Pediatric Pulmonology 48:138–145 (2013)
A Comparison of Different Bedside Techniques to Determine Endotracheal Tube Position in a Neonatal Piglet Model Georg M. Schmo¨lzer, MD,
* Risha Bhatia, MD,1,2 Peter G. Davis, MD,1,2,5 and David G. Tingay, PhD1,2,6,7
PhD,
1,2,3,4
Summary. Rationale: Endotracheal tube (ETT) malposition is common and an increasing number of non-invasive techniques to aid rapid identification of tube position are available. Electrical impedance tomography (EIT) is advocated as a tool to monitor ventilation. Objective: This study aimed to compare EIT with five other non-invasive techniques for identifying ETT position in a piglet model. Methodology: Six saline lavage surfactant-depleted piglets were studied. Periods of ventilation with ETT placed in the oesophagus or a main bronchus (MB) were compared with an appropriately placed mid-tracheal ETT. Colorimetric end-tidal CO2 (Pedi-Cap1), SpO2 and heart rate, tidal volume (VTao ) using a hot-wire anemometer at the airway opening, tidal volume using respiratory inductive plethysmography (VTRIP ) and regional tidal ventilation within each hemithorax (EIT) were measured. Results: Oesophageal ventilation: Pedi-Cap1 demonstrated absence of color change. VTao , VTRIP , and EIT correctly demonstrated no tidal ventilation. SpO2 decreased from mean (SD) 96 (2)% to 74 (12)% (P < 0.05; Bonferroni post-test), without heart rate change. MB ventilation: SpO2, heart rate and PediCap1 were unchanged compared with mid-tracheal position. VTao and VTRIP decreased from a mean (SD) 10.8 (5.6) ml/kg and 14.6 (6.2) ml/kg to 5.5 (1.9) ml/kg and 6.4 (2.6) ml/kg (both P < 0.05; Bonferroni post-test). EIT identified the side of MB ventilation, with a mean (SD) 95 (3)% reduction in tidal volume in the unventilated lung. Conclusions: EIT not only correctly identified oesophageal ventilation but also localized the side of MB ventilation. At present, no one technique is without limitations and clinicians should utilize a combination in addition to clinical judgement. 2012 Wiley Periodicals, Inc. Pediatr Pulmonol. 2013; 48:138–145. ß 2012 Wiley Periodicals, Inc.
Key words: intubation; electrical impedance tomography; infant; mechanical ventilation; respiratory function monitor; colorimetric carbon dioxide detector; respiratory inductive plethysmography. Funding source: Neonatal Research Group of the Murdoch Childrens Research Institute, Royal Women’s Hospital Postgraduate Research Degree Scholarship and Monash International Postgraduate Research Scholarship, Australian National Health and Medical Research Council Practitioner Fellowship, National Health and Medical Research Council Clinical Research Fellowship, Number: 491286, Victorian Government Operational Infrastructure Support Program.
6
Additional supporting information may be found in the online version of this article. 1
Neonatal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
Department of Neonatology, The Royal Children’s Hospital, Melbourne, Australia.
7
Department of Paediatrics, University of Melbourne, Melbourne, Australia. Conflict of interest: None.
2
Newborn Research, The Royal Women’s Hospital, Melbourne, Australia. 3
The Ritchie Centre, Monash Institute for Medical Research, Melbourne, Australia.
*Correspondence to: Georg M. Schmo¨lzer, MD, PhD, Newborn Research, The Royal Women’s Hospital, 20 Flemington Road, Parkville 3052, Victoria, Australia. E-mail:
[email protected] Received 3 January 2012; Accepted 6 March 2012.
4
Department of Pediatrics, Medical University, Graz, Austria.
5
Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.
ß 2012 Wiley Periodicals, Inc.
DOI 10.1002/ppul.22580 Published online 21 May 2012 in Wiley Online Library (wileyonlinelibrary.com).
Confirmation of Endotracheal Tube position
INTRODUCTION
Endotracheal intubation remains a common procedure in the neonatal intensive care unit (NICU) and peri-operative environment.1,2 Malposition of an endotracheal tube (ETT) in the oesophagus or the right main bronchus (MB) is common, occurring in approximately 50% of neonatal intubations.2,3 ETT malposition is associated with serious adverse outcomes, including hypoxemia, death,2,4–7 pneumothorax,8 and right upper lobe collapse.9,10 Diagnosis is often delayed in the neonatal population due to subjective clinical signs, a reliance on chest radiography,11 or invasive advanced airway visualization aids. Correctly and rapidly identifying ETT position is, thus, essential to safe intubation practice. Recently, the use of rapid bedside methods to confirm correct tube placement has become popular. These include end-tidal carbon dioxide (CO2) detectors and pneumotachograph assessment of gas flow patterns at the airway opening.4,5,12–16 However, all techniques have some limitations5,16–18 Semi-quantitative colorimetric CO2 detectors, such as the Pedi-Cap1 (Nellcor Puritan Bennett, Pleasanton, CA), can give false negative results particularly when cardiac output is low19,20 or during severe respiratory failure.17 Pneumotachograph assessment of gas flow at the airway opening continuously measures and displays tidal gas flow in and out of the ETT, but require a certain level of interpretive expertise.15,16,18 Importantly, these techniques focus on delineating whether the ETT is in the trachea or oesophagus. Arguably, malposition of the ETT in a MB is equally harmful, and harder to identify clinically, in the neonatal lung, which is vulnerable to long-term injury from volutrauma and atelectasis.21 To date, the ability of these devices to demonstrate ETT position within the respiratory tree has not been compared. Defining real-time volumetric changes during the mechanical ventilation of patients has always been challenging, but offers clear advantages. Recently, novel ABBREVIATIONS: ETT CO2 RIP EIT AaDO2 PIP VTao SpO2 Z VTRIP ZVT ZVTroi ZVT%
Endotracheal tube Carbon dioxide Respiratory inductive plethysmography Electrical impedance tomography Alveolar-arterial oxygen gradient Peak inflation pressure Tidal volume at the airway opening Oxygen saturation Relative impedance Global tidal volume (respiratory inductive plethysmography) Relative tidal volume Regional relative tidal volume Percentage of global relative tidal volume
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techniques have emerged that may offer some utility during intubation. In particular, respiratory inductive plethysmography (RIP) and electrical impedance tomography (EIT) have shown promise as non-invasive, radiation-free bedside monitoring tools in the critical care environment, and commercial models of each technology are now available. RIP is validated in infants,22–24 but is limited to assessment of global changes in thoracic volume. EIT is a relatively new, method of monitoring regional ventilation through a single cross-section of the thorax25,26 that has been used to define regional tidal volume changes during ETT suction.27 Functional images of the regional changes in tidal ventilation, expressed using a colorcoded image reflecting the time course of ventilation in different parts of the thorax, can be generated using EIT.26 The ability of EIT to demonstrate real time regional tidal ventilation changes means that it may be a useful monitoring tool following intubation. We hypothesized that EIT would correctly identify ETT position. The aim of the study was to compare EIT with five non-invasive bedside indicators of ETT malposition during oesophageal and single MB intubation in a piglet model of neonatal lung injury; these were peripheral oxygen saturation (SpO2), heart rate, colorimetric end-tidal CO2, flow waveforms, and RIP. MATERIALS AND METHODS
The study was performed in the Animal Research Laboratory Facility of the Royal Children’s Hospital, Melbourne, Australia and the institution’s Animal Ethics Committee approved all experimental procedures. Five-week old piglets were anaesthetized, sedated, orally intubated with a size 4.5 mm cuffed ETT, muscle-relaxed, and ventilated in supine position with timecycled pressure-limited ventilation (VIP Bird1 Gold, Bird Products Corporation, Palm Springs, CA). The ETT was orally inserted to 17 cm from the medial tip of the lips, the distance required to site the ETT in approximately the mid-trachea for this population.28 At the same time, the oesophagus was also intubated under direct vision with a separate size 4.5 ETT and remained in place for the duration of the experiment. Surfactantdepleted lung injury was induced using repeated 20 ml/ kg warmed saline lavages (average 10 lavages per animal), until the alveolar-arterial oxygen gradient (AaDO2) was at least 350 mmHg in 1.0 fraction of inspired oxygen (FiO2).29,30 Ventilation continued with an inspiratory time of 1.0 sec and a positive end expiratory pressure of 6 cm H2O. Peak inflation pressure (PIP) was adjusted to achieve a tidal volume of 6–10 ml/kg and an arterial CO2 between 45 and 55 mmHg at a ventilator rate of 30 breaths per minute. Ventilation Pediatric Pulmonology
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parameters, including the PIP value, were then not altered for the remainder of the study. Measurements
SpO2 and heart rate were continuously measured (HP48S monitor, Hewlett-Packard, Palo Alto, CA). End-tidal CO2 was detected using a disposable non-invasive semi-quantitative colorimetric CO2-detector (Pedi-Cap1, Nellcor Puritan Bennett), placed between the ventilator and the ETT connector. Using this device, the absence of CO2 in the detector window is purple and changes to yellow in the presence of end-tidal CO2.14 In our model, a persistent purple color during tidal inflations indicated that the ETT was not in the trachea4–6 or the lungs were under ventilated17 in the presence of a normal cardiac output.19,20 Tidal flow waveforms were measured using a Florian Respiratory Function Monitor (Acutronic Medical System AG, Zug, Switzerland) sampling at 200 Hz. This system employs a hot-wire anemometer placed at the airway opening, between the PediCap1 and the ventilator circuit.15 Airway pressure and displayed tidal volume (VTao ) were also measured at the airway opening using the Florian monitor. Placement within the subglottic respiratory system was defined as the presence of gas flow during both phases of the tidal cycle. Oesophageal ventilation was defined as gas flow seen only during the inspiratory phase.15,16,18 Relative impedance (Z) was measured by EIT (GoeMF II EIT system, Carefusion, Hoechberg, Germany; Supplementary E-Fig. 1), sampling at 25 Hz, using a method we have described previously.27 Sixteen EIT electrodes (Kendall Puppydog 1042PTS; Tyco Healthcare, Mansfield, MA) were placed equidistant at the level of the sixth parasternal intercostal space to avoid sampling the right upper lobe. A DC-coupled respiratory inductive plethysmograph (RIP; Respitrace 200, North Bay Village, FL), sampling at 200 Hz, was used to measure global tidal volume (VTRIP ). The raw RIP voltage signal was calibrated to the tidal volume measured at the airway opening over 10 consecutive inflations during a baseline recording after stable ventilator settings were established and expressed as ml/kg.23,24 ETT Position Protocol
Initially all parameters were recorded for 120 sec with the ETT approximately located in the mid-trachea. The ventilator circuit, Pedi-Cap1 and flow sensor were then transferred to the oesophageal ETT and the animal ventilated at the same settings for 90 sec and data collected for the last 30 sec. Ventilation was then recommenced via the ETT located in the trachea for at least 5-min, to allow re-recruitment of lung volume and recovery of SpO2 and heart rate, prior to advancing this Pediatric Pulmonology
ETT to 30 cm at the lips, to ensure ventilation exclusively via either the left or right main bronchus (MB ventilation). Five minutes after advancing the ETT to this position, a 120 sec recording of all parameters was made. Finally, the ETT was withdrawn to its correct location over 15 sec and all parameters were recorded during this period and for an additional 2-min period (ETT withdrawal). The short period of oesophageal ventilation was chosen to ensure animal safety during the study, and was confirmed in pilot studies to be adequate to ensure clinical change. Data Acquisition and Analysis
Gas flow, VTao , airway pressure, VTRIP , SpO2, and heart rate were continuously recorded at 200 Hz during each recording phase using a computerized data acquisition system (Powerlab, AD Instruments, Sydney, Australia). VTRIP was defined as the average tidal trough to peak value for each measurement. The color change at the PediCap1 was independently determined by two investigators (G.S. and R.B.) and recorded. Electrical impedance tomography data was analyzed offline using proprietary software (AUSPEX V1.5, Carefusion). To isolate the impedance change within the respiratory domain, a low-pass filter was applied to each EIT recording at 60 cycles per minute.27,31,32 EIT data was divided into two regions of interest; the left and right hemithorax. During each tidal inflation, relative VT (ZVT ) within each region was defined as the trough to peak (amplitude) change in impedance.27 Regional ZVT was then expressed as a percentage of the average ZVT value in each hemithorax during the midtrachea recording (DZVTroi ). For example, a DZVTroi of 30% in the left hemithorax represents a VT of 30% of the VT within that region when the ETT was correctly positioned. To determine the distribution of ventilation within the thorax during each recording, ZVT within each hemithorax was also expressed as a percentage of the global ZVT value for each recording (ZVT% ). A functional EIT (fEIT) image was also generated from each recording using the standard deviation (SD) of the impedance time course of each individual pixel within the cross-sectional slice. This method creates a visual display of relative ventilation within the thorax using a colorimetric display in real time (unfiltered data) or offline (filtered ZVT ) and is being employed on commercially available EIT systems.26 Statistical Analysis
The data were tested for normality and mean and SD of each parameter calculated during each ETT position and compared using repeated measures ANOVA with Bonferroni post-test analysis. Statistical analysis was performed using Stata (Intercooled 10,
Confirmation of Endotracheal Tube position
Statacorp LP, College Station, TX) value < 0.05 was considered significant.
and
a
P-
RESULTS
Six piglets with a mean (SD) weight 5.0 (1.2) kg were studied. The mid-trachea ETT mean (SD) PIP was 23.9 (3.6) cm H2O, and did not vary during each ETT position. During baseline mid-tracheal ventilation the mean (SD) HR was 160 (36) bpm and SpO2 96 (2)%. The mean (SD) VTao and VTRIP were 10.8 (5.6) and 14.6 (6.2) ml/kg, respectively. There was no difference in these parameters between the baseline mid-tracheal ventilation and the period of mid-tracheal ventilation immediately prior to advancing the ETT into the MB. Oesophageal Ventilation
Compared with mid-trachea ETT position, all indicators, except heart rate, significantly changed during the 90 sec the oesophagus was ventilated (Table 1). SpO2 rapidly decreased from mean (SD) 92 (2)% to 74 (12)% (P < 0.05; Bonferroni post-test). The Pedi-Cap1 demonstrated absence of color change. No VTao was measured by the flow sensor. The mean (SD) VTRIP was 0.7 (0.2) ml/kg. DZVTroi was 7 (9)% and 9 (8)% of the VT during mid-tracheal ETT ventilation in the right and left lung, respectively (Fig. 1 and Supplementary E-Fig. 2). MB Ventilation
Compared with the mid-trachea, there were no significant differences in SpO2 and heart rate after advancing the ETT into a MB. The Pedi-Cap1 continued to change color consistent with tidal ventilation. Peak expiratory tidal flow, VT and VTRIP were significantly reduced during MB ventilation (Table 1). EIT demonstrated a significant change in the distribution of
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tidal ventilation, with 97% occurring in the ventilated lung and 3% in the unventilated lung. DZVTroi decreased by 95 (3)% from baseline in the unventilated lung. Flow, VT, VTRIP , and DZVTroi all rapidly returned to baseline values after withdrawing the ETT to mid-trachea (Fig. 2). fEIT images rapidly demonstrated unilateral ventilation in the intubated bronchus and return of ventilation to each hemithorax during withdrawal of the ETT into the trachea (Fig. 1 and Supplementary E-video 1). DISCUSSION
This is, to our knowledge, the first study that has systematically compared multiple bedside indicators of ETT position. ETT malposition is common after intubation9,10 and rapid, and reliable, identification is essential to minimize morbidity.2,4–7,10 All methods were able to correctly detect malposition during oesophageal ventilation, as was SpO2 monitoring. Only VTao , VTRIP , peak expiratory flow and EIT (fEIT and regional tidal impedance changes) were able to delineate single MB ventilation. EIT, by measuring, and displaying, regional distribution of VT in real-time, had the additional advantage of allowing rapid easy visual confirmation of ETT location and presence or absence of tidal ventilation in different hemithoraces. Unlike previous comparisons of techniques to confirm ETT position,2,4–7 our study also included ETT malposition in a single bronchus. As demonstrated in our study, and others,4–6 oesophageal intubation can be rapidly detected with many different techniques, as well as being associated with rapid deoxygenation, but not bradycardia, in our animal model receiving musclerelaxants and pre-oxygenation. In contrast, deoxygenation was not observed during the 7 min the animals received MB ventilation. Intubation of a single bronchus is very common in the newborn infant, and
TABLE 1— Comparison of all Assessment Tools for ETT Placement: Trachea, Oesophagus, Main Bronchus, and After Pull Back From Main Bronchus into Trachea ZVTroi HR (bpm) Mid-tracheal baseline Oesophagus MB 30 in. after MB pull back
160 (36) 163 (35) 162 (37) 168 (37)
1
SpO2 (%)
Pedi-Cap (Color)
96 (2) 74 (12) 88 (8) 89 (9)
Yellow Purple Yellow Yellow
Peak expiratory flow (L/min) 8.7 (2.8) 0.29 (0.64) 4.9 (1.5) 7.1 (2.0)
VTao (ml/kg)
RIP VT (ml/kg)
A (%)
B (%)
10.8 (5.6) 0.0 5.5 (1.9) 11.5 (4.4)
14.6 (6.2) 0.7 (0.2) 6.4 (2.6) 15.4 (5.0)
100 (0) 7 (9) 80 (30) 104 (19)
100 (0) 9 (8) 4 (2) 87 (36)
ZVTroi A, ventilated hemithorax during MB phase and B, non-ventilated compared to mid-trachea. HR, heart rate; SpO2, peripheral oxygen saturation; VTao , tidal volume at airway opening; RIP, respiratory inductive plethysmography; relative tidal ventilation within a hemithorax, as measured by electrical impedance tomography, ZVTroi , expressed as % of the tidal ventilation within that region of interest during mid-tracheal baseline; bpm, Beats per minute. All data mean (standard deviation). P < 0.05 against both mid-tracheal baseline and 30 in. after MB pull back (repeated measures ANOVA with Bonferroni multiple comparison post test).
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Fig. 1. Representative functional EIT images (SD of the impedance time course signal) of the relative ventilation during different tube placements. Magnitude of ventilation is demonstrated using a gray scale (as indicated in the panels). The baseline image (A) is homogenous bilaterally; (B) demonstrates oesophageal tube placement; (C) ETT placement in the left MB and (D) after ETT pulled back into the trachea. A full color version of this figure is available in the Online Data Supplement (E-Fig. 1).
clinical confirmation, including auscultation of the chest, can be difficult. Without a rapid bedside tool to identify this scenario the clinician is reliant on chest radiography. This is often delayed11 and exposes the infant to radiation. In addition, prolonged single bronchus ventilation creates a highly injurious state for the fragile neonatal lung.21 The Pedi-Cap1 is widely advocated as an essential adjunct during neonatal intubation due to its ease of use and interpretation4–6,17,18 and ability to demonstrate tidal color change with volumes as little as 1 ml.14 Our study supports this in the context of identifying oesophageal versus respiratory tree placement only, especially when considered in conjunction with SpO2. Importantly, Pedi-Cap1 was unable to distinguish between tracheal or MB tube placements. During MB ventilation the delivered VTao of approximately 4 ml/kg exceeded the Pedi-Cap1 threshold by approximately 20-fold.14 On all six occasions, a flow sensor distinguished between correct and oesophageal tube placement within the first or second inflation. This has been recently demonstrated in other animal and human observational Pediatric Pulmonology
studies.2,15,16,18 Measurement of gas flow, and tidal volume, at the airway opening is now almost universal in NICU, and increasingly being used in peri-operative and resuscitation environments. The findings of our study suggest that the use of a flow sensor is a reasonable alternative to the Pedi-Cap1 in rapidly identifying oesophageal intubation, and allows additional information on lung mechanics. Our study is, the first to our knowledge, to report the flow patterns with the ETT at different locations within the respiratory tree. Despite a significant reduction in expiratory gas flow, after advancing the ETT into the MB, the observed waveform patterns looked similar. The observer would require reference to the waveform during tracheal intubation, and knowledge of the inspiratory flow to identify this change. These technical limitations may reduce the utility of flow waveforms as a simple clinical tool when tube position within the trachea is uncertain, especially in untrained hands. EIT, VTao , and VTRIP were all able to detect significant reduction in tidal ventilation when the ETT was located in the oesophagus and MB. Modern RIP systems can be easily calibrated, integrated into
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Fig. 2. Change in the flow (A), RIP determined lung volume (VRIP) (B) and regional filtered EIT time-course signals in the right (C) and left (D) hemithoraces during ETT withdrawal from left MB into trachea (indicated by dashed line) in a representative subject. Minimal change in the EIT signal is noted in the right hemithorax in contrast to the left.
commercially available monitors and are known to be reliable over short periods of time, making them an alternative to measurement of VTao at the airway opening.22–24 Again, interpretation of VTao and VTRIP requires knowledge of the tidal patterns during the midtracheal location. None of these devices can determine why the tidal volume decreased. For example, it is possible that an underventilated and atelectatic lung would demonstrate the same results even with a correctly positioned ETT. Similarly, a pneumothorax or bronchial obstruction may cause a significant heterogeneous pattern of ventilation,33,34 which may be difficult to distinguish from malposition in a MB using EIT, without clinical context to guide interpretation. This study highlights the importance of understanding the principles, and limitations, of all adjunctive tools used during intubation. Our findings indicate that by providing information on the distribution of ventilation in a visual format, EIT is potentially a powerful tool for the assessment of ETT placement.27,35 EIT is the only tool that provides information on the regional characteristics of tidal ventilation in real-time. EIT is unable to be calibrated and displays relative, rather than absolute, changes. This limitation is not relevant for detection of rapid changes during short term monitoring, especially regional differences as dramatic as those seen during single MB ventilation.31 The fEIT image, in particular, provides a rapid
visual aid that is relatively easy to interpret during major events like single bronchus ventilation, suction related derecruitment,27 and pneumothoraces.33,34 Until now, EIT was predominantly used as a research tool.25–27,31–35 Recently, commercial systems designed to monitor ventilation in critical care patients have become available. The major limitation of these systems are the electrodes; equidistant attachment of the 16 electrodes is cumbersome and requires precision to minimize artefacts.32 Furthermore, data acquisition is time consuming and, although real time monitoring is possible, evaluation is usually performed offline. Notwithstanding this limitation, our study, and others,33–35 suggest that EIT may be a valuable clinical tool. This study has some additional limitations. Each animal was subjected to all ETT positions and acted as their own control. We contend that intra-subject comparison is valuable, and limits animal reduction, compared to the physiological bias inherent in any critically ill animal model. The study was performed in animals receiving muscle relaxants and ventilated in a leak-free state. It is not ethical to systematically study different methods to detect malposition of the ETT in human infants. Further studies are required in order to determine performance during different clinical scenarios, including different PEEP states and adjusting tidal volume at the bedside. Application of these results to Pediatric Pulmonology
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spontaneously breathing ventilated infants with variable leak should be made with caution. In this situation EIT, flow, VTao and VTRIP will be harder to interpret. It is also likely that SpO2 would be more stable in spontaneously breathing infants. The animals, which had a model of moderately severe lung disease, were also ventilated in FiO2 1.0. Pre-oxygenation before intubation is a common practice but it is possible that the SpO2 response would have been greater using a lower FiO2. We did not have access to chest radiography or bronchoscopy. Being blinded to the side of MB ventilation created a clinically relevant scenario. Consequently, the exact position of the ETT within the trachea may have varied between subjects. The piglet is an established respiratory model of neonatal lung disease. Piglets have a long trachea and the position of the carina well described,28 so failure to achieve the intended ETT location was unlikely. We intentionally elected to record EIT at a level well below the independent bronchus for the right upper lobe.28 We did not report commonly used subjective clinical signs, such as presence of ETT condensation, chest wall movement and auscultation, as the location of the ETT was not blinded in these muscle-relaxed animals. In clinical practice the relevance of these clinical signs should not be discounted, although interpretation can be difficult in the neonate. CONCLUSIONS
The Pedi-Cap1, flow sensor, RIP, and SpO2 were able to distinguish between location of ETT in the subglottic respiratory tree and oesophagus. EIT could correctly, and easily, identify the location of the tube within the respiratory tree, and may have a role in bedside monitoring of ventilated infants. At present, no one technique is without limitations and clinicians should utilize a combination in addition to clinical acumen. ACKNOWLEDGMENTS
We thank Dr Magdy Sourial and Mr Shane Osterfield for their assistance with the preparation of the animal model and anesthesia. The study was funded by departmental funds from the Neonatal Research Group of the Murdoch Childrens Research Institute; no external funding was received. GMS is supported in part by a Royal Women’s Hospital Postgraduate Research Degree Scholarship and Monash International Postgraduate Research Scholarship. PGD is supported in part by an Australian National Health and Medical Research Council Practitioner Fellowship. DGT is supported by a National Health and Medical Research Council Clinical Research Fellowship (grant ID 491286) and the Victorian Government Operational Infrastructure Support Program. Pediatric Pulmonology
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Pediatric Pulmonology