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Nasal CPAP After Extubation

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Levels of Nasal CPAP Applied During the Immediate Post-Extubation Phase: A Randomized Controlled Pilot Trial

Ratchada Kitsommart MD1,2, Angela Kalyn MHSc, RNC1, Noura Al-Saleem MD1, Marianne Janes RNC1, Guilherme M. Sant’Anna MD, PhD3

1Department of Pediatrics, Neonatal Division, McMaster Children’s Hospital, McMaster University, Hamilton, Ontario, Canada

2Department of Pediatrics, Neonatal Division, Siriraj hospital, Mahidol University, Bangkok, Thailand

3Department of Pediatrics, Neonatal Division, Montreal Children’s Hospital, McGill University, Montreal, Québec, Canada


Address correspondence:

Guilherme Mendes Sant’Anna, MD, PhD, FRCPC

Department of Pediatrics

Division of Neonatology

Montreal Children’s Hospital
McGill University

2300 Tupper Street

Room C912

Montreal, Québec, Canada H3H 1P3


Author Disclosure: The authors have nothing to disclose. Dr. Sant’Anna was supported by research funds from the Research Institute of the Montreal Children’s Hospital, McGill University.  This trial was registered at as NCT00636324


Background: Nasal continuous positive airway pressure (nCPAP) is a common form of non-invasive respiratory support used in newborns. The adequate level of pressure that should be used during the post-extubation phase is unknown. The most often used pressure is 5 cmH2O but different levels have never been compared. The objective of this study was compare the effect of high (HP) versus normal (NP) nCPAP levels on the rate of successful extubation. 

Methods: Randomized controlled pilot trial on preterm infants born with birth weight <1250 g. After extubation, infants were randomized to nCPAP of 8 cmH2O (HP) or 5 cmH2O (NP). Primary outcome was successful extubation. Failure was defined as the need of re-intubation within 72 hours post-extubation.

Results: A total of 24 infants were enrolled; 13 patients to HP and 11 to NP. There were no difference in the rates of successful extubation (54% vs 55%), extubation failure (46% vs. 45%; OR 1.03 CI 0.21, 5.15), air leaks, late reintubation, nasal septum trauma, feeding intolerance, or maximum FiO2 between the two groups. Infants in the HP group spent more days on nCPAP than infants in the NP group.

Conclusion: In this pilot study there were no differences in the rate of successful extubation or complications in infants extubated to higher or normal nCPAP levels, but due to the small sample size our results are inconclusive. Further trials with larger sample size and long-term clinical outcomes are required.

Key Words: extubation failure, nasal CPAP, airway pressure, preterm infants, very low birth weight infants


Nasal continuous positive airway pressure (nCPAP) has been used for decades as a form of non-invasive respiratory support in newborns.1-3 Two large randomized control trials have demonstrated that early use of nCPAP can provide adequate support to extreme preterm infants but 46% to 83% of these infants ultimately required endotracheal intubation and ventilation during their hospital stay.4,5 To minimize complications associated with mechanical ventilation, early extubation has been proposed6-8 but some infants can develop progressive respiratory failure and require re-intubation within hours or days.9-11

Preterm infants have a relatively high chest wall compliance which does not favor the maintenance of functional residual capacity above the closing volume; an essential requirement for adequate gas exchange without the need of a large work of breathing.12 Physiological and clinical studies have demonstrated improvements in lung volume and respiratory system mechanics in preterm infant’s extubated to nCPAP.13,14 The use of nCPAP also decreases the rates of extubation failure at variable reported rates.15,16 This large variability can be partially explained by differences between interfaces, delivering systems, local experience with the use of nCPAP and/or the level of nCPAP pressure applied.17-19

The adequate level of nCPAP pressure that should be used during the post-extubation period is still unknown; a meta-analysis of previous studies suggested a minimum pressure of 5 cmH2O.15 Several physiological studies have demonstrated that inadequate low pressures increases work of breathing and chest wall distortion whereas higher pressures improve thoraco-abdominal synchrony and end-expiratory lung volume.14,20,21 However, different levels of nCPAP have never been compared. Therefore, we designed this randomized controlled trial to investigate a possible beneficial effect of higher nCPAP levels during the first 72 hours post-extubation. The primary objective of the study was to compare the rate of successful extubation in preterm infants extubated to high (8 cmH2O) or normal nCPAP levels (5 cmH2O).



Eligible patients were infants with a birth weight (BW) between 500 – 1250 grams, appropriate for gestational age, on mechanical ventilation, and ready for the first elective extubation attempt before 14 days of age. Infants with lethal or upper airway abnormalities, severe intraventricular hemorrhage (grade III or IV), neuromuscular disorders, and congenital heart disease were excluded. The trial was registered on under the number NCT00636324 and the protocol was approved by the Hamilton Health Sciences Research Ethics Board. Informed consent from parents or legal guardians was obtained before randomization.

Study Design

During the study period mechanical ventilation was managed according to a protocol previously reported.8 Preterm infants would be considered for extubation if: a) BW ≤ 1000 g: Mean airway pressure (MAP) < 7 cmH2O and FiO2 ≤ 0.30; or b) BW > 1000 g: MAP < 8 cmH2O and FiO2 ≤ 0.30. However, the final decision was made by the team responsible for the infant care. The study was an unblinded randomized controlled trial where we applied block randomization, in random blocks of four or six, to assign eligible infants into the groups in a 1:1 ratio. The randomization used sequential numbered sealed opaque envelopes from a computer-generated randomization list. Multiple birth infants were randomized independently. Although blinding was not possible, the person responsible for the data analysis was not aware of the group assignment.

Study Intervention

After randomization, infants were extubated to a normal pressure (NP) – 5cmH2O or high pressure (HP) – 8cmH2O nasal CPAP. In the NP group, the pressure could be weaned to 4 cmH2O in infants with low PaCO2 (< 50 mmHg and pH > 7.25), minimal O2 requirements (FiO2 < 0.25) or anterior-posterior chest x-rays showing increased lung volume (> 9 intercostal spaces) or increased to 6 cmH2O if the infant revealed any sign of respiratory deterioration, which included increase in PaCO2 (> 70 mmHg and pH < 7.25), oxygen requirement (FiO2 > 0.3), and work of breathing (significant intercostal and/or subdiaphragmatic retractions), persistent tachypnea, and/or apneic episodes (> 6 episodes within a 6-hour period). For the HP group, the pressure could be decreased to 7 cmH2O or increased to 9 cmH2O based on the same criteria used for the NP group. Therefore, pressure ranges of 4 to 6 cmH2O or 7 to 9 cmH2O were used and kept for the entire 72 hour period. Infants failing NP nCPAP could be changed to HP nCPAP or nasal intermittent positive pressure ventilation (NIPPV) but were considered a failure. Blood gas analysis was obtained four hours after extubation and every 12 hours thereafter.

Nasal CPAP was provided through short binasal prongs (INCA® prongs; Ackrad Labs, Copper Surgical, Trumbull, CT) and the Drager Babylog 8000+ ventilator (Dräger Medical, Lübeck, Germany). During nCPAP infants were fed according to the unit protocol, through an orogastric tube. Suctioning of the airways, use of seal (Cannulaide; Beevers Manufacturing, McMinnville, OR), and positioning of a roll below the shoulders was performed whenever necessary, to assure upper airway patency and adequate sealing. These details were checked frequently in infants presenting with episodes of desaturation, bradycardia, and increased oxygen requirement and/or hypercapnia before any change in ventilatory support was made. The FiO2 was set to maintain SaO2 between 88% and 92% per unit protocol.

The primary outcome was continued extubation 72 hours post-extubation. Extubation failure was defined by the presence of one of the following criteria: a) persistent respiratory acidosis (pH < 7.20 and PaCO2 > 70 mm Hg) on two consecutive arterial or capillary measurements that were performed within a minimal interval of 1 hour; b) consistent increase in FiO2 requirement above 0.5 (> 2 hours) to maintain SaO2 between 88 % and 92%; c) six or more episodes of apnea requiring mild or moderate stimulation within a 6-hour period, or d) one severe episode of apnea requiring bag and mask positive pressure ventilation. The study ended 72 hours after extubation or when infants satisfied failure criteria. Secondary outcomes were reintubation within 72 hours and between 72 hours and 7 days after extubation, duration of nCPAP, maximum FiO2 during nCPAP therapy and occurrence of potential side effects such as air leak, intraventricular hemorrhage, nasal septum trauma, and feeding intolerance that required interruption of feeding for more than 24 hours.

Statistical Analysis

Analysis was on an intention-to-treat basis. Baseline characteristics were described separately for each group using descriptive statistics. Differences between treatment groups in categorical variables were tested with the Fisher’s exact test and odds ratio (95% confidence interval). The number of days on nCPAP and the maximum FiO2 during nCPAP treatment were compared using the unpaired t-test and mean difference (95% confidence interval). Data were analyzed using SPSS version 17.0 (SPSS Inc., Chicago, IL).


From July 2007 to December 2008 a total of 24 infants were enrolled in the study. (Figure 1) During this period the unit adopted the use of nCPAP immediately after birth as standard of care resulting in fewer infants submitted to invasive ventilation. There were no differences between NP and HP groups in patient demographics (Table 1) and rate of extubation failure (45% and 46%, respectively; OR = 1.03, 95% CI, 0.21 to 5.15). In the NP group infants failed extubation due to respiratory acidosis (1), FiO2 requirements > 0.5 (1), protocol violation (1) or frequent apneas (2) whereas in the HP group the causes of failure were respiratory acidosis (1), FiO2 requirement > 0.5 (3) and frequent apneas (2).

In the NP group, 3 out of 5 infants that failed the clinical criteria had their nCPAP level increased above the pre-specified range and one infant was switched to NIPPV. These 4 infants remained extubated. Only one infant was re-intubated after the nCPAP pressure was increased to 8 cmH2O for a period of < 1 hour, due to a gram negative sepsis. In the HP group only one infant with frequent apneas was switched to NIPPV and did not require re-intubation. The other 5 were re-intubated; four of them while receiving nCPAP pressure of 9 cmH2O and one due to sudden apnea requiring bag and mask ventilation. Therefore, the overall rate of re-intubation within 72 hours was 25%; 9% and 38% in the NP and HP groups, respectively.

Secondary outcomes are shown in Table 2. There were no significant differences between the groups in the occurrence of air leak syndrome, re-intubation after 72 hours and before 7 days post-extubation, intraventricular hemorrhage, trauma of the nasal septum, feeding intolerance, and maximum FiO2. However, infants in the HP group spent more days on nCPAP than infants in the NP group.


Our study is the first randomized controlled trial that has compared the effects of different nCPAP levels applied immediately after extubation on the rate of successful extubation in preterm infants. In the available scientific literature, there is little evidence for the adequate level of nCPAP that should be used during the post extubation phase. A systematic review on the subject suggested that ≥ 5 cmH2O is more effective than lower levels; a conclusion based on the lack of demonstrable benefits of lower nCPAP pressures rather than any comparison with higher levels. Therefore, our study re-opens the question on the level of nCPAP that should be applied to these infants during the immediate post-extubation phase and provide some new data on that.

Unfortunately the study was interrupted prematurely because the unit adopted the use of nCPAP immediately after birth as standard of care resulting in fewer infants submitted to invasive ventilation, presence of a concomitant study competing for patient enrollment and difficulties in obtaining informed consent before the first extubation attempt. After the enrollment of 24 patients, we calculated that we had 80% power to detect differences in proportions from 84% to 42%, anticipating that between 75 to 85% of the neonates assigned to the HP group would remain extubated at 72 hours post-extubation.

The rate of extubation failure in preterm infants depends on a number of factors such as birth weight, gestational age, type of respiratory support applied after extubation, age of extubation, and definitions of failure or success.8,22-24 A meta-analysis on the use of nCPAP or NIPPV after extubation has reported a failure rate similar to our study; between 37 to 44% in infants extubated to nCPAP.16 In the overall population the need of re-intubation within the first 72 hours after extubation was 25%, which was similar to our previous experience8 and other reports.5,25 Re-intubation occurred in only one infant (9%) in the NP group compared to 5 (38%) of the HP group. Of the infants that failed extubation according to our clinical criteria only 1/5 (20%) in the NP group compared to 5/6 (83%) in the HP group required re-intubation. Any inference about these findings is limited given the small number of patients. High levels of nCPAP have been associated with thoraco-abdominal asynchrony and diaphragm dysfunction26,27 and animal studies have demonstrated that nCPAP levels of 8 cmH2O can induce over distention and lung injury in the presence of lung and systemic inflammation.28,29 Physiological studies showing beneficial effects of higher nCPAP levels have evaluated more mature infants over very short periods of time.13,14,30 Therefore, it is possible that high nCPAP levels applied immediately after extubation, in extreme immature infants with minimal lung disease, can lead to over distention, progressive respiratory fatigue, and need of re-intubation. Perhaps, nCPAP should be initiated at lower levels and titrated towards higher values only in infants presenting with progressive respiratory deterioration; an approach that should be investigated in the future.

Although high nCPAP levels may cause air leaks and cardiovascular compromise, in the present study we did not find any differences in the rate of adverse events between the two groups. Infants in the HP group stayed longer under nCPAP therapy when compared to infants in the NP group. We speculate that this was likely due to a slower weaning strategy in infants receiving higher pressures; probably related to the lack of blinding.

Our study has some important limitations. We did not measure the levels of positive pressure at the nasal prongs or proximal airways. In vitro studies have demonstrated that the pressure transmitted is very similar to the set pressure31 but in the clinical setting this is quite different since variable leaks and dynamic changes in respiratory mechanics are common. A short report in preterm infants showed a significant decrease in the pressure transmitted to the pharynx when the infant’s mouth was open, even when the pressure was increased from 5 to 8 cmH2O.32 However, active measures to close the mouth of preterm infants over an extended period of time are difficult to perform and were not used as part of our protocol. Therefore, it is possible that the higher level of nCPAP used has not translated into significant differences on the transmitted pressures between the two groups. Another limitation was the small sample size and our results should be interpreted as data that can be used in a systematic review, meta-analysis and/or for the design of future trials in this important subject. This investigation has several strengths. Although it was not possible to blind, the trial was designed and implemented properly. We blinded whenever possible (e.g. data analyst), used standard clinical criteria for the primary outcome of extubation success, and minimized bias by proper randomization, adequate allocation concealment and participant retention. We used ranges of pressure that reflect current practices and nCPAP was applied to both groups with the same device and delivery systems, which are known to be confounders for effectiveness and side effects. Therefore, this is the first randomized controlled pilot trial to provide an unbiased estimate of the short-term effects of different nCPAP levels during the immediate post-extubation period.


There were no important differences in rates of successful extubation or morbidity in the 72 hours following extubation with a higher rather than standard nCPAP level. Infants randomized to the HP group stayed longer on nCPAP.  Further trials with larger sample sizes and long-term clinical outcomes are required.


The authors would like to thank E. Pullenayegum (Department of Clinical Epidemiology and Biostatistics and Center for Evaluation of Medicines, McMaster University) for guidance with the trial design and statistical analysis.


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Written by Jonathan Swanson

February 7th, 2013 at 9:00 pm

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