Objectives: To determine clinical and paraclinical manifestations and outcome of severe burn patient with acute respiratory distress syndrome. Subjects and methods: A prospective study was conducted on 66 severe burn patients with acute respiratory distress syndrome (ARDS), treated at Burn Intesive care Unit, National Institute of Burns from 11 - 2013 to 10 - 2016.
Journal of military pharmaco-medicine no7-2017 CHARACTERISTICS AND OUTCOME OF ACUTE RESPIRATORY DISTRESS SYNDROME AMONG SEVERE BURN PATIENTS Tran Dinh Hung*; Dong Khac Hung**; Nguyen Nhu Lam* SUMMARY Objectives: To determine clinical and paraclinical manifestations and outcome of severe burn patient with acute respiratory distress syndrome Subjects and methods: A prospective study was conducted on 66 severe burn patients with acute respiratory distress syndrome (ARDS), treated at Burn Intesive care Unit, National Institute of Burns from 11 - 2013 to 10 - 2016 Diagnosis of ARDS was based on the Berlin criteria in 2012 Clinical and paraclinical manifestations of the patients at ARDS onset until discharged or death were recorded and analyzed Results: Over a half (53.03%) of ARDS cases developed during the first week post burn Most of cases were classified as moderate and severe levels (72.72% and 25.75%, respectively) Common characteristics were mental disorder (86.36%), fever, leukocytosis (54.55%), dyspnea, tachypnea, diffuse rales, cyanosis, tachycardia, chest pain and dry cough Fully bilateral alveolar infiltrate on chest radiograph was recorded in 40.91% of cases Plasma cytokine levels (IL1-β, IL-6, IL-8, IL-10 and TNF-α) increased significantly since admission and prolonged Overall mortality rate was 61.12% with the main cause of multiple organ failure (56%) Conclusion: ARDS was a serious complication post burn with typical acute pulmonary abnormalities, significantly prolong raising plasma cytokines levels and high mortality rate due to multiple organ failure * Keywords: Burn; Acute respiratory distress syndrome; Characters INTRODUCTION Acute respiratory distress syndrome which was first described by Ashbaugh et al in 1967 characterized by acute onset, severe hypoxemia with bilateral infiltrate and non-hydrostatic pulmonary edema [1] In 1994, a formal definition and classification of ARDS was reported by the American-European Consensus Conference committee on ARDS (AECC) [3] The definition has been widely applied to define patient with ARDS therapeutic trials Despite the simplicity of this definition, some clinical limitations are recognized In 2012, a new definition of ARDS was introduced at Berlin meeting to overcome limitation of 1994 AECC definition and to make easier for diagnosing and classifying ARDS [10] ARDS is one of common syndromes in intensive care unit ARDS can lead to multiple organ failure and has high mortality up to 40 - 80% Previous studies reported that about 200,000 cases of ARDS per year in the United States, leading to significant patient morbidity and health care burden In many burn centers, ARDS is still a leading cause of death in patients with severe burns * Natio nal Institute of Burn ** Vietnam Military Medical University Corresponding author: Tran Dinh Hung (hung73vb@yahoo.com.vn) Date received: 10/06/2017 Date accepted: 11/08/2017 89 Journal of military pharmaco-medicine No7-2017 treated at Burn Intensive Care Unit, National Institute of Burns from 11 - 2013 to 10 - 2016 with selected criteria: admission within 48 hours post burn, aged from 16 to 60, burn surface area ≥ 15% of total body surface area (TBSA), without concomitant trauma or peexisting morbidities Berlin definition was used to determine the development of as well as severity of ARDS as described at table [7] Currently, in Vietnam, there are not many reports about ARDS complication in burn patients The aims of this study are to: Investigate clinical and subclinical characteristics and outcome of ARDS among severe burn patients SUBJECTS AND METHOD A prospective study was conducted on 66 severe burn patients with ARDS, Table 1: The severity of ARDS (Berlin 2012) Timing* Oxygenation (PaO2/FiO2) Radiological abnormalities Mild Acute 200 < P/F < 300 Moderate Acute 100 < P/F < 200 Chest bilateral opacities Severe Acute P/F < 100 Severity Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload (*: Within week of a known clinical insult or new/worsening respiratory symptoms) Inhalation injury was diagnosed by the circumstance of burn injury (closed space), clinical manifestations (facial burn, soot in mouth or pharynx, hoarseness and carbonaceous) and confirmation by flexible bronchoscopy performed during the first days of admission Once ARDS diagnosed, lung protective mechanical ventilation as ARDS networt protocol was implemented [11] Blood gas was tested times a day and as demanded Serum levels of cytokines including IL1-β, IL-6, IL-8, IL-10 and TNF-α were determined at times: admission, ARDS onset and days thereafter by ELISA method (DAR-800, Diagnostic Automation InC, the US) at Pathophysiological Department, Military Medical University Clinical and paraclinical manifestations of patients were recorded and monitored until discharge or death Stata intercool 11.0 software was used to analyze the data and a p value ≤ 0.05 was seen as significant RESULTS Table 2: Demographic criteria of patients (n = 66) Criteria Mean value Min - max Age (year) 39.18 ± 11.11 18 - 59 Burn surface area (%) 54.82 ± 17.85 18 - 92 Full thickness burn area (%) 26.83 ± 15.49 - 65 90 Journal of military pharmaco-medicine no7-2017 Apacher II 16.80 ± 4.07 - 26 Prognostic burn index (PBI) 93.26 ± 21.93 51.5 - 139 Inhalation injury; n (%) 33 (50) Male/female 52/14 (78.79%) The mean of age was 39.18 years Male was predominant with the mean of total burn surface area was 54.82% and 26.83% of full-thickness area Inhalation injury was diagnosed in 33 patients (50%) with prognostic burn index (PBI) of 93.26 and admission Apacher II score of 16.8 Table 3: Onset time and severity of ARDS Criteria Onset time post burn (day) Severity of ARDS n % 14 07 10.61 Mild 01 1.52 Moderate 48 72.73 Severe 17 25.75 Over a half of ARDS cases (53.03%) developed during the 1st week post burn with average of 8.50 ± 4.61 days, ranging from 2rd day to 27th day According to Berlin 2012 definition, 72.73% of patients were classified as moderate, 25.75% was severe and only one case was mild ARDS Table 4: Clinical characteristics of patients at ARDS onset (n = 66) Criteria Body temparature (0C) Glasgow score (n = 44)* Heart rate (beat/min) MAP** (mmHg) Respiratory rate (beat/min) (n = 44)* n % ≤ 38 03 4.55 38.1 - 39 48 72.73 > 39 15 22.72 15 04 9.09 10 - 14 38 86.36 6-9 02 4.55 < 120 01 1.52 ≥ 120 65 98.48 < 65 01 1.55 65 - 70 05 7.58 > 70 59 90.87 25 - 29 4.55 30 - 45 40 90.9 > 45 4.55 Mean 38.86 ± 0.46 12.57 ± 1.55 133.35 ± 11.75 87.17 ± 11.60 36.82 ± 5.03 91 Journal of military pharmaco-medicine No7-2017 < 80 3.03 80 - 90 40 60.61 91 - 100 24 36.36 SpO2 (%) 88.42 ± 5.59 Diffuse rales 41 62.12 Cyanosis 42 63.64 Chest pain and dry cough (n = 44)* 44 100 (*: Only for patients without mechanical ventilation; **: MAP: Mean arterial blood pressure) All 66 patients were in the severe situation with tachypnea (30.14 ± 2.26 breath/minute), fever, low SPO2 82%, diffuse rales (62.12%), cyanosis (63.64%), dry cough and chest pain In addition, most patients suffered from mild mental disorder with Glasgow score of 12.57 ± 1.55 Table 5: Arterial blood gas and chest radiography at ARDS onset (n = 66) Parameters PaO2 (mmHg) SaO2 (%) Lactat (mmol/L) Bilateral infiltrate on chest radiograph n % Mean value < 70 47 71.21 70 - 90 11 16.67 > 90 12.12 < 95 49 74.24 ≥ 95 17 25.76 3 16 24.24 Partial 39 59.09 Full 27 40.91 62.5 ± 2.31 88.77 ± 7.79 2.43 ± 0.14 Table revealed criteria of arterial blood gas at the time of meeting ARDS criteria, most of patients had disorder of blood gas in term of low level of PaO2 (PaO2 < 70 mmHg in 71.21% of cases) with mean value for all patients was of 62.5 ± 2.31 mmHg and slightly increased lactic acidosis (2.43 ± 0.14 mmol/L) Result of initial chest radiography showed 27 cases (40.91%) has fully bilateral alveolar infiltrate Table 6: Hematology parameter at time point of ARDS (n = 66) Parameter ˂ 60 Hemoglobin (g/L) 92 n % 1.52 70 - 90 30 45.45 91- 119 26 39.39 ≥ 120 13.64 X ± SD 98.89 ± 3.45 Journal of military pharmaco-medicine no7-2017 White blood cells (G/L) Platelets (G/L) ˂4 3.03 4-9 28 42.42 >9 36 54.55 ˂ 70 14 21.21 ≥ 70 52 78.79 12.01 ± 0.73 187.44 ± 16.16 At the time point of ARD, leukocytosis was recorded in over a half of cases (36 patients, accounting for 54.55%) and there were cases with leucopenia In addition, 46.97% of patients suffered from severe anemia and 78.79% significantly reduced counted platelet Table 7: Concentrations of plasma cytokines Normal value* Admission ARDS onset 3rd day post ARDS IL-1β < 3.2 586.57 ± 32.42 594.25 ± 47.36 601.09 ± 42.21 IL-6 < 10 462.56 ± 177.01 653.03 ± 143.04 348.86 ± 72.78 IL-8 29.30 503.19 ± 167.13 379.49 ± 204.96 398.19 ± 157.57 IL-10 12.6 33.45 ± 9.65 27.34 ± 7.22 18.25 ± 5.56 TNF-α 30 67.74 ± 10.46 44.74 ± 3.83 68.40 ± 11.62 Cytokine (pg/mL) (* Kliener G et al, 2013) [8]) As can be seen from table 7, plasma cytokine levels of at admission, at the time point of ARDS and days after ARDS diagnosed all much greater than normally physiological values There was no difference between plasma cytokine levels when comparing time to time Table 8: Mortality, time and causes of death Outcomes Mild Mortality according to ARDS severity Times of death (from ARDS onset) Causes of death n % 0 Moderate 31 64.38 Severe 10 58.82 Total 41 62.12 < days 29 70.73 - 14 days 10 24.39 > 14 days 4.88 Multiple organ failure 23 56.10 Refractory septic shock 16 39.02 Refractory respiratory failure 4.88 Forty one cases accounting for 62.12% did not survive Main causes of death were multiple organ failure (56.10%), followed by refractory septic shock (39.02%) Most death occurred during the first week since ARDS onset (70.73%) 93 Journal of military pharmaco-medicine No7-2017 DISCUSSION Despite substantial progress in understanding ARDS pathophysiology, ARDS remains a major clinical problem and mortality is still high During the past decades, outcome of burn patients has improved as a results of better management of burn shock, more effective topical antimicrobials used, better systemic antibiotics, earlier excision, and alternative measures for wound closure However, ARDS has recently been claimed to be important in respiratory dysfunction in burns and studies have indicated ARDS is still one of leading complications causing death among burn patients According to previous studies, the incidence of ARDS in burn patients is about 20 - 56% depending on burn severity Recently, in 2014, a prospective study of ARDS characteristics in burned military casualties by using the Berlin definition showed that prevalence of ARDS was 32.6% [1] Most studies have an agreement that the onset of ARDS was around to days post burn In our study, the time point of ARDS was during the first week post burn (53.03%) As Berlin classification, most ARDS cases in our study was moderate and severe, these results were accordant with those of other reports According to Hansen-Flaschen J and Siegel M.D (2010), common clinical symptoms of patients with ARDS were dyspnea, tachypnea, cyanosis, dry cough, chest pain and tachycardia [5] In addition, at onset time of ARDS, patients 94 usually underwent metal disorder These characteristics are same to our records At time ARDS was diagnosed, most patients suffered from mild mental disorder with Glasgow ranged from 10 to 14 (86.36%), fever (72.73%), tachypnea with low SpO2 as well as arterial blood gas values and bilateral infiltrate on chest radiograph Patients may also suffered from anemia, leucocytosis and thrombocytopenia This finding was accordant with the results of Hodgson C.L et al (2011) [6] Inflammatory reaction plays an important role in pathological mechanism of ARDS In severe burn patients, it has been proven that significantly inflammatory response along with burn severity leading to complications including sepsis, septic shock, ARDS and MOF Our study showed that both inflammatory and anti-inflammatory cytokines increased considerably right after admission and prolonged even days after ARDS onset This can be explained by severe burn, with large extent of burn injuries, especially with concominant inhalation injuries in our studied patients Study by Bhadade et al in 2011 revealed that mortality rate of ARDS was 57% and up to 88% when ARDS combined with severe sepsis [4] Recently, Villar et al reviewed ARDS studies since 2000 for all patients categories, concluded that despite the use of lung protective mechanical ventilation, the mortality rate of ARDS patients was still greater than 40% [12] For burn patients, works by Dancey et al Journal of military pharmaco-medicine no7-2017 in 1999 indicated mortality among burn patients with ARDS was 41.8% and those by Steinvall I (2008) was 44% [10] Recently, Belenkiy et al reported nearly one third of patients with ARDS did not survive and moderate and severe ARDS increased the odds of death by more than fourfold and ninefold, respectively [2] As other reports, our study showed that mortality rate among ARDS burn patients was still high (62.12%) Up to date, leading cause of death among patients ARDS is multiple organ failure (MOF) According to Stapleton et al (2005), 50% of ARDS patients died due to MOF [9] Villar et al (2006) reported that MOF contributed to the highest part among causes of death for ARDS patients [12] Bhadade et al (2011) concluded that mortality increased with the number of failure organs [4] For burn patients, most studies indicated the main cause of death among ARDS patients was also MOF rather than lung disorder In this study, among 41 deaths of all patients, MOF contributed to 23 cases accounting for 56.10% Mortality rate in our study was higher than that of other studies, this can be explained as our patients experienced more TBSA and deep burn area CONCLUSION Acute respiratory distress syndrome onset was mainly occured during the first week after burn (53.03%), most of cases were classified as moderate and severe levels Common symptoms were tachypnea, tachycardia, cyanosis, hypoxcemia, anemia, leucocytosis, mental disorder, hyperthermia Concentration of cytokines increased sharply at time of admission until days of ARDS, mortality rate was 61.12% and leading cause of death was multiple organ failure REFERENCE Ashbaugh D.G, Bigelow D.B, Petty T.L et al Acute respiratory distress in adults Lancet 1967, 2, pp.319-323 Belenkiy S.M, Buel A.R, Cannon J.W et al Acute respiratory distress syndrome in wartime military burns: Application of the Berlin criteria J Trauma Acute Care Surg 2014, 76 (3), pp.821-827 Bernard G.R, Artigas A, Brigham K.L, Carlet J, Falke K, Hudson L et al The American-European consensus conference committee on ARDS, definitions, mechanisms, relevant outcomes and clinical trial coordination Am.J Respir Crit Care Med 1994, Vol 149, pp.818-824 Bhadade R.R, Souza de R.A, Harde M.J et al Clinical characteristics and outcome of patients with acute lung injury and ARDS J Postgrad Med 2011, Vol 57, pp.286-290 Hansen-Flaschen J, SiegelM.D et al Acute respiratory distress syndrome: Definition; clinical features and diagnosis www.uptodate.com 2010 Hodgson C.L, Tuxen D.V et al A randomized controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome Critical Care 2011, Vol 15 (R133), pp.1-9 Kleiner G, Marcuzzi A at al Cytokine levels in the serum of healthy subjects Mediators of Inflammation 2013, pp.1-6 95 Journal of military pharmaco-medicine No7-2017 Ranieri V.M, Rubenfeld G.D, Thompson B.T, Ferguson N.D, Caldwell E et al ARDS definition task force Acute respiratory distress syndrome The Berlin Definition JAMA 2012, 307 (23), pp.2526-2533 Stapleton R.D, Wang B.M, Hudson L.D et al Causes and timing of death in patients with ARDS Chest 2005, 128 (2), pp 525-532 10 Steinvall I, Bak Z, Sjoberg F Acute respiratory distress syndrome is as important as inhalation injury for the development of respiratory dysfunction in major burns Burns 2008, 34 (4), pp.441-451 96 11 The Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volume as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome N Engl J Med 2000, Vol 342, pp.1301-1308 12 Villar J, Kacmarek R.M, Pérez Méndez L et al A high positive end expiratory pressure, low tidal volume ventilation strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial Crit Care Med 2006, 34 (5), pp.1311-1318 ... subclinical characteristics and outcome of ARDS among severe burn patients SUBJECTS AND METHOD A prospective study was conducted on 66 severe burn patients with ARDS, Table 1: The severity of ARDS... number of failure organs [4] For burn patients, most studies indicated the main cause of death among ARDS patients was also MOF rather than lung disorder In this study, among 41 deaths of all patients, ... Sjoberg F Acute respiratory distress syndrome is as important as inhalation injury for the development of respiratory dysfunction in major burns Burns 2008, 34 (4), pp.441-451 96 11 The Acute Respiratory