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Hyperoxemia as a risk factor for ventilator-associated pneumonia

  • 1,
  • 1,
  • 1,
  • 1,
  • 2 and
  • 1, 3Email author
Contributed equally
Critical Care201620:195

https://doi.org/10.1186/s13054-016-1368-4

  • Received: 28 January 2016
  • Accepted: 1 June 2016
  • Published:

The Commentary to this article has been published in Critical Care 2016 20:239

Abstract

Background

Consequences of hyperoxemia, such as acute lung injury, atelectasis, and reduced bacterial clearance, might promote ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between hyperoxemia and VAP.

Methods

This retrospective observational study was performed in a 30-bed mixed ICU. All patients receiving invasive mechanical ventilation for more than 48 hours were eligible. VAP was defined using clinical, radiologic, and quantitative microbiological criteria. Hyperoxemia was defined as PaO2 > 120 mmHg. All data, except those related to hyperoxemia, were prospectively collected. Risk factors for VAP were determined using univariate and multivariate analysis.

Results

VAP was diagnosed in 141 of the 503 enrolled patients (28 %). The incidence rate of VAP was 14.7 per 1000 ventilator days. Hyperoxemia at intensive care unit admission (67 % vs 53 %, OR = 1.8, 95 % CI (1.2, 29), p <0.05) and number of days spent with hyperoxemia were significantly more frequent in patients with VAP, compared with those with no VAP. Multivariate analysis identified number of days spent with hyperoxemia (OR = 1.1, 95 % CI (1.04, 1.2) per day, p = 0.004), simplified acute physiology score (SAPS) II (OR = 1.01, 95 % CI (1.002, 1.024) per point, p < 0 .05), red blood cell transfusion (OR = 1.8, 95 % CI (1.2, 2.7), p = 0.01), and proton pomp inhibitor use (OR = 1.9, 95 % CI (1.03, 1.2), p < 0.05) as independent risk factors for VAP. Other multiple regression models also identified hyperoxemia at ICU admission (OR = 1.89, 95 % CI (1.23, 2.89), p = 0.004), and percentage of days with hyperoxemia (OR = 2.2, 95 % CI (1.08, 4.48), p = 0.029) as independent risk factors for VAP.

Conclusion

Hyperoxemia is independently associated with VAP. Further studies are required to confirm our results.

Keywords

  • Arterial oxygen tension
  • Ventilator-associated pneumonia
  • Critical care
  • Prevention
  • Outcome, Hyperoxemia
  • Hyperoxia

Background

Hyperoxemia is common in mechanically ventilated critically ill patients. Its incidence ranges from 16–50 % in this population [15]. Liberal oxygen therapy is supposed to prevent hypoxia and improve the oxygen supply to the different affected organs. However, evidence from several recent studies suggests that hyperoxemia is probably not safe. Hyperoxemia is responsible for vasoconstriction and decreased cardiac output, resulting in reduced blood flow and oxygen transport [6, 7]. A negative impact of hyperoxemia on mortality is also reported in different patient populations, such as patients undergoing resuscitation from cardiac arrest [8], patients with acute ischemic stroke [5], and patients with ST-segment elevation [9]. In mechanically ventilated patients, the relationship between mortality and hyperoxemia is still controversial [1012]. The definition of hyperoxemia, measurement methods, and patient population are very heterogeneous in the available studies, making it difficult to interpret the results.
Fig. 1
Fig. 1

Distribution of ventilator-associated pneumonia (VAP) episodes based on number of days with hyperoxemia

Exposure to hyperoxia is responsible for hyperoxic acute lung injury (HALI). Pulmonary edema, hyaline membrane formation, pulmonary arteriole thickening, and alteration in the ventilation/perfusion fraction are the main mechanisms described in HALI [13, 14]. In addition, denitrogenation phenomena, and inhibition of surfactant production are observed at high levels of inspired oxygen fraction (FiO2), promoting expiratory collapse and atelectasis [15, 16]. Hyperoxia also impairs mucociliary clearance and the antimicrobial action capacity of macrophages and immune cells [17]. Acute lung injury, atelectasis, and reduced bacterial clearance are well-known risk factors for VAP [1820].

VAP is the most common ICU-acquired infection, and is associated with high mortality, duration of mechanical ventilation, and cost [21]. Therefore, prevention of VAP is a key issue in critically ill patients. Understanding the pathophysiology of VAP, and identification of risk factors are important in order to improve preventive strategies [22].

Previous animal studies strongly suggest a relationship between hyperoxemia and VAP. However, in spite of the obvious potential link between hyperoxemia and VAP, to our knowledge no study to date has evaluated the relationship between these two conditions. Therefore, we conducted this retrospective observational study to determine whether hyperoxemia is a risk factor for VAP.

Methods

Study characteristics

This retrospective observational study was performed in a 30-bed mixed ICU, located in the University Hospital of Lille, France. All data, except blood gases results, were collected prospectively during an 18-month period. Because of the observational design, and in accordance with French law, written informed consent was not required. The local institutional review board (Comité de Protection des Personnes Nord-Ouest IV) approved the study. All patients requiring invasive mechanical ventilation for more than 48 h, during an 18-month period, were eligible. The only exclusion criterion was duration of mechanical ventilation for ≤48 h.

Definitions

VAP was defined as the presence of new or progressive pulmonary infiltrate, and at least two of the following criteria: (1) fever (body temperature ≥38 °C) or hypothermia (<36 °C); (2) leukocytosis (>12 × 109/L leukocytes) or leukopenia (<3.5 × 109/L); and (3) purulent respiratory secretions. Microbiological confirmation was required in all patients (positive bronchoalveolar lavage ≥104 colony-forming units (cfu)/mL, or positive tracheal aspirate ≥105 cfu/mL) [23]. Only first episodes of VAP diagnosed >48 h after starting mechanical ventilation were taken into account. Early-onset episodes were defined as VAP diagnosed <5 days after starting mechanical ventilation, and late-onset episodes as VAP diagnosed ≥5 days after mechanical ventilation. Hyperoxemia was defined as arterial oxygen tension (PaO2) >120 mmHg. Arterial blood gases were analyzed on a daily basis, and each day with at least one PaO2 value >120 mmHg (>16 kPa) was considered as a day with hyperoxemia.

The following microorganisms were defined as multidrug-resistant bacteria: ceftazidime or imipenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, β-lactamase-producing Gram-negative bacilli and methicillin-resistant Staphylococcus aureus. Prior antibiotic use was defined as antimicrobial treatment during the 3 months preceding ICU admission. Immunosuppression was defined by the presence of neutropenia (neutrophils <500/μL), active solid or hematological malignancy, long-term corticosteroid therapy (≥1 mg/kg/d for >1 month), or HIV infection (CD4 < 50/μL during the previous 6 months).

Study patients

A VAP prevention strategy was routinely used during the study period. The ventilator circuit was not changed routinely. In all patients, a heat-moisture exchanger was positioned between the Y piece and the patient. These exchangers were changed every 48 h or more frequently if visibly soiled. Sedation and weaning were based on a written protocol. A minimal positive end-expiratory pressure of 5 cm H2O was used in all patients. Selective digestive decontamination and subglottic secretion drainage were not used. The oral cavity was cleaned with chlorehexidine three times daily. Cuff pressure was measured and adjusted (25 cm H2O) by nurses thrice a day. Tracheal suctioning was routinely performed by nurses, using an open tracheal suction system. Patients remained in the semi-recumbent position, and received enteral nutrition based on a written protocol.

Antibiotic treatment for patients with suspected VAP was based on American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines [23]. Antibiotic treatment for other infections was based on written local guidelines adapted from international and national guidelines. Stress ulcer prophylaxis was not routinely used.

Data collection

All data were prospectively recorded, except blood gases results. The following characteristics were recorded at ICU admission: age, male gender, severity of illness based on simplified acute physiology score (SAPS) II, logistic organ dysfunction (LOD) score, and McCabe score; comorbidities (diabetes, chronic obstructive pulmonary disease (COPD), chronic heart failure, cirrhosis, chronic renal failure requiring dialysis, or immunosuppression), location before ICU admission, admission category (medical or surgical), reason for ICU admission (acute exacerbation of COPD, acute respiratory distress syndrome, pneumonia, congestive heart failure, neurologic failure, poisoning, shock [24], cellulitis, or infection), and prior antibiotic use.

During the ICU stay data were collected on tracheostomy, red blood cell transfusion, sedation, stress ulcer prophylaxis, use of neuromuscular-blocking agents, number of days with PaO2 > 120 mmHg, percentage of days with PaO2 > 120 mmHg, occurrence of VAP, duration of mechanical ventilation, and ICU mortality.

Statistical analysis

SPSS software (SPSS, Chicago, IL, USA) was used for data analysis. Categorical variables were described as frequency (%). The distribution of continuous variables was tested for normality. Normally distributed and skewed continuous variables were described as mean ± standard deviation (SD) or as median and interquartile range (IQR), respectively. All p values were two-tailed. Differences were considered significant if p values were <0.05.

In order to determine factors associated with VAP, patients with VAP were compared with those without VAP using bivariate and multivariate analyses. The chi-square (χ2) test or Fischer’s exact test was used to compare qualitative variables, as appropriate. Student’s t test or the Mann-Whitney U test was used to compare normally distributed, and skewed continuous variables, respectively. Potential interactions were tested, and the Hosmer-Lemeshow goodness-of-fit was calculated. The odds ratio (OR) and 95 % confidence interval (CI) were calculated for all significant variables in univariate analysis and in multivariate analysis. Exposure to potential risk factors for VAP was taken into account until the occurrence of VAP, or until ICU discharge in patients with and without VAP, respectively.

Because of obvious interaction between hyperoxemia at ICU admission, number of days with hyperoxemia, and percentage of days with hyperoxemia, three different models of multivariate analysis were used. Each of these models included all variables with p values <0.1 on univariate analysis, and hyperoxemia at ICU admission, number of days with hyperoxemia, or percentage of days with hyperoxemia. Further, univariable and multivariable Cox proportional hazard models were used to determine risk factors for VAP. All variables with p values <0.1 in the univariable model, and hyperoxemia at ICU admission, or percentage of days with hyperoxemia were included in the final multivariable models.

Results

Patient characteristics

During the study period 503 patients received mechanical ventilation for >48 h, including 141 patients (28 %) who had at least one episode of VAP. The incidence rate of VAP was 14.7 per 1000 ventilator days. Early-onset and late-onset episodes occurred in 14 (10 %), and 127 (90 %) patients with VAP, respectively. The median (IQR) duration from starting mechanical ventilation to diagnosis of VAP was 14 (8, 23) days.

No significant difference was found in age (median (interquartile range) 60 (49, 73) vs 59 (47, 70), years, p = 0.265), SAPS II (48 (35, 61) vs 48 (36, 62), p = 0.772), LOD score (5 (2, 7) vs 5 (2, 9), p = 0.817), mortality rate (121 out of 289 (41.8 %) vs 82 out of 214 (38.3 %), p = 0.265), duration of mechanical ventilation (12 (6, 24) vs 13 (7, 26), p = 0.427), and ICU length of stay (15 (8, 29) vs 18 (10, 31), p = 0.243), between patients with hyperoxemia and those with no hyperoxemia at ICU admission.

Risk factors for VAP by univariate analysis

At ICU admission, age, SAPS II, LOD score, and percentage of patients with shock, or with PaO2 > 120 mmHg were significantly higher in VAP patients, compared with those with no VAP (Table 1).
Table 1

Characteristics of study patients at ICU admission

 

VAP

P

 

Yes

No

 

n = 141

n = 362

Age, years

62 (51.5–74)

57 (46–71)

0.004

Male gender

102 (72)

246 (67)

0.339

SAPS II

53 (41–65)

45 (33–59)

<0.001

LOD score

6 (3–9)

5 (2–7)

0.241

McCabe score >2

20 (14)

37 (10)

0.382

Transfer from other wards

96 (68)

216 (60)

0.081

Chronic diseases

   

 Diabetes

16 (11)

62 (17)

0.108

 COPD

41 (29)

98 (27)

0.651

 Cardiac failure

34 (24)

67 (18)

0.159

 Cirrhosis

4 (3)

14 (4)

0.576

 Chronic dialysis

2 (1)

10 (3)

0.375

 Immunosuppression

38 (27)

78 (22)

0.196

Admission category

  

0.499

 Medical

91 (65)

245 (67)

 

 Surgical

48 (34)

114 (31)

 

Cause for ICU admission

   

 Acute exacerbation of COPD

16 (11)

46 (12)

0.677

 ARDS

22 (15)

38 (10)

0.113

 Pneumonia

40 (28)

91 (25)

0.458

 Congestive heart failure

5 (3)

9 (2)

0.516

 Neurologic failure

16 (11)

50 (13)

0.462

 Poisoning

16 (11)

30 (8)

0.285

 Shock

64 (45)

111 (30)

0.002a

 Cellulitis

10 (7)

48 (13)

0.052

 Infection

97 (69)

246 (67)

0.856

Prior antimicrobial treatment

70 (50)

178 (49)

0.924

PaO2 > 120 mmHg

95 (67)

193 (53)

0.004b

aOR = 1.9, 95 % CI (1.3, 2.8); bOR = 1.8, 95 % CI (1.2, 2.7). The results are expressed in number (%) for categorical variables and in median (IQR) for quantitative variables. ARDS acute respiratory distress syndrome, COPD, chronic obstructive pulmonary disease, CI confidence interval, ICU intensive care unit, LOD logistic organ dysfunction, MV mechanical ventilation, OR odds ratio, PaO 2 arterial oxygen tension, SAPS simplified acute physiology score, VAP ventilated-associated pneumonia

During the ICU stay, the percentage of patients with stress ulcer prophylaxis, red blood cell transfusion, or sedation was significantly higher in patients with VAP compared to patients without VAP. Number of days with hyperoxemia was also significantly higher in patients with VAP compared to patients without VAP (Table 2). The percentage of patients with VAP, based on the number of days with hyperoxemia is presented in Fig. 1.
Table 2

Patient characteristics during the ICU stay

 

VAP

P

Yes

No

 

n = 141

n = 362

Stress ulcer prophylaxis

  

0.002

 Proton-pump inhibitor

122 (86)

279 (77)

 

 Sucralfate

9 (6)

46 (13)

 

 No

10 (7)

40 (11)

 

Tracheostomy

24 (17)

47 (13)

0.243

Red blood cell transfusion

86 (61)

139 (38)

<0.001a

Sedation

122 (86)

284 (78)

0.039b

Neuromuscular-blocking agent use

10 (7)

20 (6)

0.505

Mean number of ABG per day

3 (1–6)

2 (1–5)

0.261

Number of days with PaO2 > 120 mmHg

5 (2–7)

3 (1–5)

<0.001

Percentage of days with PaO2 > 120 mmHg

0.33 (0.19–0.58)

0.33 (0.14–0.50)

0.282

Duration of MV prior to VAP, days

14 (8–23)

9 (5–17)

<0.001

Total duration of MV, days

30 (17–43)

9 (5–17)

<0.001

Length of ICU stay, days

34 (19–45.5)

12 (7–21)

<0.001

ICU mortality

73 (52)

130 (35)

0.001c

The results are expressed in number (%) for categorical variables and in median (IQR) for quantitative variables. Exposure to potential risk factors for VAP was taken into account until VAP occurrence, or until ICU discharge in patients with and without VAP, respectively. aOR = 2.5 (1.7, 3.7); bOR = 1.8 (1.02, 3.0); cOR = 1.9 (1.3, 2.8)

VAP ventilator-associated pneumonia, CI confidence interval, ICU intensive care unit, OR odds ratio, ABG arterial blood gas, PaO 2 arterial oxygen tension, MV mechanical ventilation

Microbiological results

VAP was polymicrobial in 8 patients (6 %), and related to multidrug resistant (MDR) bacteria in 58 patients (41 %). Gram-negative bacteria represented 78 % of all bacteria, and were identified in 82 % of patients with VAP. P. aeruginosa (34 %), S. aureus (11 %), and A. baumannii (9 %) were the most common bacteria in patients with VAP. MDR bacteria represented 41 % of all bacteria (58 out of 149) (Table 3).
Table 3

Microorganisms isolated in patients with ventilator-associated pneumonia

Microorganisms

Number (%)

Gram-negative bacilli

116 (82)

Pseudomonas aeruginosa

48 (34)

Escherichia Coli

14 (10)

Acinetobacter baumannii

13 (9)

 Enterobacter sp.

13 (9)

 Klebsiella sp.

8 (5)

Proteus mirabilis

6 (4)

 Serratia sp.

5 (3.5)

Stenotrophomonas maltophilia

4 (2.8)

 Others

5 (3.5)

Gram-positive cocci

33 (23)

 Methicillin-resistant Staphylococcus aureus

11 (7.8)

Staphylococcus epidermidis

7 (5)

 Methicillin-sensitive Staphylococcus aureus

5 (3.5)

 Enterococcus sp.

5 (3.5)

Streptococcus pneumoniae

5 (3.3)

Risk factors for VAP by multivariate analysis

Because of significant (p < 0.05) interactions between hyperoxemia at ICU admission, number of days with hyperoxemia, and percentage of days with hyperoxemia, three different logistic regression models were used with only one of these factors in each model. No other significant (p > 0.1) interactions were found between other factors introduced in the multivariable models.

The results of the three logistic regression models are presented in Table 4. Number of days with hyperoxemia, hyperoxemia at ICU admission, and percentage of days with hyperoxemia were independently associated with VAP in models 1, 2, and 3, respectively.
Table 4

Factors associated with ventilator-associated pneumonia by multivariate analysis

Variables

P

OR (95 % CI)

Model 1

  

 SAPS II

0.019

1.01 (1.00, 1.02)*

 Red blood cell transfusion

0.009

1.75 (1.14, 2.70)

 Proton pump inhibitor use

0.040

1.86 (1.03, 3.39)

 Number of days with hyperoxemia

0.001

1.10 (1.04, 1.16)**

Model 2

  

 SAPS II

0.017

1.01 (1.00, 1.02)*

 Red blood cell transfusion

0.009

1.79 (1.16, 2.78)

 Proton pump inhibitor use

0.031

1.92 (1.06, 3.50)

 MV duration prior to VAP

0.012

1.10 (1.01, 1.04)**

 Hyperoxemia at ICU admission

0.004

1.89 (1.23, 2.89)

Model 3

  

 Red blood cell transfusion

0.018

1.71 (1.10, 2.65)

 Proton pump inhibitor use

0.017

2.10 (1.14, 3.79)

 MV duration prior to VAP

0.005

1.03 (1.01, 1.04)*

 Percentage of days with hyperoxemia

0.029

2.20 (1.08, 4.48)**

SAPS simplified acute physiology score; MV mechanical ventilation, VAP ventilator-associated pneumonia. Model 1: *per point of SAPS II, **per day with hyperoxemia; Hosmer-Lemshow goodness-of-fit, p = 0.62. Other non-significant variables included in the model: transfer from other wards, shock, sedation, and duration of MV prior to VAP. Model 2: *per point of SAPS II, **per day of mechanical ventilation; Hosmer-Lemshow goodness-of-fit, p = 0.81. Other non-significant variables included in the model: transfer from other wards, shock, and sedation. Model 3: *per day of mechanical ventilation, **per centile of days with hyperoxemia; Hosmer-Lemshow goodness-of-fit, p = 0.78. Other non-significant variables included in the model: SAPS II, transfer from other wards, shock, and sedation

Risk factors for VAP by univariate and multivariate Cox proportional hazards models

Hyperoxemia at ICU admission and percentage of days with hyperoxemia were independently associated with VAP, using two different Cox proportional hazards models (Table 5).
Table 5

Risk factors for ventilator-associated pneumonia by Cox proportional hazards model

Variable

Univariate analysis

Multivariate analysis (model 1)

Multivariate analysis (model 2)

HR (95 % CI)

P

HR (95 % CI)

P

HR (95 % CI)

P

At ICU admission

      

 LOD score

1.04 (1.01, 1.09)

0.044

-

0.922

-

0.138

 Transfer from other wards

0.65 (0.45, 0.93)

0.018

-

0.356

-

0.952

 Prior antibiotic treatment

0.67 (0.48, 0.94)

0.021

-

0.483

-

0.184

 Neurologic failure

1.82 (1.07, 3.09)

0.027

-

0.111

-

0.197

 Poisoning

3.24 (1.9, 5.51)

<0.001

2.49 (1.31, 4.72)

0.005

2.16 (1.14, 4.09)

0.018

 COPD

0.55 (0.37, 0.89)

0.003

-

0.063

-

0.065

 McCabe score >2

0.76 (0.59, 0.99)

0.042

-

0.169

 

0.726

 PaO2 > 120 mmHg

1.58 (1.11, 2.25)

0.011

NA

NA

1.68 (1.16, 2.42)

0.006

During ICU stay

      

 Percentage of days with PaO2 > 120 mmHg

5.67 (3.15, 10.20)

<0.001

6.23 (3.26, 11.9)

<0.001

NA

NA

HR hazard ratio, LOD logistic organ dysfunction, COPD chronic obstructive pulmonary disease, NA not applicable. P > 0.1 by univariate analysis for: age, male gender, simplified acute physiology score II, diabetes, cardiac failure, cirrhosis, chronic dialysis, immunosuppression, all causes of ICU admission except neurologic failure, stress ulcer prophylaxis, tracheostomy, red blood cell transfusion, sedation, and neuromuscular-blocking agent use

Discussion

Our results suggest that hyperoxemia is an independent risk factor for VAP. To our knowledge, our study is the first to evaluate the relationship between hyperoxemia and VAP. As discussed previously, this result could be explained by the occurrence of HALI, atelectasis, and reduced mucocilliary clearance in patients with hyperoxemia [2528]. Previous studies reported high rates of VAP in patients with acute respiratory distress syndrome [18, 29]. Further, positive expiratory pressure was identified as a preventive measure against VAP [30], by reducing atelectasis in mechanically ventilated patients [31]. Excess oxygen administration could damage tissues through the production of reactive oxygen species (ROS). In excessive concentrations, ROS-mediated stress can lead to cellular necrosis and apoptosis [32]. Therefore, the process of oxidative stress might promote the development of multi-organ failure [33]. In addition, oxidative stress is responsible for direct damage to biological molecules (DNA oxidation, proteins, lipids and carbohydrates) and indirect injury through the release of cytotoxic products and mutagenic effects of lipid oxidation [16].

Recent animal studies support the role of hyperoxemia in the pathogenesis of VAP. Entezari and colleagues demonstrated that prolonged exposure to hyperoxia can compromise the ability of macrophages, an essential part of innate immunity, to phagocytose P. aeruginosa [34]. The same group of investigators reported that hyperoxia results in elevated concentrations of high mobility group box-1 (HMGB1), and mortality in mice infected with P. aeruginosa [17]. Treatment of these animals with a neutralizing anti-HMGB1 monoclonal antibody allowed a reduction in bacterial counts, injury, and numbers of neutrophils in the lungs, and an increase in leucocyte phagocytic activity compared with control animals. Another recent animal study suggests that hyperoxia increases mortality in mice with A. baumannii pneumonia, and that procysteine improves survival by increasing the phagocytic activity of alveolar macrophages [35].

The incidence of multidrug resistant bacteria was relatively high in patients with VAP. This could be explained by the high percentage of patients with late-onset VAP, prior antibiotic treatment, or COPD, and the high severity of illness at ICU admission. All these factors were previously identified as independent risk factors for multidrug resistant bacteria [3639].

Our study has several limitations. First, it was a retrospective study performed in a single center. Therefore, our results could not be generalized and further prospective multicenter studies are needed to confirm these findings. However, all data, except those related to hyperoxemia, were prospectively collected. Second, the cutoff used for hyperoxemia (>120 mmHg) was selected based on the current literature [12, 40, 41]. For example, normal PaO2 is defined by the British Thoracic Society as between 90 and 110 mmHg for patients under 70 years of age and according to the sea level [42]. However, other studies used a different cutoff (i.e., to PaO2 ≥ 300 mmHg) to define hyperoxemia [8, 43, 44]. Because a day with at least one PaO2 value >120 mmHg was considered as a day with hyperoxemia, our definition of hyperoxemia might have overestimated the time period of hyperoxemia. Continuous control of pulse oximetry could be more appropriate to accurately determine time spent with hyperoxemia. Third, no information was collected on PaO2, FiO2, or positive end-expiratory (PEEP) values. Some risk factors, such as head-of-bed elevation and under-inflation of tracheal cuff, were not evaluated in this study. Finally, because of the retrospective design, exploratory investigations, such as measurement of ROS or evaluation of immune function could not be performed.

Two recent small studies [2, 5], one before-after and one randomized controlled study, suggested that a conservative oxygenation strategy might be safe in intubated critically ill patients, compared with a liberal strategy. However, none of these studies evaluated the impact of oxygenation strategy on VAP incidence. Further large randomized controlled trials are required to confirm these data, and to determine the impact of oxygenation strategy on VAP incidence.

Conclusion

Our results suggest a link between hyperoxemia and VAP. However, further large prospective studies are required to confirm these findings and to evaluate the impact of a conservative oxygen strategy vs a conventional strategy, on the incidence of VAP.

Key messages

  • Hyperoxemia is independently associated with ventilator-associated pneumonia

  • This association could be explained by the consequences of hyperoxemia, including acute lung injury, atelectasis, and reduced bacterial clearance

  • Further large multicenter studies are required to confirm our results

Abbreviations

ARDS, acute respiratory distress syndrome; cfu, colony-forming units; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FiO2, inspired oxygen fraction; HALI, hyperoxic acute lung injury; ICU, intensive care unit; LOD, logistic organ dysfunction; MDR, multidrug resistant; OR, odds ratio; PaO, arterial oxygen tension; ROS, reactive oxygen species; SAPS, simplified acute physiology score; VAP, ventilated-associated pneumonia

Notes

Declarations

Authors’ contributions

SN, SS, KJ, and FW designed the study. SS, KJ, GL, and EJ collected the data. SS, KJ, and SN wrote the manuscript. All authors made substantial contribution. All authors read and approved the final version of the manuscript.

Competing interests

SN is involved with Bayer, Basilea, and Medtrocic (advisory board, and lecture); all other authors have no competing interests.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
CHU Lille, Centre de Réanimation, F-59000 Lille, France
(2)
CHU Lille, Centre de Biologie et de Pathologie, F-59000 Lille, France
(3)
Univ Lille, Faculté de Médecine, F-59000 Lille, France

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