Nghiên cứu đặc điểm lâm sàng, cận lâm sàng và kết quả điều trị hội chứng suy hô hấp cấp (ARDS) ở trẻ em theo tiêu chuẩn berlin 2012 tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY TRAN VAN TRUNG RESEARCH CLINICAL, SUBCLINICAL CHARACTERISTICS AND TREATMENT RESULTS OF ARDS IN CHILDREN ACCORDING TO BERLIN 2012 Major: Pediatrics Code: 62720135 SUMMARY OF DOCTORAL DISSERTATION IN MEDICINE HANOI - 2019 THE WORK COMPLETED IN HANOI MEDICAL UNIVERSITY Scientific Supervisor: ASSO.PROF.DR PHAM VAN THANG Opponent 1: Opponent 2: Opponent 3: The dissertation is presented in front of the Board of Examiners – University level held in Hanoi Medical University At on 2019 Dissertation may be seen at: - National Library of Vietnam - Library of Hanoi Medical University LIST OF RESEARCHES IN RELATION TO THE DISSERTATION Tran Van Trung, Pham Van Thang (2017) Some epidemiological - clinical characteristics and cause of ARDS in children according to Berlin 2012 Pediatrics Journal, 10 (6): – Tran Van Trung, Pham Van Thang (2017) Treatment outcomes and some factors relating to treatment outcomes of ARDS in children Pediatrics Journal, 10 (3): 13 – 19 PREAMBLE Acute Respiratory Distress Syndrome (ARDS) is serious and critical disease condition in the intensive care departments, occurring in both adults and children Although Although there has been much progress in intensive car for ARDS patients so far mortality rate of this disease is still high that is 40-60% Vietnam is a developing country, the rate of children with bacterial or viral respiratory infections, septic shock, poisoning, drowning is at high risk of developing ARDS Previously, ARDS diagnosis was based on AECC 1994 In 2012, a new diagnostic standard for ARDS, called Berlin 2012 was published This standard is considered to be simpler, easier to apply, allowing for early diagnosis and different levels of severity of ARDS, which helps to have better prognosis Therefore, if the Berlin 2012 is used, it is possible to help the pediatricians, especially in the lower levels, to identify and classify ARDS patients according to their severity in order to solve it in timely manner with the right method resulting in reducing the mortality rate of this disease In Vietnam, no systematic study has been conducted to assess the clinical and subclinical characteristics of ARDS and its treatment results in children recommended by the Berlin 2012 Conference As a result, we have researched: “Research clinical and subclinical characteristics and treatment results of ARDS in children according to Berlin 2012” with following objectives: Describe clinical and subclinical characteristics of ARDS in children according to Berlin 2012 Comments on treatment results of ARDS in children as recommended by Berlin 2012 Identify some factors associated with the mortality ratio of ARDS in children Rationale of the research ARDS in children is a serious disease in the intensive care departments with very high mortality rate The new diagnostic standard for ARDS published in 2012 is evaluated as simple, easy to apply, allowing early diagnosis with different levels of severity, which help to have better prognosis Therefore, a systematic study of clinical, subclinical characteristics and mortality-related factors of ARDS in children according to the Berlin 2012 may help pediatricians, especially those in lower level, to early identify and classify ARDS patients according to their severity in order to solve it in timely manner with the right method resulting in reducing the mortality rate of this disease New contributions of the dissertation The dissertation is the first systematic study on ARDS in children according to Berlin 2012 The dissertation has identified the clinical and subclinical characteristics of ARDS patients treated in the intensive care departments of Vietnam National Children Hospital at the average age of 15.8 ± 26.5 months, with 45% at serious level, 92% of the cases due to lung causes, mainly viral pneumonia, especially related to measles Regarding treatment: despite intensive care with modern facilities the mortality rate is still very high (58.2%) Mortality rate depends on the severity of the disease: from 27.3% in mild to 81.8% in severe form Most deaths occur during the first week of illness The rate of hospital infection is 28.6% The factors related to mortality of ARDS by multiple regression analysis include: origin related to measles, pre-treatment indicatoprs PaO2 ≤ 80mmHg, P/E ≤ 100; S/F ≤ 117, OI > 18,5 and OSI > 15, with mmultiple organ failure Oxygen index (OI) and oxygen saturation index (OSI) found during treatment process may help predict the risk of death in ARDS patients Structure of the dissertation The dissertation consists of 122 pages In addition to the preamble (3 pages), the conclusion (2 pages) and the recommendation (1 page) it has chapters including: Chapter 1: Overview with 34 pages; Chapter 2: Object and research method with 16 pages; Chapter 3: Research results with 34 pages; Chapter 4: Discussion with 32 pages The dissertation consists of 37 tables, diagrams, figures, 10 charts, 160 documents of reference (Vietnamese: 8; English: 152) Chapter OVERVIEW 1.1 Concept and criteria of diagnosis ARDS was first described in 1967 by Ashbaugh with the characteristics: acute respiratory failure after a lung injury or a injury in other organ, the patient has severe hypoxemia, poor response to conventional ventilation measures, chest radiograph images showed diffuse alveolar damage in both sides of the lung, rapid evolution between the times of radiography However, in 1994, at the American-European Consensus Conference (AECC) on ARDS, the specific diagnostic criteria for this syndrome were given Table 1.1 AECC 1994 In 2012, a new diagnostic criterion for ARDS called Berlin 2012 (Table 1.2) was published to replace the criterion in 1994 This new criterion was assessed as more specific, enabling early diagnosis and the severity levels are classified resulting in better prognosis and may be applied to children Table 1.2 Berlin 2012 Criterion Acute onset within 01 week with new or more seriou Onset symptoms Bilateral opacities on chest X-ray which were not fully Chest X-ray effusions, lung collapse or nodules Respiratory failure not caused by cardiac failure or flu Cause of respiratory Echo-cardiography, if needed, to rule out cardiogenic failure edema Hypoxemia PaO2/FiO2 ≤ 300 with PEEP or CPAP ≥ 5cmH2O Classification + Mild: 200 < PaO2/FiO2 ≤ 300 + Moderate: 100 < PaO2/FiO2 ≤ 200 + Severe: PaO2/FiO2 ≤ 100 1.2 Cause of ARDS in children ARDS may be triggered after a direct injury to lung parenchyma or by an indirect system-derived agent causing lung damage through pulmonary circulation In children, lung-related causes are mainly bacterial or viral pneumonia and non-pulmonary causes are mainly shock, especially septic shock 1.3 Clinical and subclinical characteristics of ARDS - The clinical course of ARDS usually undergoes stages: onset, full development and recovery Onset symptoms are usually nonspecific and marked by the signs of new respiratory symptoms such as dyspnea, rapid breathing, respiratory muscle retractions, moist rales lung sounds may be heard with bilateral infiltrates on X-ray film Full development stage usually lasts within to weeks depending on each patient In this stage, most ARDS patients have severe hypoxia and need oxygen or mechanical ventilation Clinically recognizable signs include: the patient looks pale gray, reduction of SpO2 and needs more oxygen to breath (FiO2) Other indicators help further assess the patient's hypoxia such as PaO2, PaO2 / FiO2 ratio, oxygen index (OI) Patients also have signs of multiple organ dysfunction, acid-base disorder as a result of respiratory failure The patients who go through the full development will move to the stage of fibrosis and recovery Full recovery depends much on the level of pulmonary fibrosis and its complications -In the subclinical tests, arterial blood gas usually has severe hypoxemia: SaO2 and PaO2 are often low, the oxygen pressure difference between the alveolus and artery (DO2) increases The injury image on the X-ray of ARDS is the alveolar lesions and interstitial spaces, spreading to both sides and evolving rapidly Other tests such as blood counts, electrolytes, liver and kidney function, coagulation tests are usually not specific to help assess the cause or complication of ARDS or homeostasis of the patients 1.4 Treatment of ARDS The most basic and important treatment for ARDS patients is still mechanical ventilation The goal of ventilation for ARDS patients is to maintain adequate oxidation and ventilation levels, limiting the impact from mechanical ventilation There have been many strategies, methods and mechanical ventilation procedures mentioned and studied such as: mechanical ventilation with positive end-expiratory pressure (PEEP), lung protective ventilation with low tidal volume (Vt), mechanical ventilation by lung opening strategy, high frequency oscillatory ventilation, prone ventilation some of which have been proved to improve blood oxidation and reduction of mortality ratio caused by ARDS As recommended by Berlin 2012 Conference, lung protective ventilation with low tidal volume (Vt) in combination with PEEP remains the primary ventilation method for ARDS patients High high frequency oscillatory ventilation (HFO) and prone ventilation are indicated for severe ARDS patients and unsuccessful with conventional ventilation methods Muscle relaxants are considered for the severe ARDS patients Other conventional treatments are to support the damaged lung, improve homeostasis, support multi-organ function and reduce mortality 1.5 Some factors relating to mortality in children caused by ARDS There have been many studies in the factors associated with mortality of ARDS patients to help clinicians better make prognosis of the patients The studies focused on a number of factors such as the severity of ARDS patients at the time of diagnosis, host factor and underlying disease of the patient, response to treatment and complications during treatment process The factors assessing the severity of patients include: degree of hypoxia (assessed by the SpO2, PaO2 blood index, PaO2 / FiO2 ratio, OI index ), initial ventilation parameters and FiO2 demand, multi-organ failure status of patients Special host factors and underlying diseases of the patient such as history of severe illness or the presence of one or more underlying diseases such as immunodeficiency diseases, congenital metabolic disorders accidents or complications during the course of treatment such as: complications due to ventilation (pneumothorax, pneumomediastinum), gastrointestinal hemorrhage, hospital infection 10 Chapter OBJECT AND RESEARCH METHOD 2.1 Object of the research 98 patients at the age of month - 15 year old, hospitalized into Intensive care department – Vietnam National Children Hospital, diagnosed ARDS and treated from 01/2014 to 7/2016 - Criteria for ARDS diagnosis and classification: applying Berlin 2012  Onset of respiratory failure within 01 week, new/more serious symptoms appear  Lung X-ray: Bilateral opacities on chest X-ray which were not fully explained by effusions, lung collapse or nodules  Respiratory failure not caused by cardiac failure or fluid overload Echo-cardiography, if needed, to rule out cardiogenic pulmonary edema  Hypoxemia: PaO2/FiO2 ≤ 300 với PEEP/CPAP ≥ 5cmH2O  Mild ARDS: 200 < PaO2/FiO2 ≤ 300 with PEEP/CPAP ≥ 5cmH2O  Moderate ARDS: 100 < PaO2/FiO2 ≤ 200 with PEEP ≥ 5cmH2O  Severe ARDS: PaO2/FiO2 ≤ 100 with PEEP ≥ 5cmH2O - Exclusions  ARDS patients who have suffered the disease more than days before hospitalization  ARDS patients died quickly (< hours) after hospitalization  ARDS patients have congenital cardiac disease with pale gray 2.2 Research methods Research design: Descriptive prospective study, interventional non-control treatment Sampling method: - Objective 1: Total selection - Objective and 3: using the formula for calculating 16 deviation (%) ≤ 90 > 90 Average ± deviation PaO2 ≤ 60 (mmHg) 61 - 80 > 80 OI Average ± deviation 7.45 27.3 6.3 10 22.7 18 18.4 Average ± deviation PaCO2 (mmHg < 35 ) 35 - 45 48.6 ± 21.3 47.3 ± 14.9 49.9 ± 15.9 p % 0.0 48.7 ± 16.8 22.7 9.4 6.8 22.7 19 59.4 19 43.2 11.2 0.0 43 43.9 > 45 12 54.5 10 31.3 22 50.0 44 44.9 Average ± deviation 24.5 ± 3.5 HCO3 < 22 (mEq/l) 22 - 26 11 23.3 ± 2.7 23.6 ± 3.7 23.7 ± 3.4 13.6 18.8 12 27.3 21 21.4 13 59.1 23 71.9 23 52.3 59 60.2 > 26 27.3 9.4 20.5 18 18.4 Average ± deviation -0.01 ± 5.01 BE < -2 (mEq/l) -2 – >2 -0.53 ± 3.29 0.52 ± 4.71 0.3 0.06 ± 4.35 40.9 10 31.2 15 34.1 34 34.7 31.8 16 50.0 18.2 27.3 18.8 21 47.7 31 31.6 0.0 33 33.7 18 Table 3.9 Results of blood formula tests Indicators Mild (n1=22) n % Moderate (n2=32) n % Average ± deviation 11.9 ± 7.4 11.4 ± 4.5 Normal 40.9 12 31.6 Increased 10 45.5 23 60.5 Decreased 13.6 7.9 Average ± Hb deviation 96.5 ± 14.4 95.8 ± 10.8 concentratio Normal 17 77.3 24 75.0 n (g/l) Decreased 22.7 25.0 Average ± 251.1 ± 282.3±148 Platelet deviation 172.9 count (G/l) Normal 17 77.3 25 78.1 Decreased 22.7 21.9 Number of white blood cells (G/l) Severe (n3=44) n % General (n=98) n % 12.9 ± 8.1 20.4 27 61.4 18.2 100.3 ± 14.2 34 77.3 10 22.7 250.8 ± 161.3 31 70.5 13 29.5 12.2 ± 6.9 30 28.8 60 57.7 14 13.5 Lactate (mmol/l) Normal Increased Glucose n/ Average ± (mmol/l) deviation Normal 20/3,8 ± 5,4 25/2,4 ± 2,9 37/2,9 ± 3,5 p 82/2,9 ± 3,8 40.0 14 56.0 23 62.2 45 54.9 12 60.0 11 44.0 14 37.8 37 45.1 18/7.1 ± 3.3 31/6.2 ± 1.6 43/6.8 ± 3.5 92/6.8 ± 2.9 13 72.2 20 64.5 27 62.8 60 65.2 Increased 22.2 10 32.3 14 32.6 28 30.4 Decreased 5.6 Electrolyt Normal es Abnormal 97.9 ± 13.2 75 76.5 23 23.5 261.2 ± 159.0 73 74.5 25 25.5 Table 3.10 Results of biochemical blood tests Mild Moderate Severe General Indicators n % n % n % n % n/ Average ± deviation p 3.2 4.7 4.3 13 59.1 18 56.3 28 63.6 59 60.2 40.9 14 43.8 16 36.4 39 39.8 19 3.3 Treatment results All 98 patients were treated with a common treatment protocol by the Vietnam National Children Hospital for the ARDS patients as recommended by Berlin 2012 Conference The treatment results are as follows: 3.3.1 Effects of blood oxygenation after treatment - Changes in SpO2 after treatment: Chart 3.1 Changes in SpO2 before and after treatment - Changes in PaO2 after treatment: Chart 3.2 Changes of PaO2 before and after treatment - Changes in P/F before and after treatment: Chart 3.3 Changes of P/F before and after treatment Day Day Day Day Day - Changes of OIGeneral beforegroup and after treatment: Survival group Day Day Mortality group Chart 3.4 Changes in OI before and after treatment Day Day Day Day Day Day Day 3.3.2 MortalityGeneral ratio at Intensive Care Department group Survival Mortality group group - The general Mortality ratio is 58.2% - Mortality ratio in ARDS patients at mild level is 27.3%, at Moderate Day Day Day Day Day Day Day level is 53.1% and at Severe level is 81.8% Mortality ratio in groups of General group Survival group patients are different significantly with p < 0.001 Mortality group - Mortality ratio by causes: DayTable Day Mortality Day ratio Day 4by causes Day 3.11 General group Causes Pulmonary causes (n = 90) Survival group Survival Day Mortality Death group n % n % 35 35.7 55 64.3 Day p 20 Bacterial pneumonia (n = 16) 37.5 10 62.5 Viral pneumonia (n = 49) 20 40.8 29 59.2 CRNN pneumonia (n = 21) 38.1 13 61.9 Inhaling drowning (n = 4) 25.0 75.0 75.0 25.0 Septic shock (n = 6) 83.3 16.7 Anaphylaxis (n = 2) 50.0 50.0 Other causes: (n = 8) 0.4 (1) (1) : Comparison between group of causes in lung and group of other causes 3.3.3 Time of mortality and duration of treatment - Mortality is around in the first seven days and gradually reduced from the second week After day 50, no patient mortality detected - Average duration of treatment in Intensive Care Department spent by a patient is 13.7 ± 8.7 (days), the minimum duration is days while maximum is 53 days Average Mechanical ventilation duration is 11.1 ± 6.8 (days), the minimum duration is days while the maximum is 41 days 3.3.4 Treatment complications Table 3.12 Treatment complications Complications Pressure accident Pneumothorax Pneumomediastinum Hospital infection Pneumonia Blood infections Blood infections + Pneumonia Pressure ulcers n 28 19 16 % 6.1 5.1 1.0 28.6 19.4 6.1 3.1 16.3 3.4 Some factor associated with ARDS mortality in children 3.4.1 Relation between some pre-treatment factor and mortality ratio Table 3.14 Relation between some epidemiological characteristics and mortality ratio Factor Surv Mor p OR 21 talit y (95%CI) n % n % Age ≤ 12 group: months 0.94 5 (0.34 – > 12 1 2.61) months Gender: male 0 1.07 (0.46 – 5 2.46) female 7 Underlyin g disease / No 1.46 special (0.63 host 2 3.39) factor: Yes 3 Table 3.15 Relation between Onset characteristics and ARDS mortality ratio Survival Mortality p OR (95%CI) Factor n % n % Onset time: 1-3 days 17 43.6 22 56.4 0.8 1.13 (0.49 – 2.56) 4-7 days 16 40.0 24 60.0 Onset New Onset 27 44.3 34 55.7 0.3 1.31 (0.57 – 3.01) characteristics More severe 14 37.8 23 62.2 direct 35 38.9 55 61.1 Onset cause: 0.06 0.20 (0.04 – 1.11) indirect 75.0 25.0 Measlesyes 23.8 17 77.3 related 0.05 3.06 (1.03 – 9.14) no 36 46.8 40 52.6 pneumonia: Table 3.16 Relation between pre-treatment SpO2 and PaO2 and mortality ratio Mortality % 70.9 ival n 39 22 18 41 41.9 77.4 35.6 16 Table 3.17 Relation between S/F and P/F and mortality ratio Factor > P/ F 100 ≤ 100 > S/ F 117 ≤ 117 Survival n % 60 31 21 10 55 26 44 15 Mortality n % 39 20 78 37 46 21 55 36 p OR (95%CI) 0.0 5.74 (2.34 – 01 14.06) 0.0 2.97(1.29 – 09 6.83) Table 3.18 Relation between OI and OSI and mortality ratio Factor ≤ 18 O I > 18 O S I ≤ Surv Mortal ival n % 2 6 ity n % OR (95%CI) 35 6 < 0.00 77 1 6.19 (2.55 – 15.03) 33 15 6 p < 5.87 (2.42 0.00 – 14.24) 23 > 15 4 74 Table 3.19 Relation between multiple organ failure and mortality ratio Factor Pre-treatment multiple no yes Survival n % 17 68.0 24 32.9 Mortality n % 32.0 49 67.1 organ failure p 0.006 OR (95%CI) 3.78 (1.47 – 9.72) - Multivariate analysis between pre-treatment factor and mortality: Table 3.20 Results of multivariate analysis of pre-treatment factor O95%C R I Cause of 61.54 – measles- 23.37 related pneumonia Pre- > No treatment meani SpO2 ≤ ng 92% Pre- 41.89 – treatment 12.38 PaO2 ≤ 80 mmHg Factor p 24 Pre- treatment S/F ≤ 117 Pre- treatment P/F ≤ 100 0 Pre- treatment OSI > 15 0 Pre- treatment OI > 18,5 Pre- treatment multiple organ failure 1.32 6.80 42.10 – 8.29 41.75 – 11.62 31.09 – 9.31 41.47 – 14.61 3.4.2 Relation between some monitoring factor during treatment and mortality ratio Table 3.21 Relation between P/F, S/F, OI and OSI monitoring and mortality ratio Mortality ratio Factor p OR (95%CI) (%) > 100 40.6 P/F < 0.001 4.55 (3.66 – 5.66) ≤ 100 75.7 > 117 38.9 S/F < 0.001 4.83 (3.84 – 6.07) ≤ 117 75.4 ≤ 18.5 36.7 OI < 0.001 5.54 (4.28 – 7.16) > 18.5 76.2 25 OS I ≤ 15 > 15 31.1 75.2 < 0.001 6.71 (5.16 – 8.71) Table 3.22 Relation between treatment complications and mortality Mor Surv OR talit Factor p ival (95%CI) y n % n % 2 Hospital yes 5 2.83 infection 0 (1.07 – complication 7.52) no s: 1 yes 3.85 Pressure (0.43 – 4 5 accident: 34.24) no 5 - Multivariate analysis between factor of treatment monitoring and mortality ratio: Table 3.23 Results of multivariate analysis of treatment monitoring factor Factor p OR 95%CI P/F 0.2 Meaningless S/F 0.5 Meaningless OI 0.01 1.91 1.14 – 3.19 OSI 0.001 3.35 2.13 – 5.28 Hospital infection complications 0.3 Meaningless - There is a strong correlation between OI and OSI with p = 0.001 and correlation coefficient r = 0.807 26 Chapter DISCUSSION 4.1 Clinical and subclinical characteristics of ARDS in children - The research results show that the severity rate is high (44.9%) It is possible that our research was conducted in the Intensive Care Department of a central hospital, before hospitalization the patients have been treated at the medical station of lower level resulting in the long period of illness - The average age of patients is 15.8 months and the infant age (≤ 12 months) accounts for a high proportion (75.5%) There is no average age difference between the groups of mild, moderate and severe patients, which indicates that the severity of the patient is not related to the age of the patient There is a high proportion (36.7%) of patients with special underlying diseases such as premature birth, malnutrition or chronic diseases - The research results showed that the onset of ARDS patients was relatively long, averaging 4.1 days Perhaps because this research was conducted at the Central Hospital, most patients were treated through different medical stations However, the onset time has not been shown to be related to the severity of ARDS - ARDS in children is primarily due to lung causes, accounting for 91.8% The non-lung causes of account for only 8.2% Among lung causes, viral pneumonia accounts for the highest proportion (47.9%) In this research, we had a high proportion of ARDS patients initiated by measles-associated pneumonia (22 patients, accounting for 22.4%) However, this ratio may not reflect the true cause of ARDS in children because measles outbreaks are at the time of the research and most of the serious complications of measles were treated at the National Hospital of Pediatrics - Level of respiratory failure at the time of diagnosis: all of our patients have severe hypoxia and need mechanical ventilation (91 patients 27 with conventional mechanical ventilation and patients with HFO breathing) Comparison of indicators reflecting oxidation levels in three groups of mild, moderate and severe patients, we found that all indicators of SpO2, PaO2 and OI were significantly different with p 15 Patients with associated multi-organ failure also increase mortality of ARDS patients The results of multivariate analysis showed that the factor that was not really related to the mortality ratio was SpO2 at the time before treatment ≤ 92 and factors associated with mortality were the cause of measles-related pneumonia, pre-treatment level of hypoxia (PaO2 before treatment ≤ 80 mmHg, P / F before treatment ≤ 100, S / F before treatment ≤ 117, OI before treatment> 18.5, OSI before treatment> 15) and have the multi-organ failure state attached - Relation between P/F, S/F, OI and OSI monitoring and mortality ratio: We investigated the association between the follow-up of blood oxidation indicators, P/F, S/F, OI and OSI during ARDS mortality treatment, to assess the predictability of mortality of the indicators The results showed that all indicators are closely related to the mortality ratio of ARDS with p 18.5, pre-treatment OSI > 15, followed by multiple organ failure ... ARDS in children according to Berlin 2012 with following objectives: Describe clinical and subclinical characteristics of ARDS in children according to Berlin 2012 Comments on treatment results... developing ARDS Previously, ARDS diagnosis was based on AECC 1994 In 2012, a new diagnostic standard for ARDS, called Berlin 2012 was published This standard is considered to be simpler, easier... early diagnosis and different levels of severity of ARDS, which helps to have better prognosis Therefore, if the Berlin 2012 is used, it is possible to help the pediatricians, especially in the lower