ajrc kronik stridor

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Am J Respir Crit Care Med Vol 164. pp 18741878, 2001DOI: 10.1164/rccm2012141Internet address: www.atsjournals.org

Breathing pattern, gas exchange, and respiratory effort were as-sessed in five awake children with chronic stridor caused by laryn-gomalacia during spontaneous breathing (SB) and noninvasivemechanical ventilation (NIMV). During SB, the youngest childrenwere able to maintain normal gas exchange at the expense of anincreased work of breathing as assessed by calculated diaphrag-matic pressure-time product (PTPdi), whereas the opposite wasobserved in the older children. NIMV increased tidal volume, from8.77 2.04 ml/kg during SB to 11.67 2.52 ml/kg during NIMV,p 0.04, and decreased respiratory rate, from 24.4 5.6 breaths/min during SB to 16.6

0.9 breaths/min during NIMV, p

0.04.NIMV unloaded the respiratory muscles as reflected by the signifi-

cant reduction in PTPdi, from a mean value of 541.0

196.6 cmH

2

O s min

1

during SB to 214.8

116.0 cm H

2

O s min

1

dur-ing NIMV, p

0.04. Therefore, NIMV successfully relieves the ad-ditional load imposed on the respiratory muscles. Long-term homeNIMV was provided to a total of 12 children with laryngomalacia(including these five) and was associated with clinical improve-ment in sleep and growth.

Keywords: stridor; laryngomalacia; diaphragmatic pressure-time prod-uct; noninvasive mechanical ventilation

Laryngomalacia is an anomaly of the larynx with laxity of thepharyngeal tissues causing the epiglottis, arythenoids, and aryepi-glottic folds to involute and partially obstruct breathing duringinspiration. Laryngomalacia accounts for more than 75% ofcases of congenital stridor and is the most common cause ofsymptomatic partial upper airway obstruction in infants (1, 2).The majority of infants with laryngomalacia do well with reso-lution of stridor during the first 2 yr of life (3). However, po-tentially serious complications, including airway obstructionand sudden death (4, 5), pulmonary hypertension and cor pul-monale (5, 6), failure to thrive (5, 7), and possibly intellectualimpairment can develop (8). In some severe cases of laryngo-malacia, even surgery (for example, endoscopic resection ofthe aryepiglottic folds or epiglottoplasty) can fail to relieveupper airway obstruction (5, 7). When respiratory problemspersist after surgery, a tracheostomy may be required. How-ever, tracheostomy is associated with a significant morbidityand impairs normal development and, particularly, languagedevelopment (9, 10).

Noninvasive mechanical ventilation (NIMV) has beenshown to reduce the work of breathing, and in particular pres-sure support (PS), associated with positive end-expiratorypressure (PEEP), has been recognized as an efficient treat-ment of upper airway obstruction associated with alveolar hy-poventilation (11). Our hypothesis is that NIMV may be pro-posed as an effective treatment for laryngomalacia, which mightbe an alternative to a tracheostomy.

To confirm our hypothesis, the aim of the study was, first,to analyze the breathing pattern and the respiratory effort inchildren with stridor caused by severe laryngomalacia; second,to evaluate the immediate physiologic value of NIMV in un-

loading the respiratory muscles in these children; and third, toinvestigate the long-term clinical effects of intermittent NIMV.

METHODS

The study was approved by our institutional board, and written in-formed consent was obtained from all parents. Criteria for enrollmentwere severe laryngomalacia with symptoms of upper airway obstruc-tion and nocturnal hypoventilation. (Methods are detailed in the on-line supplement.)

The first part of the study evaluated the gas exchange, breathingpattern, and respiratory effort in five patients (Group 1) during spon-taneous breathing (SB) and NIMV. The second part of the study eval-uated the clinical long-term follow up of these five patients and sevenadditional patients (Group 2).

Two conditions were analyzed and compared; SB and NIMV (PSventilation) delivered through a well-fitting nasal mask. Custom-mademasks were used in infants (dead space

5 ml) and commercialmasks in older children. For NIMV, the initial PS level was set at 6 cmH

2

O and the initial positive PEEP at its lowest level, i.e., 2 cm H

2

O.PS and PEEP were titrated alternatively and progressively by 1 to 2 cmH

2

O steps, as has been used successfully by other groups (12, 13). Thefinal pressure settings were the highest values tolerated by the pa-tients. Therefore, target swings for esophageal pressure (Pes) and trans-diaphragmatic pressure (Pdi) were the lowest value that we could ob-tain according to the tolerance of the patients. Other parameters wereset in line with consensus guidelines (14).

Data were recorded during the last 5 min after a stable period forat least 20 min. Nasal mask was not tolerated during the SB period bythe two youngest infants who desaturated immediately. For this rea-son, recording of flow and determination of tidal volume (V

T

) and in-spiratory time/duty cycle ratio (T

I

/Ttot) during SB were only made inthe three oldest patients.

We measured respiratory flow (this was integrated to yield V

T

), air-

way pressure (Paw), Sa

O

2

, respiratory rate (RR), heart rate, and end-tidal carbon dioxide (P

ETCO

2

) directly from the mask. Pes and gastricpressures (Pga) were measured using catheter-mounted transducers(Gaeltec, Dunvegan, Isle of Skye, UK) (15) positioned using standardtechniques (16). We measured the Pdi swings and the diaphragmaticpressure-time products (PTPdi) on the whole duty cycle as previouslydescribed (17, 18).

Long-term follow up was obtained in these five patients (Group 1)and seven additional patients (Group 2). The setting of the PS andPEEP levels in Group 2 were determined on a clinical basis, i.e., thedisappearance of stridor, chest retractions, and snoring, as well as de-saturations and hypercapnia during sleep (19, 20). Compliance to the

(

Received in original form December 29, 2000; accepted in final form September 4, 2001

)

Supported by Breas Medical (Molndal, Sweden).

Correspondence and requests for reprints should be addressed to Dr. BrigitteFauroux, Service de Pneumologie Pdiatrique, Hpital dEnfants Armand Trous-seau, 28 avenue du Docteur Arnold Netter, 75012 Paris, France. E-mail: [email protected]

This article has an online data supplement, which is accessible from this issuestable of contents online at www.atsjournals.org

Chronic Stridor Caused by Laryngomalacia in Children

Work of Breathing and Effects of Noninvasive Ventilatory Assistance

BRIGITTE FAUROUX, JRME PIGEOT, MICHAEL I. POLKEY, GILLES ROGER, MICHLE BOUL, ANNICK CLMENT,and FRDRIC LOFASO

Pediatric Pulmonary Department and Otorhinolaryngology Department, Armand Trousseau Hospital, Assistance Publique, Hpitaux de Paris, Paris,France; Physiology Department, Raymond Poincare Hospital, Assistance Publique, Hpitaux de Paris, Garches; INSERM U492, Henri MondorFaculty, Crteil, France; Respiratory Muscle Laboratory, Royal Brompton Hospital, London, United Kingdom


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: Work of Breathing in Chronic Stridor in Children 1875

treatment was systematically assessed at home at a monthly basis bymeans of a data logger that recorded date and time as well as the du-ration of the NIMV use. The effects of NIMV on nocturnal Sa

O

2

andgrowth was assessed in all patients as well as the tolerance and dura-tion of NIMV.

Statistical Analysis

Data are given as mean

SD. Comparison between SB and NIMVwere made using Wilcoxons rank test. Correlation between the dif-ferent variables was made by simple regression.

RESULTS

Patients

The characteristics of the patients are presented in Table 1.Five infants had chest wall deformity and six had failure tothrive requiring nutritional support (Patients 1, 2, and 6 to 9).All the patients were naive to NIMV. The mean age of the pa-tients was 32.9

25.8 mo, with three patients being youngerthan 1 yr of age. The four youngest patients (Patients 1, 6, 7,and 8) had the most severe upper airway obstruction. Levelsof PS ranged from 4 to 8 cm H

2

O and levels of PEEP from 4 to10 cm H

2

O (Table 1).

Gas Exchange and Breathing Pattern during SB and the Effect

of NIMV

Gas exchange was severely impaired in Patient 5 and withinnormal range in the other patients (Figure 1). Sa

O2

increasedfrom 94.9

2.7% during SB to 96.9

2.0% during NIMV, p

0.07, and P

ETCO2

decreased from 41.0

6.5 mm Hg during SBto 34.8

6.2 mm Hg during NIMV, p

0.04 (Figure 1).Respiratory rate decreased from 24.4

5.6 breaths/minduring SB to 16.6

0.9 breaths/min during NIMV, p

0.04(Figure 2). In the three oldest patients, mean V

T

increasedfrom 8.77

2.04 ml/kg during SB to 11.67

2.52 ml/kg duringNIMV (Figure 2), and mean T

I

/Ttot decreased significantlyduring NIMV, with a value of 0.59

0.25 during SB and 0.35

0.04 during NIMV. There was a negative correlation betweenage and Sa

O2

, r

2

0.526, p

0.0001, a positive correlation be-

tween age and P

ETCO2

, r

2

0.374, p

0.009 (Figure 3) and apositive correlation between age and T

I

/Ttot, r

2

0.570, p

0.04.

Respiratory Effort during SB and the Effect of NIMV

A tracing from Patient 3 during SB and NIMV is presented inFigure 4, which shows a decrease in Pes and Pdi swings duringNIMV. In addition, Figure 5 shows the dynamic relationship

between Pes and Pga during a representative cycle of SB andNIMV in Patient 3. It demonstrates, as in all patients of Group1, the absence of an abnormal increase of Pga during expira-tion, i.e., during the increase of Pes during SB and/or NIMV.These results permit us to state that no patient expiratorymuscle recruitment was present during SB and/or duringNIMV.

Pdi swing decreased from 20.7

4.3 cm H

2

O during SB to

8.9

4.3 cm H

2

O during NIMV, p

0.04 (Figure 6). Similarreductions were observed for PTPdi with mean PTPdi decreas-ing from 541.0

196.6 cm H

2

O

s

min

1

to 214.8

116.0 cmH

2

O

s

min

1

during NIMV, p

0.04 (Figure 6). In addition,we observed an excellent relationship for the five patients be-tween the decrease in Pes and Pdi swings and the disappear-ance of inspiratory dyspnea characterized by stridor, loudbreathing, chest deformity, sweats, and a low Sa

O2

. There wasalso a negative correlation between age and indices of respira-

tory effort, as reflected by

Pdi, r

2

0.461, p

0.03, andPTPdi, r

2

0.730, p

0.01 (Figure 7).

Clinical Follow-up of the Patients

NIMV was associated with important clinical improvements in

all the patients.

Patients of Group 1. NIMV was started at the age of 8 moin Patient 1, when his weight was 5.4 kg (

3.5 SD) and height63 cm (

3 SD). He slept with his NIMV for a mean of 12

2h/d. A significant growth catch-up was observed duringNIMV, with a weight gain of 3.6 kg during the first 6 mo de-spite the discontinuation of his nasogastric feeding 3 wk afterthe start of NIMV. At the age of 14 mo, he weighted 9 kg (

1 SD)

TABLE 1. CHARACTERISTICS OF THE PATIENTS

PatientNo. Sex

AssociatedDiagnosis

At Start of NIMV

Level of PS/PEEP(

cm H

2

O

)

Duration ofNIMV(

mo

) OutcomeAge(

mo

)Height(

cm

)Weight

(

kg

)

1 M None 8 63 5.3 4 / 6 24 Still on NIMV 2 F Lymphangioma 25 87 12 4 / 6 16 Still on NIMV

3 F Mental retardation 64 135 30 10 / 6 12 Died AH4 M Recklinghausen 77 113 27 6 / 8 6 On LTOT5 M Dysautonomia 79 115 39 8 / 8 23 Still on NIMV 6 M Prematurity 10 68 7.1 6 / 6 30 Well 1 yr later

7 M Lymphangioma 11 70 8.0 4 / 6 14 Well 18 mo later 8 M Mental retardation 16 70 7.9 6 / 4 6 Still on NIMV 9 M Laryngeal cleft 19 77 9.2 4 / 6 6 Well 2 yr later

10 M Picnodysostosis 25 79 9.0 4 / 8 52 Still on NIMV 11 M CHARGE syndrome 25 85 11.8 4 / 6 22 Well 30 mo later 12 M None 36 85 11.5 8 / 7 2 Still on NIMV

Definition of abbreviations

: AH

alveolar hemorrhage; LTOT

long-term oxygen therapy; NIMV

noninvasive mechanical ventilation;PEEP

positive end-expiratory pressure; PS

pressure support.

Figure 1. Pulse oximetry (SaO2) and end-tidal carbon dioxide tension(PETCO2) during spontaneous breathing (SB) and noninvasive mechani-cal ventilation (NIMV) in the five patients of Group 1. Patients 1 and 2are represented by open circlesand the three older patients by closedcircles.


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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 164 2001

and measured 73 cm (

1.5 SD). One year later, a trial of dis-continuation of NIMV because of an improvement of his sleepunder room air, was associated with a 1 kg weight loss in 3 wk,which was regained after recommencing NIMV. This infantalso had an important chest-wall deformity with xyphoid andsubcostal recession, which totally regressed 8 mo after thestart of NIMV.

The tracheostomy of Patient 2, which was performed at theage of 2 mo, was closed 1 wk before starting NIMV, allowingher and her family to return home. She had been fed by a gas-trostomy since birth, and oral nutrition was not possible be-cause of a psychological blockage to eating by mouth. It istherefore of particular interest that despite similar caloric in-take, she gained 1 kg in 3 mo. After 1 yr of NIMV, she beganto eat by mouth and to attend nursery school without any prob-lem. Her chest-wall deformity has also noticeably regressed.

Nocturnal Sa

O2

of Patient 3 before NIMV showed signifi-

cant desaturations breathing room air, with a mean Sa

O2

of 85

9.8% with 61% of the nocturnal time spent with a Sa

O2

below90%. She also had excessive daytime sleepiness, falling asleepwhile at school. While using NIMV, nocturnal Sa

O2

improvedgreatly, with a mean Sa

O2

of 95 2.3%, 70% of the time spentwith a SaO2 95% and no time spent with a SaO2 90%. Theexcessive daytime sleepiness disappeared, and the school teach-ers noticed a dramatic improvement in her school perfor-mances. Sadly, she died 1 yr after starting NIMV from an un-explained alveolar hemorrhage. Autopsy was not performed.

Patient 4 was started on NIMV because of severe sleep distur-bance and sleep apnea. These symptoms totally disappeared dur-ing NIMV, which was also associated with consistent progress inhis psychoneurologic development. Because of familial problemsand the discovery of glioma of the optic chiasma, NIMV waschanged to long-term oxygen therapy after 6 mo.

Patient 5 had laryngomalacia associated with familial dys-autonomia. NIMV resulted in a stabilization of his obesity andimprovement in his daytime stamina and school performances.

Compliance with NIMV was excellent, with a mean daily useof 8.2 1.5 h.

Patients of Group 2. NIMV was well tolerated in all thepatients. The chest wall deformity, which was present in threepatients (Patients 6, 7, and 11) improved noticeably after amean of 6 mo of NIMV. NIMV was also associated with signif-icant weight gain in four patients (Patients 6 to 9).

In this group, SaO2 was checked during a whole night in thehospital before discharge, once the patient was totally adaptedto the ventilator, which occurred generally within 2 wk afterthe start of NIMV. Mean nocturnal SaO2 improved signifi-cantly from 91.7 2.3% before to 96.2 2.0% during NIMV,p 0.03. The nocturnal nadir SaO2also improved significantlyafter the initiation of NIMV, with a mean nadir SaO2of 74.7 7.5% before NIMV to a nadir of 88.0 2.5% while receivingNIMV. The percentage of night time spent with a SaO290%fell from 29.5 19.6% before NIMV to 0.5 0.8% while re-ceiving NIMV, p 0.03.

Successful discontinuation of NIMV was possible in fourpatients after 6 to 30 mo. Patient 10, who has a picnodysosto-sis, is still dependent on NIMV after 52 mo.

Figure 2. Respiratory rate and tidal volume (VT) during spontaneousbreathing (SB) and noninvasive mechanical ventilation (NIMV) in thepatients of Group 1. Patients 1 and 2 are represented by open circlesand the three older patients by closed circles. VTcould not be measuredin the two infants because of nontolerance of the nasal mask withoutNIMV.

Figure 3. Correlation between the age of the patients of Group 1 andpulse oximetry (SaO2) and end-tidal carbon dioxide tension (PETCO2).

Figure 4. A representative tracing of Patient 3 during spontaneous breath-ing (SB) during noninvasive mechanical ventilation (NIMV) showingthe decrease in esophageal pressure (Pes) and transdiaphragmaticpressure (Pdi) swings during NIMV compared with SB. Flow airflow;Paw airway pressure; Pgas gastric pressure swing; I inspiration;E expiration.

Figure 5. Schematic tracing of esophageal pressure (Pes) and gastricpressure (Pgas) swings of a representative patient (Patient 3) duringspontaneous breathing (SB, loop on the left) and noninvasive mechan-ical ventilation (NIMV: pressure support [PS] 10 cm H2O and posi-tive end-expiratory pressure 6 cm H2O, loop on the right) showingthe decrease of the inspiratory muscle activity during NIMV comparedwith that during SB and the absence of expiratory muscle recruitmentduring the two situations. End-expiratory pressure values have beennormalized to zero. The solid bars indicate the beginning and the endof the inspiration.


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Compliance was systematically assessed at home in the twogroups of patients on a monthly basis and was excellent, with amean daily use of 10.2 2.3 h/d in the patients performing adaytime nap and a mean daily use of 7.9 1.9 h per night inthe other patients.

DISCUSSION

This study is the first to quantify the breathing effort in childrenwith stridor caused by laryngomalacia and to demonstrate thatNIMV can adequately unload the respiratory muscles and im-prove the clinical status of these children on a long-term follow up.

The Importance of the Ventilator Equipment

Different nasal masks and ventilators were used in this study.A limited number of commercial masks are available for in-fants. Furthermore, the volume of the mask is often too large,therefore limiting the benefit of NIMV because of the in-crease in dead space, especially in these young children. Forthis reason, we recommend custom-made masks, moldedwhen the child sucks his or her pacifier, which favors simulta-neous closure of the mouth during NIMV. The dead space ofthe custom-made masks did not exceed 5 ml. Concerning the

ventilators, no specific comparison was made in this study.The most efficient ventilator and ventilatory mode, based onthe lowest Pdi swings, as well as what was best tolerated by thepatient, was adopted (Table 1).

The Influence of Age

Breathing pattern, gas exchange, and PTPdi were related toage. Normal gas exchange was preserved in the youngest chil-dren at the expense of an increased PTPdi, whereas the oppo-site was observed in older children. We speculate that thelonger duration of the resistive load in these older childrencould have caused a resetting of the respiratory centers sothat the penalty of a reduced oxygen cost of breathing was an

increase in arterial CO2. Whether respiratory muscle fatiguecould also be implicated in this response cannot be excluded,though the present data do not address this.

NIMV Can Adequately Decrease the Respiratory Effort

This study shows that NIMV can effectively unload the respi-ratory muscles in children with severe laryngomalacia. The main-tenance of a continuous pressure by PEEP is the most impor-tant component of a ventilatory assistance in patients with an

upper airway obstruction. This PEEP alleviates the airway ob-struction, either by splinting the upper airway open, or by in-creasing functional residual capacity, which in turn reflexivelydilates the pharynx (21, 22). The level of PEEP sufficient torelieve airway obstruction depends on the severity of the ob-struction and the patients state, i.e., sleep or wakefulness. Inthis study, the relatively low levels of PEEP, sufficient to ade-quately decrease Pes and Pdi during wakefulness, are proba-bly insufficient during sleep. Most investigators agree that therecording of Pes represents the gold standard to adjustCPAP and bilevel PS titration (23, 24). However, because inthe patients of Group 1, we observed an excellent relationshipbetween the decrease in Pes and Pdi swings and the disappear-ance of the clinical signs of loud breathing, we decided to use anoninvasive method on the patients of Group 2 for the titra-

tion of PEEP and PS.

Long-term Beneficial Effect of NIMV

The tolerance of NIMV was excellent in all patients. This cer-tainly contributed to the good compliance in these patients.The better comfort of this noninvasive technique, as com-pared with a tracheostomy, is likely to translate into a betterquality of life, not only for the patients but also for their families.

We did not perform polysomnography in our population,but we clearly observed an improvement of nocturnal SaO2inGroup 2. In addition, all the families claimed a subjective im-provement in the quality of sleep, daytime sleepiness, andquality of life of their child when NIMV was used. Abnormalrespiratory effort during sleep has been shown to worsen sleep

architecture (25). This makes us speculate that NIMV couldimprove the quality of sleep of our population by reducing therespiratory effort.

Moreover, we observed a decrease in clinical indices ofmalnutrition after initiation of NIMV. If the cost of breathingrepresents less than 5% of the total energy expenditure in nor-mal subjects, it is well known that it can be markedly elevatedin critically ill patients. This is also probably the case in ourpopulation, as reflected by the improvement of anthropomet-ric indices during chronic NIMV, which suggests that the de-crease of work of breathing during NIMV observed in a veryshort period (20 to 30 min) persists in a longer and nonexperi-mental period such as home NIMV.

In conclusion, our study documents for the first time the

presence of an increase in the resistive load during wakefulnessin infants and in children with severe stridor caused by laryngo-malacia. This results in an increase in respiratory effort, evenduring wakefulness. This increase in respiratory effort was in-versely related to age and resulted in abnormalities of breathingpattern and gas exchange. Although this evaluation was per-formed in a small group, the benefits of NIMV are of potentialrelevance in view of the systematic improvement of work ofbreathing, quality of life, and anthropometric parameters.

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Figure 6. Indices of respiratory effort as assessed by transdiaphrag-matic pressure swings (Swing Pdi) and diaphragmatic pressure-timeproduct (PTPdi) during wakefulness in the patients of Group 1 duringspontaneous breathing (SB) and during noninvasive mechanical venti-lation (NIMV).

Figure 7. Correlation between the age of the patients and the indices ofwork of breathing as assessed by transdiaphragmatic pressure swing(Swing Pdi) and diaphragmatic pressure-time product (PTPdi) in Group 1.


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