Population and study criteria
This was a single-center, prospective randomized controlled study conducted in the cardiac intensive care unit (CICU) from January 2020 to December 2020 at a provincial hospital in China. The trial was approved by the ethics committee of Fujian Maternity and Child Health Hospital (NO. 2020YJ181) and adhered to the tenets of the Declaration of Helsinki (as revised in 2013). Informed parental written consent from all subjects were obtained.
The inclusion criteria were as follows: 1. Infants were suffering from ARDS in our CICU. 2. The patient’s anatomical treatment was satisfactory, cardiac function recovered well after the operation, and hemodynamics was stable. The exclusion criteria included hemodynamically significant residual lesions, pulmonary venous obstruction, parents’ decision not to participate.
After documenting parental consent, all infants were assigned using a table of computer-generated random numbers and sealed opaque envelopes to either HFOV + PS or CMV + PS.
Pulmonary surfactant (PS): The PS (porcine surfactant, Curosurf®, Chiesi Pharmaceutical SpA, Parma, Italy) was used for intratracheal injection. The infants in both groups were given a dose of 100 mg/kg in one dose within 6 h after ARDS diagnosis. Before application, the airway secretions were aspirated, and the circulation was maintained stable to correct the acid-base disorder. After PS injection, pressurize and ventilate rapidly for 1 min, then connect to a ventilator to maintain HFOV/CMV ventilation.
Mechanical ventilation: HFOV+PS group: High frequency oscillating ventilator (SLE 5000, SLE UK, Croyden, United Kingdom) was used for mechanical ventilation before PS application. The ventilator’s initial parameters were as follows: a frequency of 8-12 Hz and an inspiratory: expiratory ratio of 1:1 were used in each case; The mean airway pressure (MAP) was initially set at 10-15 cmH2O and then gradually increased with steps of 1 cmH2O every 2–3 min until the oxygenation no longer improved or the FiO2 was ≤ 0.40; Then, the MAP was decreased by 1–2 cmH2O every 2–3 min until FiO2 began to rise again. The amplitude was initially set at 30-40 cmH2O. After one hour of mechanical ventilation, ideal lung inflation was examined by chest radiography, and the right diaphragm was generally kept at the level of the ninth rib. The parameter adjustment is determined according to the results of the dynamic monitoring of blood gas analysis. After continuous ventilation for at least 10 minutes, PS was injected through the tracheal tube. The changes in oxygen saturation (SaO2), heart rate, respiration, and blood pressure were closely monitored during the treatment. If the infant suffered from apnea, SaO2 or the heart rate dropped, the injection was suspended and oxygen was rapidly pressurized until the stable state was restored. After PS was applied, mechanical ventilation was continued, and the ventilator parameters were readjusted according to the results of SaO2, blood gas analysis and chest radiograph. Infants were extubated when they achieved the following criteria: hemodynamic stability, MAP < 8 cmH2O, FiO2 < 40%, and weaned sedation. The infants were transferred to conventional ventilation before extubation. After weaning, nasal continuous positive pressure ventilation (NCPAP) was administered through a nasal interface.
CMV+PS group: The Stephanie ventilator (Fritz Stephan GmbH, Gackenbach, Germany) was used for CMV. The initial parameters: FiO2: 30%～50%, PIP: 18-25cmH2O, PEEP: 4～6 cmH2O, I/E: 1-1.5:1, RR: 30～40 times/min. According to the results of SaO2, arterial blood gas (ABG) analysis and chest radiograph, the parameters of the ventilator were adjusted, and continuous positive pressure ventilation (NCPAP) was given through nasal congestion after weaning.
Definitions and data collection
Outcome measures: The ventilatory settings, ABG analysis, oxygenation index (OI), duration of mechanical ventilation, and complications of ventilation were recorded during the study period. The primary outcome was short term oxygenation, and the secondary outcome was the duration of mechanical ventilation and length of hospitalization. The diagnosis of ARDS was established according to the medical history, clinical manifestations, and chest radiograph results which defined in 2015 by the Pediatric Acute Lung Injury Consensus Conference Group (PALCCG)1, and met the following conditions: (1) hypoxemia with OI ≥ 4 or oxygenation saturation index (OSI) ≥ 5; (2) new radiological lung infiltrates; (3) occurred within 7 days of a known clinical insult; and (4) could not be explained by cardiac failure or fluid overload. (5) other patients with chronic lung/heart diseases, such as cyanotic heart disease, chronic lung disease, and left ventricular dysfunction to be included as long as they fulfilled the criteria above and the acute deterioration in oxygenation and pulmonary infiltrates could not be explained by their pre-existing diseases. (6) excluded patients with perinatal related lung disease. The diagnosis of ventilator-associated pneumonia (VAP) was based on the criteria established by the Centers for Disease Control and Prevention, with diagnosis aided by chest radiographs, positive sputum cultures, transtracheal fluid, bronchial washings, and clinical findings11. A diagnosis of VAP was considered when it was identified after 48 hours of mechanical ventilation. We analyzed demographics and clinical characteristics, surgical and CPB techniques, radiology and laboratory test results, ABG analysis, short-term outcomes, such as VAP, sepsis, length of mechanical ventilation, length of ICU stay and in-hospital mortality. ABG analysis was evaluated 30 minutes after HFOV was started using a blood gas analyzer (ABLTM 700 radiometer, Copenhagen, Denmark) and repeated every 4-6 hours or more often as needed. We elected to use OI ([FiO2 × mean airway pressure ×100] ÷ PaO2) to define the severity of PARDS. The severity of ARDS was defined as follows: mild 4 ≤ OI < 8, moderate 8 ≤ OI < 16 or 7.5, severe OI ≥ 16.1
Based on the improvement of the ABG in the pre-experiment, assuming the difference between the two independent populations was 15%, α=0.05, and β=0.2, the number of participants needed was 27 in each group. Assuming a 10% attrition rate, the total sample size was 60 (30 per group).
Data were analyzed using SPSS software version 25.0 for Windows (IBM SPSS Inc., Chicago, IL, USA). Independent continuous variables are presented as the mean ± standard deviation (SD) and were analyzed by t-tests. Counts and percentages describe the enumeration data. Means were compared using Student’s t test, and Fisher’s exact test was used for categorical data. The Mann–Whitney U test was applied for nonnormally distributed data. A two-sided P-value of <0.05 was regarded as statistically significant.