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An Official American Thoracic Society/European Respiratory Society Workshop Report: Evaluation of Respiratory Mechanics and Function in the Pediatric and Neonatal Intensive Care Units Stacey Peterson-Carmichael*, Paul C. Seddon*, Ira M. Cheifetz, Inez ´ Frerichs, Graham L. Hall, Jurg ¨ Hammer, Zoltan ´ Hantos, Anton H. van Kaam, Cindy T. McEvoy, Christopher J. L. Newth, J. Jane Pillow, Gerrard F. Rafferty, Margaret Rosenfeld, Janet Stocks, and Sarath C. Ranganathan; on behalf of the ATS/ERS Working Group on Infant and Young Children Pulmonary Function Testing

THIS OFFICIAL WORKSHOP REPORT OF THE AMERICAN THORACIC SOCIETY (ATS) AND THE EUROPEAN RESPIRATORY SOCIETY (ERS) WAS APPROVED BY THE ATS BOARD OF DIRECTORS,OCTOBER 2015, AND BY THE ERS SCIENCE COUNCIL AND EXECUTIVE COMMITTEE,SEPTEMBER 2015

Abstract research collaboration. From expert panel discussions and literature reviews, we conclude that many of the techniques can aid in optimizing Ready access to physiologic measures, including respiratory mechanics, respiratory support in the PICU and NICU, quantifying the effect of volumes, and ventilation/ inhomogeneity, could optimize therapeutic interventions, and guiding ventilator weaning and the clinical management of the critically ill pediatric or neonatal patient extubation. Most techniques now have commercially available and minimize lung injury. There are many techniques for measuring equipment for the PICU and NICU, and many can generate continuous respiratory function in infants and children but very limited information data points to help with ventilator weaning and other interventions. on the technical ease and applicability of these tests in the pediatric and Technical and validation studies in the PICU and NICU are published neonatal intensive care unit (PICU, NICU) environments. This report for the majority of techniques; some have been used as outcome summarizes the proceedings of a 2011 American Thoracic Society measures in clinical trials, but few have been assessed specifically for their Workshop critically reviewing techniques available for ventilated and ability to improve clinical outcomes. Although they show considerable spontaneously infants and children in the ICU. It outlines for promise, these techniques still require further study in the PICU and each test how readily it is performed at the bedside and how it may NICU together with increased availability of commercial equipment impact patient management as well as indicating future areas of potential before wider incorporation into daily clinical practice.

*Joint first authors. This document has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org Ann Am Thorac Soc Vol 13, No 2, pp S1–S11, Feb 2016 Copyright © 2016 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201511-730ST Internet address: www.atsjournals.org

Contents Chest Wall Measurements funded by the ATS and was held at the 2011 Occlusion Pressures ATS International Conference meeting in Overview Discussion and Future Directions Denver, Colorado, with a follow-on meeting Introduction Proposed Areas of Future Research at the 2012 ATS Conference. The workshop Methods Collaboration was initiated by the joint ATS/European Measurement Techniques Respiratory Society Working Group on Dynamic/Passive Mechanics Infant and Young Children Pulmonary Forced Deflation Overview Function Testing to address the lack of Forced Oscillation Technique information on respiratory function Ventilator Graphics The American Thoracic Society (ATS) techniques available to assist in the Volumetric workshop on Evaluation of Respiratory management of patients in pediatric Inert Gas Washout Mechanics and Function in the Pediatric and neonatal intensive care units (PICU, Electrical Impedance Tomography and Neonatal Intensive Care Units was NICU).

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The principal conclusions are as ∘ Once equipment is in situ, each technique stable child in the outpatient or ambulatory follows: can be performed within approximately setting. Discussions within and beyond the d The main clinical issues for which 15 minutes on each patient, and some Working Group in 2010 to 2011 indicated respiratory function measurements can can give continuous real-time data (1) the availability of respiratory provide useful information to guide during supported ventilation. measurement techniques potentially management are: ∘ Additional time needs to be allowed for applicable in pediatric intensive care ∘ assessing the physiologic nature and equipment setup, to await patient unit/neonatal intensive care unit progression of stability, and for calculation/ (PICU/NICU), and (2) a desire by ∘ optimizing respiratory support and interpretation of results; this will depend clinicians to know more about these minimizing ventilator-associated lung on the technique, the child’s clinical techniques. These discussions led directly to injury condition, and the experience of the an ATS-funded project: “Evaluation of ∘ assessing the effect of therapeutic operator. respiratory mechanics and function in the interventions (e.g., drugs, physiotherapy) ∘ Risks are minimal, but the following pediatric and neonatal intensive care units.” ∘ assessing readiness to wean from precautions are important: The aim of this Workshop Report respiratory support - infection control issues must be addressed document is to identify and concisely review - awareness of increased during respiratory function tests that show the most d The techniques considered currently some types of measurement promise for the clinical monitoring of useful or promising in providing this - disconnection times must be minimized vulnerable and critically ill young patients, information are: to avoid derecruitment in positive end- requiring care in a PICU, NICU, or similar ∘ measurement of respiratory mechanics expiratory pressure (PEEP)–dependent facility. The objectives were to (1) review the (compliance and resistance of lung or patients safety, feasibility, and published data to date ) using both dynamic on the relevant techniques; (2) list possible and passive techniques d There is a wealth of published data on applications to guide clinical management ∘ measurement of forced expiratory flows the validity and technical aspects of the in the PICU and NICU; and (3) identify and volumes using the negative pressure various techniques. Most techniques future directions and research needs. Use of forced deflation technique have been used as outcome measures in such techniques in the PICU and NICU ∘ measurement of respiratory resistance studies on therapeutic interventions. may benefit patients through enhancing and reactance using the forced Empirical data on the ability of these optimization of ventilator management and oscillation technique (FOT) measurements to assist in clinical monitoring the response to therapeutic ∘ use of ventilator graphics to provide management of individual patients are interventions. In addition, measurements qualitative visual information (both scarce: available data are restricted can form a baseline to aid with monitoring time-based and XY plots) primarily to respiratory mechanics evolution of respiratory disease both acutely ∘ measurement of carbon dioxide measurements, ventilator graphics, and in the PICU/NICU and at follow up. elimination as a function of exhaled volumetric capnography. Finally, it should be stressed that volume of gas (volumetric capnography) despite the potential clinical benefit many of ∘ measurement of and these tests may provide, more research is ventilation distribution using inert gas Introduction warranted for each technique before any washout techniques clinical recommendations on specific ages, ∘ dynamic assessment of regional Respiratory disease dominates admissions disease entities, or outcome measures ventilation using electrical impedance to both pediatric and neonatal intensive associated with testing. We aim to provide tomography care units (PICU, NICU) to a greater the pediatric and neonatal intensivist with a ∘ measurement of tidal volumes, flow extent than equivalent adult units (1). guide for choosing potential respiratory parameters, and thoracoabdominal Nonetheless, the use of respiratory function tests and information regarding asynchrony at the chest wall measurement techniques to guide future research areas of interest, specifically (6simultaneous esophageal manometry) management in children has lagged behind bedside evaluations of lung volumes, ∘ assessment of respiratory drive and adult intensive care practices. Rapid ventilation inhomogeneity, and respiratory respiratory muscle strength using advances in the development of respiratory mechanics in ventilated patients. occlusion pressures function tests applicable to infants and d All of these techniques are feasible and young children have been achieved in have been performed in PICU/NICU recent years. Methods settings. Since its establishment in 1990, the ∘ Suitable commercial equipment is joint American Thoracic Society/European This project originated in a Clinical currently available for all techniques Respiratory Society (ATS/ERS) Working Workshop run at the American Thoracic except FOT, forced deflation, and Group on Infant and Young Children Society Annual Conference in New Orleans occlusion pressures. Pulmonary Function Testing has published in 2010 (May 18, 2010) entitled “Making the ∘ Adequate training and quality control are several statements and guidelines on the use Physiology Work for You: Lung Function essential before any of the techniques of pediatric respiratory function tests for Tests in the Pediatric and Neonatal are introduced into a PICU or NICU researchers and clinicians (2–14), but to Intensive Care Units.” This educational setting. date these publications have focused on the workshop was proposed by the ATS/ERS

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Working Group on Infant and Young b. How long do measurements take to individual techniques, written by the Children Pulmonary Function Testing and obtain? participant subgroups and then collated was organized and chaired by S.P.-C. and c. Any risks to patient?/Which patients are and edited by the co-chairs. P.C.S. Formal feedback was sought from suitable/unsuitable? the 45 attendees: the responses indicated d. Ease of interpretation/training required the need for increased knowledge of the 4. Existing published data Measurement Techniques various techniques available and how these a. Reference data might influence clinical practice. b. Data in disease conditions outside The measurement techniques are fl Participants expressed a desire to have NICU/PICU described brie yfortheclinician.The information regarding the application and c. Research studies to date in NICU/PICU online supplement includes detailed 5. Clinical Indications based on published interpretation of data from these various sections on each reviewed technique and data techniques. Furthermore, they noted that references. there was limited published information on The ATS/ERS Evaluation of the clinical applicability of lung function Respiratory Mechanics and Function in the Dynamic/Passive Mechanics techniques in the PICU/NICU settings. Pediatric and Neonatal Intensive Care Units These techniques use classical mechanics Consequently, we submitted an writing group was created, consisting of to derive measurements of the resistance application to the ATS on behalf of the working groups for each of the physiologic and compliance of the lung or the entire Working Group for a project entitled parameters to be evaluated. Each working respiratory system (i.e., including chest wall). Airflow is measured at the airway “Evaluation of respiratory mechanics and group was charged with performing a opening (usually endotracheal tube or function in the pediatric and neonatal comprehensive literature search of facemask) using a pneumotachometer intensive care units.” P.C.S. and S.P.-C. standardized content for its specific lung or ultrasonic flowmeter and integrated contacted members of the ATS/ERS function test, including background to give volume changes. The pressure Working Group on Infant and Young physiology, procedural requirements, driving airflow (the driving pressure) Children Pulmonary Function Testing to procedural feasibility in a clinical setting, 1 is estimated in a variety of ways. In collect opinion on ( ) techniques to assess and existing published data with possible dynamic mechanics, the driving pressure respiratory function that have been used in clinical indications. 2 is measured continuously. For the PICU/NICU, and ( ) relevant experts who Thorough literature searches were spontaneously breathing child, driving could contribute for each technique. performed on multiple occasions up to fi pressure is generated by respiratory A provisional list of techniques was nalization of the Workshop Report by the muscles creating a negative intrapleural fi drawn up, and the identi ed experts for each members of the subgroups using the pressure; this is measured via a technique were invited to a workshop at the following databases: MEDLINE, PubMed, catheter, balloon, or transducer in the ATS Annual Conference in Denver in 2011. and EMBASE. Initial searches and topic midesophagus. For the ventilated and The workshop was attended by advisors reviews by the individual subgroup/ paralyzed child, the driving pressure is from the Working Group to give an section authors were often done with the ’ positive pressure at the airway opening, overview, together with a technical advisor aid of medical librarians at each author s measured within the ventilator circuit and a librarian from the ATS. Data for the individual academic institution. Studies ’ as close as possible to the airway various techniques were presented, and the and reports relevant to the subgroup s opening. Flow and volume are measured scope and overall plan of the document was assigned physiologic technique were fi continuously and simultaneously to discussed. At the end of the workshop, selected, and reference lists of identi ed driving pressure. attendees agreed on the finalized list of studies were further perused for For passive mechanics, driving pressure techniques to be covered within the additional relevant studies. is measured during a brief airway occlusion, document. For each technique, a subgroup Subsequent follow-on meetings were when respiratory muscles are relaxed held at ERS 2011 and ATS 2012, at which fl of individuals was then tasked with fi (Hering-Breuer re ex) and pressures searching the literature for evidence on each each subgroup presented its ndings, which equilibrate across the airways during a of the techniques to address the following were then collated and discussed. Further period of no flow. Flow and volume are issues: work was done at these workshops to measured during the passive expiration 1. Background physiology of the technique address overarching issues of topic (respiratory muscles still relaxed) that 2. Logistics and procedural requirements: relevance, study methodology, outcome follows release of the occlusion. a. What equipment is needed?/technical measures, and clinical applicability. Table 1 In both dynamic and passive specifications is a checklist summarizing the methods techniques, these values of flow, volume, and fl b. What technical data are gathered/ used. Con icts of interest were disclosed, driving pressure are used to solve the presented/available? vetted, and managed in accordance with equation of motion of the lung and yield c. Variability, including interrater/ ATS policy and procedures. The Workshop values for compliance and resistance. For intrarater, repeatability within/between Report was written by the co-chairs (P.C.S., situations where airflow cannot be measured occasions S.P.-C., and S.C.R.) then modified with accurately, a variant of dynamic mechanics 3. Feasibility detailed feedback from the workshop uses esophageal pressure measurements a. Availability of commercial equipment/ participants. The online supplement alone to derive measures of respiratory approximate costs consists of the detailed sections on effort (e.g., amplitude or amplitude-time

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Table 1. Methods used in producing this Workshop Report Document excessive inflation pressure (pressure–volume loop). In conjunction Panel assembly with ventilator graphics, additional Included experts from relevant clinical and Yes information can be obtained by plotting nonclinical disciplines esophageal pressures (obtained by Included an individual who represents views of No esophageal manometry), as mentioned in patients and society at large Included methodologist with appropriate Applicable only to clinical Tables 2 and 3. expertise (documented expertise in practice guidelines development of conducting systematic reviews Volumetric Capnography to identify the evidence base and development Capnography describes the continuous of evidence-based recommendations) display of carbon dioxide (CO2) partial Literature review — Performed in collaboration with librarian No pressure in expired breath widely used Searched multiple electronic databases Yes clinically in, for example, end-tidal CO2 Reviewed reference lists of retrieved articles Yes monitoring. Volumetric capnography Evidence synthesis combines end-tidal CO2 monitoring with Applied prespecified inclusion and exclusion Yes fl criteria continuous ow (and hence volume) Evaluated included studies for sources of bias No measurement, to provide a continuous Explicitly summarized benefits and harms Yes measure and visual display of quantity of Used PRISMA1 to report systematic review Applicable only to systematic CO2 eliminated and how it relates to reviews Used GRADE to describe quality of evidence Applicable only to clinical practice expired breath volume. The measurements guidelines are used to estimate anatomical and Generation of recommendations physiological dead space and ventilation Used GRADE to rate the strength of Applicable only to clinical practice effectiveness, whereas pattern recognition recommendations guidelines of displayed waveforms is used to identify Definition of abbreviations: GRADE = Grading of Recommendations Assessment, Development, and pathophysiological problems (e.g., airway Evaluation; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses. distension due to excessive positive end- expiratory pressure, esophageal intubation). product of esophageal pressure swings). is superimposed on the tidal (spontaneous Inert Gas Washout This is referred to below as esophageal or ventilator-driven) breathing pattern. The This technique measures how an inert gas fl fi manometry. This technique is sometimes resulting high-frequency changes in ow marker (arti cially introduced [SF6, He] or used in combination with chest wall and volume are separated out from the tidal naturally present [N2]) is eliminated or measurements (see below). flow/volume changes by signal processing. “washed out” from the . The Pressure, flow, and volume changes are then measurement applicable to PICU and Forced Deflation used to calculate the resistance and NICU is performed during a period of tidal Forced deflation is essentially a form of reactance (and the combined measure, breathing (ventilator or spontaneous) and for the intubated, ventilated impedance) of the respiratory system at the is hence called multiple breath washout child, aiming to produce a maximal imposed frequency. The technique is also (MBW). For SF6 or He, the gas is first expiratory flow-volume curve. For the test performed at low frequencies during apneic washed into the lungs by adding it to the fi fl procedure, the lungs are rst in ated by pauses (essentially equivalent to dynamic inspired air. For N2, the gas already present 1 manual ventilation to 40 cm H2O mechanics as described above in the in the lungs is washed out by breathing fl fi in ation pressure (de ned as the total lung ventilated, paralyzed child). Alternatively, 100% O2. Inert gas concentration in expired capacity). After the inflation pressure is measurements can be made during breath is measured continuously using a held static for at least 3 seconds, the lung is high-frequency oscillatory ventilation, when mass spectrometer or ultrasonic flowmeter, deflated by applying a constant negative the imposed high-frequency waveform and expiratory airflow and/or volume are 2 pressure of 40 cm H2O to the temporarily replaces the ventilator measured using a pneumotachometer endotracheal tube until expiratory flow waveform. or ultrasonic flowmeter. The total inert ceases. The rapid deflation produces gas volume washed out allows the reproducible maximal expiratory Ventilator Graphics measurement of lung volume (FRC), and flow-volume curves demonstrating flow Ventilator graphics refers to the real-time the rate at which it is washed out yields limitation, from which measures including display of continuous measurements of measures of gas mixing efficiency (e.g., lung FVC and maximal expiratory flow at 25% pressure, flow, and volume change on a clearance index), a marker of ventilation and 10% of FVC are derived. screen at the bedside, either as time-based inhomogeneity that is sensitive to small plots or as XY loops (e.g., flow–volume or airway disease. Forced Oscillation Technique pressure–volume). Rather than yielding Forced oscillation technique (FOT) is an numerical variables, pattern recognition is Electrical Impedance Tomography alternative technique for measuring used to identify specific pathophysiological Electrical impedance tomography (EIT) is a respiratory system mechanics, in which a situations—for example, small airway radiation-free dynamic imaging technique high-frequency driving pressure waveform obstruction (flow–volume loop) or that transmits very small alternating

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Table 2. Clinical issues that could be addressed by respiratory function measurements in the pediatric and neonatal intensive care units DOCUMENTS SOCIETY THORACIC AMERICAN

Clinical Issue Specific Clinical Question Physiological Parameters Measurement Techniques

Nature of disease? Obstructive, restrictive, or mixed lung disease? Lung/respiratory system compliance, resistance, and Dynamic/passive mechanics impedance FOT Lung volume Inert gas washout Lung disease diffuse or patchy, large or small airways? Ventilation inhomogeneity Capnography Inert gas washout Regional distribution of ventilation, perfusion EIT Regional mismatching of ventilation and Regional distribution of ventilation, perfusion EIT perfusion? Chest wall or respiratory muscle problems? Chest wall compliance Dynamic mechanics PImax Occlusion pressures

Optimizing respiratory support, On optimal portion of the pressure-volume Pressure-volume curve Dynamic mechanics minimizing ventilator-associated curve? Vent graphics lung injury? EIT At optimal lung volume for pulmonary blood Regional distribution of ventilation, perfusion EIT : : fi flow and V=Q matching? Gas exchange ef ciency Capnography Minimizing patient–ventilator dyssynchrony? Timing of respiratory effort vs. ventilator breaths Vent graphics Esophageal manometry Inspiratory time/flow sufficient to deliver Time-based flow and volume waveforms Vent graphics adequate ? Expiratory time sufficient to prevent breath-stacking/auto- Measurement of respiratory time constant Passive mechanics PEEP? Time-based flow and volume waveforms 6 expiratory hold Vent graphics Identify problems before serious complication Continuous measurement of R and C Dynamic mechanics (e.g., tube blockage/malposition, pneumothorax)? Time-based and XY plots of pressure, flow, volume Vent graphics Gas exchange efficiency Capnography Ventilation distribution EIT

Effect of therapeutic interventions? Suctioning, positioning, chest physiotherapy? Lung/respiratory system compliance, resistance and Dynamic/passive mechanics

impedance Vent graphics FOT Lung volume EIT Inert gas washout Gas exchange efficiency Capnography Medications (e.g., mucolytics, , surfactant, Lung/respiratory system compliance, resistance, and Dynamic/passive mechanics steroids)? impedance Vent graphics FOT Lung volume EIT Inert gas washout Gas exchange efficiency Capnography Changes in ventilator settings? Lung/respiratory system compliance, resistance, and Dynamic/passive mechanics impedance changes Vent graphics FOT Lung volume EIT Esophageal manometry Gas exchange efficiency Inert gas washout Capnography

Ready to wean? Work of breathing too high? Resistance, compliance, impedance, work of breathing Dynamic/passive mechanics Esophageal pressure-rate product Esophageal manometry Thoracoabdominal asynchrony Chest wall measurements Respiratory muscle strength too poor? PImax Occlusion pressures Respiratory drive too poor, inconsistent, or P0.1 Occlusion pressures uncoordinated? Respiratory dead space a problem? Physiological dead space Capnography (volumetric) Inert gas washout

Definition of abbreviations: EIT = electrical impedance tomography; FOT = forced oscillation technique; P0.1 = negative pressure developed after 100 ms of occlusion; PEEP = positive end-expiratory pressure; PImax = maximum inspiratory pressure. S5

AMERICAN THORACIC SOCIETY DOCUMENTS electrical currents through the lungs from a unobstructed breath (100 ms is too short Further technological development belt-like array of electrical transmitter/ a time to allow a response to occlusion). of EIT hardware and software and receivers around the outside of the chest By contrast, maximum inspiratory availability of commercial EIT devices at wall. The resulting voltages are used to pressure (PImax)isthemaximumnegative a reasonable cost will likely enhance construct a two-dimensional “slice” pressure measured at the airway opening thefutureclinicaluseofEIT.The showing the distribution of electrical during an occlusion sustained for a practicability of EIT examinations will impedance throughout the chest at that number of breaths (usually five to seven) improve with development of electrode level. Because the major factor in and is used to estimate respiratory belts for the smallest neonatal patients and determining impedance in any area of lung muscle strength. In the cooperative child, by increased robustness of the devices tissue is the air content, the image maps out maximal effort is requested; in the infant against electrical interference. It is crucial the relative distribution of air in the lungs it is inferred. Table 2 summarizes the that EIT-derived indices relevant for at that time point. By taking repeated scans potential of each technique for assessing clinical decision making are available (up to 50 per second) during tidal important clinical issues in the PICU or online to clinicians. Following these breathing, a measure of total and regional NICU. necessary steps, EIT has the potential to be ventilation of the lungs is obtained. of great value in the NICU and PICU as Although absolute lung volume is not a bedside, noninvasive tool to monitor measured, relative changes in end- Discussion and Future Directions changes in the distribution of lung volume expiratory volume are estimated from the and ventilation, especially in those infants cross-section sampled. The respiratory function techniques and children receiving respiratory reviewed in this document could aid in the support. Chest Wall Measurements clinical management of individual Potential future clinical indications Chest wall measurement techniques patients in the PICU and NICU setting. of MBW in the PICU and NICU are involve assessment of tidal breathing by Specifically, they could potentially help dependent on widespread availability of estimatingchangeinvolumeofthe pediatric and neonatal intensive care suitable portable low dead space chest at the chest wall, rather than by clinicians to identify the nature of equipment and the evolving availability of airflow at the airway opening. Chest respiratory disease, optimize respiratory MBW as an integrated option within wall measurements are useful in the support to minimize ventilator-associated ventilators and circuits. An additional sick but nonintubated child, in whom lung injury, assess the effect of therapeutic consideration is the potential impact of measuring flow at the airway opening interventions, and assess readiness to leak around uncuffed endotracheal tubes is impracticable. The best known wean from ventilatory support. on some of these measurements. This technique is respiratory inductance Commercial equipment is now available remains a significant issue for many of plethysmography, which measures for most of the aforementioned these measures in the NICU, especially changes in the cross-sectional area of the techniques; measurements are obtained for measures of lung volume. This chest by changes in inductance in coils quickly to avoid undue interference with issue can be minimized with the use of bearing weak current around the chest clinical care, and patient risks are cuffed endotracheal tubes for the purpose and abdomen. As well as giving a measure minimal. of the measurements of pulmonary of changes in overall tidal volume, The future impact in the PICU and mechanics but may impact standard the time lag between abdominal and NICU of the various techniques presented clinical practice. chest excursions (thoracoabdominal depends on a few key questions: How In addition, true “normal” reference asynchrony [TAA]) is used as an invasive is the technique, and does it values for FRC in ventilated patients indirect measure of work of breathing. A interfere with normal care? Is there in the PICU and NICU do not exist number of newer chest wall techniques, commercially available equipment, at a price and will require a large series of using for example electromagnetic affordable to most units? Can the procedure measurements across a range of inductance or light reflection, are now be easily taught to staff? Can it be used easily gestations and postnatal ages using available. in the intubated pediatric patient to provide standardized conditions. Equipment continuous data? Does it improve clinical needstobeabletocopewiththewarm, Occlusion Pressures outcomes? Based on these criteria, the most humidified environment of a ventilator Occlusion pressure techniques focus on likely bedside clinical tools in the near future circuit and ideally with rapid respiratory the respiratory muscles and central are: dynamic and passive respiratory rates. Measurements during high- respiratory drive rather than respiratory mechanics, volumetric capnography, EIT, frequency oscillatory ventilation mechanics, lung volumes, and gas MBW, and chest wall measurements. To represent a particular technical challenge exchange. Pressure at the airway opening date, the volumetric capnogram has been but have been achieved for FOT, EIT during a complete airway occlusion will used successfully in the measurement of (16), and chest wall measurements tend to equilibrate with alveolar pressure. anatomical dead space, pulmonary capillary (17). Adaptation of techniques for The negative pressure developed after 100 perfusion, and effective ventilation (15). bedside assessment of the alveolar ms of occlusion (P0.1)isameasureof Randomized controlled trials evaluating capillary membrane surface such as respiratory drive, because it reflects the routine use of capnography are needed to the and the diffusing alveolar pressure that would have been evaluate associated potential improvements coefficient may facilitate noninvasive developed by the respiratory muscles in an in patient care. measures of the

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Table 3. Technical issues for pulmonary function testing techniques in the neonatal and pediatric intensive care units DOCUMENTS SOCIETY THORACIC AMERICAN

Question Dynamic/ Forced FOT Graphics Capnography Inert Gas EIT Chest Wall Occlusion Passive Deflation Washout Measurements Pressures Mechanics

Logistics What equipment Low dead space Flowmeter, Low dead space Mechanical Low dead space Low dead space Electrode Inductance bands or Airway pressure is needed? flowmeter, timed oscillatory ventilator or sidestream or flowmeter and array, EIT alternative (e.g., transducer, airway; with or positive and signal stand-alone mainstream rapid response hardware magnetic balloon or without negative generator; respiratory capnograph gas analyzer and analysis inductance, light slide valves esophageal pressure pressure monitor with software reflection) pressure sources, transducer and graphics transducer 3-way valve flowmeter software

What is Dynamic/passive FVC, maximal Resistance and Airway pressure- End-tidal partial FRC, lung Dynamic Quantitative or P0.1 measured? resistance and flows at reactance of time, flow-time, pressure of clearance cross- semiquantitative PImax compliance, of specific respiratory and volume- CO2; partial index, other sectional tidal volumes and lungs or volumes system time plots; pressure of CO2 indices of scans of flows; respiratory airway exhaled over ventilation regional thoracoabdominal system pressure- time; quantity distribution ventilation asynchrony Work of breathing volume and of CO2 as a flow-volume function of loops exhaled gas (esophageal volume pressure)

Feasibility Availability of Available Available Not available Available Available Available Available Available Components commercial (outside available at

equipment United low cost—no States) specific system for PICU/NICU use

How long do 15 min 15 min 10 min Continuous data Continuous data 10 min (3 3 3-min Continuous Continuous data 10 min measurements tests) data take to obtain? Risks to patient? Minimal Low Minimal Minimal Minimal Minimal Minimal Minimal Minimal Which patients Leak . 10% at Leak . 10%, Leak . 10% Leak . 10% Leak . 10% Leak . 10% Birth None Leak . 10%, are unsuitable? airway opening unintubated weight muscle (20); strong patients; , 600 g relaxants. respiratory most Fragile or drive (passive patients broken skin mechanics) with on chest; uncuffed ETT’s

Studies in NICU/PICU Technical/ Yes (21–30) Yes (31–35) Yes (36–44) Yes (20, 45–51) Yes (52–55) Yes (47, 56–60) Yes (61–64) Yes (65) Yes (66, 67) validation studies Using technique Yes (68–94) Yes (95–99) Yes (100) Yes (101, 102) Yes (103, 104) Yes (105–111) No No Yes (112) as outcome measure in trial Using technique Yes (113–115) No Yes (116–118) Yes (119–121) Yes (15, 122, 123) No No Yes (18) No to guide clinical management

S7 Definition of abbreviations: EIT = electrical impedance tomography; ETT = endotracheal tube; FOT = forced oscillation technique; NICU = neonatal intensive care unit; P0.1 = negative pressure developed after 100 ms of occlusion; PICU = pediatric intensive care unit; PImax = maximum inspiratory pressure.

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and help achieve optimal balance additional data not easily obtained d Establish clinical protocols for the between ventilation and perfusion. In the otherwise. reviewed techniques and rigorous models future, this would be an amazing for data analysis. technical advance for the population of Proposed Areas of Future d Study whether the use of EIT can shorten patients in the NICU and PICU. Research Collaboration time to weaning from ventilation and For chest wall measures such as TAA, minimize lung injury. n normal values for phase angles in full- d For all techniques, establish “normal” term infants and children have been reference values using current This official statement was prepared by the ATS/ reported independent of sleep state (18, commercial equipment in ventilated ERS Evaluation of Respiratory Mechanics and 19), but further studies will be needed to patients (e.g., studies of surgical patients Function in the Pediatric and Neonatal Intensive explore whether the integration of new without respiratory disease/chest or Care Units writing group and automated analysis procedures will abdominal ). increase the clinical potential of TAA d Conduct pre- and postintervention Members of the committee: monitoring in the intensive care unit. studies (surfactant, altered ventilation STACEY PETERSON-CARMICHAEL, M.D., (Co-Chair) Although there are some data on strategy, mucolytics, etc.) studying effect PAUL C. SEDDON, M.B. CH.B., (Co-Chair) TAA in preterm infants, there are on dead space using capnography and IRA M. CHEIFETZ, M.D. InEZ´ FRERICHS, M.D., PH.D. still inadequate normative data for MBW (FRC). GRAHAM L. HALL,PH.D. respiratory inductance plethysmography d Conduct randomized trials to assess if JURG¨ HAMMER, M.D. measures in this population. Thus, we knowledge of/discussion of routine ZOLTAN´ HANTOS,PH.D., D.Sc. first require preterm normative data measures of respiratory mechanics ANTON H. VAN KAAM, M.D., PH.D. before studying preterm infants in the affects patient outcomes in the CINDY T. MCEVOY, M.D. CHRISTOPHER J. L. NEWTH, M.D. acute phases of lung injury. PICU and NICU, such as length of J. JANE PILLOW,PH.D. Finally, it should be stressed that more and/or length GERRARD F. RAFFERTY,PH.D. research is warranted for each technique of stay. MARGARET ROSENFELD, M.D., M.P.H. JANET STOCKS,PH.D. before issuing detailed recommendations d Conduct randomized controlled trial of SARATH C. RANGANATHAN, M.B. CH.B., PH.D. on specificages,diseaseentities,or patients in the PICU to evaluate the outcome measures associated with testing. impact of volumetric capnography on Author disclosures: I.M.C. was on advisory There is a requirement to develop length of ventilation, length of stay, and committees of Ikaria and Phillips Electronics and standardized procedures/protocols, cost effectiveness. received research support from Hill-Rom. I.F. received speaker fees and reimbursement of minimum standards for equipment, and d Work with ventilator manufacturers to travel expenses from Drager and Swisstrom. ideally normative data to differentiate incorporate appropriate measurement and J.H. received consulting fees from Olympus and normal from disease states before display of resistance, compliance, and speaker fees from Bayer Suisse SA, Colloquium incorporation of a technique into our daily volumetric capnography in commercial Conferences, and Olympus; he received clinical practice. Nonetheless, there is ventilators for the PICU and NICU. textbook royalties from Karger and Springer. S.P.-C., P.C.S., G.L.H., Z.H., A.H.v.K. C.T.M. d already a body of experience with these Measure oscillation mechanics during C.J.L.N., J.J.P., G.F.R., M.R., J.S., and S.C.R. techniques as research tools, most are mechanical ventilation in a large group of reported no financial interests relevant to the noninvasive, and they can provide patients in the PICU. document subject matter.

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52 McSwain SD, Hamel DS, Smith PB, Gentile MA, Srinivasan S, 73 Durand M, Mendoza ME, Tantivit P, Kugelman A, McEvoy C. A Meliones JN, Cheifetz IM. End-tidal and arterial carbon dioxide randomized trial of moderately early low-dose dexamethasone measurements correlate across all levels of physiologic dead therapy in very low birth weight infants: dynamic pulmonary space. Respir Care 2010;55:288–293. mechanics, oxygenation, and ventilation. Pediatrics 2002;109: 53McDonaldMJ,MontgomeryVL,CerritoPB,ParrishCJ,Boland 262–268. KA, Sullivan JE. Comparison of end-tidal CO2 and Paco2 in 74 Kugelman A, Durand M, Garg M. Pulmonary effect of inhaled children receiving mechanical ventilation. Pediatr Crit Care Med furosemide in ventilated infants with severe bronchopulmonary 2002;3:244–249. dysplasia. Pediatrics 1997;99:71–75. 54 Tobias JD, Meyer DJ. Noninvasive monitoring of carbon dioxide 75 Gappa M, Gartner ¨ M, Poets CF, von der Hardt H. 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94 McEvoy C, Schilling D, Peters D, Tillotson C, Spitale P, Wallen L, Segel S, residual capacity and ventilation homogeneity impairment in Bowling S, Gravett M, Durand M. Respiratory compliance in preterm anesthetized children exposed to high levels of inspired oxygen. infants after a single rescue course of antenatal steroids: a randomized Anesth Analg 2007;104:1364–1368. controlled trial. Am J Obstet Gynecol 2010;202:544.e1–544.e9. 110 von Ungern-Sternberg BS, Regli A, Frei FJ, Ritz EM, Hammer J, 95 Hammer J, Numa A, Newth CJ. Albuterol responsiveness in infants Schibler A, Erb TO. A deeper level of ketamine anesthesia does with respiratory failure caused by respiratory syncytial virus not affect functional residual capacity and ventilation distribution infection. J Pediatr 1995;127:485–490. in healthy preschool children. Paediatr Anaesth 2007;17: 96 Newth CJ, Stretton M, Deakers TW, Hammer J. 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