|Year : 2015 | Volume
| Issue : 2 | Page : 96-100
Continuous positive airway pressure in meconium aspiration syndrome: An observational study
Priya Bhagwat1, Srinivas Murki1, Ashish Mehta2, Tejopratap Oleti1, Dhanraj Gannavaram3
1 Department of Neonatology, Fernandez Hospital, Hyderabad, Andhra Pradesh, India
2 Department of Neonatology, Arpan Children's Hospital, Ahmedabad, Gujarat, India
3 Department of Pediatrics, Paramitha Children Hospital, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||6-Apr-2015|
Dr. Srinivas Murki
Department of Neonatology, Fernandez Hospital, Hyderabad, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Continuous positive airway pressure (CPAP) as a treatment modality is well established in respiratory distress syndrome. There is still a lot of skepticism for use of CPAP in meconium aspiration syndrome (MAS). We studied the use of CPAP as a primary treatment modality in MAS and tried to identify factors predicting CPAP failure. Objectives: The aim was to identify failure rates of MAS on bubble or ventilator nasal CPAP and potential predictors of CPAP failures in MAS cases. Design: Multicenter observational analytical study. CPAP failures were compared with CPAP success for perinatal and neonatal variables. Methods: From January 2012 to May 2013, 97 babies were admitted with diagnosis of MAS, out of which 66 babies were enrolled in the study. Bubble or ventilator nasal CPAP was started if the SpO 2 in room air was <90%. CPAP failure was defined as the need for mechanical ventilation (MV). Outcome variables were compared between the MAS infants who failed CPAP and those who were successfully managed with CPAP. Results: Sixteen infants (24%) out of 66 failed to CPAP. Reasons for failure were: 10 infants had increased oxygen requirement (7 had persistent pulmonary hypertension and 3 had sepsis with multiorgan dysfunction). Two infants were ventilated for poor efforts (due to recurrent seizures), 3 (4.5%) for worsening pneumothorax and one infant for severe metabolic acidosis. Baseline variables were compared between the infants who failed CPAP and those who were successfully managed with CPAP alone. On univariate analysis, factors significantly associated with CPAP failure were out-born status, abnormal cardiotocograph, high FiO 2 at 1 h and high positive end-expiratory pressure at 1 h (P < 0.05) of starting CPAP. On logistic regression analysis, only out-born status was independently associated with CPAP failure (OR = 25, 95% CI: 1.5-300, P < 0.01) and there was a trend toward CPAP failure in infants depressed at birth (OR = 10, 95% CI: 0.9-122). Conclusion: CPAP when applied early may reduce the need for MV in newborns with moderate to severe MAS infants.
Keywords: Continuous positive airway pressure failure, meconium aspiration syndrome, predictors of Continuous positive airway pressure failure
|How to cite this article:|
Bhagwat P, Murki S, Mehta A, Oleti T, Gannavaram D. Continuous positive airway pressure in meconium aspiration syndrome: An observational study. J Clin Neonatol 2015;4:96-100
|How to cite this URL:|
Bhagwat P, Murki S, Mehta A, Oleti T, Gannavaram D. Continuous positive airway pressure in meconium aspiration syndrome: An observational study. J Clin Neonatol [serial online] 2015 [cited 2020 Apr 5];4:96-100. Available from: http://www.jcnonweb.com/text.asp?2015/4/2/96/154107
| Introduction|| |
Babies born with meconium-stained amniotic fluid (MSAF) are hundred fold more likely to develop substantial respiratory distress than those born with clear amniotic fluid.  About 2-9% of infants born through MSAF develop meconium aspiration syndrome (MAS).  Mortality rates of MAS have decreased over the years from 28% to 40% in 1970s and 1980s to around 15% being reported in recent literature. , This reduction in mortality rates appears to be related (a) to reduction in incidence of MAS, directly related to changes in obstetric practices (b) to use of adjunct respiratory therapies, such as exogenous surfactant, nitric oxide and high-frequency ventilation. Infants with MAS in developing countries still continue to have worse outcomes due to factors such as poor monitoring during labor, low Apgar scores and need for mechanical ventilation (MV) among infants with MAS and nonavailability of the adjunct respiratory therapies associated with reduction in mortality.  In developing countries like ours, it is not uncommon for infants with MAS with no access to a tertiary level neonatal intensive care unit (NICU) for MV.
Most of our centers treat respiratory distress in newborns with oxygen alone and accept high morbidity and mortality. Approximately, 50% of neonates with MAS will have severe form defined as the need for MV.  Although ventilation can be lifesaving, need for MV translates into prolonged hospital stay, increased burden on health care delivery system and escalating treatment costs. Both invasive and noninvasive ventilation (NIV) play an equal role in the management of MAS. ,
As an initial modality of treatment in MAS, continuous positive airway pressure (CPAP) has tremendous untapped potential especially in resource-limited country like ours. The aim of this work was to study the role of CPAP in MAS, its success/failure rates and the predictors of CPAP failures.
| Methods|| |
Multicenter prospective observational analytical study
The study was conducted in the Neonatal departments of Fernandez Hospital and Paramita Hospital Hyderabad, Arpan Children's Hospital, Ahmedabad during the period from January 2012 to May 2013.The study was approved by the institutional review board at Fernandez Hospital. Informed written parental consent was taken before enrollment and also for ventilation and surfactant administration.
Ninety-seven infants were admitted to NICU during the study period from January 2012 to May 2013 (17 months), with a diagnosis of MAS. MAS in a neonate was defined as the presence of MSAF at birth, clinical evidence of respiratory distress within 6 h of life and CXR suggestive of aspiration pneumonia. Term/late preterm infants admitted to NICU within the first 24 h of life and with a diagnosis of MAS, saturation <90% on room air, and Downe score >5 was included in the study. Downe score is an objective method to assess the severity of respiratory distress in newborns. It includes respiratory rate (RR), recessions, grunt, air entry and fractional oxygen requirement. Each parameter is score on a scale of 0, 1 and 2 with increasing severity. Total score ranges from 0 to 10. Late preterm gestation was defined as a gestation age from 34 1/7 days to 36 6/7 days. Gestational age assessment was done from the mothers LMP and later confirmed by New Ballards examination. Infants who were intubated at admission to NICU, having lethal congenital malformations, infants with pneumothorax were excluded from the study. No a priori sample size was estimated.
Interventions and monitoring
Enrolled infants were administered CPAP after obtaining the consent from the parents or guardian. CPAP was started with any of the available ventilators/bubble CPAP generator. The interface was bilateral nasal prongs (Hudson prongs or Rams cannula). Hudson prongs were fixed as per standard guidelines. CPAP was started at a CPAP pressure of 5 cm, FiO 2 50% and flow of 5 L/min. CPAP pressure and FiO 2 was adjusted to maintain a SpO 2 between 89% and 95% with a maximum pressure limit of 6 cm and FiO 2 of 100%. CPAP was removed when the SpO 2 was >90% with FiO 2 requirement <25% and when the respiratory distress was passive (RR < 60/min, no or mild retractions and no grunt). Postextubation oxygen was given either with hood or with binasal oxygen prongs as appropriate. Port holes of the hood were closed or opened to maintain SpO 2 between 90% and 95%. Those with SpO 2 >95% were gradually weaned off from the oxygen. Management of other co-morbid conditions such as pulmonary hypertension, shock, seizures, renal dysfunction, therapeutic hypothermia, fluid, electrolyte, acid and base imbalances were at the discretion of the attending physician.
All neonates enrolled in the study were constantly monitored for clinical signs of respiratory distress using the Downe's score. A chest radiograph was done before enrollment into the study. An arterial blood gas analysis was done at enrollment and at 6 h after intervention. Neonates failing CPAP were started on synchronous intermittent mandatory ventilation (SIMV) mode of ventilation. Criteria for MV was defined as SpO 2 <90% or PaO 2 <50 mm of Hg on FiO 2 100% or PaCO 2 >60 mm of Hg with a pH <7.25 or poor respiratory efforts or new onset pneumothorax with unstable vitals. Higher modes of ventilation such as high-frequency oscillatory (HFO), and iNO were used as per existing unit protocol. Surfactant was given by InSurE technique if the FiO 2 was consistently (>2 h) above 50%. All relevant perinatal data and neonatal data till discharge or death were collected in a predesigned case reporting form.
Outcomes and predictors of continuous positive airway pressure failure
Primary outcome variable was need for MV (CPAP failure). Secondary outcome variables were rate of survival, duration of oxygen in hours, duration of ventilation in hours, duration of hospital stay in days and change in Downe score, heart rate, RR and FiO 2 from enrolment to 6 h of intervention.
Predictors of CPAP failure studied include birth weight, gestation, sex, abnormal cardiotocography, Apgar score at 1 and 5 min, echo diagnosis of persistent pulmonary hypertension (PPHN), chest X-ray (CXR) categorization (low volume/hyperinflation/mild or moderate or severe infiltrates), maximum FiO 2 requirements in the first hour of CPAP, maximum pressure requirement at the end of first hour of CPAP. Infiltrates were classified as mild if they were present in one or two zones, moderate if they were present in 3-5 zones and severe if all zones of the lung were showing infiltrates. X-rays were read by neonatologist (Dr. MS and Dr. AM).
Outcome variables were compared between the infants who failed CPAP and those who were successfully managed with CPAP. Categorical variables were compared with Chi-square test, while continuous variables were analyzed using Student's t-test for normal distributions. Significance was defined as P < 0.05 for the predefined outcome variables and P < 0.01 for other outcome variables explored post-hoc. Odds for CPAP failure were analyzed using logistic regression analysis.
| Results|| |
During the study period, a total of 97 infants were admitted to NICU with a diagnosis of MAS. Sixty-six infants were enrolled in the study [Figure 1]. The mean birth weight of enrolled infants was 3073 ± 426 g and mean gestational age was 38 ± 1.2 weeks. Sixty-eight percent of enrolled infants were males (n = 44). Growth restriction at birth was present in four infants. Thirty-eight percent of infants were out-born (n = 25). Caesarean section was the mode of delivery in 60% of infants. Out of them, 47% were emergency Caesarean sections.
Twenty-five (37%) infants were depressed at birth requiring intubation and endotracheal suction. Median Apgar score at 1 min was 6 (IQR 1-7) and median Apgar score at 5 min was 7 (IQR 3-9). Mean time for the start of CPAP was 5.34 ± 0.69 h. Mean SpO 2 off oxygen supplementation was 70.23 ± 12%, mean Downe score before starting CPAP was 6 (IQR 5-6), mean RR and heart rate were 76 ± 10 and 162 ± 16/min respectively. Sixty-one chest radiographs were available for analysis. Hyperinflation on chest radiographs (>8 intercostal spaces) was seen in four patients (6.5%). Moderate infiltrates on chest radiographs were seen in 12 (20%) infants, bilateral severe infiltrates were seen in 24 (39%) infants. Cardiothoracic ratio on radiograph > 0.6 was observed in 11 (18.11%) infants.
A significant decline in the need for FiO 2 , mean Downe score and mean RR, and heart rate was observed from the baseline to 6 h of CPAP [Table 1]. Median duration of CPAP was 23.5 h (IQR 12-48), median duration of oxygen supplementation was 45.5 h (IQR 10-96) and median duration of hospital stay was 8 days (IQR 4-11).
Twenty-five (38%) infants had shock requiring vasoactive agents. Five infants had pneumothorax (7.5%), one had pneumothorax before starting of CPAP and in four after initiation of CPAP. Of the four infants with pneumothorax post CPAP, one infant was continued on CPAP and did not require insertion of chest drain. Thirty-five (53%) infants had ECHO proven PPHN and of these, 13 (37%) had moderate to severe PPHN. Twenty-three infants (35%) developed culture positive sepsis during the hospital stay. Seven infants were treated for neonatal seizures (11%). None of enrolled infants required sedation during CPAP and none had significant nasal trauma due to CPAP interface, and no infant developed NEC. One enrolled infant died of severe PPHN.
Sixteen of the 66 infants failed CPAP and required MV (SIMV and or HFO). Six of the 16 infant's also required high frequency ventilation (4 for failed SIMV and 2 for pneumothorax). Reasons for failure were: 10 infants for increased oxygen requirement (7 had PPHN and 3 had sepsis with multiorgan dysfunction), two infants for poor respiratory efforts (recurrent seizures), in three infants for worsening pneumothorax and in one infant for severe metabolic acidosis. Median time for initiation of ventilation was 11 h (IQR 5-18 h) and the median duration of ventilation 144 h (IQR 45-168 h). One infant was managed with NIV. Fourteen infants were given surfactant for high oxygen requirement and radiograph suggesting secondary RDS.
Sixteen infants failed CPAP. On univariate analysis, factors significantly associated with CPAP failure were out-born status, abnormal cardiotocograph, high FiO 2 at 1 h and high positive end-expiratory pressure at 1 h (P < 0.05) of starting CPAP [Table 2]. There was a trend towards CPAP failure in infants who had moderate to severe PPHN and antenatal oligohydromnios. On logistic regression analysis, only outborn status was independently associated with CPAP failure (OR = 25, 95% CI: 1.5-300, P < 0.01) and there was a trend towards CPAP failure in infants depressed at birth (OR = 10, 95% CI: 0.9-122). On subgroup analysis, outborn babies were more immature (37.5 ± 0.6 vs. 38.9 ± 1.1 weeks) and a higher proportion of infants were nonvigorous at birth (68% vs. 41%, P = 0.03).
| Discussion|| |
In this prospective observational study, nearly 75% of infants with moderate to severe MAS were managed with CPAP alone. The incidence of pneumothorax was 4.5% (n = 3). Use of early CPAP in our study resulted in a lesser need for ventilation and a similar rate of pneumothorax in comparison to a recently published trial on MAS.  In the trial by Vain et al., among the 99 infants with MAS, ventilation was required in 42 infants (42%) and the incidence of pneumothorax was seen in 6 infants (6%). However, the duration of oxygen days, hospitalization and ventilation days in our study is very similar or lower than reported by Vain et al. 
Application of moderate CPAP pressure as in this study may resolve atelectasis by sufficiently expanding partially obstructed small airways to result in ventilation of the previously under-ventilated but perfused areas. Also, CPAP pressure would keep the airways open and wider during expiration, thereby prevent and reduce air trapping. This is evident from the improved RR, heart rate, Downe score and partial pressure of oxygen from enrolment to 6 h post-CPAP application as seen in this study.
Role of CPAP pressure for MAS was evaluated by Fox et al. in as early as 1970s. They did a retrospective analysis of records of 14 patients with MAS on the application of End Expiratory pressure. End expiratory pressure was employed in a range of 1-14 cm H 2 O with MV or CPAP. The mean change of PO 2 response to EEP at low (1-3 cm H 2 O), middle (4-7 cm H 2 O), and high (8-14 cm H 2 O) pressures revealed that the maximum Po 2 response was observed in the middle range of EEP with a decreased response in the higher range. Ten of the 14 patients survived. The study revealed that EEP can be effective without simultaneous MV. 
Malik and Gupta conducted a prospective study on the role of CPAP in 116 consecutive neonates suffering from respiratory distress including 18 babies with MAS. Babies with respiratory distress were first treated with humidified oxygen by hood at a rate of 4-6 L/min. Indications for shifting to CPAP ventilation were (i) Failure to maintain SaO 2 >85% (ii) Persistent or increasing Downes score of 6 or more (iii) recurrent apneic spells. All MAS infants required CPAP, one failed CPAP and required MV, 12 of the 18 infants (66%) survived. Reasons for CPAP failure and mortality were not reported in the study. 
Many studies have been done to identify risk factors for developing severe MAS in live born babies ,,,, but no study has been done to identify risk factors for success or failure of CPAP treatment in this group. Being out-born was an important predictor of CPAP failure in our study. Increased risk of unreported asphyxia, lack of antenatal and perinatal monitoring, poor availability of skilled personnel for resuscitation at birth and delay in initiation of respiratory support in out-born infants may be the reasons for increased severity of MAS and CPAP failure in these infants. On subgroup analysis, out-born infants were more immature and a higher proportion depressed at birth compared with inborn infants.
This is one of the first studies evaluating the role of CPAP in neonates with moderate to severe MAS. Well defined inclusion criteria, uniform implementation of study protocol, inclusion of infants from multicenter are some of the merits of this study. Lack of randomization, nonavailability of perinatal data in all out-born infants and inability to generalize the data to all infants with MAS were major limitations.
| Conclusion|| |
Continuous positive airway pressure applied early in the course of MAS is safe and may reduce the need for MV.
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[Table 1], [Table 2]