Study on the value of minimally invasive high-dose pulmonary surfactant at different depths in the treatment of respiratory distress syndrome in premature infants

 There is a gradual increase in the number of elderly pregnant women with second child and test-tube assisted pregnancy, and the birth rate of premature infants is gradually rising. Affected by the development of lung function of premature infants, the incidence of respiratory distress syndrome in premature infants has gradually increased and the mortality rate is high [1]. Insufficient pulmonary surfactant (PS) is the main cause of this disease, which requires combined TREATMENT with PS on the basis of supplementary ventilation to promote the development of lung function and improve the status of lung function [2]. The conventional PS administration method was tracheal intubation, use of pulmonary surfactant, extubation and continuous positive respiratory pressure ventilation (INSURE). However, spontaneous apnea during PS administration may increase the frequency of pulmonary function injury and invasive ventilator use. Minimally invasive PS administration can ensure stable respiratory function of children during treatment, but drug reflux and airway blockage may occur during high-dose PS administration. Therefore, at present, minimally invasive PS administration is mostly low-dose, but it is difficult to meet clinical treatment needs [3]. In order to ensure the administration effect and avoid adverse drug reactions, it is considered to use a large dose of fractional administration to meet the therapeutic effect, but there are few studies on minimally invasive PS administration at different depths. Therefore, qinzhou Maternal and Child Health Hospital was selected in 2020

From March to April 2021, 60 infants with respiratory distress syndrome in premature infants were selected as the study subjects to explore the clinical value of minimally invasive PS administration at different depths.

1. Data and methods

1.1 General Data a total of 60 children with respiratory distress syndrome of premature infants in our hospital from March 2020 to April 2021 were selected as the research subjects, and they were divided into control group and observation group by random number table method, with 30 cases in each group. Inclusion criteria :(1) all met the diagnostic criteria for respiratory distress syndrome in premature infants [4]; (2) No serious congenital disease; (3) pregnant women have not used glucocorticoid therapy; (4) The hemodynamics of the children was stable. Exclusion criteria :(1) complicated with severe respiratory and circulatory disorders and requiring continuous mechanical ventilation; (2) Endotracheal intubation immediately after birth; (3) Endotracheal intubation assisted ventilation time ≥6 h after PS treatment; (4) Withdrawal during the study. The study was approved by the hospital's ethics committee. Parents gave informed consent to the study.

1.2 Method PS (commodity name: Guersu, manufacturer: Italian Casi Pharmaceutical Co., LTD., Approval No. : Registration No. H20080429, specification: 1.5ml: 120 mg) dosage standard is 200 mg/kg; The drug was preheated before administration, and all drugs were extracted with a 5 mL sterile syringe for reserve use. Clear airway before administration to keep airway unobstructed. Control group (conventional administration of pulmonary surfactant) : In supine position, direct laryngoscope was used to expose the glottis, and the tracheal catheter was inserted. After the position of the catheter was determined (the insertion depth was just to the lower opening of the tracheal intubation), the catheter was fixed to the upper lip of the child with adhesive tape, positive pressure ventilation was connected to the resuscitation capsule, and the syringe with extracted drugs was connected to the 5.5 scalp needle and inserted into the tracheal intubation at 30° ~ 40°. Continue to insert the needle along the endotracheal intubation until the needle is 2/3 or completely entered, and slowly push the PS injection, while positive pressure ventilation of the recovery capsule was given. After the drug administration, positive pressure ventilation of the resuscitation capsule was performed for 5 min. The tracheal tube was removed and the nasal continuous positive airway pressure (nCPAP) assisted ventilation was re-administered. The observation group was treated with minimally invasive PS administration at different depths: 6FG gastric tube was used for administration. The children were kept in the supine position under nCPAP non-invasive assisted ventilation. The front end of the gastric tube with lateral holes was cut off 4 cm with sterile scissors, and the gastric tube was connected to the syringe that absorbed surfactant from pig lung. The glottis was exposed by direct laryngoscopy. Magill forceps were used to insert the gastric tube into the glottis to confirm the intubation depth (the insertion depth was just to the lower mouth of the endotracheal intubation + 1.5cm), and the upper lip was fixed. The laryngoscopy was removed and the mouth was kept closed to ensure that nCPAP positive end-expiratory pressure was maintained at or above 6 cmH2O. The syringe that had been extracted was connected to the end of the gastric tube, and half of the DOSE of PS (100 mg/kg) was slowly injected within 1 min. When part of the gastric tube was withdrawn outward so that the depth was at the lower opening of the endotracheal tube, the remaining half of the dose of PS was slowly injected within 1 min in the left decubed position of 45°. Use a syringe to push 1 mL of air into the gastric tube to ensure complete injection of medication into the trachea. After drug injection, the gastric tube was removed and nCPAP non-invasive ventilation continued. After medication, if inhaled oxygen concentration fraction (FiO2) & GT; If there is no obvious relief or continuous aggravation of symptoms at 0.5, or frequent apnea, or blood oxygen saturation cannot be maintained above 88%, the drug should be given twice at an interval of 6-12 h with the same dose.

1.3 Indicators and Evaluation Criteria (1) The respiratory function before and 1 and 12 h after administration was compared between the two groups, including FiO2 and positive end expiratory pressure (PEEP); (2) The incidence of complications, including decreased oxygen saturation, drug regurgitation, bradycardia, intracranial hemorrhage, pneumothorax and bronchial dysplasia, was compared between the two groups at 28 days after birth. (3) The mortality rates during 28 days after birth were compared between the two groups; (4) The prognosis of the two groups was compared, including the proportion of above grade ⅱ (bronchial aeration sign, background was diffuse atrescent alveoli, visible aerated dendrite bronchial shadow) on chest radiographs 12 h after medication, the proportion of secondary use of pulmonary surface active substances, and invasive mechanical ventilation within 72 h; (5) The rehabilitation indexes of the two groups were compared, including oxygen use time, length of stay and hospitalization cost.

1.4 Statistical Processing The data were analyzed by SPSS 24.0. The measurement and counting data were expressed by (x±s) and rate (%), and t and χ2 tests were used. When P< 0.05, the difference between groups was statistically significant.

2 the results

2.1 Comparison of general data between the two groups The general data between the two groups were similar, and the difference was not statistically significant (P> 0.05), are comparable, as shown in Table 1.

2.2 Comparison of respiratory function between the two groups before and 1 and 12 h after administration

Before medication, there was no significant difference in PEEP and FiO2 levels between the two groups (P> 0.05); At 1 and 12 h after administration, PEEP and FiO2 levels in the observation group were lower than those in the control group (P< 0.05). Are shown in table 2.

2.3 Comparison of complication rate and mortality between the two groups The complication rate in the observation group was 13.33%, which was lower than that in the control group (χ2=5.455, P=0.020). There was no significant difference in mortality between the observation group and the control group (χ2=1.017, P=0.313). See table 3.

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2.4 Comparison of prognosis between the two groups The proportions of grade ⅱ or above on chest X-ray, secondary use of lung surfactant and invasive mechanical ventilation within 72 h in the observation group were 13.33%, 3.33% and 3.33%, respectively, which were lower than 36.67%, 26.67% and 20.00% in the control group (P< 0.05), see Table 4.

2.5 Comparison of rehabilitation indexes between the two groups The duration of oxygen use and hospitalization in the observation group were shorter than those in the control group, and the hospitalization cost was lower than that in the control group (P< 0.05), see Table 5.

3 discuss

PS is a lipoprotein secreted by alveolar type ⅱ epithelial cells, distributed on the surface of the molecular layer of alveolar fluid, which can reduce alveolar surface tension, reduce aspiration resistance, and prevent lung atrophy and atelectasis [5-6]. In the treatment of infants with respiratory distress syndrome of premature infants, the application of mechanical ventilation for assisted respiration and PS at the same time can improve their autonomous ventilation ability, promote the recovery of their lung function, shorten their recovery time and improve their prognosis [7-8].

INSURE main treatment for preterm infant respiratory distress syndrome, but due to the need to endotracheal intubation during treatment and positive pressure ventilation, influenced the stability of the children with respiratory function, influence children with spontaneous breathing synchronicity with breathing machine movement, increase with immature lung tissue and respiratory tract mucosa damage, increase the risk of bronchial pulmonary dysplasia occurs late [9]. Minimally invasive PS administration can be completed under the condition of continuous ventilation for children. Compared with INSURE, it can avoid affecting the children's respiratory rhythm, keep their respiratory rate stable, and reduce their lung function injury [10-11]. But during minimally invasive PS dosing, small dose of PS and reliable noninvasive ventilator pressure and spontaneous breathing will drugs into the airway, but when large doses, the faint, noninvasive ventilator pressure drugs into the airway is difficult, and easy to induce airway blocking, drug reflux, apnea, affect drug quality, influence children with independent ventilation recovery ability [12]; At the same time, a large dose of PS injected by microtubules at the same depth may induce complications such as decreased blood oxygen saturation, intracranial hemorrhage, and periventricular white matter softening [13]. Low-dose administration can reduce the risk of drug reflux and airway blockage, but it is difficult to meet the clinical treatment needs of PS in low-dose administration [14].

The main purpose of minimally invasive PS administration at different depths is to ensure patency of left bronchus during administration and avoid complete airway blockage by applying a half-dose of drug in right bronchus at the first depth. Second dose, will use the normal endotracheal intubation depth, the PS to dose for the general dosage, belongs to the small dose of medication, to improve drug safety, ensure children during drug therapy in airway unobstructed condition, avoid airway jams slow heart beat (bradycardia) and ery low blood oxygen desaturation, etc., at the same time ensures the PS total dose, meet the demand of drug dose, Promote the recovery of lung function in children [15-16].

In this study, the observation group with the implementation of minimally invasive depth of different points in time PS medication, compared with the conventional drug delivery way, 1, 12 h after the treatment PEEP, FiO2 were significantly lower than the control group, consider the reasons for, children with respiratory dysfunction, there will be a fast shallow breathing and lung ventilation capacity, oxygen desaturation fall; Minimally invasive PS administration at different depths can help children receive PS treatment in a stable state of respiratory movement. Moreover, PS administration at different depths can meet the dosage of PS without affecting the lung ventilation ability of children, and help children to stabilize their lung function and achieve the effect of reducing PEEP and FiO2 [17]. The results showed that the complication rate of observation group was lower than those of control group, the mortality was similar to control, consider the reasons for, the application of minimally invasive depth of different points in time PS medication, can avoid a single large dose and the impact on children with ventilation capacity, reduce airway blockage caused by complications, and with the air quality improved, It can further reduce the incidence of intracranial hemorrhage and periventricular white matter malacia and reduce the incidence of complications. However, there was no difference in mortality between the two groups in this study, which may be related to the small number of cases [14,18]. Research results found that observation group after 12 h chest radiograph Ⅱ magnitude, secondary use lung surface active substance and 72 h has a mechanical ventilation accounts for less than than the control group, and recovery index were superior to control group, consider the reasons for, in the observation group of patients during treatment, lung function can maintain its stability, promote lung function in children with developmental, children improve lung function, Reducing the number of PS treatments, shortening the duration of mechanical ventilation and hospitalization can improve the prognosis [19].

In conclusion, in the treatment of respiratory distress syndrome in premature infants, the application of minimally invasive PS administration with different depths can improve the children's respiratory function, reduce the incidence of complications, shorten the rehabilitation time and reduce the frequency of the use of secondary pulmonary surfactant, which has a significant effect compared with the application of INSURE.