|Year : 2019 | Volume
| Issue : 2 | Page : 93-100
Study of the effects of the use of sustained lung inflation in treatment of preterm infants with respiratory distress in the delivery room
Hesham Ghazal, Hassan Heshmat, Khalid M Saad, Marwa Abdel Karim
Department of Pediatrics, Neonatology, NICU, Alexandria University, Alexandria, Egypt
|Date of Submission||08-Apr-2019|
|Date of Decision||06-May-2019|
|Date of Acceptance||06-May-2019|
|Date of Web Publication||6-Feb-2020|
BSc, MSc, PhD Hassan Heshmat
Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria
Source of Support: None, Conflict of Interest: None
Objective To assess the effect of sustained lung inflation (SLI) on the need for invasive mechanical ventilation (MV) within the first 72 h of age in preterm infants with respiratory distress.
Study design In this controlled trial, we randomly assigned preterm infants 33 weeks of gestation or less to receive SLI (25 cmH2O) at birth, to be repeated if needed for a second time (30 cmH2O) followed by continuous positive airway pressure (CPAP), or assistance according to the recommendations of the American Academy of Pediatrics. The primary outcome was the need for invasive MV within the first 72 h of life. The secondary outcomes included development of bronchopulmonary dysplasia or death. The risk ratios (RRs) and 95% confidence intervals of the outcomes were calculated for the SLI group and compared with the control group.
Results A total of 145 infants were enrolled: 71 in the SLI group and 74 in the control group. Less preterm infants needed invasive MV in the SLI of preterm group compared with the control group (19.72 vs. 29.73%; RR, 0.6633; 95% confidence interval, 0.2693–1.2517), with a number needed to treat of 10 patients; the difference was statistically significant by multivariate logistic regression (P=0.032). No statistically significant difference was detected between the studied groups regarding the occurrence of bronchopulmonary dysplasia, and also the median cumulative survival for the SLI of preterms group showed no statistically significant difference when compared with the median of the standard group.
Conclusion A sustained inflation followed by early nasal CPAP, delivered through a nasopharyngeal tube, is a more efficient strategy than repeated manual inflations with a self-inflating bag and mask followed by nasal CPAP on admission to the neonatal intensive care unit.
Keywords: delivery room, preterm, sustained lung inflation
|How to cite this article:|
Ghazal H, Heshmat H, Saad KM, Karim MA. Study of the effects of the use of sustained lung inflation in treatment of preterm infants with respiratory distress in the delivery room. Alex J Pediatr 2019;32:93-100
|How to cite this URL:|
Ghazal H, Heshmat H, Saad KM, Karim MA. Study of the effects of the use of sustained lung inflation in treatment of preterm infants with respiratory distress in the delivery room. Alex J Pediatr [serial online] 2019 [cited 2020 Apr 9];32:93-100. Available from: http://www.ajp.eg.net/text.asp?2019/32/2/93/277838
| Introduction|| |
A normal functional residual capacity (FRC) is important in determining optimum lung mechanics and alveolar gas exchange. So an adequate FRC must be established shortly after birth and then be sustained. In premature infants, specific compliance remains low, owing in part to diffuse microatelectasis and failure to achieve a normal FRC, because the lung recoil forces are incompletely opposed by the excessively compliant chest wall . Surfactant replacement therapy has dramatically improved the outcome of newborns with respiratory distress syndrome (RDS) . Selective administration of surfactant to infants requiring intubation is now a preferred alternative to prophylactic surfactant administration . Delivery of distending pressure to maintain airway and alveolar expansion via invasive and noninvasive support is the cornerstone for treatment of RDS. In contrast with the impressive improvement in mortality, the incidence of bronchopulmonary dysplasia (BPD) remains unaltered in most studies. Infants who have BPD experience both higher morbidity and mortality than infants who do not. Sustained inflation has been proposed as a method of optimizing lung aeration at birth, decreasing the need for intubation and mechanical ventilation (MV), together with decreased oxygen requirements. It is defined as positive pressure inflation designed to establish FRC and applied over a longer period of time than would normally be used to deliver subsequent tidal inflations .
| Aim|| |
The aim was to assess the effect of sustained lung inflation (SLI) on the need for invasive MV within the first 72 h of age in preterm with respiratory distress.
| Patients and methods|| |
We conducted this unblinded randomized controlled trial at the delivery rooms (DRs) and the neonatal intensive care unit (NICU) of Alexandria University Maternity Hospital. The study included 160 preterm infants less than or equal to 33 weeks of gestation requiring respiratory support in the DR. Exclusion criteria included major congenital anomalies, infants considered nonviable by the attending neonatologist (<24 weeks of gestational age), and fetal hydrops. This study was approved by Medical Research Ethics Committee at Alexandria Faculty of Medicine, and an informed consent was obtained from children’s guardians. The eligible infants were grouped as follows.
Sustained lung inflation pressure group
Eighty-three preterm infants after receiving the initial steps of resuscitation according to the neonatal resuscitation program (2011)  received SLI via a nasopharyngeal tube at 25 cmH2O for 15 s followed by nasal continuous positive airway pressure (NCPAP) at a positive end expiratory pressure (PEEP) 5 cmH2O, to be increased to 30 cmH2O for another 15 s and followed by NCPAP at a PEEP 6 cmH2O if the baby did not show improvement (apnea, gasping, labored breathing) after the initial SLI. Twelve infants were excluded (n=71).
Seventy-seven preterm infants received the standard care as recommended by the latest neonatal resuscitation program 2011 guidelines , followed by NCPAP at a PEEP from 5–7 cmH2O or endotracheal tube and positive pressure ventilation (PPV).
In both groups, an endotracheal tube was inserted and PPV started if the infants remained apnic, gasping, bradycardic, or cyanosis persisted despite the correct resuscitation maneuvers.
The patients of each group were chosen randomly by the sealed envelope method. The SLI was delivered through nasopharyngeal tube in one nostril (with manual closure of the mouth and other nostril) and using Fisher and Paykel T piece ventilator. The NCPAP was delivered using Fisher and Paykel T piece ventilator via nasopharyngeal tube in one nostril with closure of the other nostril by a nasogastric tube. PPV was given when needed during resuscitation using a self-inflating bag (ambu bag).
After stabilizing the infants in the DR, they were transferred to the NICU to continue their management.
At the neonatal intensive care unit
Preterm infants put on MV were either intubated at the DR or had failure of NCPAP in the NICU. Criteria of failure of CPAP were as follows: failure to maintain O2 saturation within the target or had Silverman Anderson Score  more than or equal to 7 or pH less than 7.25, PaO2 less than 50 mmHg, and PaCO2 more than 55–60 mmHg while on maximum CPAP support (PEEP >7 cmH2O and FiO2>40%). Infants were extubated when their requirements to maintain their O2 saturation within the target reached FiO2 less than 30% and a mean airway pressure of 6–7 cmH2O. Beractant surfactant (Survanta) was used at a dose of 4 ml/kg (Abbott Laboratories, North Chicago, Illinois, USA). Survanta was indicated for any intubated preterm infant either from DR or after failure of CPAP, and according to the unit protocol was given within the first 4 h.
The primary outcome was the need for MV within the first 3 days of life. The secondary outcomes were death in hospital or development of BPD. Diagnosis of BPD was based on the need for supplemental oxygen to maintain adequate oxygenation at 36 weeks postconceptional age in surviving infants .
Other collected data
Resuscitation time, need for intubation in DR or by 24 h of age, type of respiratory support (CPAP, PPV) on departure from DR, five-minute Apgar score, oxygen profile, and saturation over first 24 h postdelivery using hourly FiO2 and saturation records were noted. Highest FiO2 level recorded during the first 48 h after DR; use of surfactant; use of inotropes during the first 48 h of life in NICU; chest radiograph at admission; air leaks including pulmonary interstitial emphysema and pneumothorax; total and detailed duration of respiratory support (MV, CPAP, and high-flow nasal cannula) during hospitalization, intraventricular hemorrhage (IVH) at 48 h, 10 days, and at discharge (30 days) for the survivors; retinopathy of prematurity (ROP); and cumulative survival analysis were examined.
Data were collected and entered to the computer using SPSS program for statistical analysis (version 21) (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). Data were entered as numerical or categorical, as appropriate. When Kolmogorov–Smirnov test revealed no significance in the distribution of variables, parametric statistics was carried out, whereas in the not normally distributed data, the nonparametric statistics were carried out. Categorical variables were described using frequency and percentage of total. Comparisons were done using Student’s t test for parametric and the Mann–Whitney U test for nonparametric variables and χ2 test for qualitative variables. For categorical variables, relative risk (RR) with the 95% confidence interval (CI) and number needed to treat (NNT) were analyzed.
| Results|| |
The numbers of infants who were eligible for the study and who were randomly assigned to receive the SLI procedure or the standard care in the DR are shown in [Figure 1].
A total of 145 infants were enrolled between August 2015 and July 2017.
No further exclusions from the intention-to-treat population were done. All infants were followed up to their first discharge.
The baseline characteristics of the preterm infants and their mothers are listed in [Table 1] and [Table 2].
|Table 1 Comparison of demographic and clinical characteristics of the studied neonates|
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|Table 2 Comparison between studied groups regarding the delivery room data|
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In the current study, more preterm infants needed MV within the first 72 h in the control group compared with the sustained lung inflation pressure (SLIP) group (22 vs. 14), and despite that the event rate was almost doubled in the control group. This difference was not found to be statistically significant (P=0.16) ([Table 3]). Post-hoc analysis of gestational-age subgroups showed that the greatest effect was at 28–30 weeks of gestation (need for MV within the first 72 h: five (33.33%) of 15 versus seven (53.85%) of 13, though the difference was not statistically significant). Need for intubation in the DR was significantly lower in the SLIP group, with only 4.23% preterm infants needing intubation in the DR, unlike 16.22% preterm infants in the control group (P=0.03). Only 4.23% preterm infants in the SLIP group needed PPV during resuscitation in the DR in comparison with 33.78% preterm infants in the control group, a difference that is statistically significant (P<0.01). A statistically significant difference was also detected between the two groups regarding the 1- and 5-min Apgar score, being higher in the SLIP group (P=0.001). Preterm infants in the SLIP group showed less signs of respiratory distress at 1 h of age when compared with the control group using the Silverman Anderson Score (P=0.001).
|Table 3 Comparison between studied groups regarding the secondary outcomes|
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The average FiO2 requirements to maintain target saturation desired for preterms during the first 24 h revealed that the requirements were significantly lower in the SLIP group when compared with the control group (P=0.005) ([Figure 2]).
|Figure 2 Box and whisker graph of the average FiO2 (%) requirements during the first 24 h in both studied group; the thick line in the middle of the box represents the median, the box represents the interquartile range (from 25th to 75th percentiles), the whiskers represents the minimum and maximum after excluding outliers (black-filled circle), and the number indicates the serial number in the original master table.|
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Regarding the total duration of respiratory support in days, the duration was shorter in the SLIP group in comparison with the control group, a difference that was found to be statistically significant (P=0.027).
There was no statistical significant difference in the incidence of development of BPD, IVH, white matter injury, or ROP between the studied groups ([Table 3]).
In the current study, the median cumulative survival for the SLIP group showed no statistically significant difference when compared with the median of the control group.
Multivariate logistic regression analysis was used to assess the association between intervention and outcome. It demonstrated that SLIP, female sex, and higher GA were all significant contributing factors to not needing MV within the first 72 h, but not the weight.
| Discussion|| |
The current trial was held in the DR and NICU of Alexandria University Maternity Hospital. A total of 145 preterm infants (28–33 weeks of gestation) were assigned randomly in the DR to either a sustained inflation (25 cmH2O for 15 s followed by 30 cmH2O for 15 s if needed) through a nasopharyngeal tube followed by early NPCPAP (SLIP; n=71) or conventional care with early NPCPAP or repeated manual inflations with a self-inflating bag and mask followed by NPCPAP (control; n=74). The primary outcome measure was need for MV within the first 72 h of age. BPD at 36 weeks and/or death was used as measure for secondary outcome.
Need for intubation in the DR was significantly lower in the SLIP group, with only 4.23% preterm infants needing intubation in the DR, unlike 16.22% preterm infants in the control group (P<0.0311; RR, 0.2606; 95% CI, 0.0765–0.8848), with a NNT of nine patients. No statistically significant difference was detected regarding the need for intubation within 24 h after DR.
Similar result was demonstrated by Grasso et al. , in their observational analytical cross-sectional case–control study.
Comparably, El-Chimi et al.  also had a DR intubation of 5.3% in the SLI group versus 23.6% in the CMBI group, with a P=0.005. te Pas and Walther  also demonstrated a significant reduction in the DR intubation between their study groups, i.e., early functional residual capacity intervention (EFURCI) and conventional groups, with 17 versus 36%, respectively (P=0.002, OR = 0.37; 95% CI, 0.20–0.70). Lindner et al. , in their study conducted on 123 preterm infants more than or equal to 24 weeks (SLI n=67 and control n=56), showed significant decrease in DR intubation (40% in SLI group versus 84% in control group) (P<0.001).
The average FiO2 requirements during the first 24 h revealed that the FiO2 needed to keep the infants within the target saturation was lower in the SLIP group when compared with the control group, with a median [interquartile range (IQR)] of 22.54 (21.79–30.41) in the former and 25.93 (22.32–36.80) in the latter. The difference was found statistically significant (P=0.005). te Pas and Walther  and Lista et al.  showed that the FiO2 used initially at time of admission did not differ significantly between the two study groups, but they did not mention further FiO2 tracing beyond that mentioned on admission.
In the current study, more preterm infants needed invasive MV within the first 72 h in the control group compared with the SLIP group (22 vs. 14), and despite that the event rate was almost doubled in the control group; this difference was not found to be statistically significant (P<0.163; RR, 0.6633; 95% CI, 0.2693–1.2517) and a NNT of 10 patients. Moreover, the timing for initiation of MV in hours was not statistically significant between the two groups, with a range of 1–30 h in the SLIP group and 2–30 h in the control group, and a median (IQR) of 5.00 h (2.50–19.75 h) and 2.00 h (0.00–10.25 h), respectively (P<0.083).
Our results regarding the need for MV within the first 72 h were consistent with the most recent data reported in literature on the SLI maneuver; however, we failed to prove significant statistical difference owing to our small sample size. So multivariate logistic regression was done to study the effect of SLI maneuver on the outcome taking in consideration other variables that can affect the outcome as well.
Similarly, El-Chimi et al.  demonstrated that MV within the first 72 h after birth with exclusion of DR intubations did not differ between the two groups (19.3% in the SLI group versus 22% in the CMBI group) (P=0.37). They performed logistic regression analysis for predicting the association between DR SLI and MV within first 72 h. They considered the success in not using MV as the dependent variable and SLI, GA, severity of RDS, and antenatal steroids as the predictable variables and concluded that success was significantly related to SLI, increased maturity, and less severe RDS, but not related to antenatal steroids.
On the contrary, Lindner et al.  showed no difference at all regarding the need for intubation and early MV between the SLI group and the control group (61 versus 70%, respectively; P=0.59). Such result could be explained by the small sample size enrolled in the study and the lower gestational age (25–28 weeks) too.
Comparable to Lindner et al. , Harling et al.  revealed that the SLI group required more respiratory support than the CLI group (92.3 and 84.6%, respectively). They attributed this result to the lower gestation and lower birth weight of the SLI group.
Grasso et al.  demonstrated fewer infants required invasive MV in the SLI group than in the control group (P≤0.001). Lista et al.  as well reported significant statistical difference between the SLI (51%) and the control (76%) groups (P<0.0001), and a NNT of 4.
Te Pas and Walther  recorded 37 versus 51% need for MV within the first 72 h between EFURCI and control groups, respectively (P=0.04).
Schmolzer et al.  in their systematic review and meta-analysis included four randomized clinical trials comprising 611 preterm infants ,,,, comparing the effects of SI (sustained inflation) with intermittent positive pressure ventilation (IPPV) at birth in preterm infants for neonatal outcomes. They aimed at reviewing the available literature on the use of SI compared with IPPV at birth in preterm infants for major neonatal outcomes, including BPD and death. The results of this meta-analysis demonstrate that providing SI to preterm infants in the DR results in beneficial short-term respiratory effects with significantly lower numbers of infants mechanically ventilated within the first 72 h of life (RR, 0.87; 95% CI, 0.77–0.97) and a NNT of 10 patients.
O’Donnell et al.  in their meta-analysis included trials comparing SI (defined as inflations> 1 s) with IPPV (defined as inflations ≤1 s) in term or preterm infants. Only two trials, with a total of 352 infants, were eligible for inclusion 11,15]). They concluded that there was no significant difference in the pulmonary outcomes of intubation in the first 3 days of life or chronic lung disease. Of the 71 preterm infants enrolled in the SLIP group, 49.30% received SI once (25 cmH2O) and 50.70% received SI twice (30 cmH2O). Preterm infants who required SI twice (11/36) required MV within the first 72 h more frequently than those who received SI once (3/35) (78.57 versus 21.43%, respectively). The difference was found to be statistically significant (P<0.020).
Similarly, te Pas and Walther  showed that 60% of infants in the EFURCI group had SI once (20 cmH2O) and that 40% required a second inflation (25 cmH2O), and 62% of the infants needing second inflation needed intubation.
The duration of invasive respiratory support in days in ventilated infants was less in the SLIP group than the control group, with a median (IQR) of 4.00 (2.00–7.00) in the SLIP group and of 5.00 (2.00–9.00) in the control group, a difference that is not statistically significant (P<0.673).
The duration of noninvasive respiratory support in days was less in the SLIP group than the control group, with a median (IQR) of 2.00 (1.00–5.00) in the SLIP group and 4.00 (1.25–6.00) in the control group, a difference that is statistically significant (P<0.048)
We also found that the total duration of stay on NPCPAP in days was longer in the control group than in the SLIP group, a difference that was found to be statistically significant, with a median (IQR) of 3.00 (1.00–5.00) in the former and 2.00 (1.00–4.75) in the latter (P<0.032).
Regarding the total duration of respiratory support in days in the present study, the duration was shorter in the SLIP group in comparison with the control group, a difference that was found to be statistically significant, with a median (IQR) of 7.00 (3.00–11.00) in the former and 9.00 (6.00–12.25) in the latter (P<0.027).
Comparable to our results were those of Lista et al. , who demonstrated significant reduction in duration of MV (P=0.008) and O2 therapy (P=0.016).
Grasso et al.  also demonstrated that the mean duration of ventilation was significantly shorter in the SLI group than in the control group (P≤0.001).
Lista et al. , on the contrary, showed no difference between the studied groups regarding duration of ventilation or CPAP.
In the current study, there was no significant difference between the studied groups regarding the incidence of pneumothorax (P<0.765) and pulmonary interstitial emphysemas (P<0.086).
There was no statistically significant difference in the incidence of development of IVH, white matter injury, or ROP between the studied groups.
All studies ,, revised in the literature about SI of preterm infants similarly demonstrated no significant difference at all between the studied groups regarding pneumothorax, mild and severe IVH, white matter injury, and ROP.
In the present study, three preterm infants in the control group developed BPD (4.05%), whereas there was no BPD in the SLIP group; however, there was statistically insignificant difference (P<0.258).Matching our results were those of Grasso et al. , El-Chimi et al. , Lindner et al. , Harling et al. , and Lista et al. . They all demonstrated higher incidence of BPD among the control groups when compared with the SLI groups; however, the difference was not significant.
On the contrary, Lista et al.  showed significant reduction in BPD among the SLI group (P=0.004), but the control group in this study was taken retrospectively (2004–2006) and the SLI group prospectively (2007–2009). The authors declared that the presence of a historical group constitutes a bias given the number of changes that occurred over time in the care of premature infants.
The total duration of hospital stay for all infants enrolled in the study ranges from 4 to 81 days in the SLIP group and 3–168 days in the control group, with a median (IQR) of 20.00 (10.00–38.00) in the former and 20.50 (10.00–43.00) in the latter. There was no statistically significant difference (P<0.349).
Lista et al. , also showed no significant difference between SLI and control group concerning duration of hospital stay.
In the current study, the median cumulative survival for the SLIP group was 23 days (95% CI, 8.27–37.72), showing no statistically significant difference when compared with the median of control group, with 22 days (95% CI, 13.89–30.109) [χ2 (log-rank)=0.105, P=0.746]. All studies reviewed in the literature ,,,,, demonstrated no significant difference in mortality between groups.
The research was supported by Alexandria Faculty of Medicine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]