burns 40 (2014) 562–567

Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.elsevier.com/locate/burns

Comparison of the Berlin definition with the American European Consensus definition for acute respiratory distress syndrome in burn patients Julien Bordes *, Guillaume Lacroix, Pierre Esnault, Philippe Goutorbe, Jean Cotte, Eric Dantzer, Eric Meaudre Sainte Anne Military Teaching Hospital, Burn Centre, Toulon, France

article info

abstract

Article history:

Objective: Acute respiratory distress syndrome (ARDS) is a leading cause of mortality in burn

Accepted 6 March 2014

patients. Smoke inhalation, pneumonia and inflammation process are the major causes of ARDS in burn patients. The American European Consensus Conference (AECC) definition

Keywords:

proposed in 1994 has recently been revised by the Berlin definition. Our objective was to

Burn

describe the epidemiology of ARDS comparing the Berlin definition with the AECC definition

Berlin definition

in a retrospective cohort of burn patients.

Acute respiratory distress syndrome

Methods: We reviewed admitted burn adult patients for a two year period, and investigated

Inhalation injury

patient who received mechanical ventilation for more than 48 h and in whom pneumonia was diagnosed. Results: 40 patients were analyzed. According to the AECC definition, 11 patients met criteria for ALI (27.5%), and 29 patients for ARDS (72.5%). According to the Berlin definition, all patients met criteria for ARDS: 4 (10%) for a severe ARDS, 25 (62.5%) for a moderate ARDS, 11 (27.5%) for a mild ARDS. Inhalation injury was diagnosed in 10 patients (25%). Categorizing patients with the Berlin definition showed statistically significative difference of mortality within the three groups, but not with the AECC definition. Conclusion: The Berlin definition seems to be more accurate than the AECC definition to assess the severity of ARDS in term of outcome in burn patients. This definition may facilitate prompt recognition of ARDS in burn patients, and promote protective ventilation strategy to a larger number of patients. # 2014 Elsevier Ltd and ISBI. All rights reserved.

1.

Introduction

Acute respiratory distress syndrome (ARDS) is a common complication in critically ill burn patients leading to increased mortality. Smoke inhalation, pneumonia and inflammation * Corresponding author. Tel.: +33 483162385. E-mail address: [email protected] (J. Bordes). http://dx.doi.org/10.1016/j.burns.2014.03.004 0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.

process mediated by the burn are the major causes of ARDS in burn patients. A joint American European Consensus Conference (AECC) proposed in 1994 a definition based on the degree of oxygenation impairment, separating two syndromes: the ARDS and the acute lung injury (ALI) [1]. The criteria for

563

burns 40 (2014) 562–567

ARDS were a PaO2/fraction of inspired oxygen (PAFI) 200 mmHg, presence of bilateral infiltrates compatible with pulmonary edema, and absence of cardiogenic pulmonary edema defined as a pulmonary artery wedge pressure (PAWP) 18 mmHg. The term ALI was defined by the same criteria except that the PaO2/FiO2 >200 mmHg and 300 mmHg. However, it has been argued that this definition may not reflect the true prevalence, severity, and prognosis of these syndromes. The major criticism was that PaO2/FiO2 may vary in response to ventilator settings, particularly PEEP [2,3]. Moreover, patients with ARDS may have also elevated PAWP [4,5]. As a result, a revised definition of ARDS was recently proposed, the Berlin definition [6,7]. It was proposed 3 categories of ARDS based on degree of hypoxemia: mild moderate (200 mmHg < PaO2/FiO2  300 mmHg), (100 mmHg < PaO2/FiO2  200 mmHg) and severe (PaO2/ FiO2  100 mmHg), with a PEEP 5 cmH2O. This revised definition aimed to facilitate case recognition, institution of standardized best-evidence treatment and also assist with prognostication and design of new research trials. Our objective was to describe the epidemiology of ARDS comparing the Berlin definition with the AECC definition in a retrospective cohort of burn patients.

small volume bronchoalveolar lavage (FODP mini-BAL) as a routine, protocolized basis technique, described elsewhere [9]. We also considered a positive urine antigen for either Streptococcus pneumonia or Legionella as evidence of a bacterial process. During the study, day 1 of pneumonia was defined as the first day of antibiotics. Only the first episode of pneumonia was analyzed.

2.4.

Smoke inhalation injury definition

Inhalation injury was diagnosed by the presence of lesions on the respiratory tract confirmed bronchoscopically [10].

2.5.

ARDS definitions

ARDS was defined according to the AECC and Berlin definitions (Tables 1 and 2). In our ICU, cardiac failure or fluid overload is diagnosed by one of these two methods:

2.

Materials and methods

- Pulmonary artery wedge pressure (a pulmonary artery catheter is inserted in patient with total burn skin surface area (TBSA) > 40% or >20% when associated with smoke inhalation injury), with a cut off >18 mmHg. - Central venous pressure with a cut off >15 mmHg.

2.1.

Study

2.6.

This study was a retrospective review of patients admitted in the burn intensive care unit (ICU) of Sainte Military Teaching Hospital. All Patients admitted in 2010 and 2011 were screened for eligibility.

2.2.

Patients

Inclusion criteria were patients having received mechanical ventilation for more than 48 h in whom pneumonia was diagnosed.

2.3.

Pneumonia definition

The presence of pneumonia required signs of infection (elevated white blood cell (WBC) count, fever or hypothermia), with a compatible chest image (chest X-ray or Ct-scan). The modified clinical pulmonary infection score was used to diagnose pneumonia [8]. Microbiologic diagnosis was made by a positive blood culture and/or lower-airway secretions. In our burn care unit, all patients with suspected pneumonia undergo semi-invasive testing with fiberoptic bronchoscope-guided distal-protected

Data collected

On admission, the following parameters were recorded: age, gender, total burn surface area (TBSA), deep burn surface area (DBSA), burn nature, need for escharotomy, presence of inhalation injury, need for endotracheal intubation and invasive mechanical ventilation, IGS2 score, SOFA score. During ICU stay, the following parameters were collected: duration of invasive mechanical ventilation, ICU length of stay, microbiologic sample results, pneumonia episode as previously defined, data needed to assess SOFA score:

-

need for vasoactive drugs; Glasgow Coma Scale score; Creatine concentration and urine output; PaO2 and FiO2 to calculate PaO2/FiO2 ratio (PaFi); Platelet count; bilirubin concentration; mean arterial pressure.

During pneumonia episode, SOFA score, WBC counts, CRP, worse PAFI, maximal settled PEP on ventilator were recording daily.

Table 1 – The American European Conference Consensus ARDS definition [1]. Timing

Oxygenation

ALI

Acute onset

300 regardless of PEEP

ARDS

Acute onset

200 regardless of PEEP

Radiological abnormalities Bilateral infiltrates on frontal chest radiograph Bilateral infiltrates on frontal chest radiograph

Pulmonary artery wedge pressure 18 mmHg when measured or no clinical evidence of left atrial hypertension 18 mmHg when measured or no clinical evidence of left atrial hypertension

564

burns 40 (2014) 562–567

Table 2 – The Berlin ARDS definition [6]. Timing

Oxygenation a

Mild ARDS

Acute onset

Moderate ARDS

Acute onseta

Severe ARDS

Acute onseta

a

200 mmHg < PaO2/FiO2  300 mmHg 100 mmHg < PaO2/FiO2  200 mmHg PaO2/FiO2  100 mmHg

Radiological abnormalities Bilateral opacities Bilateral opacities Bilateral opacities

Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload Respiratory failure not fully explained by cardiac failure or fluid overload Respiratory failure not fully explained by cardiac failure or fluid overload

Within 1 week of a known clinical insult or new/worsening respiratory symptoms.

2.7.

Statistic analyses

Patient characteristics are summarized using number, percentages, mean values  standard deviation, or median. Statistical analysis was performed using non parametric tests: - Mann and Whitney test for quantitative parameters. - Fischer exact test for qualitative parameters. Significance level was set at p = 0.05.

3.

Results

3.1.

Patients

A total of 151 admissions were recorded in burn ICU during the study period. Among these patients, 94 patients were hospitalized more than 48 h. Forty patients developed pneumonia. The characteristics of patients are given in Table 3.

3.2.

3.4.

Outcome

When using AECC definition, patients’ categorization did not demonstrate any difference in term of mechanical ventilation duration, ICU length of stay, and mortality (Table 6). At the opposite, categorizing patients with the Berlin definition showed statistically significative difference of mortality within the three groups (Table 7). There was no difference in term of mechanical ventilation duration and ICU length of stay (Table 7).

Table 3 – Patients’ characteristics. Numbers of patients (N = 40)

Pneumonia

Forty patients developed pneumonia episode. Among these, fourteen patients developed a second pneumonia episode during ICU stay. Pneumonia occurred after a mean delay of 5 days  3.6 days after tracheal intubation and invasive mechanical ventilation. Pneumonia episode was associated with an increase in patient severity. Indeed, median SOFA score was of 3 at admission (1.75–5.25) and of 6 at day 1 of pneumonia (4– 8) (p < 0.001). Biological and oxygenation data at day 1 of pneumonia episode are summarized Table 4. The pathogen was identified in 35 patients of 40 (87.5%). Two germs were founded in 7 patients. A total of 42 bacterial strains were identified (Table 5). 25 were Staphylococcus aureus, 5 Streptococcus pneumoniae, 4 Haemophilus influenzae, 2 Escherichia coli, 1 Serratia marcescens.

3.3.

All patients presented an ARDS according to the Berlin definition: 4 patients presented a severe ARDS, 25 patients a moderate ARDS, 11 patients a mild ARDS (Table 7). Inhalation injury was diagnosed in 10 patients (25%). Presence of inhalation injury was associated with more severe hypoxemia during pneumonia episode and increased mortality (Table 8).

ARDS

During the pneumonia episode, all patients had oxygenation impairment. 11 patients presented an ALI (27.5%), and 29 patients an ARDS (72.5%) according to the AECC definition (Table 6). According to this definition, ARDS was only associated with an increase IGS 2 score at admission in our study.

Gender, n Male Female Age, year Burns nature, n Thermical Epidermolytic syndromes Chemical Burns %TBSA Deep burns %TBSA Burns site, n Head, neck Thorax Abdomen Upper limb Lower limb IGS2 score at admission SOFA score at admission Inhalation injury, n (%) Emergency escharotomies, n (%) Endotracheal intubation, n (%) Mean delay of endotracheal intubation after admission, days Tracheotomies, n (%) Mean invasive mechanical ventilation duration, days ICU length of stay, days ICU mortality, n (%)

30 10 57  22 37 2 1 23.5  18.8 10  12.5 34 22 13 33 20 28.6  10 4  2.8 10 (25%) 15 (37.5%) 40 (100%) 1.2  3.5 19 (47.5%) 27.6  26 36  27.3 8 (20%)

565

burns 40 (2014) 562–567

Table 4 – Pneumonia episode characteristics. Mean delay between intubation and pneumonia, days Mean WBC count per mm3 a Mean CRP (mg/l)a Mean PaO2/FiO2 ratio (mmHg)a Median PEP (cmH2O)a Median SOFA scorea a

5  3.6 10,699  5136 190  96 174  58 8 (6–10) 6 (4–8)

At day 1 of pneumonia episode.

Table 5 – Bacteriological findings on pulmonary samples. Pathogens Staphylococcus aureus Streptococcus pneumoniae Haemophilus influenzae Serratia marcesens Escherichia Coli

4.

42 25 5 7 1 4

Discussion

To our knowledge, this is the first study to compare the ARDS definitions in burn patients. Severe burns are identified as a risk factor for ARDS, and recognition of ARDS is a key point in the care of burn patient because this complication is frequent and a leading cause of mortality. The AECC definition was published in 1994, and was widely adopted by clinicians and researchers. It defined ARDS as an acute hypoxemia with PAFI < 200 mmHg and other criteria summarized in Table 1. It also defined ALI which used the same criteria but a PAFI < 300 mmHg and >200 mmHg. This definition has recently been revised. The new criteria are very similar to prior criterias as timing, chest imaging, origin of edema, and degree of hypoxemia. But the term ALI was removed and different levels of ARDS were defined to better categorize patients with potentially different outcome and responses to therapy. As a result, the main finding of our study is a higher incidence of ARDS in burn patients using the Berlin definition compared to AECC definition, that is an expected result. It has been previously shown that the Berlin definition was more accurate to categorize the patients’ severity, regarding their outcome. Indeed, stages of mild, moderate and severe

ARDS were associated with increased mortality and increased median duration of mechanical ventilation when tested in 4188 patients with ARDS from 4 multicenter clinical data sets [6]. We also observed a difference in term of mortality when categorizing patients with the Berlin definition that was not observed with the AECC definition. However, we did not observe any difference in term of mechanical ventilation duration nor ICU length of stay, but we have to recognize that our number of patient was low. Berlin definition categorization was also associated with difference in term of inhalation injury in our study. In burn patients, ARDS is a frequent disease due to various causes, pulmonary causes as pneumonia and inhalation injury, and extrapulmonary causes as burns themselves or associated trauma [11]. Published data in burn literature demonstrate the severity of hypoxemia in these patients, and also the degree of heterogeneity in management of hypoxemia, with the various use of conventional or not conventional therapies [12–16]. This emphasizes the need for accurate definition of ARDS in burn patients to precise indications of available therapies. Use of Berlin definition may help clinicians to promptly diagnose ARDS in burn patients and as a result to facilitate the wide use of protective ventilation. In particular, categorizing the burn patients with this definition might promote the extensive use of low tidal volume ventilation, mostly in patients that were before thought to present an acute lung injury and that now are categorized as ARDS. ARDS in burn patient result from a wide range of lung insults. Smoke inhalation injury is one of the strongest risk factors correlated with development of ARDS [11,17]. In our study, inhalation injury was associated with severe oxygenation impairment that was concordant with previously published data showing that smoke inhalation led to more severe oxygenation failure. Moreover, inhalation injury was associated with a worse outcome. Another finding is that early pneumonia is frequent in the first week of stay in burns patients and that the main pathogen is Staphylococcus aureus. In our area, Staphyloccous aureus was predominantly savage strain. We observed that oxygenation level was already decreased at the day of pneumonia diagnosis (mean PAFI of 166 mmHg). These results suggest a prior oxygenation impairment due to another cause, as inhalation or inflammatory response. It

Table 6 – Comparison of patients in ALI and ARDS group according to the AECC definition.

Age, years Burns %TBSA Deep burns %TBSA IGS2 score at admission SOFA score at admission Inhalation injury, n (%) Mechanical ventilation duration, days ICU length of stay, days ICU mortality, n (%) * **

Mann and Whitney test. Fisher’s exact test.

ALI n = 11

ARDS n = 29

46  18 23  12 10  10 22.6  7.5 3.5  2.3 1 (9%) 18  10 33  13 1 (29%)

61  17 23.6  13 10  10 30.8  7.6 3.5  2.3 9 (31%) 31  20 38  20 7 (24%)

Statistical significance p = 0.06* p = 1* p = 0.81* p = 0.02* p = 0.98* p = 0.15** p = 0.18** p = 0.73** p = 0.4*

566

burns 40 (2014) 562–567

Table 7 – Comparison of patients in mild, moderate, severe ARDS group.

Age, year Burns %TBSA Deep burns, %TBSA Inhalation injury, n (%) IGS 2 score at admission SOFA score at admission Mechanical ventilation duration, days ICU length of stay, days ICU mortality, n (%) * **

Mild ARDS N = 11

Moderate ARDS N = 25

Severe ARDS N=4

Statistical significance

46  18 23  12 10  10 1 (9%) 22.6  9.1 3.5  3 18  10 33  13 1 (9%)

61  18 24  13 98 6 (24%) 30  7.9 3  1.9 33  22.5 41  21.7 5 (20%)

63  14 24.5  9 15  15 3 (75%) 3.5  7.1 65 19.7  14.6 19.5  12 1 (25%)

p = 0.17* p = 0.75* p = 0.87* p = 0.03** p = 0.06 p = 0.51 p = 0.29* p = 0.21* p = 0.02**

Kruskal–wallis test. x2 test.

Table 8 – Comparison of patients’ characteristics and outcome with and without inhalation injury.

Burns %TBSA Deep burns %TBSA Mechanical ventilation duration, days PaO2/FiO2 ratio at Day 1 of pneumonia epidose, mmHg PEP at day 1 of pneumonia episode, cmH2O Worse PaO2/FiO2 ratio during pneumonia episode, mmHg ICU length of stay, days ICU mortality, n (%) * **

Inhalation injury N = 10

No inhalation injury N = 30

Statistical significance

36.6  26.6 19.1  13.3 45.5  40.2 1479  56.4 8  2.5 134  60 48.5  40.6 5 (50%)

19.1  13.3 6.7  9.7 21.6  16.1 185  57 9  2.8 178  51.6 32.4  17.5 3 (10%)

p = 0.01* p = 0.03* p = 0.11* p = 0.06* p = 0.8* p = 0.01* p = 0.9* p = 0.01**

Mann and Whitney test. Fisher’s exact test.

emphasizes the fact that it is challenging in the acute phase to isolate only one unique cause of ARDS in burn patient. Indeed, forward oxygenation impairment may be due to pneumonia, inhalation injury or inflammatory response.

5.

Conclusion

In conclusion, ARDS incidence may increase in burn patients when using the Berlin definition. The Berlin definition may facilitate recognition of this syndrome in burn patients, and promote protective ventilation strategy to a larger number of patients in order to reduce the consequences of lung injury during severe burns. In these patients, the Berlin definition seems to be more accurate than the previous AECC definition to categorize patients. But it would be interesting of performing a larger study to confirm whether the different categories of ARDS according to Berlin definition are associated with a mortality difference in burn patients, and so validate the accuracy of this definition in our category of critically ill patients.

Conflict of interest statement All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence this work.

references

[1] Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149(3 (Pt 1)):818–24. [2] Villar J, Perez-Mendez L, Kacmarek RM. Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome. Intensive Care Med 1999;25(9):930–5. [3] Villar J, Perez-Mendez L, Lopez J, Belda J, Blanco J, Saralegui I, et al. An early PEEP/FiO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2007;176(8):795–804. [4] Ferguson ND, Meade MO, Hallett DC, Stewart TE. High values of the pulmonary artery wedge pressure in patients with acute lung injury and acute respiratory distress syndrome. Intensive Care Med 2002;28(8):1073–7. [5] Wheeler AP, Bernard GR, Thompson BT, Schoenfeld D, Wiedemann HP, deBoisblanc B, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006;354(21):2213–24. [6] Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin definition. J Am Med Assoc 2012;307(23):2526–33. [7] Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012;38(10):1573–82.

burns 40 (2014) 562–567

[8] Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Shortcourse empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000;162(2 (Pt 1)):505–11. [9] Lacroix G, Prunet B, Bordes J, Cabon-Asencio N, Asencio Y, Gaillard T, et al. Evaluation of early mini-bronchoalveolar lavage in the diagnosis of health care-associated pneumonia: a prospective study. Crit Care 2013;17(1): R24. [10] Endorf FW, Gamelli RL. Inhalation injury, pulmonary perturbations, and fluid resuscitation. J Burn Care Res 2007;28(1):80–3. [11] Salman D, Finney SJ, Griffiths MJ. Strategies to reduce ventilator-associated lung injury (VALI). Burns 2013;39(2):200–11. [12] Cartotto R, Ellis S, Gomez M, Cooper A, Smith T. High frequency oscillatory ventilation in burn patients with the acute respiratory distress syndrome. Burns 2004;30(5): 453–63.

567

[13] Cartotto R, Cooper AB, Esmond JR, Gomez M, Fish JS, Smith T. Early clinical experience with high-frequency oscillatory ventilation for ARDS in adult burn patients. J Burn Care Rehabil 2001;22(5):325–33. [14] Cartotto R, Ellis S, Smith T. Use of high-frequency oscillatory ventilation in burn patients. Crit Care Med 2005;33(Suppl. 3):S175–81. [15] Nelson J, Cairns B, Charles A. Early extracorporeal life support as rescue therapy for severe acute respiratory distress syndrome after inhalation injury. J Burn Care Res 2009;30(6):1035–8. [16] Hale DF, Cannon JW, Batchinsky AI, Cancio LC, Aden JK, White CE, et al. Prone positioning improves oxygenation in adult burn patients with severe acute respiratory distress syndrome. J Trauma Acute Care Surg 2012;72(6):1634–9. [17] Gajic O, Dabbagh O, Park PK, Adesanya A, Chang SY, Hou P, et al. Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med 2011;183(4):462–70.