Acute Respiratory Distress Syndrome, Conventional Mechanical Ventilation, High Frequency Oscillatory Ventilation, Preterm
Conditions
Brief summary
Bronchopulmonary dysplasia (BPD) is a complex disorder and remains the most common complication in very preterm infants. Its incidence is increased with gestational age from 95.5% among infants born at 22 weeks' gestation to 22.2% among those born at 29 weeks' gestation. BPD is associated with the increased risks of delayed neurodevelopment and pulmonary impairment. High incidences of BPD and morbidities indicate inadequacy of current management guidelines of BPD.3 Caffeine reduces the development of BPD by lowering the duration of intubation.4 How to further reduce the risk of BPD and the duration of invasive ventilation remain the key focus for neonatologists.
Detailed description
Before 2017, the management guideline of pediatric and adult acute respiratory distress syndrome (ARDS) exclude perinatal triggers-induced ARDS. Moreover, there is insufficient evidence to recommend high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) as the preferred fist-line therapy in pediatric and adult ARDS. In contrast, HFOV may benefit preterm baboons with acute pulmonary dysfunction-typically due to respiratory distress syndrome (RDS)-by using low tidal volume, supra-physiologically higher respiratory rate, and lower peak inspiratory pressure to enhance oxygenation and gas exchange. The team also reported that use of HFOV is associated with a modest reduction referring to BPD. However, European consensus guideline of RDS only recommend HFOV being a reasonable alternative to CMV when high pressure is needed to achieve adequate lung inflation. Because randomized controlled trials in humans have yielded inconsistent findings. These differences between animal models-where RDS was induced and treated with surfactant alone-and clinical scenarios, where preterm birth often involved complex etiologies requiring both surfactant and antibiotics for placental insufficiency or intrauterine infection, may be the diagnosis of RDS and ARDS or the mixture of RDS and ARDS. Such findings highlighted the lack of robust evidence for optimizing ventilation strategies in preterm infants born \<32 weeks with perinatal ARDS, and the need for well-designed multi-center randomized controlled trials in this high-risk population.
Interventions
DEVICEHFOV
HFOV + volume guarantee (VG) as the intervention group HFOV was provided only with piston or membrane oscillators capable of delivering true oscillatory pressure with an active expiratory phase (i.e., Acutronic FABIAN-III, SLE 5000, Löwenstein Med LEONI+, or Sensormedics 3100A). Other machines offering high frequency ventilation were excluded. The lung recruitment maneuver was performed as previously described, and lung volume was assessed by chest radiography or lung ultrasound, targeting the right diaphragm at the level of 8th-9th rib (or 7th-8th rib in case of air leak). Crossover between HFOV and CMV This study allowed infants who failed to respond to their assigned ventilation mode to receive a trial of the alternate mode. Crossover criteria for HFOV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or signs of ventilator-induced cardiac output reduction. Non-responders to HFOV were switched to CMV.
DEVICECMV
CMV as the standard group CMV was delivered by time-cycled, pressure-limited ventilators. Only pressure regulated volume control (PRVC) will be provided by any type of neonatal ventilator. Crossover criteria for CMV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or requiring \> 30 cm H2O PIP to sustain ventilation. Non-responders to CMV were switched to HFOV. Ventilator settings were adjusted at the discretion of the attending clinician to maintain a SpO2 between 90%-94%, a PaO2 between 50 and 80 mm Hg and a PaCO2 between 35 and 60 mm Hg and a pH between 7.20 and 7.45. PO2 and PCO2 levels were monitored using arterial blood gas analysis and/or transcutaneous monitoring in both groups.
Sponsors
Children's Hospital of Chongqing Medical University
Jiulongpo No.1 People's Hospital
Chongqing Maternal and Child Health Hospital
The First Affiliated Hospital of Anhui Medical University
Children's Hospital of The Capital Institute of Pediatrics
Peking University Third Hospital
First Hospital of Tsinghua University
Women and Children's Hospital, Branch of Chongqing Sanxia Central Hospital
First Affiliated Hospital of Chongqing Medical University
Quanzhou Children's Hospital
Xiamen Maternity & Child Care Hospital
Zhujiang Hospital
Nanfang Hospital, Southern Medical University
Guangdong Academy of Medical Science and General Hospital
Guangdong Women and Children Hospital
Women and Children's Health Hospital of Yulin
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Second Affiliated Hospital of Guangzhou Medical University
Guiyang Maternal and Child Health Care Hospital
The First People's Hospital of Zunyi
Lanzhou University Second Hospital
Gansu Provincial Maternal and Child Health Care Hospital
LanZhou University
First Affiliated Hospital of Harbin Medical University
First Affiliated Hospital of Xinjiang Medical University
Zhengzhou Children's Hospital, China
Third Affiliated Hospital of Zhengzhou University
the Maternal and Child Health Hospital of Hainan Province
Bethune International Peace Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Children's Hospital of Nanjing Medical University
The First Hospital of Jilin University
Children's Hospital of Fudan University
Maternal and Children's Healthcare Hospital of Taian
The Second Hospital of Shandong University
Shanxi Provincial Maternity and Children's Hospital
Chengdu Women and Children's Center Hospital
The Affiliated Hospital Of Southwest Medical University
Affiliated Hospital of Southwest Medical University
Shenzhen People's Hospital, The Second Medical College of Jinan University
Tianjin Central Hospital of Gynecology Obstetrics
People's Hospital of Xinjiang Uygur Autonomous Region
Kunming Children's Hospital
The First People's Hospital of Yunnan
First Affiliated Hospital of Kunming Medical University
Yan'an Affiliated Hospital of Kunming Medical University
Women and Children's Health Hospital of Qujing
The People's Hospital of Dehong Autonomous Prefecture
The First People's Hospital of Yinchuan
The Children's Hospital of Zhejiang University School of Medicine
Women's Hospital School Of Medicine Zhejiang University
Beijing 302 Hospital
Hunan Children's Hospital
Women and Children Hospital of Qinghai Province
Jiangxi Province Children's Hospital
Inner Mongolia People's Hospital
Mianyang Central Hospital
People's Liberation Army No.202 Hospital
Ningbo Women & Children's Hospital
Shanghai Children's Medical Center
First Affiliated Hospital of Guangxi Medical University
Nanjing Medical University
Xianyang Children's Hospital
Qinhuangdao Maternal and Child Health Care Hospital
Xuzhou Children Hospital
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The caregivers will not be blinded, and the outcome assessors and data analysts will be blinded to the intervention.
Intervention model description
Very preterm neonates with perinatal acute respiratory distress syndrome will be randomized and assigned to high frequency oscillation ventilation (HFOV) or conventional mechanical ventilation (CMV)
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 1 Hours
Healthy volunteers
No
Inclusion criteria
1. GA was between 24+0 and 31+6 weeks. 2. Preterm neonates were admitted to NICU within 1 hours after birth, diagnosed with perinatal ARDS using Montreux guidelines and stable supported by CMV. 3. Stabilization for 2 hours before randomization: FiO2 0.40, mean airway pressure (MAP) 10-14 cmH2O, ≤ 40 bpm of respiratory rate, 90%-94% of SpO2, pH \> 7.20, PaCO2 60 mmHg, tidal volume of 5 ml/kg and \> 35% of hematocrit (these may be evaluated by arterial blood gas analysis).
Exclusion criteria
Neonates were not included if any of the following criteria were met: 1. Parents or guardians' decision not to participate. 2. Major congenital anomalies or chromosomal abnormalities 3. Need for surgery or more than grade 2nd of IVH before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the incidence of bronchopulmonary dysplasia(BPD) | 36 weeks' gestational age | BPD is defined according to the 2019 diagnostic criteria. For infants discharged before 36 weeks' GA, BPD severity was assessed based on respiratory support at the time of discharge. Infants receiving no supplemental respiratory support were divided into no BPD, those treated with nasal cannula (≤ 2 L/min) as grade 1 BPD, those treated with nasal cannula (\> 2 L/min) or noninvasive positive airway pressure as grade 2 BPD and those treated with invasive mechanical ventilation as grade 3 BPD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mortality | 36 weeks' gestational age or before discharge | the included neonates were diagnosed with death |
| air leak (pneumothorax and/or pneumomediastinum) occurred | 36 weeks' gestational age or before discharge | the included neonates were diagnosed with air leak |
| the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) | 36 weeks' gestational age or before discharge | the included neonates were diagnosed with hsPDA. |
| duration of invasive ventilation | 36 weeks' gestational age | duration of invasive ventilation for HFOV or CMV |
| the incidence of necrotizing enterocolitis(NEC)≥2nd stages | 36 weeks' gestational age or before discharge | the development of NEC, specifically focusing on cases classified as Bell's stage ≥2, according to the modified Bell's staging criteria for NEC. |
| intraventricular hemorrhage(IVH)>2nd grade | 36 weeks' gestational age or before discharge | IVH with grades 1-4 were defined by Papile et al |
| the incidence of retinopathy of prematurity(ROP)> 2nd grades | 36 weeks' gestational age or before discharge | ROP was categorized according to the International Classification of Retinopathy of Prematurity, revised in 2005 |
Countries
China
Outcome results
None listed