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13. Stetsko T, Bury K, Lubowiecka I. Safety and efficacy of a Ventralight ST echopsimplant for a laparoscopic ventral hernia repair - a prospective cohort study with a one-year follow-up. Polski przeglad chirurgiczny. 2016;88(1):7-14.
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CraTra Hagmm^a go pegaKmi' 21.10.2020
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https://doi.Org/10.26641/2307-0404.2021.3.241961
TREATMENT AND PROPHYLAXIS OF MODERATE AND SEVERE BRONCHOPULMONARY DYSPLASIA IN PREMATURE NEONATES
Dnipro State Medical University V. Vernadsky str., 9, Dnipro, 49044, Ukraine flmnpoecbKuu depwaemu Medmnuu yuieepcumem eyn. B. Вeрнадсbкого, 9, flmnpo, 49044, YKpaina e-mail: anna.bolonska@gmail.com
Цитування: Медичт перспективы. 2021. Т. 26, № 3. С. 84-93 Cited: Medicniperspektivi. 2021;26(3):84-93
Key words: bronchopulmonary dysplasia, premature, neonates, newborns, respiratory support, prophylaxis Ключовi слова: бронхолегенева дисплаз1я, недоношет, новонародженi, рестраторна тдтримка, профшактика
Ключевые слова: бронхолегочная дисплазия, недоношенные, новорожденные, респираторная поддержка, профилактика
Abstract. Treatment and prophylaxis of moderate and severe bronchopulmonary dysplasia in premature neonates. Bolonska A.V., Sorokina O.Yu. Bronchopulmonary dysplasia in premature neonates leads to physical and mental developmental disorders and behavioral problems and associated with frequent rehospitalizations and long hospital stay. Study objective: to study the predictors of bronchopulmonary dysplasia development in premature neonates in structure of intensive care. Study design: A retrospective cohort analysis was performed in 127 children recruited from two NICU of Dnipro between January 2016 to March 2020. Inclusion criteria: preterm neonates 28-32 gestation weeks with respiratory distress syndrome (RDS). Results demonstrated that every day of mechanical ventilation, supplemental oxygen with FiO2 more than 30% and cardiac drugs usage increased risk of bronchopulmonary dysplasia development by 15-20%. In conclusion, finding out predictors of bronchopulmonary dysplasia helps to improve and prudently use usual treatment regimens in premature neonates and decrease the frequency of moderate and severe bronchopulmonary dysplasia.
11. Patterson T, Cume P, Patterson S. Systematic review and meta-analysis of the post-operative adverse effects associated with mosquito net mesh in comparison to commercial hernia mesh for inguinal hernia repair in low income countries. Hernia. 2017;21(3):397-405. doi: https://doi.org/10.1007/s10029-017-1608-9
12. Salgaonkar H, Wijerathne S, Lomanto D. Managing complications in laparoscopic ventral hernia.
UDC 616.23/.24-007.21-053.3-08
A.V. Bolonska, O.Yu. Sorokina
Реферат. Лжування та профилактика середньотяжких та тяжких форм бронхолегеневоТ дисплазп в передчасно народжених новонароджених. Болонська А.В., Сорокша О.Ю. Розвиток бронхолегеневоi дисплазп в передчасно народжених новонароджених призводить до затримки неврологiчного та психомоторного розвитку, поведiнкових порушень та асоцтовано зi збшьшенням частоти повторних госпталгзацш та тривалого стацюнарного лкування. Метою цього до^дження стало визначення предикторiв розвитку середньотяжко'' та тяжко'' бронхолегенево'i дисплазп в структурi iнтенсивно'i терапп передчасно народжених новонароджених. У до^дження було включено 127 дiтей строком гестацп 28-32 тижнi з дiагнозом рестраторного дистрес синдрому з двох неонатальних вiддiлень м. Днтра в перюд з 2016 до 2020 р. Результати до^дження виявили, що тривалiсть знаходження на штучтй вентиляцп легень, дотацiя кисню вище 30% у вдихуванш сумiшi та використання кардiотропiв/вазопресорiв збтьшуе ризик розвитку бронхолегенево'1' дисплазп на 15-20% з кожним днем використання таких методiв терапп. Таким чином, виявлення цих факторiв ризику в структурi iнтенсивноi терапп недоношеностi дозволяе покращити та зважено провадити деяю тдходи в лжувант таких пацiентiв та зменшити частоту розвитку бронхолегенево '1' дисплазп середньотяжкого та тяжкого ступеня тяжкостi.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that leads to disability of premature infants. The incidence of severe forms of BPD in different countries ranges from 17% to 75%, as studies vary significantly depending on gestational age, birth weight, survival rate [3]. According to the current consensus on the treatment of RDS, the incidence of BPD in 2019 was 18% of all patients with RDS [8, 12, 14]. At the same time, it is quite difficult to know how many premature babies actually suffer from respiratory distress syndrome (RDS). Out of 8156 children from Europe, RDS was detected in 80% of children with a gestational age before 28 weeks.
The development of BPD is quite often associated with a high concentration of oxygen in the inhaled mixture, however, the use of devices that control the fluctuations of oxygen in the inhaled mixture did not show significant benefits [10]. Recent studies have focused on mitochondrial oxygen sensitivity and pulse signaling under hypoxia rather than hyperoxia. Incidentally, during oxygen fluctuations on the background of intermittent ventilation under positive pressure, the cells are triggered to exit from a hyperoxic non-hypoxic state in a hypoxia-like reaction, called "hyperoxic-hypoxic paradox" [16].
Considering early postnatal factors, the need for ventilation at birth and the duration of ventilation are among the most important [11]. Early extubation is a priority that determines the need to study all available methods of respiratory support when weaning a patient from a ventilator [29]. For example, extubation can be successful when the mean airway pressure (MAP) level is reduced to 78 cm H2O using traditional mechanical ventilation and at A P (pressure difference) at the level of 89 cm H2O on high-frequency mechanical ventilation. Spontaneous respiration tests can be used, however, their effectiveness is debatable [26]. Extubation with a transition to continuous positive airway pressure (CPAP) with a pressure of 7-9 cm H2O or on non-
invasive ventilation with pressure control (NIV PC) may increase the chances of success [7].
A retrospective analysis of infants from the National Institute of Child Health and Human Development (NICHD) has led to a proposal to modify the 2018 NICHD definition [6] to a severity scale of BPD that is based on the use of positive pressure at a 36 weeks' post-conceptual age instead of supplemental oxygen. Infants were classified as "no BPD (no support), grade 1 (nasal cannula <2 l/min), grade 2 (nasal cannula >2 l/min or non-invasive positive airway pressure), or grade 3 (invasive mechanical ventilation)". These criteria predicted death or serious respiratory morbidity at 18-26 months corrected age in 81% of infants in the study [6]. Attempts to avoid lung injury in extremely preterm infants have led to recommendations to avoid intubation and ventilation in the first minutes of life and a preference for non-invasive respiratory support [15, 17]. Besides nasal continuous positive airway pressure (NCPAP), nasal intermittent positive pressure ventilation (NIPPV) and high-flow nasal cannulae have become more popular, but the efficacy of these respiratory support methods in reducing the rates of BPD has been modest [19, 20, 21, 33].
NIPPV and NIV PC, these types of noninvasive ventilation are still being studied because there is no single approach to prescribing these types of respiratory support and there is insufficient data on their effects on comorbidities of prematurity [27]. Various studies have examined the impact of various circumstances associated with non-invasive ventilation, such as the interval between extubation and reintubation, on the development of bronchopulmonary dysplasia and mortality [29]. Even extensive reviews of noninvasive ventilation in terms of the impact of different techniques on the development of comorbidities in preterm infants do not give complete answers [17]. And the quality of prevention of reintubation and apnea does not correlate with the development and severity of BPD [18, 22]. The effect of non-invasive ventilation on delayed treatment outcomes and life is insufficient.
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There is evidence that adults with BPD in anamnesis vitae have decreased lung function which deteriorates rapidly. It leads to risk of chronic obstructive lung disease development or even death. Thus, the prophylaxis of BPD is one of the main priorities of health care and becomes actual because of potential role in chronic obstructive lung disease pathogenesis [1].
Patients with BPD are more sensitive to respiratory diseases and bronchospasm. Furthermore, BPD can be associated with other healthcare problems as low weight gain, developmental disorders, frequent primary care admissions and rehospita-lizations after discharge from NICU [2]. The children with BPD have diminished lung volumes which cause dramatic ventilation-perfusion mismatches even in simple colds [2].
Therefore, the problem of BPD is actual because of its potential role in pathogenesis of chronic lung disease and effective prophylaxis of BPD - one of the main priorities of medicine [1].
The aim of this work was to study the predictors of BPD development in premature neonates in structure of intensive care.
MATERIALS AND METHODS OF RESEARCH
Subjects (n=127) were recruited from two NICU of CE "Dnipropetrovsk Regional Clinical Children's Hospital of Dnipropetrovsk Regional Council" and CE "Dnipropetrovsk Regional Center of Perinatology of Dnipropetrovsk Regional Council" between January 2016 and March 2020. It was retrospective cohort study.
The research was conducted in accordance with the principles of bioethics set out in the WMA Declaration of Helsinki - "Ethical principles for medical research involving human subjects" and "Universal Declaration on Bioethics and Human Rights" (UNESCO).
In accordance to protocol No. 10 17.03.2021 of committee of bioethics of SE "DMA of Ministry of Health of Ukraine" the scientific study was recognized as meeting the generally accepted norms of morality, the requirements of observance of the rights, interests and personal dignity of research participants
All patients received basic treatment according to clinical protocol of treatment of neonates with respiratory disorders No. 484 21/08/2008.
Inclusion criteria were: gestational age 28-32 weeks, diagnosed RDS after delivery, the informed consent signed by parents/caregivers.
Exclusion criteria were: gestational age not less than 28 weeks and no more than 32 weeks, no need in respiratory support, the weight less than 750 g, verified IVH IV stage, congenital malformations which can independently influence respiratory effort.
127 subjects recruited for this study were divided into two groups according to respiratory support
features and priority method of non-invasive ventilation (NIV).
54 (42.5%) premature neonates who received triggered noinvasive ventilation with pressure control (NIV PC) during early or/and late neonatal period and restrictive infusion therapy in first week of life.
73 (57.5%) premature neonates who received continuous positive airway pressure ventilation (CPAP) during early or/and late neonatal period and traditional liberal infusion therapy in first week of life.
Patients were observed at different stages of treatment: on admission to the NICU (1st day of life), 3rd day of stay - relative stabilization of vital functions (IVH risk), 7th day - primary weaning from mechanical ventilation (MV) or NIV; 14th day - early complications of prematurity; 28th day - primary BPD suspicion; 56th day of life or on discharge from NICU or 36th week of gestation (diagnosis of BPD).
On primary examination of groups we took into account sex, gestation term (weeks), birth weight (g), length (cm), circumference of the head and thorax (cm). Primary assessment included ultrasound investigation protocol to exclude congenital malformations, as criteria of exclusion from the study, to find out such pathologies as IVH, to assess the hemodynamic significance of patent ductus arteriousus (PDA).
Clinical data dynamically analyzed: temperature (°C), breathing rate (per min), heart rate (per min), mean arterial pressure (MAP, mmHg), rate of consciousness according to modified Glasgow coma scale, blood saturation (SpO2, %), diuresis (ml/kg/hr), weight balance (g/day).
Effectiveness evaluation of respiratory support was available due to calculated figures as relation SpO2/FiO2 and oxygenation index (OI) [5] and laboratory tests of venous blood gases [4].
Statistics was performed with LibreOffice program and R (version 3.6.3) [24]. The Shapiro-Wilk test was used to assess normality type. Considering 75% of the data had nonnormal distribution, they were presented as median and 25 and 75 percentiles: Me [25%; 75%]. The comparison of qualitative parameters in independent groups was done with Pearson's chi-squared test (x2) without Yate's continuity correction. P values <0.05 were considered statistically significant.
Prior to performing the statistics of BPD groups to minimize risk of significant difference we used a method of standardization.
Moreover, the comparison of quantitative values in independent samplings by Kraskell-Wallis criterion was used to evaluate potential confounders of BPD.
To estimate discriminative ability of BPD severity predictors we conducted ROC-analysis (receiver operating characteristics) with calculation of area
under curve (AUC) with 95% CI. P values <0.05 were considered statistically significant [33].
RESULTS AND DUSCUSSION
The study data included 67 boys (52.8%) and 60 girls (47.2%) (p=0.27). The birth weight in general data was 1430.0 g [1205, 1765.0], body length was 40.0 cm [35.0; 42.0], gestational age was 30.0 weeks [29.0; 32.0]. There was no significant difference in sex distribution between neonates from NIV PC group: boys 31 (57.4%), girls 23 (42.5%) and in CPAP group: boys 36 (49.3%) and girls 37 (50.6%), p=0.16. Mediana of gestational age in NIV PC group and CPAP group was 31 week [30.0; 32.0] and 30 weeks [28.0; 31.0] respectively. In NIV PC group the mediana of birth weight of neonates was 1710 g [1350; 1900] and in CPAP group this parameter was 1300 g [995; 1485], respectively; body length in NIV PC group of premature neonates was 42 cm [40.2; 44] and in CPAP group body length was significantly less - 36 cm [34; 40.5] cm, p<0.01.
BPD was diagnosed in 48% of premature neonates at 36th week of postconceptual age (PCA) or on discharge from hospital. Mild BPD was verified in 29.1% of all studied infants. Moderate BPD was diagnosed in 11% of general data and in 7.9% of premature neonates severe BPD was diagnosed (Table 1).
The data of neonates of different sex, gestational age, birth weight and body length with verified BPD of all severity stages are represented in Table 1.
Gender structure of patients did not differ significantly in groups with various severity of BPD. But in severe BPD group boys prevailed: 70% in comparison to 30% girls (p=0.27).
There were no significant differences in birth weight, body length, gestational age between BPD severity groups. According to multiple regression model the role of anthropometric and demographic characteristics on BPD development was not defined.
In Table 1 the frequency of BPD development of various severity in premature neonates is presented for NIV PC and CPAP groups separately.
In CPAP group there were more patients without BPD (63,0%) in comparison to NIV PC group, where patients had no BPD in 37.0%, in NIV PC group mild and moderate BPD was recognized more often in 37% and 16,7% cases, respectively. And in CPAP group the frequency of mild BPD was 23.3%, moderate BPD - in 6.8% cases, p=0.03. Nevertheless, the frequency of severe BPD was the same in both group of the study - 5 cases in each group. It meant 9.3% of study population of NIV PC and 6.8% of CPAP group.
Table 1
Demographics of study groups depending on BPD severity
Parameter Study population (n=127) No BPD (n=66) Mild BPD (n=37) Moderate BPD (n=14) Severe BPD (n=10) P Fference
Boys (%) 67 (52.8) 31 (47.0) 23 (62.2) 6 (42.9) 7 (70.0) 0.27
Girls (%) 60 (47.2) 35 (53.0) 14 (37.8) 8 (57.1) 3 (30.0)
Group NIV PC 54 (42.5) 20 (30.3) 20 (54.1) 9 (64.3) 5 (50.0) 0.03
Group CPAP 73 (57.5) 46 (69.7) 17 (45.9) 5 (35.7) 5 (50.0)
Body length (cm) 40.0 [35.0;42.0] 39.5 [35.0;42.0] 40.0 [37.0;41.0] 41.0 [37.5;43.8] 40.0 [35.8;41.8] 0.72
Birth weight (g) 1430.0 [1205.0;1765.0] 1440.0 [1200.0;1807.5] 1350.0 [1240.0;1760.0] 1500.0 [1075.0;1730.0] 1375.0 [1270.0;1575.0] 0.91
GA (weeks) 30.0 [29.0;32.0] 30.0 [29.0;32.0] 30.0 [29.0;32.0] 30.0 [30.0;30.0] 30.0 [29.0;31.8] 0.96
Clinical characteristics of the patients depending on BPD verification are presented in Table 2.
Neonates of NIV PC group in 68.4% cases received MV on 1st day of hospital stay and in 29.8% cases still were intubated on 7th day of study. In CPAP group on 1st day 21.6% of infants were me-
chanically ventilated and on 7th day 25.7% patients still were on mechanical ventilation (MV) (p<0.01).
Subjects from NIV PC group received MV longer than those from CPAP group: 8 [4.5; 18] days and maximum 4,8 [0; 4.8] days respectively (p<0.01).
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After weaning from MV, patients from NIV PC group mainly were on triggered NIV PC and its duration was 8 [3.0; 15.0] days and it significantly differed from CPAP group. In CPAP group even if patients received triggered NIV PC its duration was only 2 [0.0; 6.0] days (pu<0.01). In patients from CPAP group respiratory support in CPAP regimen or bi-level
positive airway pressure (BiPAP) was performed and its duration was 5.5 [2; 11.8] days. In NIV PC group CPAP and BiPAP was not used (p<0.01).
We chose multiple risk factors from substantial polymorphism of intensive care approaches in premature neonates and statistically found significant factors (Table 2).
Table 2
Clinical characteristics of study groups depending on BPD verification and severity
Parameter All patients n=127 (%) No BPD n=66 (%) Mild BPD n=37 (%) Moderate BPD n=14 (%) Severe BPD n=10 (%)
Duration 4.0 0.0 6.0 7 22.5
of MV, days [0.0;9.0] [0.0;5.0] [1.0;11.0] [0.8;11.0] [20;41]
Duration 4 1.0 8.0 14 1.0
of NIV, days [0.0;11.0] [0.0;4.0] [4.0;16.0] |8.2:16| [0.0;13.5]
Suppl. O2, days 1.0 1.0 2.0 2.5 4.5
[0.0;4.0] [0.0;3.0] [0.0;5.0] [1.0;20.2] [1.5;8.2]
Cardiac drugs, days 0.0 0.0 2.0 3.5 3.5
[0.0;4.0] [0.0;2.0] [0.0;5.0] [0.0;4.8] |0.0;9.2|
Salbutamol No 64 (50.4) 55 (83.3) 4 (10.8) 0 (0.0) 5 (50.0)
usage
Yes 63 (49.6) 11 (16.7) 33 (89.2) 14 (100.0) 5 (50.0)
Inhaled corticosteroids No 62 (48.8) 54 (81.8) 3 (8.1) 0 (0.0) 5 (50.0)
Yes 65 (51.2) 12 (18.2) 34 (91.9) 14 (100.0) 5 (50.0)
Note. p<0.01 - the difference is statistically significant between groups.
The statistics was used to analyse the characteristics of respiratory support in infants with different severity of BPD. Among them: dexame-thasone for RDS prophylaxis in mothers, SpO2/FiO2 ratio and surfactant usage. Also additional factors of intensive care which influenced the respiratory support process were analysed: mean infusion intake, cardiac drugs usage, nebulizer therapy in all BPD groups.
It was estimated that patients' mothers in groups with BPD did not differ in frequency of dexa-methasone usage (p=0.23) for RDS prophylaxis. In group with mild BPD it was used in 45.9% of cases, in moderate BPD group - in 50% as well in severe BPD group. There was not found statistically significant difference in surfactant usage between groups (p=0.56). In mild BPD group it was used in 64.9%, in moderate BPD group and severe BPD group - in 71.4% and 70%, respectively.
In mild BPD group (1st day of life) SpO2/FiO2 ratio was 282.9 [155.0; 364.0] and did not significantly differ from moderate BPD and severe BPD group - 280,8 [183.8; 329.2] and 205.8 [162.6; 330.0] respectively (p=0.6). These numbers meant
that patients from all BPD groups had moderate RDS initially [5]. In comparison, premature neonates without BPD had SpO2/FiO2 ratio not significantly different from unhealthy ones - 265.7 [213.3; 352.0].
In severe BPD group the length of MV took 57.7% of time of respiratory support: 22.5 [20.0; 41.0] days, and in moderate BPD group - 7.0 [0.8; 11.0] days. This parameter differed significantly from no BPD group and mild BPD group: 0.0 [0.0; 5.0] days and 6.0 [1.0; 11.0] days, respectively (p<0.01).
MV correlated with the laboratory signs of inflammation during all period of examination, in particular, with the number of leukocytes on 1st, 5th and 7th day of intensive care (R=-0.258; p==0.006), CRP on 3rd, 5th and 7th day (R=0.347; p=0.001, R=0.395; p<0.001 and R=0.436; p<0.001, respectively), the level of platelets on 5th, 7th, 14th day of intensive care (R=-0.368; p<0.001, R=0.450; p<0.001 and R=-0.333; p<0.001, respectively).
In patients with severe BPD the duration of NIV was only 4.5% of the total respiratory support
period - 1 day [0.0; 13.5]. In moderate BPD group patients received NIV significantly longer than in mild BPD group, in fact, by 1.8 times - 14.0 days [8.2; 16.0], p<0.01.
The usage of supplemental oxygen meant gaseous-air mixture, FiO2>30%. In group without BPD duration of supplemental oxygen usage was 1.0 [0.0;3.0] days and significantly differed from groups with BPD (p<0.01). In mild BPD group the supplemental oxygen was used for 2.0 days [0.0; 5.0]. In moderate and severe BPD groups this parameter increased significantly: 2.5 days [1.0; 20.2] and 4.5 days [1.5; 8.2], respectively.
Mean infusion intake during the first 7 days of life in BPD groups did not differ significantly (p=0.08). But in group without BPD the level of intake was 111.8 [69.4; 117.6] ml/kg/day being by 17.2% higher than in moderate BPD group - 65.0
[52.2; 109.8] ml/kg/day. In group with severe BPD it was 93.3 [50.0; 112.7] ml/kg/day. As well as everyday intake in mild BPD - 89.6 [60.0; 113.2] ml/kg/day.
The prescription of cardiac drugs was dependent on the hemodynamic stability (mean arterial pressure) and cardiac index to support normal level of cerebral autoregulation [30]. We estimated that in groups with moderate BPD cardiac drugs were used for 3.5 days [0.0; 4.8], and in group with severe BPD - 3.5 days [0.0; 9.2], p<0.01.
According to primary statistics in patients from moderate BPD group the nebulizer therapy was the longest and took 53.0 days [30.8; 68.2]. It was by 2.1 times longer than in group without BPD.
We performed univariate logistic regression analysis with the calculation of the odds ratio (OR) to determine the ability of clinical characteristics of patients to predict moderate and severe BPD (Table 3).
Table 3
Predictors of moderate and severe BPD development
Predictor
OR (95% CI)
AUC (95% CI)
Duration of MV, days
Duration of NIV, days
Supplemental O2, days
Cardiac drugs, days
Salbutamol usage
1.07 (1.03-1.12) 1.07 (1.02-1.12) 1.10 (1.04-1.17) 1.22 (1.08-1.40) 5.10 (1.88-16.33)
<0.01
0.01
<0.01
<0.01
<0.01
0.74 (0.62-0.86) 0.64 (0.5-0.78) 0.70 (0.58-0.82) 0.65 (0.52-0.78) 0.68 (0.59-0.78)
IC usage
MV+ suppl. Oxygen
4.71 (1.74-15.08) 1.06 (1.03-1.11) 1.09 (1.03-1.17)
<0.01 <0.01 <0.01
0.67 (0.58-0.77) 0.78 (0.66-0.89)
The discriminate characteristics of predictors according to ROC-curves did not differ significantly, although the largest area under the curve was estimated for length of MV (AUC - 0.74 [CI 0.62-0.86]), supplemental O2 usage (AUC -0.70 [CI 0.58-0.92]), p<0.01.
Performing ROC-analysis we did not receive significant odd ratios for sex (p=0.88), group of study (NIV PC or CPAP) (p=0.09), birth weight (p=0.77), and gestational age (p=0.8). That is why we demonstrate the AUC only for discriminative signs which had OR with significant p<0.05.
Therefore, patients with moderate and severe BPD were on MV or received supplemental oxygen (Fi02>30%) significantly for longer period. So, every next day on MV or/and supplemental oxygen (Fi02>30%) leads to increased likelihood of BPD development by 15% (p=0.01), AUC=0.78 [CI 0.660.89]. The prolongation of MV for 1 day increases the risk of moderate and severe BPD development by 7%, AUC=0.74 (95% CI 0.62-0.86), p<0.01. Every day of cardiac drugs usage increases risk of BPD development by 22%. (p=0.01, AUC=0.65 [95% CI 0.52-0.77]).
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It was determined that every day of broncho-dilators and inhaled corticoids usage increased the risk of severe and moderate BPD development by 3%, AUC=0.70 (95% CI 0.56-0.84) i AUC=0.69 (95% CI 0.55-0.84), respectively. The salbutamol usage increases odd ratio of moderate and severe BPD by 5.1 times, AUC=0.68 (95% CI 0.59-0.78), fluticazone or budesonide usage - by 4.7 times, AUC=0.67 (95% CI 0.58-0.77). So, the prescription of these drugs correlates with the severity of BPD in premature neonates.
Therefore, according to our results, the significant predictors of BPD development were the duration of mechanical ventilation, that of triggered no-invasive ventilation, prolonged cardiac drugs usage, prolonged supplemental 02 usage and need for salbutamol and inhaled corticoids prescription.
CONCLUSIONS
1. Mothers of premature infants, who then developed severe forms of BPD, were 1.3 times less likely to receive dexamethasone for the prevention of RDS (50%) compared with the group without BPD (65.6%). In patients with severe BPD, the frequency of use of exogenous surfactant (71.4%) did not differ in comparison to children with mild BPD and without it (70.0%), p=0.56.
2. In patients with severe BPD, the duration of mechanical ventilation was 57.7% of the time of all
respiratory support, in moderate and mild BPD - 1.9 and 2.2 times less (p<0.01). In the group with severe BPD, the usage of Fi02>30% was probably by 1.8 times longer. An increase in the duration of mechanical ventilation for 1 day increases the chance of development of moderate/severe BPD by 7%, AUC=0.74 (95% CI 0.62-0.86), p<0.01. The prolonged non-invasive pressure control ventilation also increases the chance of development of moderate/severe BPD by 7% with every day usage, AUC=0.64 (95% CI 0.5-0.78).
3. In groups with moderate and severe broncho-pulmonary dysplasia vasopressor support lasted for 3.5 days [0.0; 4.8] and 3.5 days [0.0; 9.2], respectively (p<0.01). It was determined that each subsequent day of vasopressor support probably increased the risk of moderate/severe BPD by 22% (p=0.01, AUC=0.65, 95% CI 0.52-0.77).
4. In patients from moderate BPD group the nebulizer therapy was the longest, being 53.0 days [30.8; 68.2]. It was by 2.1 times longer than in group without BPD. The need of salbutamol presciption increases odd ratio of moderate and severe BPD by 5.1 times, AUC=0.68 (95% CI 0.59-0.78), inhaled corticoids usage - by 4.7 times, AUC=0.67 (95% CI 0.58-0.77).
Conflict of interests. The authors declare no conflict of interest.
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3. Baud O, Laughon M, Lehert P. Survival without Bronchopulmonary Dysplasia of Extremely Preterm Infants: A Predictive Model at Birth. Neonatology. 2021;18:1-9. doi: https://doi.org/10.1159/000515898
4. Bijapur MB, Kudligi NA, Asma S. Central Venous Blood Gas Analysis: An Alternative to Arterial Blood Gas Analysis for pH, PCO2, Bicarbonate, Sodium, Potassium and Chloride in the Intensive Care Unit Patients. Indian J Crit Care Med. 2019 Jun;23(6):258-62. PMID: 31435143; PMCID: PMC6698350.
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8. Cokyaman T, Kavuncuoglu S. Bronchopulmonary dysplasia frequency and risk factors in very low birth weight infants: A 3-year retrospective study. North Clin Istanb. 2019 Aug 9;7(2):124-30. PMID: 32259033; PMCID: PMC7117633.
doi: https://doi.org/10.14744/nci.2019.23427
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loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants. Arch Dis Child Fetal Neonatal Ed.; 2018.
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15. Gharehbaghi MM, Hosseini MB, Eivazi G, Yas-rebinia S. Comparing the Efficacy of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Positive Pressure Ventilation in Early Management of Respiratory Distress Syndrome in Preterm Infants. Oman Med J. 2019;34(2):99-104.
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16. Hadanny A, Efrati S. The Hyperoxic-Hypoxic Paradox. Biomolecules. 2020;10(6):958.
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18. Jain D, Bancalari E. New Developments in Respiratory Support for Preterm Infants. Am J Perinatol. 2019;36(S 02):S13-7.
doi: https://doi.org/10.1055/s-0039-1691817
19. Lemyre B, Davis PG, De Paoli AG, Kirpalani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2017;2(2):CD003212. doi: https://doi.org/10.1002/14651858.CD003212.pub3
20. Lemyre B, Laughon M, Bose C, Davis PG. Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev. 2016;12(12):CD005384.
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21. Manley BJ, Dold SK, Davis PG, Roehr CC. High-flow nasal cannulae for respiratory support of preterm infants: a review of the evidence. Neonatology. 2012;102(4):300-8.
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22. Zhu XW, Shi Y, Shi LP, et al. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multicenter prospective randomized controlled trial. Trials. 2018;19(1):319. Published 2018 Jun 14.
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23. Schmölzer GM, Kumar M, Pichler G, Aziz K, O'Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: systematic review and meta-analysis [published correction appears in BMJ. 2014;348:g58]. BMJ. 2013;347:f5980. Published 2013 Oct 17.
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26. Shalish W, Latremouille S, Papenburg J, Sant'An-na GM. Predictors of extubation readiness in preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2019;104(1):F89-F97. doi: https://doi.org/10.1136/archdischild-2017-313878
27. Shehadeh AMH. Non-invasive respiratory support for preterm infants following extubation from mechanical ventilation. A narrative review and guideline suggestion. Pediatr Neonatol. 2020;61(2):142-7. doi: https://doi.org/10.1016Zj.pedneo.2019.09.014
28. Jensen EA, Dysart K, Gantz MG, et al. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach. Am J Respir Crit Care Med. 2019;200(6):751-9.
doi: https://doi.org/10.1164/rccm.201812-2348OC
29. Shalish W, Kanbar L, Kovacs L, et al. The Impact of Time Interval between Extubation and Reintubation on Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants. J Pediatr. 2019;205:70-76.e2. doi: https://doi.org/10.1016/jjpeds.2018.09.062
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33. Wilkinson D, Andersen C, O'Donnell CP, De Paoli AG. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2011;(5):CD006405. Published 2011 May 11.
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СПИСОК Л1ТЕРАТУРИ
1. Добрянський Д. О., Меньшикова А. О., Бори-сюк О. П. Ввддалеш наслвдки бронхолегенево1 дис-плазп у недоношених немовлят. Сучасна пед1атр1я. 2019. № 4. С. 43-52.
DOI: https://doi.org/10.15574/SP.2019.100.43
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3. Baud O., Laughon M., Lehert P. Survival without Bronchopulmonary Dysplasia of Extremely Preterm Infants: A Predictive Model at Birth. Neonatology, 2021. No. 18. P. 1-9. DOI: https://doi.org/10.1159/000515898
4. Bijapur M. B., Kudligi N. A., Asma S. Central Venous Blood Gas Analysis: An Alternative to Arterial Blood G as Analysis for pH, PCO2, Bicarbonate, Sodium, Potassium and Chloride in the Intensive Care Unit Patients. Indian J Crit Care Med. 2019. Jun. (Vol. 23, No. 6). P. 258262. PMID: 31435143; PMCID: PMC6698350.
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5. Bilan N., Dastranji A., Ghalehgolab Behbahani A. Comparison of the Spo2/Fio2 ratio and the Pao2/Fio2 ratio in patients with acute lung injury or acute respiratory distress syndrome. J Cardiovasc Thorac Res. 2015. Vol. 7, No. 1. P. 28-31.
DOI: https://doi.org/10.15171/jcvtr.2014.06
6. Bronchopulmonary Dysplasia: Executive Summary of a Workshop / R. D. Higgins et al. J Pediatr. 2018. Vol. 197. P. 300-308.
DOI: https://doi.org/10.1016/jjpeds.2018.01.043
7. Buzzella B., Claure N., D'Ugard C., Bancalari E. A randomized controlled trial of two nasal continuous positive airway pressure levels after extubation in preterm infants. J. Pediatr. 2014. Vol. 164, No. 1. P. 46-51. DOI: https://doi.org/10.1016/jjpeds.2013.08.040
8. Cokyaman T., Kavuncuoglu S. Bronchopulmonary dysplasia frequency and risk factors in very low birth weight infants: A 3-year retrospective study. North Clin Istanb. 2019. 9 Aug. (Vol. 7, No. 2). P. 124-130. PMID: 32259033; PMCID: PMC7117633.
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9. DeLong E. R., DeLong D. M., Clarke-Pearson. D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988. Vol. 44, No. 3. P. 837-845. DOI: https://doi.org/10.2307/2531595
10. Effects of a new device for automated closed loop control of inspired oxygen concentration on fluctuations of arterial and different regional organ tissue oxygen saturations in preterm infants / M. Gajdos et al. Arch Dis Child Fetal Neonatal Ed. 2018. Vol. 104, No. 4. DOI: https://doi.org/10.1136/archdischild-2018-314769
11. Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants / E. A. Jensen et
al. JAMA Pediatr. 2015. Vol. 169, No. 11. P. 1011-1017. DOI: https://doi.org/10.1001/jamapediatrics.2015.2401
12. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update / D. G. Sweet et al. Neonatology. 2019. Vol. 115, No. 4. P. 432-450.
DOI: https://doi.org/10.1159/000499361
13. Firke S. janitor: Simple Tools for Examining and Cleaning Dirty Data [Internet]. 2020. Available from: https://CRAN.R-proj ect.org/package=j anitor
14. Ga Won Jeon. Changes in the Incidence of Bron-chopulmonary Dysplasia among Preterm Infants in a Single Center over 10 Years. Neonatal Medicine 2020. Vol. 27, No. 1. P. 1-7.
DOI: https://doi.org/10.5385/nm.2020.27.L1.
15. Gharehbaghi M. M., Hosseini M. B., Eivazi G., Yasrebinia S. Comparing the Efficacy of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Positive Pressure Ventilation in Early Management of Respiratory Distress Syndrome in Preterm Infants. Oman Med J., 2019. Vol. 34, No. 2. P. 99-104. DOI: https://doi.org/10.5001/omj.2019.20
16. Hadanny A., Efrati S. The Hyperoxic-Hypoxic Paradox. Biomolecules. 2020. Vol. 10, No. 6. P. 958. DOI: https://doi.org/10.3390/biom10060958
17. Hussain W. A., Marks J. D. Approaches to No-ninvasive Respiratory Support in Preterm Infants: From CPAP to NAVA. Neoreviews. 2019. Vol. 20, No. 4. P. 213-221. DOI: https://doi.org/10.1542/neo.20-4-e213
18. Jain D., Bancalari E. New Developments in Respiratory Support for Preterm Infants. Am J Perinatol. 2019. Vol. 36, S.02. P. S13-S17.
DOI: https://doi.org/10.1055/s-0039-1691817
19. Lemyre B., Davis P. G., De Paoli A. G., Kirpa-lani H. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev. 2017. Vol. 2, No. 2. P. CD003212. Published 2017 Feb 1. DOI: https://doi.org/10.1002/14651858.CD003212.pub3
20. Lemyre B., Laughon M., Bose C., Davis P. G. Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev. 2016. Vol. 12, No. 12. P. CD005384. Published 2016 Dec 15.
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21. Manley B. J., Dold S. K., Davis P. G., Roehr C. C. High-flow nasal cannulae for respiratory support of preterm infants: a review of the evidence. Neonatology. 2012. Vol. 102, No. 4. P. 300-308.
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22. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multi-center prospective randomized controlled trial / X. W. Zhu et al. Trials.
2018. Vol. 19, No. 1. P. 319. Published 2018 Jun 14. DOI: https://doi.org/10.1186/s13063-018-2673-9
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24. R Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing; 2020. Available from: https://www.R-project.org/
25. Shalabh G., Sunil S. 1,2 Non-invasive Ventilation in Premature Infants: Based on Evidence or Habit. J Clin Neonatol. 2013. Vol. 2, No. 4. P. 155159. DOI: https://doi.org/10.4103/2249-4847.123082
26. Shalish W., Latremouille S., Papenburg J., Sant'Anna G. M. Predictors of extubation readiness in preterm infants: a systematic review and metaanalysis. Arch Dis Child Fetal Neonatal Ed. 2019. Vol. 104, No. 1. P. F89-F97.
DOI: https://doi.org/10.1136/archdischild-2017-313878
27. Shehadeh A. M. H. Non-invasive respiratory support for preterm infants following extubation from mechanical ventilation. A narrative review and guideline suggestion. Pediatr Neonatol. 2020. Vol. 61, No. 2. P. 142-147.
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28. The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach / E. A. Jensen et al. Am J Respir Crit Care Med. 2019. Vol. 200, No. 6. P. 751-759.
DOI: https://doi.org/10.1164/rccm.201812-2348OC
29. The Impact of Time Interval between Extubation and Reintubation on Death or Bronchopulmonary Dys-plasia in Extremely Preterm Infants. / W. Shalish et al. J Pediatr. 2019. Vol. 205. P. 70-76.e2.
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30. The ontogeny of cerebrovascular pressure autoregulation in premature infants / C. Rhee et al. J Perinatol. 2014. Vol. 34. P. 926-931
DOI: https://doi.org/10.1038/jp.2014.122
31. Thekkeveedu R., Guaman M. C., Shivanna B. Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology. Respir Med. 2017. Nov. (Vol. 132). P. 170-177. Epub 2017 Oct 24. PMID: 29229093; PMCID: PMC5729938.
DOI: https://doi.org/10.1016/j.rmed.2017.10.014
32. Wickham H. ggplot2: Elegant Graphics for Data Analysis [Internet]. Springer-Verlag New York, 2016. Available from: https://ggplot2.tidyverse.org
33. Wilkinson D., Andersen C., O'Donnell C. P., De Paoli A. G. High flow nasal cannula for respiratory support in preterm infants. Cochrane Database Syst Rev. 2011. Vol. 5. P. CD006405. Published 2011 May 11. DOI: https://doi.org/10.1002/14651858.CD006405.pub2
Crana Haginm^a go pegaKmï 19.10.2020
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