SUMMARY
The aim of this study was to investigate factors independently affecting outcomes of post-burn ARDS patients at the time of ARDS onset. A prospective study was conducted on 66 patients with ARDS, treated in the ICU at the Le Huu Trac National Burns Hospital in Hanoi, Viet Nam, from 2014 to 2017. Patients were divided into a survivor and non-survivor group. Demographic criteria, burn severity, inhalation injury, clinical and subclinical features at ARDS onset were compared between the two groups. The results showed that overall mortality of ARDS patients was 62.12%. Logistic regression analysis indicated that at the time of ARDS onset, serum lactate level (OR=6.71), blood platelet count (OR=.99), static lung compliance (OR=.73) and driving pressure (OR=1.69) were independent risk factors for death, while patients’ demographics, burn severity and ARDS severity did not significantly affect the mortality rate.
Keywords: severe burn, ARDS, risk factor for death
RÉSUMÉ
Le but de cette étude est d’évaluer les facteurs indépendants influençant le pronostic d’un SDRA survenant chez un brûlé, présents dès sa survenue. Il s’agit d’une étude prospective conduite sur 66 patients hospitalisés en réanimation de l’hôpital brûlologique national Le Huu Trac de Hanoi entre 2014 et 2017, répartis en groupes survivants et décédés. Nous avons comparé les données démographiques, la gravité de la brûlure, l’existence d’une inhalation de fumée, les données cliniques comme paracliniques au moment du diagnostic de SDRA. La mortalité globale était de 62,12%. En régression logistique, la lactatémie (OR 6,71), le compte de plaquettes (OR 0,99), la compliance pulmonaire statique (OR 0,73) et la pression de travail (OR 1,69) sont des facteurs indépendants de mortalité quand ni les données-patient, ni la sévérité de la brûlure ou celle du SDRA lui-même n’affectent la mortalité.
Mots-clés: brûlure, SDRA, mortalité, facteurs de risque
Introduction
Acute respiratory distress syndrome (ARDS) is one of the common complications with high mortality rate in the intensive care unit (ICU).1 It is noted that variable causes lead to ARDS development, such as trauma, sepsis, pneumonia, ventilator-induced lung injury, blood transfusion, severe burn, inhalation injury and others. Over time, the ARDS definition has been changed as more understanding has been gained on the pathological mechanism of this syndrome. In 2012, an updated definition and classification of ARDS was reported at the consensus conference which was held in Berlin. Accordingly, ARDS severity was classified into 3 levels: mild, moderate and severe, based on blood oxygenation.2 Despite advances in treatment, the mortality rate of the patient with ARDS remains high, ranging between 30% and 70%, and remains a significant challenge for clinicians. Identifying factors affecting outcome of ARDS patients could help clinicians to assess and evaluate the patient’s condition and allow better treatment orientation.
ARDS is a common complication with a high mortality rate in severely burned patients. In this study, we analyzed the factors at ARDS onset that influence mortality rate of severe burn patients with ARDS.
Patients and methods
A retrospective study was conducted on 66 adult burn patients who developed ARDS complication and were treated at the burn intensive care unit (ICU), National Burn Hospital over the period 2014-2017. ARDS was defined according to the criteria of the Berlin Consensus Conference 2012.2 Accordingly, the severity of ARDS was classified based on the PaO2/FiO2 ratio as follows:
| Mild: 200mmHg <PaO2/FiO2 ≤300mmHg Moderate: 100mmHg <PaO2/FiO2 ≤200mmHg Severe: PaO2/FiO2 ≤100mmHg |
All the patients were treated with the same regimen, including lung protective ventilation with low tidal volume, broad spectrum antibiotics, early enteral nutrition, and early necrosis excision during the first week after burn.
Collected data included patient demographics (age, gender), burn features (burn extent, deep burn area, inhalation injury), ARDS severity, clinical and subclinical parameters at the time of ARDS onset, including central venous pressure, respiratory rate, PaO2/FiO2 ratio, blood hemoglobin concentration (Hb), white blood cells, platelets count, serum level of creatinine and albumin, blood gas, the ventilator setting and lung mechanics (Pplateau, driving pressure, static lung compliance, PEEP).
The factors affecting the mortality rate were bivariate analyzed to determine whether there was a difference between the survivor group and the non-survivor group, and they were multivariate regressive analyzed to determine the independent factors affecting the mortality of patients with ARDS. Stata 14.0 software was used for analysis, and p value <.05 was seen as significant level.
Results
Among the 66 ARDS patients, forty-one died, with an overall mortality rate of 62.12%. There was no remarkable difference in age, gender or incidence of inhalation injury across the groups (p >.05). Meanwhile, burn extent and full-thickness burn area were significantly higher in the non-survivor group (Table I). In addition, severity of ARDS was not significantly different between the two groups (p >.05).
Table I.
Patients’ demographic data and burn severity
| Parameters | Survivor (n=25) |
Non-survivor (n=41) |
P | |
|---|---|---|---|---|
| Gender, n(%) | Male | 21(84.0) | 31(75.61) | 1.42 |
| Female | 4 (16.0) | 10 (24.39) | ||
| Age, year | 37.32 ± 2.31 | 40.32 ± 1.69 | 0.14 | |
| Burn extent (%) | 44.92 ± 2.90 | 60.85 ± 2.67 | 0.0001 | |
| Full-thickness burn area (%) | 20.84 ± 2.07 | 30.49 ± 2.66 | 0.0065 | |
| Inhalation injury, n(%) | 13 (52.0) | 20 (48.78) | 0.8 | |
| ARDS severity, n(%) | Mild and Moderate | 18 (72.0) | 31 (75.61) | 0.38 |
| Severe | 7 (28.0) | 10 (24.39) | ||
The clinical and paraclinical parameters at the time of ARDS onset are indicated in Table II. As can be seen, clinical parameters including heart rate, respiratory rate, central venous pressure (CVP); sequential organ failure assessment (SOFA) score; acute physiology and chronic health evaluation II (APACHE II) score were similar between the two groups (p >.05). Regarding subclinical criteria, significantly lower serum albumin level (27.05±.97 vs. 30.49±1.44 g/l; p =.04) and platelet counts (150.15±17.69 vs. 248.6±27.58; p =.0025) were recorded in the survivor group. Meanwhile, lactate level was significantly higher in the non-survivor patients (2.7±.19 vs. 1.98±.16 mmol/L; p =.006). The other parameters such as hemoglobin concentration, white blood cells, serum creatinine level, pH and BE were not significantly different across the groups (p >.05).
Table II.
Clinical and subclinical parameters at the time of ARDS onset
| Parameters | Survivor (n=25) |
Non-survivor (n=41) |
P |
|---|---|---|---|
| Heart rate (beat/min) | 135 ± 2.93 | 132.34 ± 1.50 | 0.81 |
| CVP (cmH2O) | 9.64 ± 0.39 | 10.02 ± 0.27 | 0.2 |
| SOFA | 4.76 ± 0.31 | 5.29 ± 0.22 | 0.08 |
| APACHE II | 16.76 ± 0.85 | 16.83 ± 0.63 | 0.47 |
| Respiratory rate (breath/min) | 36 ± 1.32 | 37.29 ± 0.93 | 0.21 |
| PaO2/FiO2 ratio (mmHg) | 124.67 ± 7.19 | 120.09 ± 5.69 | 0.69 |
| Hb (g/L) | 96.68 ± 6.83 | 100.24 ± 3.74 | 0.31 |
| WBC(109/L) | 13.70 ± 1.25 | 10.97 ± 0.88 | 0.96 |
| Platelet counts (109/L) | 248.6 ± 27.58 | 150.15 ± 17.69 | 0.0025 |
| Creatinine (μmol/L) | 79.48 ± 3.52 | 74.65 ± 3.71 | 0.81 |
| Albumin (g/L) | 30.49 ± 1.44 | 27.05 ± 0.97 | 0.04 |
| pH | 7.45 ± 0.01 | 7.46 ± 0.01 | 0.40 |
| Lactate (mmol/l) | 1.98 ± 0.16 | 2.7 ± 0.19 | 0.006 |
| BE (mmol/l) | 3.85 ± 0.72 | 3.67 ± 0.67 | 0.57 |
CVP = central venous pressure; SOFA = sequential organ failure assessment; APACHE II = acute physiology and chronic health evaluation II; Hb = hemoglobin; WBC = white blood cell; pH = potential of hydrogen; BE = base excess
The pulmonary mechanical parameters and ventilator setting parameters at ARDS onset are shown in Table III. Pplateau and PEEP level in the ventilator setting were similar between the two groups (p>.05), while driving pressure was remarkably higher (13.05±1.25 vs. 15.41±2.14 cmH2O; p =.001) and static lung compliance was significantly lower (32.88±1.29 vs. 28.39±.73 mL/cmH2O; p <.001) in the non-survivor group.
Table III.
Lung mechanical and ventilation setting parameters at ARDS onset
| Parameters | Survivor (n=25) |
Non-survivor (n=41) |
P |
|---|---|---|---|
| Pplateau (cmH2O) | 26.72 ± 0.49 | 26.61 ± 0.39 | 0.56 |
| Driving pressure (cmH2O) | 13.05 ± 1.25 | 15.41 ± 2.14 | 0.001 |
| Static lung compliance (mL/cmH2O) | 32.88 ± 1.29 | 28.39 ± 0.73 | 0.0018 |
| PEEP (cmH2O) | 13.08 ± 0.62 | 12.27 ± 0.53 | 0.83 |
Multivariate regression analysis showed that at the time of ARDS onset, serum lactate levels (OR=6.71), platelet counts (OR=0.99), lung static compliance (OR=0.73) and driving pressure (OR=1.69) were independent risk factors for the death of ARDS patients (Table IV). Meanwhile patient demographics, burn extent, deep burn area as well as inhalation injury did not significantly affect mortality rate.
Table IV.
Multivariate analysis between mortality and influencing factors
| Parameters | OR | Coef. | P | 95%CI |
|---|---|---|---|---|
| Burn extent, %TBSA | 0.53 | 0.63 | 0.28 | -0.51-1.76 |
| Deep burn area, %TBSA | 0.28 | 1.25 | 0.27 | -1.01-3.52 |
| Serum lactate levels, mmol/l | 6.71 | -1.90 | 0.024 | -3.55- -0.25 |
| Platelet counts, 109/L | 0.99 | 0.01 | 0.04 | 0.00-0.01 |
| Serum albumin level, g/l | 0.93 | 0.07 | 0.30 | -0.07-0.21 |
| Lung static compliance, mL/cmH2O | 0.73 | 0.31 | 0.006 | 0.09-0.53 |
| Driving pressure, cmH2O | 1.69 | 0.42 | 0.006 | 0.21-1.31 |
TBSA = total body surface area
Discussion
ARDS is a common complication of severe burn patients, resulting in prolonged hospitalization, increased cost of treatment, and high mortality rate.3,4,5,6 Over the last few decades, the ARDS mortality rate has tended to decrease due to advances in intervention, such as lung protective ventilation, fluid resuscitation, new generation antibiotics, immune enhancement and early enteral nutrition. However, overall mortality is still high, especially in developing countries due to limited resources.7,8 The mortality rate of ARDS patients in our study was 62.12%, which was higher than that reported by other studies.9,10
Finding out the factors related to the mortality rate of ARDS patients will help clinicians better understand the patient’s prognosis and thereby make appropriate interventions. A study by Wu et al. in 2012 showed that APACHE II score and arterial lactate clearance were independent factors affecting the outcomes of ARDS patients.11 Other reports indicated that complications such as acute kidney injury, liver failure, heart failure, and MODS were the main cause of death in ARDS patients.12,13,14,15 In addition, some other studies have shown that high driving pressure was a predictor of death in ARDS patients.16,17,18 For example, Amato and colleagues reported that ARDS patients with a driving pressure on the first day of mechanical ventilation greater than 14 cmH2O had a higher risk of death.19 The driving pressure is an indicator that represents the periodic expansion of the lung, which is easily accessible and clinically identifiable.16 Pulmonary periodic expansion amplitude is closely related to cellular and parenchymal injury. In 2019, a multivariate analysis by Dai and coworkers found that APACHE II (OR=3.4316), the number of failed organs (OR=3.4928), mean airway pressure (OR=5.1049), driving pressure (OR=6.0017), and serum lactate levels (OR=4.0754) were independent factors affecting the mortality rate of ARDS patients.20 In our study, a multivariate analysis showed that there were four factors affecting the treatment outcome of post-burn ARDS patients, including serum lactate levels, platelet counts, static lung compliance, and driving pressure. In particular, burn parameters such as burn area, burn prognostic index and inhalation injury were not independent factors affecting the treatment outcomes.
Recent studies have shown that the survival prognosis of ARDS patients also depends on other parameters such as blood oxygenation, lung extracellular fluid volume and transpulmonary pressure.21,22,23,24,25 High level of serum lactate indicates tissue hypoxia, which is a significant sign in the prognosis of critically ill patients. In patients with ARDS, the lungs are the main lactate-producing organs. The results of recent studies show that metabolic acidosis increases mortality in critically ill patients,26,27 which was consistent with our study. In 2020, a study by Huber et al. analyzing the prognostic models predicting ARDS outcome showed that the blood oxygenation index within the first two days after ARDS onset had better predictive values for mortality than the predictive models based on the Berlin definition. In addition, extracellular fluid volume in the lungs and the transpulmonary were independent factors predicting death, besides SOFA and APACHE scores.28 In addition, study by Monchi et al. showed that the condition of the health care facility, the oxygenation status of the blood, the mechanism of lung injury, cirrhosis and right ventricle dysfunction were also independent risk factors for mortality rate in patients with ARDS.23 Some other studies reported that respiratory tract infections, ventilator-associated pneumonia, fluid overload, serum lactate levels, and concentration of some cytokines such as interleukine-1β, interleukine-6 and interleukine-18 were also risk factors for the death of ARDS patients.29,30,31,32 However, these parameters are not easy to determine at one time and in all medical facilities.
Conclusion
ARDS is a serious complication of severe burn patients with a high mortality rate. High serum lactate levels, decreased platelet counts, decreased static pulmonary compliance, and increased driving pressure in the ventilator setting to achieve the desired tidal volume are independent risk factors for patient outcomes.
Acknowledgements
We are grateful to all staff of the Intensive Care Unit, Le Huu Trac National Burn Hospital, Hanoi, for helping us to collect data.
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