Comparison of continuous positive airway pressure and non-invasive positive pressure ventilation as modes of non-invasive respiratory support for neonates in a Level III neonatal intensive care unit

Objectives: To compare the effectiveness of continuous positive airway pressure (CPAP) and non-invasive positive pressure ventilation (NIPPV) in neonates with mild to moderate respiratory distress. Method: A single centre randomized controlled trial was conducted at the Sri Jayawardenepura General Hospital, Sri Lanka from January to December 2015. The trial was registered with The Clinical Trials Registry ‘Clinical Trials.gov’ retrospectively. Eighty neonates admitted to the neonatal intensive care unit (NICU) were randomly allocated to NIPPV and CPAP. Outcomes of respiratory support were observed and information on risk factors were obtained by going through the bed head tickets of the study cohort. Data analysis was done using SPSS 20 software. Results: Infants treated with NIPPV and CPAP had comparable demographic data and clinical status at the time of enrolment into the study. Infants treated initially with NIPPV needed less endotracheal ventilation than infants treated with CPAP (35% vs 40%, p = 0.644) but this difference is not statistically significant. Conclusions: The risks for respiratory failure and the need for ventilation were not statistically significantly different whether using NIPPV or CPAP. _____________________________________ Teaching Hospital Mahamodara, Galle, Sri Lanka, Sri Jayawardenepura Teaching Hospital, Sri Lanka *Correspondence: kaushalya.gomez@yahoo.com (Received on 20 November 2017: Accepted after revision on 22 December 2017) The authors declare that there are no conflicts of interest Personal funding was used for the project. Open Access Article published under the Creative Commons Attribution CC-BY License DOI: http://dx.doi.org/10.4038/sljch.v47i3.8547 (


Introduction
Respiratory distress accounts for 30-40% of admissions to neonatal intensive care units (NICUs) and special care baby units (SCBUs) 1 .Whilst non-invasive respiratory support causes minimal damage to the developing neonatal lung parenchyma and minimal systemic damage, invasive ventilation can lead to permanent lung damage with poor respiratory capacity, frequent wheezing and broncho-pulmonary dysplasia.Invasive ventilation also predisposes the neonate to ventilator associated pneumonia, bacterial and fungal sepsis, prolonged NICU stay, over-crowding and is an economic burden to the parents and state 2,3 .
National Emergency Obstetric and Neonatal Care Needs Assessment Country Report published in 2012 by the Ministry of Health and the Family Health Bureau of Sri Lanka shows total ventilation as a percentage of total admissions to neonatal care units to be 5.4% and nasal CPAP support as 3.9%.There is no data regarding NIPPV use.Most centres in Sri Lanka use CPAP as a non-invasive method and conventional ventilation as an invasive method.
NIPPV is the augmentation of CPAP with superimposed inflations to a set peak pressure.Mechanism of action of NIPPV remains uncertain.Hypotheses include increasing pharyngeal dilation, improving respiratory drive, increasing mean airway pressure, allowing recruitment of alveoli, increasing functional residual capacity and increasing tidal and minute volume 4,5,6 .Previous studies on comparison between CPAP and NIPPV on weaning from invasive ventilation showed, weaning to NIPPV leads to better outcome 4,[7][8][9][10] .A recent synchronised NIPPV study demonstrated a relative risk reduction for intubation in the first 72 hours in the NIPPV group compared to CPAP (RR 0.60, 95% CI 0.43, 0.83) 11 .There is some evidence to suggest that NIPPV may be useful as a mode of primary respiratory support, but the evidence is not conclusive 12 .However, in Sri Lanka, such studies have not been done.Ethical aspects: Ethical approval was obtained from the Ethical Review Committee of SJGH, Kotte.Written informed consent was obtained from parents or guardians of eligible infants before randomization.The data sheets did not contain names and were anonymous.Data was stored under lock and key with restricted access only to the principal investigators.The computerized data were password protected and were only available to the investigators.

Objectives
Statistical analysis: All data were collected into an Excel database and analysed using SPSS 20 software.
Relative risk was calculated for main outcome and Chi square significance was assessed for association with risk factors.P value less than 0.05 was considered statistically significant.

Results
Total sample of 80 newborns was randomly equally allocated into two treatment categories; NIPPV (n=40) and CPAP (n=40).As shown in Table 1, the distribution of the demographic and birth variables in the 2 groups did not demonstrate statistically significant differences.Association between type of respiratory support and grades 3 and 4 intraventricular haemorrhage (IVH) is shown in Table 3.

5%) IVH: intraventricular haemorrhage
There were two neonates with grade 3/4 IVH in the NIPPV group and only one neonate in CPAP group.As the number was small, an association could not be calculated using the Chi square test.Data showed twice the risk of developing IVH among NIPPV compared to CPAP but this was not statistically significant (p=0.56).There was no significant difference in the presence of IVH between the two groups of respiratory support.
Comparison of duration of support and length of hospital stay is shown in Table 4. Mean duration of hospital stay was similar in both groups.There was no statistically significant difference noted in time taken to achieve full enteral feed.

Discussion
In this randomised trial, we found reduced need for endotracheal intubation and invasive ventilation overall within the first 72 hours in the NIPPV group (35%) when compared with CPAP (40%) but this was not statistically significant.This finding could mean that there was actually no difference with the two methods or the effect could have been masked because of sample size and heterogeneity of the sample.
The Cochrane meta-analysis done in 2016 concluded that "Early NIPPV does appear to be superior to NCPAP alone for decreasing respiratory failure and the need for intubation and endotracheal tube ventilation among preterm infants with respiratory distress syndrome" 16 .Our results not showing a significant difference may also be due to it consisting of all the newborn with respiratory distress due to various pathologies.In future research, we need to specifically target groups such as preterm.The devices used are different in other research when compared to our study.In this research no statistically significant difference was noted in the time taken to achieve full enteral feed.In both arms the mean duration to achieve full feed was 6.5 days.Previous studies did not show a reduction in necrotizing enterocolitis stage 2 [15][16][17][18][20][21][22][23] or time to achieve full feed 4,7,24,25 greater in one treatment group compared with the other.
Limitations of the study include the small sample size, the impossibility to blind caregivers and the heterogeneity of the pathogenesis in the study cohort.Future researche should focus on the effectiveness, safety and long term outcomes such as long-term survival, chronic lung disease and neurodevelopmental impairment of early NIPPV in comparison to CPAP and should focus not only on surfactant deficiency lung disease but also various other disease conditions.

Conclusions
In our study, the risks for respiratory failure and the need for ventilation were not statistically significantly different whether using NIPPV or CPAP. 4

Table 1 : Demographic data of the neonates included in the study
Around half the sample (48.7%) of neonates who needed respiratory support were babies born to mothers with no risk factors.Among the risk factors, pregnancy induced hypertension (PIH) was the commonest (21% of total sample).Association with maternal risk factors was statistically significant (p=0.013).Effectiveness of CPAP and NIPPV in neonates with mild to moderate respiratory distress is shown in Table2.
POA: Period of amenorrhoea, LSCS: lower segment caesarean section, RDS: respiratory distress syndrome, GDM: gestational diabetes mellitus, PIH: pregnancy induced hypertensionBabies born through emergency caesarean section needed more respiratory support than other modes of deliveries.Type of respiratory support did not show any association with period of amenorrhoea (POA), birth weight (BW), mode of delivery (MOD) or cause of respiratory distress.