Lung recruitment with high frequency ventilation versus volume targeted ventilation in preterm infants with respiratory distress syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Lung recruitment with high frequency ventilation versus volume targeted ventilation in preterm infants with respiratory distress syndrome Marwa Eldegwi, Ali Shaltout, Osama Elagamy, Dina Salama, Mohammed Elshaer, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4243658/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Respiratory distress syndrome (RDS) is one of the most common causes of premature infant respiratory failure. Recently, many techniques for optimizing fetal-neonatal transition and promoting lung recruitment have been accessible. To compare the effect of lung recruitment using high frequency ventilation versus volume targeted ventilation on duration of intubation as well as its effect on lung inflammation in preterm infants with respiratory distress syndrome. Forty preterm infants with RDS were randomly assigned to Group A (LRM with HFOV, n=20) or Group B (LRM with VTV/AC, n=20). TGF-β1 levels measured in BAL samples at two time points. Both groups showed no significant difference in rate of prematurity complications nor delta change of TFG- β 1 level in tracheal aspirate of those preterm infants measured before lung recruitment and five days after recruitment or at extubation. Conclusions: Lung recruitment maneuver was not associated with significant difference between both groups of preterm infants. The results obtained from our study, being the first of its kind to compare the effect of lung recruitment, provide a promising research area for further investigations. Respiratory Distress Syndrome Intensive Care Units Neonatal Bronchoalveolar Lavage. What is Known Respiratory distress syndrome (RDS) is a common cause of premature infant respiratory failure, and various techniques are available to optimize fetal-neonatal transition. What is new : Despite the lack of significant differences between the two ventilation techniques, the variation in ventilatory parameters over the study period warrants further research. Introduction Respiratory distress syndrome (RDS) is one of the most common causes of premature infant respiratory failure. Despite better neonatal care, many infants with RDS require intubation, mechanical ventilation, and exogenous surfactant treatment to restore lung function and gas exchange [ 1 ]. Mechanical ventilation, on the other hand, can harm the developing lung and is a major risk factor for developing bronchopulmonary dysplasia (BPD)[ 2 ]. An optimal management strategy should begin at birth, with the goal of achieving an early functional residual capacity and maintaining a sufficient lung volume. Recently, many techniques for optimizing fetal-neonatal transition and promoting lung recruitment have been accessible [ 3 ]. In preterm infants with RDS, high-frequency ventilation (HFV) is a common lung-protective ventilation mode [ 4 ]. In preterm infants with severe RDS, initial ventilation using high frequency oscillatory ventilation (HFOV) lowers the incidence of death and BPD and improves long-term neurodevelopmental outcomes [ 5 ]. During HFV, the open lung strategy has become standard therapy, with gradual rise in continuous distending pressure (CDP) used to lessen the requirement for fraction of inspired oxygen (FiO 2 ) via target oxygen saturation (SpO 2 ) monitoring [ 4 ]. The "open lung" approach also applies to volume-targeted ventilation, which benefits from an equitable distribution of tidal volume throughout the lungs [ 6 ]. When compared to non-recruitment, early lung recruitment maneuver (LRM) in preterm infants with RDS resulted in quicker accomplishment of reduced FiO 2 and shorter oxygen dependency [ 7 ]. These findings imply that adding the open lung concept to volume-targeted ventilation in preterm infants with RDS is a reasonable approach [ 8 ]. Inflammatory markers in bronchoalveolar lavage (BAL) have been extensively employed to assess early lung injury in ventilated preterm newborns and the subsequent progression to BPD [ 9 ]. Human Transforming Growth Factor- β 1 (TGF- β 1) is a type of cytokine that is produced by lung epithelial cells and vascular endothelial cells. TGF- β 1 increases the synthesis and deposition of extracellular matrix during the wound healing process, which aids in wound repair. TGF- β 1 production is transitory in normal tissues, but repeated lung injury culminates in overexpression. As a result, it has been employed as a fibrosis and remodeling marker [ 10 ]. TGF- β 1 levels were observed to be elevated in BAL samples from premature neonates who later had chronic lung illness. TGF- β 1 tracheal aspirate was considerably lower in high frequency ventilation (HFOV) compared to conventional breathing, indicating less lung inflammatory damage. These findings suggested that HFOV, rather than Continuous Mandatory Ventilation (CMV), may play a lung protective role [ 11 ]. Therefore, this study was designed to compare the effect of lung recruitment using high frequency ventilation versus volume targeted ventilation (VTV) on duration of intubation as well as its effect on lung inflammation in preterm infants with respiratory distress syndrome as measured by TGF- β 1 level in samples of bronchoalveolar lavage from infants studied. Methods The study was conducted on a total of 40 preterm infants, 34 weeks gestational age or less, having RDS that needed intubation and mechanical ventilation within the first 72 hours after their birth at the Neonatal Intensive Care Unit (NICU) of Mansoura University Children's Hospital during the period from July 2020 to July 2022. Infants included were randomly assigned into two groups, Group A who were subjected to LRM using HFOV (20 cases) and Group B who were subjected to LRM using VTV/AC (20 cases). Preterm infants who met the eligibility criteria were randomly assigned into one of two groups (Group A & Group B) with allocation ratio 1:1 using sealed envelopes: Group A (HFOV Group) : Twenty preterm infants were included and subjected to lung recruitment maneuver using HFOV ( SLE 5000 infant ventilator, UK ) as follows: Continuous distending pressure (CDP) was started at 6–8 cmH 2 O then increased stepwise as long as oxygen saturation (SpO 2 ) measured by pulse oximetry improved. FiO 2 was reduced stepwise, keeping SpO 2 within the target range (90–95%). The recruitment procedure was stopped if oxygenation no longer improved or if FiO 2 did not exceed 0.25. The corresponding CDP was called the opening pressure (CDPo). Next, the CDP was reduced stepwise until the SpO 2 deteriorates. The corresponding CDP was called the closing pressure (CDP c ). After a second recruitment maneuver, the optimal CDP (CDP opt ) was set to 2 cm H 2 O above the CDPc [ 12 ]. Group B (VTV/AC Group) : Twenty preterm infants were included and subjected to lung recruitment maneuver using VTV/AC ( SLE 5000 infant ventilator, UK ) as follows: The starting ventilation parameters were: Tidal volume (Vt) 6 mL/kg, inspiratory time (Ti) 0.3 seconds, respiratory rate (RR) 60/min, peak inspiratory pressure (PIP) 25 cmH 2 O, and an initial positive end expiratory pressure (PEEP) 5 cmH 2 O. The initial FiO 2 level was adjusted to maintain a preductal SpO 2 of 90 to 95%. After setting a starting PEEP level of 5 cmH 2 O, a repeated increment of 0.5 cmH 2 O of PEEP was done every 5 minutes while monitoring the FiO 2 requirements and SpO 2 levels. During the 5 minutes of monitoring, the fall of FiO 2 needs and the increase of the SpO 2 level are signals to proceed with the maneuver and progressively increase the PEEP level. When FiO 2 of 0.25 was reached, a slow stepwise PEEP reduction with SpO 2 levels monitoring was done. When the SpO 2 falls, the PEEP level was re-increased until target oxygenation was achieved, and the lowest FiO 2 level was reached [ 13 ]. Human Transforming Growth Factor- β 1 (TGF- β 1 ) was tested in bronchial aspirates of preterm infants included by Enzyme Linked-Immunosorbent assay. Bronchial aspirate samples were obtained using a well-established technique in accordance with the European Respiratory Society guidelines [ 14 ]. One ml/kg sterile 0.9% saline was instilled using a 2.5-ml syringe through a 5F-gauge feeding catheter placed in the endotracheal tube (ETT) so that the tip extended 0.5 cm beyond the distal end of the ETT. The saline was instilled and immediately aspirated back into the syringe. All samples were clarified by centrifugation, and the supernatant was immediately frozen at -70 o C and kept for subsequent analysis. Bronchial samples were collected from each infant at two time points: a) After intubation and before surfactant administration and starting lung recruitment maneuver. b) At day 5 after intubation and lung recruitment or just before extubation if extubation occurs earlier than 5 days. Results Table 1 illustrates the demographic and clinical data of preterm infants included within Group A and Group B. It showed no significant differences between both studied groups as regards GA, sex, birth weight, age at inclusion, appropriateness for gestational age (GA), caesarian section (CS), APGAR score at 5 minutes or antenatal steroids. Most of the cases were included within the first day of life (70% among Group A and 75% among Group B preterm infants). However, PROM was significantly higher among Group B compared to Group A infants ( p= 0.008). Five percent of Group A and 35% of Group B were on HFNC while 75% of Group A and 55% of Group B were on NCPAP. Twenty percent of Group A and 10% of Group B preterm infants needed endotracheal intubation in the delivery room. Time to extubation was nearly similar among both studied groups with a mean of 3.5 and 3.25 days among Group A and Group B preterm infants respectively . Thirty-seven preterm infants of both studied groups received first dose endotracheal surfactant (18 of Group A and 19 of Group B) before lung recruitment. Out of them, 4 preterm infants of Group A and five preterm infants of Group B needed a second dose surfactant with no significant difference between them in this respect. No significant difference was observed between both groups as regards type of respiratory support before inclusion in the study, CRIB score, time to extubation, need for reintubation, duration of oxygen supply or duration of hospitalization ( Table 2). Table 3 and Table 4 present the ventilatory parameters among Group A and Group B infants throughout the study. In Group A, both FiO2 and MAP were significantly higher on the first day of the study compared to the third day ( p < 0.001, p < 0.001 respectively). They were also significantly higher on the first day when compared to the fifth day of the study ( p < 0.001, p < 0.001 respectively). Frequency showed no significant differences throughout the first, third, and fifth days of the study, while delta P was significantly higher on the first day compared to the third day ( p = 0.004) and on the first day compared to the fifth day ( p = 0.038). In Group B, all ventilatory parameters showed significant differences among the first, third, and fifth days of the study. They were all significantly lower on the third day and on the fifth day when compared to the first day. Only FiO2 was significantly lower on the fifth day compared to the third day ( p = 0.03). There was no statistically significant difference in any of the arterial blood gases parameters included between both groups (Table 5). There was also no significant difference in TGF- β 1 before recruitment nor at extubation between both groups as illustrated in Table 6. Discussion Lung recruitment maneuver is thought to reduce the incidence of lung injury, increase lung compliance, and minimize the complications associated with ETT suctioning and disconnection from the ventilator [ 15 ]. By briefly elevating airway pressure to a higher level, LRM serve to recruit collapsed lung regions and increase the number of alveoli sharing in gas exchange, which helps to minimize physiological dead space and restore end-expiratory lung volume which results in increased alveolar stability and may reduce shearing injury to the alveoli associated with cyclic opening and closing [ 16 ]. The primary outcome of our study was time to extubation which showed no significant difference between both studied groups. This aligns with two RCTs conducted on preterm infants with RDS who were randomly allocated to receive HFOV or SIMV with lung recruitment to ensure adequate lung inflation. Both studies showed no significant difference in duration of mechanical ventilation between both HFOV and SIMV groups [ 17 ]. However, Sun et al. reported shorter mechanical ventilation duration in the HFOV group [ 5 ]. Similarly, Wallstrӧm et al. compared VTV with pressure limited ventilation (PLV) in very preterm infants and reported no significant difference in duration of mechanical ventilation [ 18 ]. Regarding the need for a second dose of surfactant, we found no significant difference between the two studied groups. Vento et al. also observed no significant difference in the second dose of surfactant between the HFOV group and the SIMV group [ 19 ]. In contrast, Sun and colleagues found that the second dose of surfactant was significantly lower in HFOV compared to SIMV [ 5 ]. Moreover, Gerstmann et al. reported less frequent surfactant redosing in surfactant-treated preterm infants with RDS receiving HFOV compared to CMV [ 20 ]. In our study, the lack of significant difference between both studied groups in duration of hospitalization may be explained by the comparable results of duration of oxygen supplementation, time to extubation and the rate of prematurity complications. We also demonstrated no significant difference in the rate of reintubation between both groups. This came in agreement with the results of Singh et al who also found no significant difference in extubation failure between HFOV and SIMV groups [ 21 ] and with the results by Castoldi et al [ 22 ]. In terms of duration of oxygen supplementation, we found no significant difference between HFOV and VTV groups. Similarly, Singh et al. showed no significant difference in need for oxygen supply beyond day 28 between both HFOV and SIMV groups [ 21 ]. However, Vento et al. reported shorter duration of oxygen supplementation in preterm infants subjected to LRM using HFOV compared to SIMV [ 19 ]. The difference between our results and those by Vento et al. , may be attributed to increased rate of reintubation among HFOV group of our study (55% of the included preterm infants) compared to Vento et al. who reported 100% successful extubation among HFOV group. In addition, different protocols used to wean from HFOV may aid to the longer duration of oxygen supplementation in our study [ 19 ]. Blazek et al. showed no evidence of difference in duration of oxygen supplementation between LRM using VTV and routine care of preterm infants with RDS [ 23 ]. The ventilatory parameters of HFOV used in Group A were significantly lower at both third and fifth days when compared to first day of the study. In accordance, Singh and his colleagues have also demonstrated a significant decline of mean FiO 2 and MAP when measured at 1 hour, 6 hours and 24 hours, respectively in HFOV group compared to SIMV group [ 17 ]. As regard the ventilatory parameters used in VTV/AC group, FiO 2 , rate, PIP, PEEP and Vt significantly declined at third and fifth day compared to first day of the study. Similarly, Castoldi et al . and Wu et al concluded that LRM led to earlier lowest FiO 2 during the first 12 hours of life and to a shorter O 2 dependency [7; 24]. The measured PIP in a study by Wallstrӧm et al. was significantly lower in the VTV group compared to the PLV group at 4, 8, 12, 16 and 20 hours of age [ 18 ]. In our study, there was no statistically significant difference in any of the arterial blood gases parameters included between both groups. In contrast, Zheng et al. reported a significantly improved arterial blood gas variables in HFOV group after 6, 12, 24, and 48 hours. Such improvement was explained by the fact that HFOV can achieve an alveolar ventilation mode of effective gas exchange, which can uniformly expand the alveoli in a short time and improve gas exchange and lung compliance [ 25 ]. TGF- β 1 levels in the endotracheal aspirate of extremely low birth weight neonates are generally low in the first 24 h of life. High levels and an early rise of TGF- β 1 in the BAL fluid were predictive for the development of chronic lung disease of prematurity and the need for home oxygen therapy [ 26 ]. In contrast to our results, Vento et al. , found that TGF- β 1 level in tracheal aspirate was significantly less in HFOV compared to conventional ventilation indicating milder lung inflammatory injury and suggesting a possible lung protective role during HFOV rather than CMV [ 11 ]. This may be explained by different study design from ours as we compared HFOV to volume targeted ventilation rather conventional pressure limited ventilation and the superiority of VTV over PLV has been confirmed in meta-analyses of clinical trials [ 27 ]. The conflicting reports about HFOV versus conventional mechanical ventilation are probably due to heterogeneity in study designs, subject characteristics, and outcome definitions. Although several studies conducted over a long period have explored ways to determine infants’ readiness for extubation, and thereby increased extubation success [ 28 – 30 ], no strong evidence supports the use of any predictor of extubation readiness over clinical judgment alone [ 31 ]. Our study limitations included small sample size, variable time interval between the two measurements of TGF- β 1 tracheal aspirate due to different time to extubation, lack of precise clinical data during the period between resuscitation and admission to our NICU and during neonatal transport which may affect the outcome. Conclusion The lung recruitment maneuver had no significant effect on time to extubation when comparing both HFOV and VTV/AC groups of preterm infants with RDS. Both of our studied groups showed no significant difference in rate of prematurity complications nor delta change of TFG- β 1 level in tracheal aspirate of those preterm infants measured before lung recruitment and five days after recruitment or at extubation when extubation occurred earlier. However, the results obtained from our study being the first of its kind to compare the effect of lung recruitment using HFOV versus VTV on duration of intubation and lung inflammation in preterm infants with RDS provide a promising research area for further investigations. Abbreviations AC Assist-Control AGA Appropriate for Gestational Age BAL Bronchoalveolar Lavage BPD Bronchopulmonary Dysplasia CDP Continuous Distending Pressure CMV Continuous Mandatory Ventilation CRIB Clinical Risk Index for Babies CS Caesarean Section DOL Day of Life ETT Endotracheal Tube FiO2 Fraction of Inspired Oxygen GA Gestational Age HFNC High Flow Nasal Cannula HFOV High-Frequency Oscillatory Ventilation Hz Hertz LRM Lung Recruitment Maneuver MAP Mean Airway Pressure NCPAP Nasal Continuous Positive Airway Pressure NICU Neonatal Intensive Care Unit PEEP Positive End-Expiratory Pressure PLV Pressure Limited Ventilation PIP Peak Inspiratory Pressure PROM Prolonged Rupture of Membranes RCT Randomized Controlled Trial RDS Respiratory Distress Syndrome SIMV Synchronized Intermittent Mandatory Ventilation SGA Small for Gestational Age SpO2 Oxygen Saturation TGF-β1 Transforming Growth Factor-β1 Ti Inspiratory Time VTV Volume Targeted Ventilation VT Tidal Volume Declarations Authors’ contributions: M.E and M.E wrote the main manuscript text. M.E carried out study analysis and prepared figures and tables. A.S, O.E, D.S, and M.E contributed to samples ordering and data collection. B.S revised the final draft. All authors have made a substantial, direct and intellectual contribution to the work, and approved it for publication. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors Data availability: All data supporting this article will be made available by the corresponding author to any qualified researcher upon request. Ethics approval: Approval was obtained from the ethics committee of Mansoura University (approval no. 16.07.64). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Consent to participate Parental informed consent was obtained from all individual participants included in the study. Competing interests: The authors have no competing financial or personal interests to declare. References Yadav S, Lee B, Kamity R (2023) Neonatal Respiratory Distress Syndrome. StatPearls Publishing, Treasure Island (FL) Dankhara N, Holla I, Ramarao S, Kalikkot Thekkeveedu R (2023) Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology. J Clin Med 12 Lista G, Maturana A, Moya FR (2017) Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU. Eur J Pediatr 176:1287-1293 Ackermann BW, Klotz D, Hentschel R, Thome UH, van Kaam AH (2023) High-frequency ventilation in preterm infants and neonates. Pediatr Res 93:1810-1818 Sun H, Cheng R, Kang W, Xiong H, Zhou C, Zhang Y, Wang X, Zhu C (2014) High-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation plus pressure support in preterm infants with severe respiratory distress syndrome. Respir Care 59:159-169 Hysinger EB, Ahlfeld SK (2023) Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia. Front Pediatr 11:1087857 Wu R, Li N, Hu J, Zha L, Zhu H, Zheng G, Zhao Y, Feng Z (2014) [Application of lung recruitment maneuver in preterm infants with respiratory distress syndrome ventilated by proportional assist ventilation]. Zhonghua Er Ke Za Zhi 52:741-744 Chakkarapani AA, Adappa R, Mohammad Ali SK, Gupta S, Soni NB, Chicoine L, Hummler HD (2020) "Current concepts in assisted mechanical ventilation in the neonate" - Part 2: Understanding various modes of mechanical ventilation and recommendations for individualized disease-based approach in neonates. Int J Pediatr Adolesc Med 7:201-208 Hayes J, Don, Feola DJ, Murphy BS, Shook LA, Ballard HO (2010) Pathogenesis of bronchopulmonary dysplasia. Respiration 79:425-436 Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A (2013) Critical role of transforming growth factor beta in different phases of wound healing. Advances in wound care 2:215-224 Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive care medicine 31:463-470 Miedema M, de Jongh FH, Frerichs I, van Veenendaal MB, van Kaam AH (2012) Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants. Intensive care medicine 38:294-299 Dargaville PA, Keszler M (2015) Setting the ventilator in the NICU. Pediatric and Neonatal Mechanical Ventilation: From Basics to Clinical Practice:1101-1125 De Blic J, Midulla F, Barbato A, Clement A, Dab I, Eber E, Green C, Grigg J, Kotecha S, Kurland G (2000) Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society. European Respiratory Journal 15:217-231 Lovas A, Szakmány T (2015) Haemodynamic Effects of Lung Recruitment Manoeuvres. Biomed Res Int 2015:478970 Hodgson C, Goligher EC, Young ME, Keating JL, Holland AE, Romero L, Bradley SJ, Tuxen D (2016) Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation. Cochrane database of systematic reviews Singh S, Malik G, Prashanth G, Singh A, Kumar M (2012) High frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in preterm neonates with hyaline membrane disease: a randomized controlled trial. Indian pediatrics 49:405-408 Wallström L, Sjöberg A, Sindelar R (2021) Early volume targeted ventilation in preterm infants born at 22-25 weeks of gestational age. Pediatr Pulmonol 56:1000-1007 Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463-470 Gerstmann DR, Minton SD, Stoddard RA, Meredith KS, Monaco F, Bertrand JM, Battisti O, Langhendries JP, Francois A, Clark RH (1996) The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Pediatrics 98:1044-1057 Singh S, Malik G, Prashanth G, Singh A, Kumar M (2012) High frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in preterm neonates with hyaline membrane disease: a randomized controlled trial. Indian pediatrics 49:405-408 Castoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G (2011) Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. Am J Perinatol 28:521-528 Blazek EV, East CE, Jauncey-Cooke J, Bogossian F, Grant CA, Hough J (2021) Lung recruitment manoeuvres for reducing mortality and respiratory morbidity in mechanically ventilated neonates. Cochrane Database Syst Rev 3:Cd009969 Castoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G (2011) Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. American journal of perinatology 28:521-528 Zheng YR, Lei YQ, Liu JF, Wu HL, Xu N, Huang ST, Cao H, Chen Q (2021) Effect of High-Frequency Oscillatory Ventilation Combined With Pulmonary Surfactant in the Treatment of Acute Respiratory Distress Syndrome After Cardiac Surgery: A Prospective Randomised Controlled Trial. Front Cardiovasc Med 8:675213 Lecart C, Cayabyab R, Buckley S, Morrison J, Kwong K, Warburton D, Ramanathan R, Jones C, Minoo P (2000) Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation. Neonatology 77:217-223 Klingenberg C, Wheeler KI, McCallion N, Morley CJ, Davis PG (2017) Volume-targeted versus pressure-limited ventilation in neonates. Cochrane Database Syst Rev 10:Cd003666 Chawla S, Natarajan G, Gelmini M, Kazzi SN (2013) Role of spontaneous breathing trial in predicting successful extubation in premature infants. Pediatr Pulmonol 48:443-448 Kamlin CO, Davis PG, Argus B, Mills B, Morley CJ (2008) A trial of spontaneous breathing to determine the readiness for extubation in very low birth weight infants: a prospective evaluation. Arch Dis Child Fetal Neonatal Ed 93:F305-306 Mueller M, Wagner CC, Stanislaus R, Almeida JS (2013) Machine learning to predict extubation outcome in premature infants. Proc Int Jt Conf Neural Netw 2013:1-6 Shalish W, Latremouille S, Papenburg J, Sant'Anna GM (2019) Predictors of extubation readiness in preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 104:F89-f97 Tables Table 1: Baseline characteristics of both studied groups Group A (n=20) Group B (n=20) P value Gestational age (weeks) 30.05±2.65 28.95±2.24 0.164 Sex Male Female 8(40%) 12(60%) 11(55%) 9(45%) 0.342 Birth weight (g) 1335.25±624.71 1130.25±417.08 0.230 Age at inclusion 1 st DOL 2 nd DOL 3 rd DOL 14(70%) 2(10%) 4(20%) 15(75%) 2(10%) 3(15%) 0.915 Appropriateness for GA SGA AGA 3(15%) 17(85%) 3(15%) 17(85%) 1.0 CS delivery 19(95%) 15(75%) 0.077 APGAR score at 5 minutes 8.0(8.0-9.0) 8.0(7.0-8.0) 0.119 Antenatal steroid 8(40%) 4(20%) 0.264 PROM 0(0%) 6(30%) 0.008 DOL day of life, AGA appropriate for gestational age, SGA small for gestational age, CS caesarean section, PROM prolonged rupture of membranes. Table 2: Clinical data and clinical course of both studied groups Group A (n=20) Group B (n=20) P value Respiratory support before inclusion: HFNC NCPAP Intubation 1(5%) 15(75%) 4(20%) 7(35%) 11(55%) 2(10%) 0.056 CRIB score 5.5(3.25-8.0) 5.5(3.25-7.75) 0.754 Second dose surfactant 4(20%) 5(25%) 0.705 Time to extubation (days) 3.5(1.63-8.75) 3.25(1.63-5.75) 0.968 Reintubation 11(55%) 10(50%) 0.752 Duration of O 2 supply (days) 27(9.5-41.25) 14(7.25-50.5) 0.797 Duration of hospitalization (days) 34.5(27.25-53) 30.5(9.25-60.75) 0.871 Mortality 8(40%) 7(35%) 0.744 HFNC High flow nasal cannula, NCPAP nasal continuous positive airway pressure, CRIB Clinical risk Index for babies. Table 3: Ventilatory parameters throughout the study among Group A preterm infants Parameters First day Third day Fifth day p p1 a p2 b p3 c FiO2 (%) 66.75±19.35 38.08±9.25 40.11±15.25 <0.001 p<0.001 <0.001 0.925 Frequency (Hz) 12.35±0.93 12.38±1.04 12.33±1.41 0.438 0.721 0.438 1.0 Delta P (cm H 2 O) 25.55±2.67 24.23±2.39 23.33±3.16 0.252 0.004 0.038 0.252 MAP (cm H 2 O) 15.20±1.99 12.02±1.89 11.53±2.23 <0.001 <0.001 <0.001 0.192 FiO 2 fraction of inspired oxygen, MAP mean airway pressure a p1 : difference between first & third day b p2 : difference between first & fifth day c p3 : difference between third & fifth day. Table 4: Ventilatory parameters throughout the study among Group B preterm infants Parameters First day Third day Fifth day p p1 a p2 b p3 c FIO 2 (%) 61.75±17.64 35.46±16.31 35.33±16.07 0.004 <0.001 0.004 0.03 Rate (b/min) 64.20±3.39 43.08±8.96 45.50±9.97 0.002 <0.001 0.002 0.336 PIP (cm H 2 O) 16.25±1.16 14.85±1.34 13.67±1.86 0.029 0.01 0.029 0.168 PEEP (cm H 2 O) 6.23±0.41 5.46±0.48 5.42±0.38 0.007 <0.001 0.007 0.363 VT (ml/kg) 6.0±0.0 5.71±0.33 5.55±0.36 0.027 0.008 0.027 0.089 Ti (seconds) 0.327±0.01 0.374±0.005 0.373±0.005 1.0 0.794 1.0 1.0 FiO 2 fraction of inspired oxygen, PIP peak inspiratory pressure, PEEP positive end expiratory pressure, VT tidal volume, Ti inspiratory time . a p1 : difference between first & third day b p2 : difference between first & fifth day c p3 : difference between third & fifth day. Table 5: Arterial blood gases before and after lung recruitment among both studied groups Parameter Timing Group A (n=20) Group B (n=20) p value pH Before 7.24±0.06 7.24±0.064 0.744 After 7.29±0.074 7.32±0.09 0.319 PaO 2 (mmHg) Before 60.12±8.09 65.34±9.09 0.127 After 69.17±10.11 69.91±11.04 0.785 PaCO 2 (mmHg) Before 45.085±14.70 43.54±11.06 0.708 After 41.05±8.54 36.07±10.21 0.102 HCO 3 (mmol/L) Before 18.13±4.09 18.36±3.28 0.846 After 18.84±2.90 17.47±3.09 0.157 BE (mmol/L) Before -8.42±3.55 7.32±0.094 0.487 After -6.68±3.47 -7.045±4.13 0.764 pH potential of hydrogen, PaO 2 partial arterial pressure of oxygen, PaCO 2 partial arterial pressure of carbon dioxide, HCO 3 bicarbonate, BE base excess. Table 6: Human transforming growth factor β1 (TGF- β 1 ) among both studied groups Group A (n=20) Group B (n=20) P value TGF- β 1 before recruitment 84.34 (27.74-161.14) 45.32 (32.71-132.22) 0.829 TGF- β 1 at time of extubation or 5 days after recruitment if extubation was earlier 51.84 (25.03-153.63) 52.84 (36.37-150.03) 0.387 Delta change -9.52 (-88.76-68.27) -4.97 (-50.9-517.33) 0.152 p value 0.575 0.765 TGF-β 1 Transforming growth factor. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4243658","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":291063820,"identity":"2bd24193-f3b9-4e03-9b06-768d88d29ceb","order_by":0,"name":"Marwa Eldegwi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYHACAyCWkAMxGBtsQAIJxGkxhmhJI14LQ2ID0Vp02w9vfPi1zSJ9bXvzBsYZCXUM/Ow5BgwffuHWYnYmrdhYtk0id9uZYwWMGxIOM0j2vDFgnNmHR8uBHDNpyW1ALTdyDBgf/jjAYABkMPP24NFy/o35b6CWdLP7QMMfAB1mD9LyF5+WGzlmjB+3SSSY3eAxADqMmcFAAqiF4Qc+Lc+KpRn/SRhuO5NWcHBGwmEeiTPPCg72NuBzWPLGjz/O1MmbHQcGXU9CnRx/e/LGBz/+4NYCAsw8UMYBIAazDzC24dfCiMXhBGwZBaNgFIyCEQUAZwJZutqxsmkAAAAASUVORK5CYII=","orcid":"","institution":"Kafr El-Sheikh University","correspondingAuthor":true,"prefix":"","firstName":"Marwa","middleName":"","lastName":"Eldegwi","suffix":""},{"id":291063821,"identity":"6b33bf01-c0af-400e-8c8e-a967690210a0","order_by":1,"name":"Ali Shaltout","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Shaltout","suffix":""},{"id":291063822,"identity":"0dcbc1d8-5146-4657-914d-3b6d5b7ba868","order_by":2,"name":"Osama Elagamy","email":"","orcid":"","institution":"Kafr El-Sheikh University","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"","lastName":"Elagamy","suffix":""},{"id":291063823,"identity":"130ae629-fcc6-4994-b5fe-2e34f259a652","order_by":3,"name":"Dina Salama","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Dina","middleName":"","lastName":"Salama","suffix":""},{"id":291063824,"identity":"b66a32bb-dee1-4cf6-a06b-a0e68145be0a","order_by":4,"name":"Mohammed Elshaer","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Elshaer","suffix":""},{"id":291063825,"identity":"612a0ae6-591a-4ba0-8ac3-0b5849c34c87","order_by":5,"name":"Basma Shouman","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Basma","middleName":"","lastName":"Shouman","suffix":""}],"badges":[],"createdAt":"2024-04-09 18:36:09","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4243658/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4243658/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54738064,"identity":"a0ae292a-ad8e-4b0e-8498-8b7ba1abf1af","added_by":"auto","created_at":"2024-04-16 04:56:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":536049,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4243658/v1/c1bba595-b364-49c4-9d14-4ab7b877e584.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lung recruitment with high frequency ventilation versus volume targeted ventilation in preterm infants with respiratory distress syndrome","fulltext":[{"header":"What is Known","content":"\u003cul\u003e\n \u003cli\u003eRespiratory distress syndrome (RDS) is a common cause of premature infant respiratory failure, and various techniques are available to optimize fetal-neonatal transition.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eDespite the lack of significant differences between the two ventilation techniques, the variation in ventilatory parameters over the study period warrants further research.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eRespiratory distress syndrome (RDS) is one of the most common causes of premature infant respiratory failure. Despite better neonatal care, many infants with RDS require intubation, mechanical ventilation, and exogenous surfactant treatment to restore lung function and gas exchange [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Mechanical ventilation, on the other hand, can harm the developing lung and is a major risk factor for developing bronchopulmonary dysplasia (BPD)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. An optimal management strategy should begin at birth, with the goal of achieving an early functional residual capacity and maintaining a sufficient lung volume. Recently, many techniques for optimizing fetal-neonatal transition and promoting lung recruitment have been accessible [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn preterm infants with RDS, high-frequency ventilation (HFV) is a common lung-protective ventilation mode [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In preterm infants with severe RDS, initial ventilation using high frequency oscillatory ventilation (HFOV) lowers the incidence of death and BPD and improves long-term neurodevelopmental outcomes [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. During HFV, the open lung strategy has become standard therapy, with gradual rise in continuous distending pressure (CDP) used to lessen the requirement for fraction of inspired oxygen (FiO\u003csub\u003e2\u003c/sub\u003e) via target oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e) monitoring [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe \"open lung\" approach also applies to volume-targeted ventilation, which benefits from an equitable distribution of tidal volume throughout the lungs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When compared to non-recruitment, early lung recruitment maneuver (LRM) in preterm infants with RDS resulted in quicker accomplishment of reduced FiO\u003csub\u003e2\u003c/sub\u003e and shorter oxygen dependency [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These findings imply that adding the open lung concept to volume-targeted ventilation in preterm infants with RDS is a reasonable approach [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInflammatory markers in bronchoalveolar lavage (BAL) have been extensively employed to assess early lung injury in ventilated preterm newborns and the subsequent progression to BPD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Human Transforming Growth Factor-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e (TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1)\u003c/sub\u003e is a type of cytokine that is produced by lung epithelial cells and vascular endothelial cells. TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e increases the synthesis and deposition of extracellular matrix during the wound healing process, which aids in wound repair. TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e production is transitory in normal tissues, but repeated lung injury culminates in overexpression. As a result, it has been employed as a fibrosis and remodeling marker [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e levels were observed to be elevated in BAL samples from premature neonates who later had chronic lung illness. TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e tracheal aspirate was considerably lower in high frequency ventilation (HFOV) compared to conventional breathing, indicating less lung inflammatory damage. These findings suggested that HFOV, rather than Continuous Mandatory Ventilation (CMV), may play a lung protective role [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, this study was designed to compare the effect of lung recruitment using high frequency ventilation versus volume targeted ventilation (VTV) on duration of intubation as well as its effect on lung inflammation in preterm infants with respiratory distress syndrome as measured by TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e level in samples of bronchoalveolar lavage from infants studied.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study was conducted on a total of 40 preterm infants, 34 weeks gestational age or less, having RDS that needed intubation and mechanical ventilation within the first 72 hours after their birth at the Neonatal Intensive Care Unit (NICU) of Mansoura University Children\u0026apos;s Hospital during the period from July 2020 to July 2022. Infants included were randomly assigned into two groups, Group A who were subjected to LRM using HFOV (20 cases) and Group B who were subjected to LRM using VTV/AC (20 cases).\u003c/p\u003e\n\u003cp\u003ePreterm infants who met the eligibility criteria were randomly assigned into one of two groups (Group A \u0026amp; Group B) with allocation ratio 1:1 using sealed envelopes:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A (HFOV Group)\u003c/strong\u003e: Twenty preterm infants were included and subjected to lung recruitment maneuver using HFOV (\u003cem\u003eSLE 5000 infant ventilator, UK\u003c/em\u003e) as follows: Continuous distending pressure (CDP) was started at 6\u0026ndash;8 cmH\u003csub\u003e2\u003c/sub\u003eO then increased stepwise as long as oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e) measured by pulse oximetry improved. FiO\u003csub\u003e2\u003c/sub\u003e was reduced stepwise, keeping SpO\u003csub\u003e2\u003c/sub\u003e within the target range (90\u0026ndash;95%). The recruitment procedure was stopped if oxygenation no longer improved or if FiO\u003csub\u003e2\u003c/sub\u003e did not exceed 0.25. The corresponding CDP was called the opening pressure (CDPo). Next, the CDP was reduced stepwise until the SpO\u003csub\u003e2\u003c/sub\u003e deteriorates. The corresponding CDP was called the closing pressure (CDP\u003csub\u003ec\u003c/sub\u003e). After a second recruitment maneuver, the optimal CDP (CDP\u003csub\u003eopt\u003c/sub\u003e) was set to 2 cm H\u003csub\u003e2\u003c/sub\u003eO above the CDPc [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B (VTV/AC Group)\u003c/strong\u003e: Twenty preterm infants were included and subjected to lung recruitment maneuver using VTV/AC (\u003cem\u003eSLE 5000 infant ventilator, UK\u003c/em\u003e) as follows: The starting ventilation parameters were: Tidal volume (Vt) 6 mL/kg, inspiratory time (Ti) 0.3 seconds, respiratory rate (RR) 60/min, peak inspiratory pressure (PIP) 25 cmH\u003csub\u003e2\u003c/sub\u003eO, and an initial positive end expiratory pressure (PEEP) 5 cmH\u003csub\u003e2\u003c/sub\u003eO. The initial FiO\u003csub\u003e2\u003c/sub\u003e level was adjusted to maintain a preductal SpO\u003csub\u003e2\u003c/sub\u003e of 90 to 95%. After setting a starting PEEP level of 5 cmH\u003csub\u003e2\u003c/sub\u003eO, a repeated increment of 0.5 cmH\u003csub\u003e2\u003c/sub\u003eO of PEEP was done every 5 minutes while monitoring the FiO\u003csub\u003e2\u003c/sub\u003e requirements and SpO\u003csub\u003e2\u003c/sub\u003e levels. During the 5 minutes of monitoring, the fall of FiO\u003csub\u003e2\u003c/sub\u003e needs and the increase of the SpO\u003csub\u003e2\u003c/sub\u003e level are signals to proceed with the maneuver and progressively increase the PEEP level. When FiO\u003csub\u003e2\u003c/sub\u003e of 0.25 was reached, a slow stepwise PEEP reduction with SpO\u003csub\u003e2\u003c/sub\u003e levels monitoring was done. When the SpO\u003csub\u003e2\u003c/sub\u003e falls, the PEEP level was re-increased until target oxygenation was achieved, and the lowest FiO\u003csub\u003e2\u003c/sub\u003e level was reached [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eHuman Transforming Growth Factor-\u003cem\u003e\u0026beta;\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e (TGF-\u003cem\u003e\u0026beta;\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e) was tested in bronchial aspirates of preterm infants included by Enzyme Linked-Immunosorbent assay. Bronchial aspirate samples were obtained using a well-established technique in accordance with the European Respiratory Society guidelines [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. One ml/kg sterile 0.9% saline was instilled using a 2.5-ml syringe through a 5F-gauge feeding catheter placed in the endotracheal tube (ETT) so that the tip extended 0.5 cm beyond the distal end of the ETT. The saline was instilled and immediately aspirated back into the syringe. All samples were clarified by centrifugation, and the supernatant was immediately frozen at -70\u003csup\u003eo\u003c/sup\u003e C and kept for subsequent analysis.\u003c/p\u003e\n\u003cp\u003eBronchial samples were collected from each infant at two time points:\u003c/p\u003e\n\u003cp\u003ea) After intubation and before surfactant administration and starting lung recruitment maneuver.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eb) At day 5 after intubation and lung recruitment or just before extubation if extubation occurs earlier than 5 days.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable 1 illustrates the demographic and clinical data of preterm infants included within Group A and Group B. It showed no significant differences between both studied groups as regards GA, sex, birth weight, age at inclusion, appropriateness for gestational age (GA), caesarian section (CS), APGAR score at 5 minutes or antenatal steroids. Most of the cases were included within the first day of life (70% among Group A and 75% among Group B preterm infants). However, PROM was significantly higher among Group B compared to Group A infants (\u003cem\u003ep=\u003c/em\u003e 0.008). Five percent of Group A and 35% of Group B were on HFNC while 75% of Group A and 55% of Group B were on NCPAP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwenty percent of Group A and 10% of Group B preterm infants needed endotracheal intubation in the delivery room. Time to extubation was nearly similar among both studied groups with a mean of 3.5 and 3.25 days among Group A and Group B preterm infants respectively\u003cstrong\u003e.\u003c/strong\u003e Thirty-seven preterm infants of both studied groups received first dose endotracheal surfactant (18 of Group A and 19 of Group B) before lung recruitment. Out of them, 4 preterm infants of Group A and five preterm infants of Group B needed a second dose surfactant with no significant difference between them in this respect. No significant difference was observed between both groups as regards type of respiratory support before inclusion in the study, CRIB score, time to extubation, need for reintubation, duration of oxygen supply or duration of hospitalization \u003cstrong\u003e(\u003c/strong\u003eTable 2).\u003c/p\u003e\n\u003cp\u003eTable 3 and Table 4 present the ventilatory parameters among Group A and Group B infants throughout the study. In Group A, both FiO2 and MAP were significantly higher on the first day of the study compared to the third day (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 respectively). They were also significantly higher on the first day when compared to the fifth day of the study (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 respectively). Frequency showed no significant differences throughout the first, third, and fifth days of the study, while delta P was significantly higher on the first day compared to the third day (\u003cem\u003ep\u003c/em\u003e = 0.004) and on the first day compared to the fifth day (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.038). In Group B, all ventilatory parameters showed significant differences among the first, third, and fifth days of the study. They were all significantly lower on the third day and on the fifth day when compared to the first day. Only FiO2 was significantly lower on the fifth day compared to the third day (\u003cem\u003ep\u003c/em\u003e = 0.03).\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference in any of the arterial blood gases parameters included between both groups (Table 5).\u0026nbsp; There was also no significant difference in TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e before recruitment nor at extubation between both groups as illustrated in Table 6.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLung recruitment maneuver is thought to reduce the incidence of lung injury, increase lung compliance, and minimize the complications associated with ETT suctioning and disconnection from the ventilator [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. By briefly elevating airway pressure to a higher level, LRM serve to recruit collapsed lung regions and increase the number of alveoli sharing in gas exchange, which helps to minimize physiological dead space and restore end-expiratory lung volume which results in increased alveolar stability and may reduce shearing injury to the alveoli associated with cyclic opening and closing [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary outcome of our study was time to extubation which showed no significant difference between both studied groups. This aligns with two RCTs conducted on preterm infants with RDS who were randomly allocated to receive HFOV or SIMV with lung recruitment to ensure adequate lung inflation. Both studies showed no significant difference in duration of mechanical ventilation between both HFOV and SIMV groups [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, \u003cb\u003eSun et al.\u003c/b\u003e reported shorter mechanical ventilation duration in the HFOV group [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Similarly, \u003cb\u003eWallstrӧm et al.\u003c/b\u003e compared VTV with pressure limited ventilation (PLV) in very preterm infants and reported no significant difference in duration of mechanical ventilation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRegarding the need for a second dose of surfactant, we found no significant difference between the two studied groups. \u003cb\u003eVento et al.\u003c/b\u003e also observed no significant difference in the second dose of surfactant between the HFOV group and the SIMV group [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In contrast, \u003cb\u003eSun and colleagues\u003c/b\u003e found that the second dose of surfactant was significantly lower in HFOV compared to SIMV [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover, \u003cb\u003eGerstmann et al.\u003c/b\u003e reported less frequent surfactant redosing in surfactant-treated preterm infants with RDS receiving HFOV compared to CMV [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the lack of significant difference between both studied groups in duration of hospitalization may be explained by the comparable results of duration of oxygen supplementation, time to extubation and the rate of prematurity complications. We also demonstrated no significant difference in the rate of reintubation between both groups. This came in agreement with the results of \u003cb\u003eSingh et al\u003c/b\u003e who also found no significant difference in extubation failure between HFOV and SIMV groups [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and with the results by \u003cb\u003eCastoldi et al\u003c/b\u003e [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn terms of duration of oxygen supplementation, we found no significant difference between HFOV and VTV groups. Similarly, \u003cb\u003eSingh et al.\u003c/b\u003e showed no significant difference in need for oxygen supply beyond day 28 between both HFOV and SIMV groups [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, \u003cb\u003eVento et al.\u003c/b\u003e reported shorter duration of oxygen supplementation in preterm infants subjected to LRM using HFOV compared to SIMV [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The difference between our results and those by \u003cb\u003eVento et al.\u003c/b\u003e, may be attributed to increased rate of reintubation among HFOV group of our study (55% of the included preterm infants) compared to \u003cb\u003eVento et al.\u003c/b\u003e who reported 100% successful extubation among HFOV group. In addition, different protocols used to wean from HFOV may aid to the longer duration of oxygen supplementation in our study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. \u003cb\u003eBlazek et al.\u003c/b\u003e showed no evidence of difference in duration of oxygen supplementation between LRM using VTV and routine care of preterm infants with RDS [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ventilatory parameters of HFOV used in Group A were significantly lower at both third and fifth days when compared to first day of the study. In accordance, \u003cb\u003eSingh and his colleagues\u003c/b\u003e have also demonstrated a significant decline of mean FiO\u003csub\u003e2\u003c/sub\u003e and MAP when measured at 1 hour, 6 hours and 24 hours, respectively in HFOV group compared to SIMV group [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs regard the ventilatory parameters used in VTV/AC group, FiO\u003csub\u003e2\u003c/sub\u003e, rate, PIP, PEEP and Vt significantly declined at third and fifth day compared to first day of the study. Similarly, \u003cb\u003eCastoldi et al\u003c/b\u003e. and \u003cb\u003eWu et al\u003c/b\u003e concluded that LRM led to earlier lowest FiO\u003csub\u003e2\u003c/sub\u003e during the first 12 hours of life and to a shorter O\u003csub\u003e2\u003c/sub\u003e dependency [7; 24]. The measured PIP in a study by \u003cb\u003eWallstrӧm et al.\u003c/b\u003e was significantly lower in the VTV group compared to the PLV group at 4, 8, 12, 16 and 20 hours of age [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, there was no statistically significant difference in any of the arterial blood gases parameters included between both groups. In contrast, \u003cb\u003eZheng et al.\u003c/b\u003e reported a significantly improved arterial blood gas variables in HFOV group after 6, 12, 24, and 48 hours. Such improvement was explained by the fact that HFOV can achieve an alveolar ventilation mode of effective gas exchange, which can uniformly expand the alveoli in a short time and improve gas exchange and lung compliance [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e levels in the endotracheal aspirate of extremely low birth weight neonates are generally low in the first 24 h of life. High levels and an early rise of TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e in the BAL fluid were predictive for the development of chronic lung disease of prematurity and the need for home oxygen therapy [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In contrast to our results, \u003cb\u003eVento et al.\u003c/b\u003e, found that TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e level in tracheal aspirate was significantly less in HFOV compared to conventional ventilation indicating milder lung inflammatory injury and suggesting a possible lung protective role during HFOV rather than CMV [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This may be explained by different study design from ours as we compared HFOV to volume targeted ventilation rather conventional pressure limited ventilation and the superiority of VTV over PLV has been confirmed in meta-analyses of clinical trials [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe conflicting reports about HFOV versus conventional mechanical ventilation are probably due to heterogeneity in study designs, subject characteristics, and outcome definitions. Although several studies conducted over a long period have explored ways to determine infants\u0026rsquo; readiness for extubation, and thereby increased extubation success [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], no strong evidence supports the use of any predictor of extubation readiness over clinical judgment alone [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Our study limitations included small sample size, variable time interval between the two measurements of TGF-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e tracheal aspirate due to different time to extubation, lack of precise clinical data during the period between resuscitation and admission to our NICU and during neonatal transport which may affect the outcome.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe lung recruitment maneuver had no significant effect on time to extubation when comparing both HFOV and VTV/AC groups of preterm infants with RDS. Both of our studied groups showed no significant difference in rate of prematurity complications nor delta change of TFG-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e level in tracheal aspirate of those preterm infants measured before lung recruitment and five days after recruitment or at extubation when extubation occurred earlier. However, the results obtained from our study being the first of its kind to compare the effect of lung recruitment using HFOV versus VTV on duration of intubation and lung inflammation in preterm infants with RDS provide a promising research area for further investigations.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u0026nbsp; \u0026nbsp; AC \u0026nbsp; Assist-Control\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; AGA \u0026nbsp;Appropriate for Gestational Age\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; BAL \u0026nbsp;Bronchoalveolar Lavage\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; BPD Bronchopulmonary Dysplasia\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; CDP \u0026nbsp;Continuous Distending Pressure\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; CMV \u0026nbsp;Continuous Mandatory Ventilation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; CRIB \u0026nbsp;Clinical Risk Index for Babies\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; CS \u0026nbsp; Caesarean Section\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; DOL \u0026nbsp;Day of Life\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; ETT \u0026nbsp;Endotracheal Tube\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; FiO2 \u0026nbsp;Fraction of Inspired Oxygen\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; GA \u0026nbsp; Gestational Age\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; HFNC \u0026nbsp;High Flow Nasal Cannula\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; HFOV \u0026nbsp;High-Frequency Oscillatory Ventilation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; Hz \u0026nbsp; Hertz\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; LRM \u0026nbsp;Lung Recruitment Maneuver\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; MAP Mean Airway Pressure\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; NCPAP Nasal Continuous Positive Airway Pressure\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; NICU Neonatal Intensive Care Unit\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; PEEP Positive End-Expiratory Pressure\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; PLV Pressure Limited Ventilation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; PIP Peak Inspiratory Pressure\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; PROM Prolonged Rupture of Membranes\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; RCT \u0026nbsp;Randomized Controlled Trial\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; RDS \u0026nbsp;Respiratory Distress Syndrome\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; SIMV Synchronized Intermittent Mandatory Ventilation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; SGA Small for Gestational Age\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; SpO2 \u0026nbsp;Oxygen Saturation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; TGF-\u0026beta;1 \u0026nbsp;Transforming Growth Factor-\u0026beta;1\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; Ti \u0026nbsp; Inspiratory Time\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; VTV \u0026nbsp;Volume Targeted Ventilation\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; VT Tidal Volume\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003eM.E and M.E wrote the main manuscript text. M.E carried out study analysis and prepared figures and tables. A.S, O.E, D.S, and M.E contributed to samples ordering and data collection. B.S revised the final draft. All authors have made a substantial, direct and intellectual contribution to the work, and approved it for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eAll data supporting this article will be made available by the corresponding author to any qualified researcher upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eApproval was obtained from the ethics committee of Mansoura University (approval no. 16.07.64). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e Parental informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors have no competing financial or personal interests to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eYadav S, Lee B, Kamity R (2023) Neonatal Respiratory Distress Syndrome. StatPearls Publishing, Treasure Island (FL)\u003c/li\u003e\n \u003cli\u003eDankhara N, Holla I, Ramarao S, Kalikkot Thekkeveedu R (2023) Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology. J Clin Med 12\u003c/li\u003e\n \u003cli\u003eLista G, Maturana A, Moya FR (2017) Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU. Eur J Pediatr 176:1287-1293\u003c/li\u003e\n \u003cli\u003eAckermann BW, Klotz D, Hentschel R, Thome UH, van Kaam AH (2023) High-frequency ventilation in preterm infants and neonates. Pediatr Res 93:1810-1818\u003c/li\u003e\n \u003cli\u003eSun H, Cheng R, Kang W, Xiong H, Zhou C, Zhang Y, Wang X, Zhu C (2014) High-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation plus pressure support in preterm infants with severe respiratory distress syndrome. Respir Care 59:159-169\u003c/li\u003e\n \u003cli\u003eHysinger EB, Ahlfeld SK (2023) Respiratory support strategies in the prevention and treatment of bronchopulmonary dysplasia. Front Pediatr 11:1087857\u003c/li\u003e\n \u003cli\u003eWu R, Li N, Hu J, Zha L, Zhu H, Zheng G, Zhao Y, Feng Z (2014) [Application of lung recruitment maneuver in preterm infants with respiratory distress syndrome ventilated by proportional assist ventilation]. Zhonghua Er Ke Za Zhi 52:741-744\u003c/li\u003e\n \u003cli\u003eChakkarapani AA, Adappa R, Mohammad Ali SK, Gupta S, Soni NB, Chicoine L, Hummler HD (2020) \u0026quot;Current concepts in assisted mechanical ventilation in the neonate\u0026quot; - Part 2: Understanding various modes of mechanical ventilation and recommendations for individualized disease-based approach in neonates. Int J Pediatr Adolesc Med 7:201-208\u003c/li\u003e\n \u003cli\u003eHayes J, Don, Feola DJ, Murphy BS, Shook LA, Ballard HO (2010) Pathogenesis of bronchopulmonary dysplasia. Respiration 79:425-436\u003c/li\u003e\n \u003cli\u003ePakyari M, Farrokhi A, Maharlooei MK, Ghahary A (2013) Critical role of transforming growth factor beta in different phases of wound healing. Advances in wound care 2:215-224\u003c/li\u003e\n \u003cli\u003eVento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive care medicine 31:463-470\u003c/li\u003e\n \u003cli\u003eMiedema M, de Jongh FH, Frerichs I, van Veenendaal MB, van Kaam AH (2012) Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants. Intensive care medicine 38:294-299\u003c/li\u003e\n \u003cli\u003eDargaville PA, Keszler M (2015) Setting the ventilator in the NICU. Pediatric and Neonatal Mechanical Ventilation: From Basics to Clinical Practice:1101-1125\u003c/li\u003e\n \u003cli\u003eDe Blic J, Midulla F, Barbato A, Clement A, Dab I, Eber E, Green C, Grigg J, Kotecha S, Kurland G (2000) Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society. European Respiratory Journal 15:217-231\u003c/li\u003e\n \u003cli\u003eLovas A, Szakm\u0026aacute;ny T (2015) Haemodynamic Effects of Lung Recruitment Manoeuvres. Biomed Res Int 2015:478970\u003c/li\u003e\n \u003cli\u003eHodgson C, Goligher EC, Young ME, Keating JL, Holland AE, Romero L, Bradley SJ, Tuxen D (2016) Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation. Cochrane database of systematic reviews\u003c/li\u003e\n \u003cli\u003eSingh S, Malik G, Prashanth G, Singh A, Kumar M (2012) High frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in preterm neonates with hyaline membrane disease: a randomized controlled trial. Indian pediatrics 49:405-408\u003c/li\u003e\n \u003cli\u003eWallstr\u0026ouml;m L, Sj\u0026ouml;berg A, Sindelar R (2021) Early volume targeted ventilation in preterm infants born at 22-25 weeks of gestational age. Pediatr Pulmonol 56:1000-1007\u003c/li\u003e\n \u003cli\u003eVento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463-470\u003c/li\u003e\n \u003cli\u003eGerstmann DR, Minton SD, Stoddard RA, Meredith KS, Monaco F, Bertrand JM, Battisti O, Langhendries JP, Francois A, Clark RH (1996) The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Pediatrics 98:1044-1057\u003c/li\u003e\n \u003cli\u003eSingh S, Malik G, Prashanth G, Singh A, Kumar M (2012) High frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in preterm neonates with hyaline membrane disease: a randomized controlled trial. Indian pediatrics 49:405-408\u003c/li\u003e\n \u003cli\u003eCastoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G (2011) Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. Am J Perinatol 28:521-528\u003c/li\u003e\n \u003cli\u003eBlazek EV, East CE, Jauncey-Cooke J, Bogossian F, Grant CA, Hough J (2021) Lung recruitment manoeuvres for reducing mortality and respiratory morbidity in mechanically ventilated neonates. Cochrane Database Syst Rev 3:Cd009969\u003c/li\u003e\n \u003cli\u003eCastoldi F, Daniele I, Fontana P, Cavigioli F, Lupo E, Lista G (2011) Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome. American journal of perinatology 28:521-528\u003c/li\u003e\n \u003cli\u003eZheng YR, Lei YQ, Liu JF, Wu HL, Xu N, Huang ST, Cao H, Chen Q (2021) Effect of High-Frequency Oscillatory Ventilation Combined With Pulmonary Surfactant in the Treatment of Acute Respiratory Distress Syndrome After Cardiac Surgery: A Prospective Randomised Controlled Trial. Front Cardiovasc Med 8:675213\u003c/li\u003e\n \u003cli\u003eLecart C, Cayabyab R, Buckley S, Morrison J, Kwong K, Warburton D, Ramanathan R, Jones C, Minoo P (2000) Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation. Neonatology 77:217-223\u003c/li\u003e\n \u003cli\u003eKlingenberg C, Wheeler KI, McCallion N, Morley CJ, Davis PG (2017) Volume-targeted versus pressure-limited ventilation in neonates. Cochrane Database Syst Rev 10:Cd003666\u003c/li\u003e\n \u003cli\u003eChawla S, Natarajan G, Gelmini M, Kazzi SN (2013) Role of spontaneous breathing trial in predicting successful extubation in premature infants. Pediatr Pulmonol 48:443-448\u003c/li\u003e\n \u003cli\u003eKamlin CO, Davis PG, Argus B, Mills B, Morley CJ (2008) A trial of spontaneous breathing to determine the readiness for extubation in very low birth weight infants: a prospective evaluation. Arch Dis Child Fetal Neonatal Ed 93:F305-306\u003c/li\u003e\n \u003cli\u003eMueller M, Wagner CC, Stanislaus R, Almeida JS (2013) Machine learning to predict extubation outcome in premature infants. Proc Int Jt Conf Neural Netw 2013:1-6\u003c/li\u003e\n \u003cli\u003eShalish W, Latremouille S, Papenburg J, Sant\u0026apos;Anna GM (2019) Predictors of extubation readiness in preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 104:F89-f97\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eBaseline characteristics of both studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGestational age (weeks)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e30.05\u0026plusmn;2.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e28.95\u0026plusmn;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eMale\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8(40%)\u003c/p\u003e\n \u003cp\u003e12(60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11(55%)\u003c/p\u003e\n \u003cp\u003e9(45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBirth weight (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e1335.25\u0026plusmn;624.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e1130.25\u0026plusmn;417.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at inclusion\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e1\u003csup\u003est\u0026nbsp;\u003c/sup\u003eDOL\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2\u003csup\u003end\u0026nbsp;\u003c/sup\u003eDOL\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 3\u003csup\u003erd\u0026nbsp;\u003c/sup\u003eDOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14(70%)\u003c/p\u003e\n \u003cp\u003e2(10%)\u003c/p\u003e\n \u003cp\u003e4(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(75%)\u003c/p\u003e\n \u003cp\u003e2(10%)\u003c/p\u003e\n \u003cp\u003e3(15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.915\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAppropriateness for GA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eSGA\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; AGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3(15%)\u003c/p\u003e\n \u003cp\u003e17(85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3(15%)\u003c/p\u003e\n \u003cp\u003e17(85%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCS delivery\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e19(95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e15(75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPGAR score at 5 minutes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e8.0(8.0-9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e8.0(7.0-8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntenatal steroid\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e8(40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e4(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.24914675767918%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePROM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.331058020477816%\" valign=\"top\"\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.160409556313994%\" valign=\"top\"\u003e\n \u003cp\u003e6(30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.25938566552901%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eDOL\u003c/em\u003e day of life, \u003cem\u003eAGA\u003c/em\u003e appropriate for gestational age, \u003cem\u003eSGA\u003c/em\u003e small for gestational age, \u003cem\u003eCS\u003c/em\u003e caesarean section, \u003cem\u003ePROM\u003c/em\u003e prolonged rupture of membranes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; Table 2:\u0026nbsp;\u003c/strong\u003eClinical data and clinical course of both studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory support before inclusion:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eHFNC\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; NCPAP\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1(5%)\u003c/p\u003e\n \u003cp\u003e15(75%)\u003c/p\u003e\n \u003cp\u003e4(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7(35%)\u003c/p\u003e\n \u003cp\u003e11(55%)\u003c/p\u003e\n \u003cp\u003e2(10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRIB score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e5.5(3.25-8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e5.5(3.25-7.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.754\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond dose surfactant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e4(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e5(25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.705\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to extubation (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e3.5(1.63-8.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e3.25(1.63-5.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.968\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eReintubation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e11(55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e10(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.752\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of O\u003csub\u003e2\u0026nbsp;\u003c/sub\u003esupply (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e27(9.5-41.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e14(7.25-50.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.797\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of hospitalization (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e34.5(27.25-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e30.5(9.25-60.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.871\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.34188034188034%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMortality\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.564102564102566%\" valign=\"top\"\u003e\n \u003cp\u003e8(40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.316239316239315%\" valign=\"top\"\u003e\n \u003cp\u003e7(35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.77777777777778%\" valign=\"top\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eHFNC\u003c/em\u003e High flow nasal cannula, \u003cem\u003eNCPAP\u003c/em\u003e nasal continuous positive airway pressure, \u003cem\u003eCRIB\u003c/em\u003e Clinical risk Index for babies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eVentilatory parameters throughout the study among Group A preterm infants\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.385826771653543%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eThird day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.960629921259843%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFifth day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.181102362204724%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep1\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep2\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep3\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFiO2 (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e66.75\u0026plusmn;19.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.385826771653543%\" valign=\"top\"\u003e\n \u003cp\u003e38.08\u0026plusmn;9.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.960629921259843%\" valign=\"top\"\u003e\n \u003cp\u003e40.11\u0026plusmn;15.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.181102362204724%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e0.925\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrequency (Hz)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e12.35\u0026plusmn;0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.385826771653543%\" valign=\"top\"\u003e\n \u003cp\u003e12.38\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.960629921259843%\" valign=\"top\"\u003e\n \u003cp\u003e12.33\u0026plusmn;1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.181102362204724%\" valign=\"top\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta P (cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e25.55\u0026plusmn;2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.385826771653543%\" valign=\"top\"\u003e\n \u003cp\u003e24.23\u0026plusmn;2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.960629921259843%\" valign=\"top\"\u003e\n \u003cp\u003e23.33\u0026plusmn;3.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.181102362204724%\" valign=\"top\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.038\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMAP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.803149606299213%\" valign=\"top\"\u003e\n \u003cp\u003e15.20\u0026plusmn;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.385826771653543%\" valign=\"top\"\u003e\n \u003cp\u003e12.02\u0026plusmn;1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.960629921259843%\" valign=\"top\"\u003e\n \u003cp\u003e11.53\u0026plusmn;2.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.181102362204724%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.078740157480315%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.393700787401574%\" valign=\"top\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eFiO\u003csub\u003e2\u003c/sub\u003e\u003c/em\u003e fraction of inspired oxygen, \u003cem\u003eMAP\u003c/em\u003e mean airway pressure\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003ep1\u003c/em\u003e: difference between first \u0026amp; third day\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003ep2\u003c/em\u003e: difference between first \u0026amp; fifth day\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;p3\u003c/em\u003e: difference between third \u0026amp; fifth day.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; Table 4:\u0026nbsp;\u003c/strong\u003eVentilatory parameters throughout the study among Group B preterm\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003einfants\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"637\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eThird day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFifth day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep1\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep2\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep3\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFIO\u003csub\u003e2\u003c/sub\u003e (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e61.75\u0026plusmn;17.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e35.46\u0026plusmn;16.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e35.33\u0026plusmn;16.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate (b/min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e64.20\u0026plusmn;3.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e43.08\u0026plusmn;8.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e45.50\u0026plusmn;9.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePIP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e16.25\u0026plusmn;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e14.85\u0026plusmn;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e13.67\u0026plusmn;1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePEEP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e6.23\u0026plusmn;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e5.46\u0026plusmn;0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e5.42\u0026plusmn;0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVT (ml/kg)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e6.0\u0026plusmn;0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e5.71\u0026plusmn;0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e5.55\u0026plusmn;0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.138364779874212%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTi (seconds)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.836477987421384%\" valign=\"top\"\u003e\n \u003cp\u003e0.327\u0026plusmn;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.937106918238994%\" valign=\"top\"\u003e\n \u003cp\u003e0.374\u0026plusmn;0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.30817610062893%\" valign=\"top\"\u003e\n \u003cp\u003e0.373\u0026plusmn;0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.220125786163521%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.0062893081761%\" valign=\"top\"\u003e\n \u003cp\u003e0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.748427672955975%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.80503144654088%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eFiO\u003csub\u003e2\u003c/sub\u003e\u003c/em\u003e fraction of inspired oxygen, \u003cem\u003ePIP\u003c/em\u003e peak inspiratory pressure, \u003cem\u003ePEEP\u003c/em\u003e positive end expiratory pressure, \u003cem\u003eVT\u0026nbsp;\u003c/em\u003etidal volume, \u003cem\u003eTi\u003c/em\u003e inspiratory time\u003cem\u003e\u003csup\u003e.\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003ep1\u003c/em\u003e: difference between first \u0026amp; third day\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003eb\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003ep2\u003c/em\u003e: difference between first \u0026amp; fifth day\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\u0026nbsp;p3\u003c/em\u003e: difference between third \u0026amp; fifth day.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5:\u0026nbsp;\u003c/strong\u003eArterial blood gases before and after lung recruitment among both studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTiming\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003epH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e7.24\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e7.24\u0026plusmn;0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.492723492723492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.442827442827443%\" valign=\"top\"\u003e\n \u003cp\u003e7.29\u0026plusmn;0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.52182952182952%\" valign=\"top\"\u003e\n \u003cp\u003e7.32\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.542619542619544%\" valign=\"top\"\u003e\n \u003cp\u003e0.319\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaO\u003csub\u003e2\u003c/sub\u003e (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e60.12\u0026plusmn;8.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e65.34\u0026plusmn;9.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.492723492723492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.442827442827443%\" valign=\"top\"\u003e\n \u003cp\u003e69.17\u0026plusmn;10.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.52182952182952%\" valign=\"top\"\u003e\n \u003cp\u003e69.91\u0026plusmn;11.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.542619542619544%\" valign=\"top\"\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePaCO\u003csub\u003e2\u003c/sub\u003e (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e45.085\u0026plusmn;14.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e43.54\u0026plusmn;11.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e0.708\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.492723492723492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.442827442827443%\" valign=\"top\"\u003e\n \u003cp\u003e41.05\u0026plusmn;8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.52182952182952%\" valign=\"top\"\u003e\n \u003cp\u003e36.07\u0026plusmn;10.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.542619542619544%\" valign=\"top\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCO\u003csub\u003e3\u003c/sub\u003e (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e18.13\u0026plusmn;4.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e18.36\u0026plusmn;3.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e0.846\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.492723492723492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.442827442827443%\" valign=\"top\"\u003e\n \u003cp\u003e18.84\u0026plusmn;2.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.52182952182952%\" valign=\"top\"\u003e\n \u003cp\u003e17.47\u0026plusmn;3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.542619542619544%\" valign=\"top\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.364238410596027%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBE (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.70860927152318%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBefore\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.85430463576159%\" valign=\"top\"\u003e\n \u003cp\u003e-8.42\u0026plusmn;3.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.509933774834437%\" valign=\"top\"\u003e\n \u003cp\u003e7.32\u0026plusmn;0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.562913907284768%\" valign=\"top\"\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.492723492723492%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAfter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.442827442827443%\" valign=\"top\"\u003e\n \u003cp\u003e-6.68\u0026plusmn;3.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.52182952182952%\" valign=\"top\"\u003e\n \u003cp\u003e-7.045\u0026plusmn;4.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.542619542619544%\" valign=\"top\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003epH\u003c/em\u003e potential of hydrogen, \u003cem\u003ePaO\u003csub\u003e2\u003c/sub\u003e\u003c/em\u003e partial arterial pressure of oxygen, \u003cem\u003ePaCO\u003csub\u003e2\u003c/sub\u003e\u003c/em\u003e partial arterial pressure of carbon\u0026nbsp;\u003c/p\u003e\n\u003cp\u003edioxide, \u003cem\u003eHCO\u003csub\u003e3\u003c/sub\u003e\u003c/em\u003e bicarbonate, \u003cem\u003eBE\u003c/em\u003e base excess.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; Table 6:\u0026nbsp;\u003c/strong\u003eHuman transforming growth factor \u0026beta;1 (TGF-\u003cem\u003e\u0026beta;\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e) among both studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.01605136436597%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.85553772070626%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.113964686998393%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.014446227929373%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.01605136436597%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTGF-\u003cem\u003e\u0026beta;\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e before recruitment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.85553772070626%\" valign=\"top\"\u003e\n \u003cp\u003e84.34 (27.74-161.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.113964686998393%\" valign=\"top\"\u003e\n \u003cp\u003e45.32 (32.71-132.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.014446227929373%\" valign=\"top\"\u003e\n \u003cp\u003e0.829\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.01605136436597%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;TGF-\u003cem\u003e\u0026beta;\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e at time of extubation or 5 days after recruitment if extubation was earlier\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.85553772070626%\" valign=\"top\"\u003e\n \u003cp\u003e51.84 (25.03-153.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.113964686998393%\" valign=\"top\"\u003e\n \u003cp\u003e52.84 (36.37-150.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.014446227929373%\" valign=\"top\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.01605136436597%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta change\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.85553772070626%\" valign=\"top\"\u003e\n \u003cp\u003e-9.52 (-88.76-68.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.113964686998393%\" valign=\"top\"\u003e\n \u003cp\u003e-4.97 (-50.9-517.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.014446227929373%\" valign=\"top\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.01605136436597%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.85553772070626%\" valign=\"top\"\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.113964686998393%\" valign=\"top\"\u003e\n \u003cp\u003e0.765\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.014446227929373%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTGF-\u0026beta;\u003csub\u003e1\u003c/sub\u003e\u003c/em\u003e Transforming growth factor.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Respiratory Distress Syndrome, Intensive Care Units, Neonatal, Bronchoalveolar Lavage.","lastPublishedDoi":"10.21203/rs.3.rs-4243658/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4243658/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRespiratory distress syndrome (RDS) is one of the most common causes of premature infant respiratory failure. Recently, many techniques for optimizing fetal-neonatal transition and promoting lung recruitment have been accessible. To compare the effect of lung recruitment using high frequency ventilation versus volume targeted ventilation on duration of intubation as well as its effect on lung inflammation in preterm infants with respiratory distress syndrome.\u003c/p\u003e\n\u003cp\u003eForty preterm infants with RDS were randomly assigned to Group A (LRM with HFOV, n=20) or Group B (LRM with VTV/AC, n=20). TGF-β1 levels measured in BAL samples at two time points. Both groups showed no significant difference in rate of prematurity complications nor delta change of TFG-\u003cem\u003eβ\u003c/em\u003e\u003csub\u003e1\u003c/sub\u003e level in tracheal aspirate of those preterm infants measured before lung recruitment and five days after recruitment or at extubation.\u003c/p\u003e\n\u003cp\u003eConclusions: Lung recruitment maneuver was not associated with significant difference between both groups of preterm infants. The results obtained from our study, being the first of its kind to compare the effect of lung recruitment, provide a promising research area for further investigations.\u003c/p\u003e","manuscriptTitle":"Lung recruitment with high frequency ventilation versus volume targeted ventilation in preterm infants with respiratory distress syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-16 04:48:36","doi":"10.21203/rs.3.rs-4243658/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c12c44a9-9ab6-489b-96f5-b674c12b0fb3","owner":[],"postedDate":"April 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-16T04:48:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-16 04:48:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4243658","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4243658","identity":"rs-4243658","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.