr. Duclos,

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: Thank you for your work, which explores a little more the Traumabase in a little-studied area of blunt thoracic trauma reveiving mechanical ventilation.

You rightly note that your 30-days mortality is low because you exluded the most severe patients inducing a non-exposure bias and the possible lack of association with massive transfusion.

Concerning the statistical analysis : Why have you runned two multivariate models that include redundancies ? If you use two different models, you may be tempted to choose the model that performs better. You also conclude with the results of the two models but I don't see how each model offers anything different.

I would have liked to know a little more about the micro-organisms found (and a possible difference with pure traumatic brain injuries). I found this work very interesting, it prompts reflection on VAP prevention. The role of prehospital antibiotic therapy and its generalisation beyond open bones fractures infections prevention is a field of research.

Reviewer #2: I thank the editor for the opportunity to evaluate this manuscript, which aims to identify risk factors for early VAP in patients admitted for severe thoracic blunt trauma and requiring mechanical ventilation in France between 2014 and 2021.

The strengths of this work lie in:

• A large, homogeneous national cohort (sourced from the Traumabase registry),

• Clearly stated objectives and methodology,

• A manuscript that is overall well-written.

Below are my comments:

Major comments:

1. Definition of VAP:

The definition of VAP used in this article is insufficiently detailed. The declarative nature of the diagnosis and the absence of an adjudication committee represent significant limitations, especially in a population where, as the authors rightly highlight, differential diagnoses are common. While the authors explain the criteria for suspecting VAP, they do not mention any qualitative or quantitative microbiological criterion. It appears that the mere initiation of empirical antibiotic therapy for suspected VAP was sufficient for diagnosis. Is the rate of microbiologically documented VAP known in this cohort? If no microbiological criterion was required, I suggest replacing the term "VAP" with "suspected VAP" throughout the manuscript.

2. Statistical methodology:

The authors used a logistic regression model for their analysis. To account for bias related to mechanical ventilation exposure, they excluded patients who died before day 5. However, they did not exclude patients extubated before day 5, which raises questions. This methodology does not appear optimal to address the notable competing risks of death and extubation. A Fine and Gray model would be more appropriate, as it accounts for the time to VAP occurrence (like a Cox model) and the cumulative incidence of events (like a logistic model).

3. Flow Chart details:

The flow chart mentions exclusion criteria that are not detailed in the main text, such as pneumonia identified before 48 hours of mechanical ventilation (a reasonable criterion) and late-onset pneumonia, which is unexpected.

4. Prehospital antibiotics as a protective factor:

Logistic regression identified prehospital antibiotic administration as a protective factor against VAP. This is an interesting finding, echoing recent literature advocating very short-duration antibioprophylaxis (1 dose to 3 days) to prevent VAP in high-risk ICU patients. However, in this cohort, patients received prehospital antibiotics primarily for associated open fractures. The authors do not specify whether antibiotics were continued after hospital admission and their duration, which significantly affects the interpretation and message of this result.

5. Discussion Section:

Some factors identified as independently associated with VAP diagnosis are not discussed, such as male gender, ASA score, ISS, and absolute thoracic AIS value. The authors' explanation for the non-significant association between massive transfusion and VAP could be clarified by simply noting that the number of events was likely insufficient, and the study was underpowered to detect this association.

Minor comments:

1. Paragraph numbering is inconsistent.

2. Author affiliations are repetitive.

3. The citation formatting needs revision (references should be placed before the period, not after).

4. The “Definitions of Analyzed Variables” section contains redundancies and could be streamlined.

5. The variables included in the two logistic regression models differ between Table 2 and the text (e.g., ASA score is missing in the text for the second model).

6. Use "our study" instead of "this study" in the discussion section to improve clarity.

7. Page 14, lines 274-275: The odds ratio mentioned in the text does not match the results in Table 2.

8. The conclusion omits ASA score from the list of factors independently associated with VAP.

9. Several English language errors require correction, such as:

o "our study was aimed,"

o "who were the most susceptible to received massive transfusion,"

o "biomarkers of IL-10,"

o "are reflection a pragmatic approach,"

o "was could be an independent protective factor."

10. The abbreviation AIS is defined differently in the abstract and main text ("acute injury score" vs. "abbreviated injury scale").

11. The ISS abbreviation is not introduced in the main text.

12. Using “ISS score” or “AIS score” is redundant.

13. Replace "male sex" with "male gender."

Thank you to the authors for their work on this important topic. I hope these comments will be helpful in refining and strengthening this valuable contribution to the field.

Reviewer #3: Thank you to the authors for the opportunity to review their well written manuscript. I applaud their efforts to further define a distinct population of patients with blunt thoracic injury as separate from a general ICU population at risk for VAP. I have a few questions for the authors:

1. The authors describe the selection of variables for the multivariable models as “a priori from the literature.” Could the authors provide more detail about how these variables were selected, and which studies influenced the decisions?

2. Was a larger model run that included variables from both smaller models? The exclusion of certain variables clouds the conclusions drawn when, for example ISS, is excluded in one of the models.

3. Did the authors find particular types of thoracic injuries to be more significant in any models run? In Model 2, lung contusion, flail chest, and hemothorax are all included together which may represent significant collinearity.

4. In the methods section the authors note that they included patients who received mechanical ventilation for “any length of time.” Were patients intubated for the entire 5-day period of interest or were some patients extubated in this period, but still found to have VAP?

5. In both multivariable models variables such as ASA >1, AIS >2, ISS >15 were included. Were these categorical variables? How were these cutoffs determined? An ASA patient of 4 is quite different from an ASA 2, but these are treated the same in both models.

6. The authors mention in the discussion that GCS <9 was used as a substitute for aspiration event. While I agree that aspiration is difficult to assess clinically, could the authors further comment on this decision? Many patients with aspiration do not have a traumatic brain injury, and vice versa.

7. The increased risk of the combination of TBI and thoracic injury is very interesting. Were there enough patients in this group to perform any subgroup analyses?

8. Did any patients undergo surgical fixation of rib fractures and did the affect the rates of VAP?

9. Given the identification of particular risk factors, do the authors suggest any change in practice to help prevent VAP in the higher risk patients?

Overall, this is an excellent study that will expand the literature on this important topic. Trauma patients, and particularly those with blunt thoracic trauma, are certainly high risk for pulmonary infection and should be considered distinct from a general ICU patient population. Thank you again to the authors for this opportunity.

**********

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Reviewer #1: Yes: Alejandro Villaamil

Reviewer #2: No

Reviewer #3: Yes: Kevin N Harrell

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PLoS One. 2025 May 27;20(5):e0324120. doi: 10.1371/journal.pone.0324120.r003

Author response to Decision Letter 0

27 Mar 2025

Reviewer #1: Thank you for your work, which explores a little more the Traumabase in a little-studied area of blunt thoracic trauma reveiving mechanical ventilation.

You rightly note that your 30-days mortality is low because you exluded the most severe patients inducing a non-exposure bias and the possible lack of association with massive transfusion.

Dear reviewer, thanks for the time you ve spent in reading this manuscript.

We wanted to explore 2 different kind of injury what was susceptible to lead to pneumonia.

First we wanted to evaluate the global severity of thoracic injury by performing the first model and then we wanted to explore some specific kind of lesions as contusion, hemothoraces or chest flail. We were not able to put all the variable in a same model because of redundancies so we ve chosen to run 2 models.

To rule out any redundancies in the model we have now added the Variance inflation factors which remains low for every variable.

Unfortunately the microbiological characteristics of the VAP were not available in the data base. This is, indeed a major bias of the study. Even when following guidelines, pneumonia remains a difficult diagnosis. We have tried to attenuate it by exploring only pneumonia occurring after 2 days of admission in ICU. We supposed that physicians would be less susceptible to over treat simple pneumonia suspicion or confounding diagnosis such as contusions.

Reviewer #2: I thank the editor for the opportunity to evaluate this manuscript, which aims to identify risk factors for early VAP in patients admitted for severe thoracic blunt trauma and requiring mechanical ventilation in France between 2014 and 2021.

The strengths of this work lie in:

• A large, homogeneous national cohort (sourced from the Traumabase registry),

• Clearly stated objectives and methodology,

• A manuscript that is overall well-written.

Below are my comments:

Major comments:

1. Definition of VAP:

Dear reviewer, thank you very much for the time you ve spent in correcting and improving this manuscript. Our remarks will be very useful.

Regarding the diagnosis of VAP, as you ve highlighted, its declarative nature is a major bias and no microbiological document was available to prevent it. As you suggested we have replaced the VAP term with suspected VAP when it was referring our data.

2. Statistical methodology:

Dear reviewer, thank you for this remark.

To simplify the understanding of the work and to clarify the take home message for the readers we have chosen to remove all patients without at least 5 days of mechanical ventilation from the analysis. 5 patients were excluded and the analysis and tables have been totally remade.

New results stay coherent with the previous one but we can now insure the lack of exposition bias regarding the exposure of mechanical ventilation.

3. Flow Chart details:

Dear reviewer, the flow chart and the main text are now coherent. The misunderstanding provides from the inclusion criterion of early onset suspected VAP (between 2 and 5 days of mechanical ventilation exposure) that forces the exclusion of immediate pneumonia and late VAP.

Sorry for this mistake.

4. Prehospital antibiotics as a protective factor:

Dear reviewer, you re right but unfortunately this information is not available in the data base. We have added this limitation in the discussion.

5. Discussion Section:

Dear reviewer, I have added some discussion point about the points you have highlighted.

Minor comments:

1. Paragraph numbering is inconsistent.

Dear reviewer, we ve corrected this point. Thank you.

2. Author affiliations are repetitive.

3. The citation formatting needs revision (references should be placed before the period, not after).

This point has been corrected. Thank you.

4. The “Definitions of Analyzed Variables” section contains redundancies and could be streamlined.

Dear reviewer, this section has been slightly reworked.

5. The variables included in the two logistic regression models differ between Table 2 and the text (e.g., ASA score is missing in the text for the second model).

Dear reviewer, thank you. This has been corrected.

6. Use "our study" instead of "this study" in the discussion section to improve clarity.

Dear reviewer, this has been corrected.

7. Page 14, lines 274-275: The odds ratio mentioned in the text does not match the results in Table 2.

Dear reviewer, this point has been corrected. Thank you.

8. The conclusion omits ASA score from the list of factors independently associated with VAP.

This point has been corrected.

9. Several English language errors require correction, such as:

o "our study was aimed,"

o "who were the most susceptible to received massive transfusion,"

o "biomarkers of IL-10,"

o "are reflection a pragmatic approach,"

o "was could be an independent protective factor."

10. The abbreviation AIS is defined differently in the abstract and main text ("acute injury score" vs. "abbreviated injury scale").

11. The ISS abbreviation is not introduced in the main text.

12. Using “ISS score” or “AIS score” is redundant.

13. Replace "male sex" with "male gender."

Dear reviewer, all errors have been corrected. Thank you for your helpful reviewing

Thank you to the authors for their work on this important topic. I hope these comments will be helpful in refining and strengthening this valuable contribution to the field.

Reviewer #3: Thank you to the authors for the opportunity to review their well written manuscript. I applaud their efforts to further define a distinct population of patients with blunt thoracic injury as separate from a general ICU population at risk for VAP. I have a few questions for the authors:

Dear reviewer, thank you for the time you ve spent in reading and correcting this work.

We have added the reference inside the material and method section. Also, variables are extensively discussed in the appropriate section.

2. Was a larger model run that included variables from both smaller models? The exclusion of certain variables clouds the conclusions drawn when, for example ISS, is excluded in one of the models.

Dear reviewer, thank you for this good question. Indeed we had issues in having a larger model for some reason. First, the number of variable is limited depending the number of events. In this case, we could have added some more variable but the variance interference factors were raising. That could have introduced some redundancies into the model. So we have chosen 2 different approaches, the first was to focus about the global severity of the whole trauma (ISS) and adding some specific kind of lesion. The second was to focus about the severity of the thoracic injuries (AIS thoracic).

Dear reviewer, we have checked the collinearity of the variable by calculating the VIF. We have added them in the table 2. All VIF were low in both model, insuring the no-collinearity of them.

Dear Reviewer, this is an excellent question.

Indeed after checking the data we found that 5 patients were weaned of mechanical ventilation before day 5. We wanted to present clean results so excluded the patients and made the whole analysis again. That explains why we took so long before responding the reviewing. Guaranteed without exposition bias this time.

Dear reviewer, we wanted to class comorbid and no-comorbid patient by this bias. As you can see in table 1, the number of comorbid patients was very low (but populations of trauma patients are often young). The number of patients presenting ASA 3 and 4 was too low to be analyzed in an efficient way. This is why we have chosen to determine the ASA cut-off of 2.

Dear reviewer, this decision is indeed arguable. We wanted to prevent any bias and redundancies for the logistic models. The most severe risk for aspiration event seems to be coma whatever its cause. By choosing a GCS < 9 we think that we included most situations with risk of aspiration events (TBI, cardiac arrest, intoxication).

7. The increased risk of the combination of TBI and thoracic injury is very interesting. Were there enough patients in this group to perform any subgroup analyses?

Dear reviewer, unfortunately the number of patients was too low to perform a subgroup analyses. Moreover we wanted to keep the manuscript clear and adding another subgroup could have complicated the analysis and the understanding of the text for an underpowered side analysis.

8. Did any patients undergo surgical fixation of rib fractures and did the affect the rates of VAP?

Dear reviewer, 75 rib flail chest were reported in our cohort but only 8 patients underwent a rib fracture surgery. It was not enough to be analyzed apart. (Data are available in supplemental table 1).

9. Given the identification of particular risk factors, do the authors suggest any change in practice to help prevent VAP in the higher risk patients?

Dear reviewer, thank you for this question. It is probability to soon considering the data available to recommend extensive use of short duration antibiotic use at trauma admission. Nevertheless we are working on an RCT at the moment to explore this hypothesis

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PLoS One. doi: 10.1371/journal.pone.0324120.r004

Decision Letter 1

Jean Baptiste Lascarrou

17 Apr 2025

Dear Dr. Duclos,

Please submit your revised manuscript by Jun 01 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

**********

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Reviewer #2: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: Thank you for your corrections. As you say in the discussion, the declarative nature of the diagnosis, the absence of an adjudication committee and the absence of any microbiological features represent significant limitations.

Reviewer #2: I would like to thank the authors for addressing my comments and revising the manuscript accordingly. I appreciate the effort made to improve the clarity and precision of the text.

However, I noticed that the term "suspected VAP" has been incorrectly replaced with "suggested VAP" throughout the manuscript. The term "suggested VAP" is not appropriate and should be corrected to "suspected VAP" everywhere. Additionally, the title should clearly indicate that the study focuses on early suspected VAP.

Some other points remain unaddressed:

• The conclusion of the abstract still omits ASA score from the list of factors independently associated with VAP.

• The abbreviation AIS is still inconsistently defined in the abstract and main text ("acute injury score" vs. "abbreviated injury scale").

• The redundancy in "ISS score" has not been fully corrected, as "ISS score" still appears in some instances.

• "Male sex" should be replaced with "male gender" throughout the manuscript.

Finally, in the second-to-last sentence before the conclusion on page 15, "this results" should be corrected to "this result."

I have no further comments.

I wish the authors much success in their future interventional project, which may further validate the preliminary findings of this study. It’s great to see such work progressing in this field!

Reviewer #3: Thank you for your response to my comments. The authors have addressed all my concerns and strengthened this paper.

**********

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Reviewer #1: Yes: Alejandro Villaamil

Reviewer #2: No

Reviewer #3: Yes: Kevin Harrell, MD

**********

PLoS One. 2025 May 27;20(5):e0324120. doi: 10.1371/journal.pone.0324120.r005

Author response to Decision Letter 1

18 Apr 2025

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: I would like to thank the authors for addressing my comments and revising the manuscript accordingly. I appreciate the effort made to improve the clarity and precision of the text.

Dear reviewer, this mistake has been corrected everywhere in the text and tables

Some other points remain unaddressed:

• The conclusion of the abstract still omits ASA score from the list of factors independently associated with VAP.

Dear reviewer, ASA score has been added

• The abbreviation AIS is still inconsistently defined in the abstract and main text ("acute injury score" vs. "abbreviated injury scale").

Dear Reviewer, sorry for this omission. It has been corrected

• The redundancy in "ISS score" has not been fully corrected, as "ISS score" still appears in some instances.

Dear reviewer, this redundancy has been corrected.

• "Male sex" should be replaced with "male gender" throughout the manuscript.

Dear Reviewer, it has been corrected

Finally, in the second-to-last sentence before the conclusion on page 15, "this results" should be corrected to "this result."

Dear Reviewer, it has been corrected

I have no further comments.

I wish the authors much success in their future interventional project, which may further validate the preliminary findings of this study. It’s great to see such work progressing in this field!

Reviewer #3: Thank you for your response to my comments. The authors have addressed all my concerns and strengthened this paper.

________________________________________

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PLoS One. doi: 10.1371/journal.pone.0324120.r006

Decision Letter 2

Jean Baptiste Lascarrou

22 Apr 2025

Risk factors for early suspected ventilator-associated pneumonia in severe thoracic blunt trauma patient: a French national cohort study.

PONE-D-24-45522R2

Dear Dr. Duclos,

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Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0324120.r007

Acceptance letter

Jean Baptiste Lascarrou

PONE-D-24-45522R2

PLOS ONE

Dear Dr. Duclos,

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 File. STROBE Statement—Checklist of items that should be included in reports of case-control studies.

(DOC)

pone.0324120.s001.doc^{(99.5KB, doc)}

(DOC)

pone.0324120.s002.docx^{(26.4KB, docx)}

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pone.0324120.s003.docx^{(18.9KB, docx)}

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pone.0324120.s004.docx^{(13.2KB, docx)}

Data Availability Statement

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PERMALINK

Risk factors for early suspected ventilator-associated pneumonia in severe thoracic blunt trauma patient: A French national cohort study

Gary Duclos

Victor Vidal

Noemie Resseguier

Mathieu Boutonnet

Thomas Botrel

Gerard Audibert

Manon Séguret

Vincent Legros

Caroline Jeantrelle

Anh Dao Phan

Olivier Langeron

Elisabeth Gaertner

Jean-Luc Hanouz

Thomas Clavier

Véronique Ramonda

Fanny Bounes

Paër-selim Abback

Mathieu Willig

Julien Pottecher

Marc Leone

Roles

Abstract

Background

Materials and Methods

Results

Conclusion

Background

Materials and methods

Study design

Inclusion and exclusion criteria

Outcome

Definitions of analyzed variables

Statistical Analysis

Results

Patient characteristics

Fig 1. Flowchart of the study.

Table 1. Descriptive statistics and univariate analyses comparing the early VAP and no early VAP groups.

Univariate analyses

Multivariate analyses

Table 2. Multivariate analysis for prediction of VAP occurrence.

Discussion

Conclusion

Supporting information

Data Availability

Funding Statement

References

Author response to Decision Letter 0

Decision Letter 0

Jean Baptiste Lascarrou

Roles

Author response to Decision Letter 0

Decision Letter 1

Jean Baptiste Lascarrou

Roles

Author response to Decision Letter 1

Decision Letter 2

Jean Baptiste Lascarrou

Roles

Acceptance letter

Jean Baptiste Lascarrou

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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