tidal breathing in preterm infants receiving and weaning from continuous positive airway pressure

7
Tidal Breathing in Preterm Infants Receiving and Weaning from Continuous Positive Airway Pressure Nicole Pickerd, MB, BS, MD 1 , Edgar Mark Williams, PhD 2 , William John Watkins, PhD 1 , and Sailesh Kotecha, FRCPCH, PhD 1 Objective To compare tidal breathing on different continuous positive airway pressure (CPAP) devices and pres- sures and to serially measure tidal breathing during weaning off CPAP using electromagnetic inductive plethysmog- raphy. Study design Using electromagnetic inductive plethysmography, tidal breathing was measured in 29 preterm in- fants receiving CPAP, gestational age 28 2 weeks. Variable-flow nasal CPAP (nCPAP), bubble CPAP (bCPAP) at pressures of 5, 7, and 9 cmH 2 O, nasal bi-level positive airway pressure (nBiPAP) system at pressures of 5, 7/5, and 9/5 cmH 2 O, and unsupported breathing were studied. Twenty-one infants had weekly tidal breathing measure- ments on and off nCPAP. Results Minute volume (MV/kg) was similar between all devices (0.30-0.33 L/kg/min). On bCPAP, weight corrected tidal volume (V T /kg) was the least, changing little with increasing pressures. On nCPAP and nBiPAP, V T /kg increased with increasing pressure and the respiratory rate (fR) decreased. The delivered pressure varied slightly from the set pressure being most dissimilar on nBiPAP and similar on bCPAP. Compared with unsupported breathing, all devices decreased V T /kg, MV/kg, and phase angle, but did not alter fR. Serial tidal breathing measure- ments showed decreasing difference for V T /kg over time on and off nCPAP. Conclusions At different pressure settings, on all CPAP devices the measured MV/kg was similar either through increasing V T /kg and decreasing fR (nCPAP and nBiPAP) or maintaining both (bCPAP). Serial tidal breathing mea- surements may aid weaning from CPAP. (J Pediatr 2014;164:1058-63). C ontinuous positive airway pressure (CPAP) has been used since 1971 1 in preterm infants to treat respiratory distress syndrome (RDS), to reduce apnea of prematurity, and to prevent extubation failure. 2 There are suggestions that early treatment of RDS with CPAP reduces the need for intubation and the incidence of bronchopulmonary dysplasia. 3-5 There are several devices available for infants to generate and deliver CPAP, 6,7 and although short binasal prongs are most suit- able to deliver nasal CPAP (nCPAP), it is not known which is the most suitable CPAP generator. 6 Several studies have compared different CPAP generators and their ability to improve lung function and breathing patterns in preterm infants, 8-18 but have provided contradictory results. So far, no study has compared the effects of bubble CPAP (bCPAP), variable flow CPAP, and nasal bi-level positive airway pressure (nBiPAP) on tidal breathing variables in preterm infants. Tidal breathing measurements in infants during nCPAP are difficult to perform as pneumotachography or other airflow sen- sors rely on a leak-free CPAP interface seal and, therefore, cannot be performed while infants are receiving CPAP through nasal prongs where leaks have been shown to often exceed 90%. 19 Most tidal volume (V T ) measurements on CPAP have been per- formed using respiratory inductive plethysmography, 8,9,11,12,14,15,17 but the accuracy of volume measurements with respiratory inductive plethysmography is limited if the breathing pattern is variable as in preterm infants 20 and results in lower V T compared with other techniques. 21 In this study, we used the noninvasive technique of electromagnetic inductive plethysmography (EIP), which measures volume changes of an infant’s chest and abdomen via recording of thoraco-abdominal movements. It does not require an airway connection or patient-dependent calibration. EIP has been validated in preterm and term infants 22,23 and has been used successfully in infants without respiratory support between 29 and 42 weeks postmenstrual age. 21-23 Although tidal breathing measurements are routinely used to guide weaning in intubated infants, 24 infants on CPAP are weaned by “trial and error” with wide variation of practice. 25 The most effective strategy of weaning infants from CPAP is not known. 26,27 From the 1 Department of Child Health, Cardiff University, Cardiff, United Kingdom and 2 Faculty of Life Sciences and Education, University of South Wales, Pontypridd, United Kingdom Partially funded by VoluSense, Norway; the study team received technical and equipment support from the company. The study design, collection, analysis and interpretation of data, writing of the manuscript and de- cision to submit the paper for publication were made by the authors independent of company personnel. Since the end of the study, S.K. serves as a consultant to the company. The other authors have no other conflicts of interest to disclose. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.12.049 bCPAP Bubble CPAP CPAP Continuous positive airway pressure EIP Electromagnetic inductive plethysmography FiO 2 Fraction of inspired oxygen fR Respiratory rate MV Minute volume nCPAP Variable flow nasal CPAP nBiPAP Nasal bi-level positive airway pressure PEEP Positive end expiratory pressure RDS Respiratory distress syndrome t PTEF /t E Time to peak tidal expiratory flow as a proportion of expiratory time V T Tidal volume V T /kg Weight corrected tidal volume 1058

Upload: sailesh

Post on 30-Dec-2016

213 views

Category:

Documents


0 download

TRANSCRIPT

Tidal Breathing in Preterm Infants Receiving and Weaning fromContinuous Positive Airway Pressure

Nicole Pickerd, MB, BS, MD1, Edgar Mark Williams, PhD2, William John Watkins, PhD1, and Sailesh Kotecha, FRCPCH, PhD1

Objective To compare tidal breathing on different continuous positive airway pressure (CPAP) devices and pres-sures and to serially measure tidal breathing during weaning off CPAP using electromagnetic inductive plethysmog-raphy.Study design Using electromagnetic inductive plethysmography, tidal breathing was measured in 29 preterm in-fants receiving CPAP, gestational age 28 � 2 weeks. Variable-flow nasal CPAP (nCPAP), bubble CPAP (bCPAP) atpressures of 5, 7, and 9 cmH2O, nasal bi-level positive airway pressure (nBiPAP) system at pressures of 5, 7/5, and9/5 cmH2O, and unsupported breathing were studied. Twenty-one infants had weekly tidal breathing measure-ments on and off nCPAP.Results Minute volume (MV/kg) was similar between all devices (0.30-0.33 L/kg/min). On bCPAP, weightcorrected tidal volume (VT/kg) was the least, changing little with increasing pressures. On nCPAP and nBiPAP,VT/kg increased with increasing pressure and the respiratory rate (fR) decreased. The delivered pressure variedslightly from the set pressure being most dissimilar on nBiPAP and similar on bCPAP. Compared with unsupportedbreathing, all devices decreased VT/kg, MV/kg, and phase angle, but did not alter fR. Serial tidal breathingmeasure-ments showed decreasing difference for VT/kg over time on and off nCPAP.Conclusions At different pressure settings, on all CPAP devices the measured MV/kg was similar either throughincreasing VT/kg and decreasing fR (nCPAP and nBiPAP) or maintaining both (bCPAP). Serial tidal breathing mea-surements may aid weaning from CPAP. (J Pediatr 2014;164:1058-63).

Continuous positive airway pressure (CPAP) has been used since 19711 in preterm infants to treat respiratory distresssyndrome (RDS), to reduce apnea of prematurity, and to prevent extubation failure.2 There are suggestions that earlytreatment of RDS with CPAP reduces the need for intubation and the incidence of bronchopulmonary dysplasia.3-5

There are several devices available for infants to generate and deliver CPAP,6,7 and although short binasal prongs are most suit-able to deliver nasal CPAP (nCPAP), it is not known which is the most suitable CPAP generator.6

Several studies have compared different CPAP generators and their ability to improve lung function and breathing patterns inpreterm infants,8-18 but have provided contradictory results. So far, no study has compared the effects of bubble CPAP (bCPAP),variable flow CPAP, and nasal bi-level positive airway pressure (nBiPAP) on tidal breathing variables in preterm infants.

Tidal breathing measurements in infants during nCPAP are difficult to perform as pneumotachography or other airflow sen-sors rely on a leak-free CPAP interface seal and, therefore, cannot be performed while infants are receiving CPAP through nasalprongs where leaks have been shown to often exceed 90%.19 Most tidal volume (VT) measurements on CPAP have been per-formed using respiratory inductive plethysmography,8,9,11,12,14,15,17 but the accuracy of volume measurements with respiratoryinductive plethysmography is limited if the breathing pattern is variable as in preterm infants20 and results in lower VT comparedwith other techniques.21 In this study, we used the noninvasive technique of electromagnetic inductive plethysmography (EIP),which measures volume changes of an infant’s chest and abdomen via recording of thoraco-abdominal movements. It does notrequire an airway connection or patient-dependent calibration. EIP has been validated in preterm and term infants22,23 and hasbeen used successfully in infants without respiratory support between 29 and 42 weeks postmenstrual age.21-23

Although tidal breathing measurements are routinely used to guide weaning in intubated infants,24 infants on CPAP are

weaned by “trial and error” with wide variation of practice.25 The most effectivestrategy of weaning infants from CPAP is not known.26,27

From the 1Department of Child Health, Cardiff University,Cardiff, United Kingdom and 2Faculty of Life Sciencesand Education, University of South Wales, Pontypridd,United Kingdom

Partially funded by VoluSense, Norway; the study teamreceived technical and equipment support from thecompany. The study design, collection, analysis andinterpretation of data, writing of the manuscript and de-cision to submit the paper for publication were made bythe authors independent of company personnel. Sincethe end of the study, S.K. serves as a consultant to thecompany. The other authors have no other conflicts ofinterest to disclose.

0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc.

All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.12.049

bCPAP Bubble CPAP

CPAP Continuous positive airway

pressure

EIP Electromagnetic inductive

plethysmography

FiO2 Fraction of inspired oxygen

fR Respiratory rate

MV Minute volume

nCPAP Variable flow nasal CPAP

nBiPAP Nasal bi-level positive airway

pressure

PEEP Positive end expiratory pressure

RDS Respiratory distress syndrome

tPTEF/tE Time to peak tidal expiratory flow

as a proportion of expiratory time

VT Tidal volume

VT/kg Weight corrected tidal volume

1058

Vol. 164, No. 5 � May 2014

Our aim was to compare the effects of 3 CPAP devices thatare commonly used in neonatal units in the United Kingdomat different pressure settings on tidal breathing in preterm in-fants and to assess changes in tidal breathing measurementsduring weaning from CPAP.

Methods

Infants born at 34 weeks gestation or less, receiving nasalCPAP and clinically stable were eligible. Exclusions includedcongenital anomalies, neuromuscular disease, or surgicalconditions, lack of parental consent, or if the attendingteam deemed the baby unsuitable for study due to clinicalor social reasons. The study was approved by the SouthEast Wales Research Ethics Committee, with informed writ-ten consent from the parents.

The EIP system, FloRight (Volusense AS, Oslo, Norway),was described in detail previously.21-23 Briefly, it includes avolume sensor and a snug elastic vest worn by the infant,which covers the chest and abdomen and contains poweredcoils. These coils use a weak electric current of 100 mA toinduce an electromagnetic field. The size of the electromag-netic field changes with tidal breathing and is sensed by anantenna, which is placed above the infant. The changes inthe electromagnetic field are proportional to the changes inthe volume of the infant’s chest and abdomen. A referencevolume with a corresponding reference magnetic field wasused to calibrate the device.21

All measurements were performed with the infant lying su-pine in an incubator. The appropriately sized vest for each in-fant was identified by measuring the chest circumference. Noinfant was sedated for the study.

Tidal breathing was measured while the infant wasreceiving nasal CPAP provided by 3 CPAP devices at 3 pres-sure settings each and also while breathing without respira-tory support. The 3 CPAP devices were the Infant FlowSystem (EME, Brighton, United Kingdom; nCPAP), the In-fant Flow SiPAP System (Care Fusion, Warwick, UnitedKingdom; nBiPAP), and a bCPAP system (Fisher and PaykelHealthcare Ltd, Berkshire, United Kingdom; bCPAP). Eachdevice was set up according to manufacturers’ instructionsand the device-specific short bi-nasal prongs were used.The largest size prongs which fit into the nostrils withoutblanching were used.

The CPAP pressures for nCPAP and bCPAP were 5, 7,and 9 cmH2O positive end expiratory pressure (PEEP)and for nBiPAP PEEP 5 cmH2O, peak inspiratory pressure7/PEEP 5 cmH2O, backup rate 30/min, inspiratory time0.3 seconds, and peak inspiratory pressure 9/PEEP 5cmH2O, backup rate 30/min, inspiratory time 0.3 seconds.A Graseby capsule was taped to the abdomen of the infantsto sense respiration and used with nBiPAP at pressures of 7and 9/5 cmH2O.

The pressure delivered was continuously monitored usingthe auxiliary pressure port of a differential pressure trans-ducer (RSS100 HR; Hans Rudolph, Shawnee, Kansas). Theorder of the CPAP devices was randomized using sealed

envelopes. Each setting and breathing without respiratorysupport was studied for 15 minutes if tolerated by the infant.If an infant had recurrent desaturations (below 85%) or bra-dycardias (below <100 beats per minute) on a setting, therecording was discontinued and the infant was placed backon the original CPAP setting. During data collection, thefraction of inspired oxygen (FiO2) was adjusted to maintainthe oxygen saturation between 92% and 98%.After the initial measurements, the infants were followed

up weekly during weaning off nasal CPAP. The infants wereweaned by their clinician by increasing the time spent offCPAP as tolerated. Measurements were performed for15 minutes with and without nCPAP delivered by the In-fant Flow System. The order was randomized at the firstfollow-up and then alternated weekly. The last measure-ment was performed when the infant was weaned off nasalCPAP.Of the 15-minute recording, minute 13-14 was used for

analysis. If the infant was unsettled during this minute, min-ute 12-13 was used. If the recording had to be abandonedearlier than 15 minutes the penultimate minute of recordingwas used. The following variables were calculated for eachbreath with the EIP device software: VT, respiratory rate(fR), minute volume (MV), time to peak tidal expiratoryflow as a proportion of expiratory time (tPTEF/tE), and phaseangle.20,21 The number of sighs in 1 minute were calculatedmanually. A sigh was defined as a breath with an inspiratorytime more than 1.5 times the mean VT.

Statistical AnalysesSample size was based on similar studies comparing changesin VT achieved with different CPAP devices. A sample size of28-32 patients is required to attain a statistical power of 0.8when one assumes a 20% difference between the VT

measured on 2 different devices to be significant with aP < .05. Statistical analysis was performed using SPSS(version 16.0, IBM, Chicago, Illinois). Single value t testswere used to compare each delivery pressure with the ex-pected pressure. For each other variable of interest, two-way ANOVA was used to compare each device and pressuresetting. The Bonferroni correction was applied to mitigatethe inaccuracies that may result from multiple testing.Consequently, 9 values for each variable were comparedwithin the analysis. Only complete cases were analyzed,which led to 3 of the 29 cases being excluded from the anal-ysis. One-way repeated measures were used to compare eachof the 9 CPAP measurements with the case when no CPAPwas employed. A paired Student t test was used to compareinspiratory time/kg with and without CPAP each week overthe follow-up period. The statistical significance for individ-ual tests was set at P < .05.

Results

Parents of 52 infants were approached, 13 declined consent,and 39 infants were recruited. Out of these, 3 withdrew,3 were transferred out, and 4 were weaned off CPAP before

1059

Table I. Characteristics of infants studied (mean � SD,range)

CharacteristicsInfants on

CPAP (n = 29)Infants

followed-up (n = 21)

Sex 15 male (52%) 11 male (52%)Gestation at birth (wk) 28 � 2 (23-33) 28 � 2 (23-32)Birth weight (kg) 1.16 � 0.35

(0.66-2.07)1.16 � 0.34(0.66-1.94)

Postnatal age at firststudy (d)

28 � 28 (3-111) 30 � 28 (3-111)

PMA at first study (wk) 32 � 3 (29-39) 32 � 3 (29-39)Weight at first study (kg) 1.38 � 0.39

(0.74-2.51)1.44 � 0.37(0.93-2.51)

PMA, postmenstrual age.

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 164, No. 5

they could be studied; thus, 29 infants were studied (Table I).Of the 29 infants, 20 had previously been invasivelyventilated; all had received surfactant and 7 had chroniclung disease of prematurity defined as the need forsupplemental oxygen at 28 days of age. Twenty-three werereceiving caffeine at the time of the study. Six of the infantscould not be studied on all different modes and settingsas they did not tolerate certain CPAP settings or got tired.Nine infants were receiving supplemental oxygen before thestart of the study (FiO2 0.23-0.3). Their FiO2 variednonsignificantly between the different device settings.

Twenty-one of the infants were followed up during weaningoffCPAP (Table I). Eight infants couldnot complete the follow-up, 4 infants died of causes unrelated to the study, 2 had consentwithdrawn, 1 required prolonged ventilation, and 1 developedenterobacter sepsis. Of the infants who were followed-up, notall infants could be followed-up at weekly intervals and thenumber of infants who had paired measurements performedon and off CPAP varied each week (Table II).

Delivered PressuresThe delivered mean pressure was similar for all 3 devices at apressure of 5 cmH2O (Table III). The delivered meanpressure on nBiPAP 7/5 and 9/5 cmH2O was significantlyless than on nCPAP and bCPAP at 7 and 9 cmH2O(P < .001 for all) and also significantly different than theexpected pressure of 5.3 cmH2O for nBiPAP 7/5, but it wasnot significantly different from the expected pressure of 5.6cmH2O for nBiPAP 9/5. Overall, the delivered mean

Table II. Follow-up data during weaning from nCPAP

Wk n

VT/kg (mL/kg) MV/kg (L/kg/min)

nCPAPno

nCPAP nCPAPno

nCPAP nCPA

0 26 5.3 � 0.3 6.7 � 0.3 0.32 � 0.02 0.39 � 0.02 67 �P value .006 .019 .4351 12 4.9 � 0.2 7.1 � 0.5 0.31 � 0.01 0.43 � 0.03 70 �P value <.001 .002 .4432 12 5.3 � 0.5 6.9 � 0.5 0.34 � 0.04 0.40 � 0.02 69 �P value .033 .169 .4373 11 5.9 � 0.5 6.8 � 0.7 0.38 � 0.03 0.43 � 0.03 67 �P value .218 .250 .255

1060

pressure on bCPAP was closest to the set pressures(Table III).

Tidal Breathing Variables on Different CPAPDevicesOn a pressure setting of 5 cmH2O, the weight corrected VT

(VT/kg) was similar for the three devices (Figure 1 andTable III; Figure 1 available at www.jpeds.com). OnnCPAP and nBiPAP, there was a significant increase in theVT/kg when increasing the set pressure from 5 to 7 or 7/5cmH2O (P = .04 and .02, respectively) and again from 5 to9 or 9/5 cmH2O (P = .02 and <.001). This increase was notnoted on bCPAP. At pressures of 7 and 7/5 as well as 9 and9/5 cmH2O, the VT/kg was significantly larger on nCPAP(P = .02 and .002 respectively) and nBiPAP (both P = .01)compared with bCPAP (Figure 1 and Table III).The fR decreased with increasing pressure on all 3 CPAP

devices and overall was significantly higher on 5 cmH2Ocompared with 7 cmH2O (P = .04) and 9 cmH2O(P = .001). The decrease was greatest on nCPAP (P # .001for both) and smallest and nonsignificant on bCPAP. Therewas no significant difference in the fR between the deviceson each of the set pressures. The MV/kg did not differ be-tween the different ventilators and pressure settings; a signif-icant increase was only noted on nBiPAP between 5 and7 cmH2O (P = .03) and when using a pressure of 9 cmH2Obetween bCPAP and nBiPAP (P = .02).There was no significant difference in the tPTEF/tE and

phase angle between the different CPAP devices or pressuresettings.The sigh number was greatest at 5 cmH2O when using

bCPAP compared with nCPAP (P = .03) and nBiPAP(P = .003) and when using nBiPAP on 9/5 compared with5 cmH2O (P = .006).The VT/kg was significantly higher without CPAP than on

all support modes and settings apart from nCPAP at7 cmH2O and 9 cmH2O, nBiPAP at 7/5 cmH2O and 9/5cmH2O, and bCPAP at 5 cmH2O (Figure 1 and Table III).There was no difference in the fR. Without CPAP, theMV/kg was significantly higher for bCPAP at 9 cmH2O andnBiPAP at 5 cmH2O. Also the phase angle was onlysignificantly greater when off CPAP for nBiPAP at5 cmH2O. There was no difference in tPTEF/tE and number

fR tPTEF/tE Phase angle Sighs

Pno

nCPAP nCPAPno

nCPAP nCPAPno

nCPAP nCPAPno

nCPAP

3 64 � 3 41 � 2 41 � 2 13 � 3 27 � 7 4 � 1 6 � 1.916 .054 .304

3 66 � 4 42 � 3 40 � 3 11 � 3 18 � 3 4 � 1 5 � 1.422 .183 .794

3 65 � 4 39 � 2 35 � 3 6 � 2 18 � 3 4 � 2 5 � 1.239 .006 .625

5 75 � 5 36 � 4 35 � 2 13 � 3 26 � 5 3 � 1 6 � 2.718 .047 .182

Pickerd et al

Table III. Tidal breathing results on the different CPAP settings and without CPAP

VT/kg(mL/kg)

fR(Breaths/min)

MV/kg(L/kg/min)

tPTEF/tE%

Phase angle(Degrees) Sighs Delivered pressure

cmH2ONo CPAP

6.7 � 0.4 64 � 3 0.39 � 0.02 41 � 2 27 � 7 6 � 1

nCPAP5(n = 29)

5.2 � 0.3 70 � 3 0.32 � 0.02 42 � 2 13 � 4 4 � 1 5.3 � 0.1

nCPAP7(n = 29)

5.7 � 0.3 63 � 3 0.32 � 0.01 40 � 2 11 � 3 5 � 1 6.9 � 0.1

nCPAP9(n = 28)

5.9 � 0.3 60 � 3 0.32 � 0.02 41 � 2 11 � 2 4 � 1 8.0 � 0.1

nBiPAP5(n = 29)

5.2 � 0.3 66 � 3 0.30 � 0.01 40 � 3 12 � 5 3 � 1 5.1 � 0.1

nBiPAP7/5(n = 29)

6.1 � 0.5 64 � 4 0.33 � 0.02 41 � 2 12 � 3 4 � 1 5.6 � 0.1

nBiPAP9/5(n = 27)

6.2 � 0.4 60 � 3 0.33 � 0.02 42 � 2 15 � 4 5 � 1 5.9 � 0.1

bCPAP5(n = 27)

5.4 � 0.2 67 � 3 0.33 � 0.02 44 � 2 11 � 2 6 � 1 5.1 � 0.1

bCPAP7(n = 27)

5.0 � 0.3 65 � 4 0.31 � 0.02 44 � 2 14 � 5 3 � 1 7.1 � 0.1

bCPAP9(n = 27)

5.1 � 0.3 65 � 3 0.30 � 0.02 42 � 2 9 � 7 4 � 1 8.8 � 0.1

May 2014 ORIGINAL ARTICLES

of sighs when breathing without CPAP compared with any ofthe CPAP devices.

Serial Tidal Breathing Measurements with andwithout Respiratory SupportOver the follow-up period, the VT/kg without nCPAPdecreased, and the VT/kg on nCPAP increased (Figure 2and Table II). The difference in the VT/kg betweenbreathing with and without nCPAP decreased graduallyand lost significance after 3 weeks of follow-up (Figure 2).

Discussion

In preterm infants on different CPAP devices and pressuresettings, MV/kg was similar. However, the way the MV/kgwas achieved differed with ventilation mode and pressuresetting. At a set pressure of 5 cmH2O, the delivered pressureand measured VT/kg was similar for all 3 devices, which wasexpected for the nCPAP and nBiPAP device as they deliverCPAP at this setting in the same way. When the set pressurewas increased to 7 and then 9 cmH2O, VT/kg and fR re-mained unchanged on bCPAP. This suggests that respiratorydrive was not increased by bCPAP with no increases inPaCO2 or increased volume or stretch receptor activity inthe lungs. bCPAP may achieve this through some extra-high frequency ventilation produced by the bubbling proce-dure in the device. On bCPAP, the delivered pressure wasclosest to the set pressure compared with other devices(Figure 1). On nCPAP, the MV/kg was achieved by anincrease in the VT/kg and decrease in the fR with increasedpressures. A set pressure of 9 cmH2O with the deliveredpressure was closer to 8 cmH2O. With nBiPAP, MV/kg wasmet by a significant increase in VT/kg and a drop in fR asthe set pressure increased. The increase in VT/kg onnBiPAP occurred despite a lower delivered mean airwaypressure. The VT/kg did not increase much further when

Tidal Breathing in Preterm Infants Receiving and Weaning from C

changing from 7/5 to 9/5 cmH2O. This may indicate that at5 cmH2O, the end-expiratory lung volume was insufficientand lung compliance low, the higher driving pressuresserving to augment dead space volume, which elicited anincrease in inspiratory effort to keep alveolar ventilationunchanged. Other factors could be that the shortinspiratory time characteristic of nBiPAP was insufficientto allow the set upper pressure to be reached or the use ofthe Graseby capsule, which has been reported to assistaround 70% of breaths.28 Despite the different deliverymodes the VT/kg and fR measured on nCPAP and nBiPAPwere not significantly different as reported previously.8,9,11

A raised VT may aid gas exchange but could in the long-term be disadvantageous to the infant as maintaining anincreased respiratory effort for a prolonged period maydelay weaning.A few studies have reported tidal breathing variables on

different pressure settings. Liptsen et al15 showed a reductionin fR with increasing pressures but no change in VT/kg orMVon bCPAP or variable flow CPAP. The same was noted byPandit et al14 on variable and constant flow nasal CPAP. El-gellab et al29 and Magnenant et al30 reported a gradual in-crease in VT and a gradual but nonsignificant decrease infR with increasing pressures on nasal CPAP. Although theexact mechanisms for these changes in VT/kg with increasingpressures are unknown, recruitment ofmore alveoli could ac-count for some of these changes. Furthermore, infants mayhave increased their breathing effort to maintain alveolarventilation in response to a larger anatomical dead spacecreated by the higher distending pressures.The different devices and pressure settings did not signifi-

cantly affect the phase angle or tPTEF/tE. A significantly largernumber of sighs was noted on bCPAP at 5 cmH2O comparedwith the other settings, which may be related to the differenttypes of nasal prongs used for bCPAP that are not routinelyused in our unit.

ontinuous Positive Airway Pressure 1061

Figure 2. A, Weight corrected VT on (C) and off nCPAP (B)over a 3-week follow-up period. B, Differences in VT/kg be-tween on and off nCPAP. *Significantly different, P < .05. NS,not significantly different.

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 164, No. 5

Thus far, no studies have been published comparing tidalbreathing on CPAP to breathing without respiratory sup-port probably attributable to difficulties in removingCPAP from infants who need it. We were able to study in-fants commencing weaning from their CPAP using thenovel EIP method, as it does not interfere with the infant’sbreathing. Other studies14,15,30,31 have used a pressure of0 cmH2O on CPAP to compare with other pressure settings,but the nasal prongs in situ would add resistance to the res-piratory system. Compared with breathing without respira-tory support, all CPAP devices and pressures reduced theVT/kg, MV/kg, and phase angle. The reduction in VT/kgand MV/kg when on CPAP is probably due to a reductionin dead space ventilation attributable to establishment of asatisfactory functional residual capacity leading to decreasedwork of breathing, whereas there was increased work ofbreathing without CPAP. The reduction in phase angle isnot unexpected as CPAP stabilizes the chest wall as reported

1062

previously.12,30-32 Pulmonary maturation improves lungmechanics, which stabilizes lung volumes and alters breath-ing patterns, as tPTEF/tE occurs earlier; when and how thiscontributes to a readiness to wean requires further investi-gation.We noted that the difference in VT/kg on and off CPAP

decreased during the follow-up. During the first weeks, theCPAP support reduced the VT/kg significantly but after3 weeks a significant reduction of VT/kg by CPAP wasnot observed, suggesting that the need for CPAP becomesless. Phase angle also improved with time. Prospective se-rial tidal breathing measurements on and off CPAP could,therefore, be an useful objective tool to guide weaning fromCPAP.There are some limitations to our study. The FloRight,

which uses EIP to measure tidal breathing is sensitive to elec-tromagnetic interference,21-23 which was resolved with ma-chine repositioning. The intra-prong pressure measured onthe different CPAP devices was not identical for the sameset pressure. For bCPAP, the delivered pressure is dependenton the flow.30-32 In this study, a constant flow of 9 L/min wasused for all pressures and created a steady bubbling. The clin-ical importance of these small differences between set anddelivered pressures remains questionable.33 The Infant FlowDriver prongs, which were used for nCPAP and nBiPAP,affect the delivered pressure less than others.34 Fisher andPaykel nasal prongs, which are supplied for use with theFisher and Paykel bCPAP system, have a larger pressuredrop at VT of 3-6 mL. The infants may have required a longeradaptation period to a new setting than 10 minutes, although10 minutes is longer than most studies have used. The infantsstudied were all well and stable preterm infants who wererecovering from RDS. It was our aim to study stable infantsas they needed to tolerate at least 15 minutes without respi-ratory support to measure tidal breathing without CPAP.The MV/kg measured in preterm infants remained the

same when receiving nCPAP, nBiPAP, or bCPAP at set pres-sures of 5, 7, and 9 cmH2O, but the way of achieving itdiffered among the devices and pressure settings. On bCPAP,VT/Kg, and fR remained stable despite increasing set anddriving pressures, and a significant increase in VT/kg anddecrease in fR with increasing pressures was noted on nCPAPand nBiPAP. Serial tidal breathing measurements on and offCPAP have shown that the difference in VT/kg with andwithout CPAP decreases over time. A prospective clinicalstudy to assess whether serial tidal breathing measurementscould aid weaning from CPAP would be useful. n

We are very grateful to the infants and their parents for taking part inthe study. We would also like to thank the staff of the Neonatal Unit atthe University Hospital of Wales, Cardiff, and the research nurses Jen-nifer Webb, Louise Bridge, Biji Kumar, and Anwen Howells. Ourthanks goes to Kjell Øygarden and Morten Eriksen (VoluSense,Norway) for technical support for this study.

Submitted for publication May 21, 2013; last revision received Dec 2, 2013;

accepted Dec 26, 2013.

Pickerd et al

May 2014 ORIGINAL ARTICLES

Reprint requests: Sailesh Kotecha, FRCPCH, PhD, Department of Child

Health, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN,

UK. E-mail: [email protected]

References

1. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK.

Treatment of the idiopathic respiratory-distress syndrome with contin-

uous positive airway pressure. N Engl J Med 1971;284:1333-40.

2. Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pres-

sure immediately after extubation for preventing morbidity in preterm

infants. Cochrane Database Syst Rev 2003;CD000143.

3. Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB, et al.

Is chronic lung disease in low birth weight infants preventable? A survey

of eight centers. Pediatrics 1987;79:26-30.

4. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB. Nasal

CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;

358:700-8.

5. Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R, Moore M,

et al. Do clinical markers of barotrauma and oxygen toxicity explain in-

terhospital variation in rates of chronic lung disease? The Neonatology

Committee for the Developmental Network. Pediatrics 2000;105:1194-

201.

6. De Paoli AG, Davis PG, Faber B, Morley CJ. Devices and pressure sour-

ces for administration of nasal continuous positive airway pressure

(NCPAP) in preterm neonates. Cochrane Database Syst Rev

2008;CD002977.

7. Morley C. Continuous distending pressure. Arch Dis Child Fetal

Neonatal Ed 1999;81:F152-6.

8. Aghai ZH, Saslow JG, Nakhla T, Milcarek B, Hart J, Lawrysh-Plunkett R,

et al. Synchronized nasal intermittent positive pressure ventilation

(SNIPPV) decreases work of breathing (WOB) in premature infants

with respiratory distress syndrome (RDS) compared to nasal continuous

positive airway pressure (NCPAP). Pediatr Pulmonol 2006;41:875-81.

9. Ali N, Claure N, Alegria X, D’Ugard C, Organero R, Bancalari E. Effects

of noninvasive pressure support ventilation (NI-PSV) on ventilation and

respiratory effort in very low birth weight infants. Pediatr Pulmonol

2007;42:704-10.

10. Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G,

et al. Comparing the effects of nasal synchronized intermittent positive

pressure ventilation (nSIPPV) and nasal continuous positive airway

pressure (nCPAP) after extubation in very low birth weight infants. Early

Hum Dev 1999;56:167-77.

11. Chang HY, Claure N, D’Ugard C, Torres J, Nwajei P, Bancalari E. Effects

of synchronization during nasal ventilation in clinically stable preterm

infants. Pediatr Res 2011;69:84-9.

12. Boumecid H, Rakza T, Abazine A, Klosowski S, Matran R, Storme L. In-

fluence of three nasal continuous positive airway pressure devices on

breathing pattern in preterm infants. Arch Dis Child Fetal Neonatal

Ed 2007;92:F298-300.

13. Huckstadt T, Foitzik B, Wauer RR, Schmalisch G. Comparison of two

different CPAP systems by tidal breathing parameters. Intensive Care

Med 2003;29:1134-40.

14. Pandit PB, Courtney SE, Pyon KH, Saslow JG, Habib RH. Work of

breathing during constant- and variable-flow nasal continuous positive

airway pressure in preterm neonates. Pediatrics 2001;108:682-5.

15. Liptsen E, Aghai ZH, Pyon KH, Saslow JG, Nakhla T, Long J, et al. Work

of breathing during nasal continuous positive airway pressure in preterm

infants: a comparison of bubble vs variable-flow devices. J Perinatol

2005;25:453-8.

16. Lee KS, Dunn MS, Fenwick M, Shennan AT. A comparison of underwa-

ter bubble continuous positive airway pressure with ventilator-derived

Tidal Breathing in Preterm Infants Receiving and Weaning from C

continuous positive airway pressure in premature neonates ready for ex-

tubation. Biol Neonate 1998;73:69-75.

17. Courtney SE, Kahn DJ, Singh R, Habib RH. Bubble and ventilator-

derived nasal continuous positive airway pressure in premature infants:

work of breathing and gas exchange. J Perinatol 2011;31:44-50.

18. Pillow JJ, Hillman N, Moss TJ, Polglase G, Bold G, Beaumont C, et al.

Bubble continuous positive airway pressure enhances lung volume and

gas exchange in preterm lambs. Am J Respir Crit Care Med 2007;176:

63-9.

19. Fischer HS, Roehr CC, Proquitte H, Hammer H, Wauer RR,

Schmalisch G. Is volume and leak monitoring feasible during nasopha-

ryngeal continuous positive airway pressure in neonates? Intensive Care

Med 2009;35:1934-41.

20. Brown K, Aun C, Jackson E, Mackersie A, Hatch D, Stocks J. Validation

of respiratory inductive plethysmography using the Qualitative Diag-

nostic Calibration method in anaesthetized infants. Eur Respir J 1998;

12:935-43.

21. Pickerd N, Williams EM, Kotecha S. Electromagnetic inductance pleth-

ysmography to measure tidal breathing in preterm and term infants. Pe-

diatr Pulmonol 2013;48:160-7.

22. Williams EM, Pickerd N, Eriksen M, Øygarden K, Kotecha S. Estima-

tion of tidal ventilation in preterm and term newborn infants using

electromagnetic inductance plethysmography. Physiol Meas 2011;32:

1833-45.

23. Olden C, Symes E, Seddon P. Measuring tidal breathing parameters us-

ing a volumetric vest in neonates with and without lung disease. Pediatr

Pulmonol 2010;45:1070-5.

24. Bancalari E, Claure N. Weaning preterm infants from mechanical venti-

lation. Neonatology 2008;94:197-202.

25. Jardine L, Davies MW. Withdrawal of neonatal continuous positive

airway pressure: current practice in Australia. Pediatr Int 2008;50:572-5.

26. De Paoli AG, Morley C, Davis PG. Nasal CPAP for neonates: what do we

know in 2003? Arch Dis Child Fetal Neonatal Ed 2003;88:F168-72.

27. Todd DA,Wright A, BroomM, CjauhanM,Meskell S, Cameron C, et al.

Methods of weaning preterm babies <30 weeks gestation off CPAP: a

multicentre randomized controlled trial. Arch Dis Child Fetal Neonatal

Ed 2012;97:F236-40.

28. Stern DJ, Weisner MD, Courtney SE. Synchronized neonatal noninva-

sive ventilation—a pilot study: the Graseby capsule with bi-level

NCPAP. Pediatr Pulmonol 2013 Sep 9; http://dx.doi.org/10.1002/

ppul.22880. Epub ahead of print.

29. Elgellab A, Riou Y, Abbazine A, Truffert P, Matran R, Lequien P, et al.

Effects of nasal continuous positive airway pressure (NCPAP) on breath-

ing pattern in spontaneously breathing premature newborn infants.

Intensive Care Med 2001;27:1782-7.

30. Magnenant E, Rakza T, Riou Y, Elgellab A, Matran R, Lequien P, et al.

Dynamic behavior of respiratory system during nasal continuous posi-

tive airway pressure in spontaneously breathing premature newborn in-

fants. Pediatr Pulmonol 2004;37:485-91.

31. Courtney SE, Pyon KH, Saslow JG, Arnold GK, Pandit PB, Habib RH.

Lung recruitment and breathing pattern during variable versus contin-

uous flow nasal continuous positive airway pressure in premature in-

fants: an evaluation of three devices. Pediatrics 2001;107:304-8.

32. Locke R, Greenspan JS, Shaffer TH, Rubenstein SD, Wolfson MR. Effect

of nasal CPAP on thoracoabdominal motion in neonates with respira-

tory insufficiency. Pediatr Pulmonol 1991;11:259-64.

33. Morley CJ, Lau R, De Paoli A, Davis PG. Nasal continuous positive

airway pressure: does bubbling improve gas exchange? Arch Dis Child

Fetal Neonatal Ed 2005;90:F343-4.

34. De Paoli AG, Morley CJ, Davis PG, Lau R, Hingeley E. In vitro compar-

ison of nasal continuous positive airway pressure devices for neonates.

Arch Dis Child Fetal Neonatal Ed 2002;87:F42-5.

ontinuous Positive Airway Pressure 1063

Figure 1. Mean weight corrected VT � SEM on nCPAP (C),nBiPAP (-), bCPAP (:) at set pressures of 5, 7, and 9 cmH2O(5, 7/5, and 9/5 cmH2O on nBiPAP) and without respiratorysupport (B). The mean � SEM is shown.

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 164, No. 5

1063.e1 Pickerd et al