The Role of Artificial Ventilation, Oxygen, and CPAP in the Pathogenesis of Lung Damage in Neonates: Assessment by Serial Measurements of Lung Function

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The

Role of Artificial

Ventilation,

Oxygen,

and CPAP

in

the Pathogenesis

of Lung

Damage

in Neonates:

Assessment

by Serial

Measurements

of Lung

Function

Janet Stocks, B.Sc., S.R.N., and S. Godfrey, M.D., Ph.D., M.R.C.P.

From the Department of Paediatrics and Neonatal Medicine, Hanzniersmith Hospital, London, England

ABSTRACT. Lung volume, airway resistance, and corn-pliance have been measured in 19 infants, 18 of whom suffered from the respiratory distress syndrome (RDS) at birth, while the remaining infant was ventilated for

persis-tent apnea and a pneumothorax. Prior to discharge from the neonatal unit, and after recovery from RDS, most infants were found to have essentially normal lung function. When retested between 4 and 1 1 months of age, every infant who had received artificial ventilation during the acute illness was found to have developed a raised airway resistance, whereas the remaining infants, who had been treated with continuous positive airway pressure and/or oxygen were all entirely normal. The implications of these results for the management of RDS are discussed. Pediatrics, 57:352-362, 1976, ASSISTED VENTILATION, RESPIRATORY DISTRESS

SYN-DROME, LUNG DAMAGE, BRONCHOPULMONARY DYSPLASIA.

There is no doubt that infants with the

respira-tory distress

syndrome (RDS) suffer impairment of

the mechanical function of their lungs during the acute phase of the illness’ There is equally no doubt that many infants survive the initial illness only to suffer from chronic lung damage, usually

classified as bronchopulmonary dysplasia (BPD),

which may either kill the infant or lead to long-term changes.’- At this point the agreement ends because the etiology of this disease has been variously ascribed to oxygen toxicity,46 ventilator damage,79 or persistence of the original disease

process.”’2 It has been extremely difficult to

exclude any one of these factors, since the majori-ty of cases reported have been severely ill infants who have received both prolonged ventilation and high concentrations of oxygen. In addition, many of the arguments have been based on

autopsy material and have, therefore, dealt only

with the most severely affected infants, while the presence of BPD in survivors has usually been judged by radiological criteria,’-4 which is

probably imprecise and must exclude lesser degrees of the disease. The generally good

prog-nosis for affected infants who survive after 7

months has been based on gradually resolving

radiological changes during the first 5 years of

life4-” and on measurements of lung function when the patient has reached an adequate age

(usually 5 to 6 years) to cooperate with routine

tests of lung function.’4

In order to determine whether or not the ventilator per se was responsible for lung damage, it seemed to be more appropriate to study sur-viving infants by means of lung function tests, at a time when any residual lung damage was likely to be active but after the acute phase of RDS had

passed.

We therefore carried out detailed

measurements of lung mechanics in a group of infants

using

a

whole-body plethysmograph before their discharge from the neonatal intensive

care unit and again at approximately 7 months of age.

SUBJECTS AND METHODS

Measurements were made on 19 infants, 18 of

whom had suffered from RDS at birth, presumed

(Received March 27; revision accepted for publication July 31, 1975.)

ADDRESS FOR REPRINTS: (S.C.) Department of Paedia-trics and Neonatal Medicine, Harnmersmith Hospital, Du

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ARTICLES 353

TABLE I CLINICAL DETAILS OF INFANTS

No.

Birthweight

(kg)

Gestational

Age (wk)

Duration of 0

,__-&

Total

xygen (hr)

-.

> 60%

Duration of

CPAP (hr)

Duration of

IPPV (lir)

1 1.4 30

Ventilated

398 74 50 70

2 2.8 35 122 64 - 49

3 1.6 32 260 32 22 74

4* 1.6 35 17 3 - 28

5 2.0 31 182 60 10 81

6 1.4 30 394 - - 51

7 1.2 30 268 - - 52

8 1.8 33 166 41 11 94

9 1.3 29 503 64 - 103

10 1.5 32 118 3 63 4

11 1.4 31 21 4 2 11

Mean 1.64 31.7 223 38.0 26 56.0

SEM 0.14 0.6 48 9.7 10 9.7

12 3.2 35

Nonventilated

120 19 72

-13 2.6 38 120 6 60

-14 1.7 34 36 - 19

-15 2.5 35 75 10 36

-16 2.6 37 115 9 53

-17 1.2 29 45 - -

-18 1.7 30 74 - -

-19 2.6 35 70 - -

-Mean 2.20 34.1 82 1LO 48.0

-SEM 0.24 1.1 12 2.8 9.3

-#{176}Infantwithout signs of HMD who was ventilated in air.

to be due to hyaline membrane disease (HMD), which was diagnosed by clinical and radiological criteria.’5 The remaining infant (No. 4) was venti-lated for apneic attacks and had also suffered a spontaneous pneumothorax but did not have signs of HMD. Eleven of these infants were treated by

intermittent positive-pressure ventilation (IPPV), five were treated with continuous positive airway pressure (CPAP), and three infants received

oxygen

therapy alone, without assisted

ventila-tion. Details of the infants are given in Table I. There was no difference between those who

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received IPPV and the other eight infants in terms of mode of delivery, but the ventilated babies had a lower mean birthweight (P = <

.05)

than the nonventilated infants, and also had a lower mean gestational age, although the latter difference was not statistically significant.

The treatment used for the classification in Table I was begun within 12 hours of birth in every case.

The infants were managed according to the well-established principles originally developed in this department’5-” except that we now employ CPAP in situations where umbilical arterial Po2 cannot be maintained between 60 and 90 mm Hg with ambient oxygen of less than 40%. Our indications for using IPPV are essentially the inability to maintain oxygenation with CPAP and 80% or more ambient oxygen or, alternatively, for very frequent apneic attacks whatever the previous treatment. IPPV was given by nasotra-cheal tube using the Hammersmith Infant Venti-lator which is a pressure-cycled device.’5 Venti-lator pressure was normally kept at 25 cm of water with 5 cm of water positive end-expiratory pressure and the inspiratory to expiratory ratio was 2: 1. Frequency was adjusted to gain control

over the infant if he made a spontaneous effort, and was then slowed to approximately 35 breaths per minute. Ventilator settings rarely differed from those outlined above, and only one infant

(

No. 1) needed a ventilator pressure above 30 cm of water, receiving 40 to 50 cm of water for 30 hours. Six of the ventilated infants also received

CPAP

for

the

purpose

of

weaning

from the ventilator. CPAP was given via a nasotracheal tube with most of the infants being managed with between 5 to 10 cm of water. Five infants were later extubated and CPAP was continued using nasal adaptors that we have developed in the department. From the detailed nursing records kept on each infant we were able to determine the number of hours of oxygen therapy, CPAP, and IPPV in each case. These details are also given in Table I.

Lung mechanics were studied in an infant whole-body plethysmograph both before dis-charge from the unit and at approximately 7 months of age in seven IPPV-treated infants, five CPAP-treated infants, and three oxygen-treated infants. An additional four IPPV-treated infants were studied at 7 months of age only. The ages and weights of the infants at the times of study are given in Tables II and III. It can be seen that the nonventilated infants were initially studied at a

younger age (mean, 19 days) than the ventilated

group (mean, 49 days) since they recovered more

quickly from the initial disease and were, there-fore, ready for discharge earlier.

The whole-body infant plethysmograph was used to measure thoracic gas volume (TGV) at the end of a normal expiration, and airway resistance

(Raw) at two thirds of maximum inspiratory flow

by the classic techniques of Dubois et al.’7-’8

suitably modified for infants. The important

difference from the adult method is that, since the infant cannot pant at will, it is necessary to use a heated, humidified rebreathing system to avoid box pressure changes due to the heating and cooling of respired gas. The whole procedure was repeated two to three times on each baby. Raw

was calculated from the mean of ten consecutive breaths in each run when flow and pressure

signals were well in phase, while TGV

measure-ments were calculated from four to six breaths in

each run during occlusion. The principles of the

method that have been developed by our group have been described elsewhere.’ Infants were

lightly sedated with chloral hydrate (40 to 50 mgI

kg) and were studied in the supine position 30 to 60 minutes after feeding. An infant face-mask, which was connected to a heated rebreathing bag via a heated pneumotachograph and a pneumat-ically operated tap, was sealed around the infant’s nose and mouth using silicone putty, taking care to avoid pressure on the nose and to ensure an airtight fit. The seal was checked both visually and by briefly occluding the infant, to ensure that there was no leak around the sides of the mask, which was immediately detected by the appear-ance of looping on the oscilloscope. All measure-ments were corrected for apparatus dead space (8 ml) and resistance (1.5 cm of water per liter per second). The coefficient of variation of duplicate

estimates for this method was 4.7% for TGV and

6.1% for Raw, based on measurements made in 24

infants.

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No.

Postnatal Age (wk)

Weight (kg)

Tidal Volume (ml/kg)

Frequency (per mm)

TGV (ml/kg)

ScL (ml/cm H20/

ml TGV)

Raw

(cm HO/ liter/sec)

SGaw

(sec I

cm H20 ‘

Ventilated

2 - - -

-3 - - - - -

-4

5

6

8

9

10

11

Mean

SEM

Expected

3.0

10.0

9.0

2.5

15.0

6.0

4-5

7.1

1.7

2.30 6.5 40 30.4 0.077 29.0 0.48

2.50 8.0 42 36.0 0.054 34.0 0.27

2.30 8.7 54 47.8 0.021 29.0 0.30

2.30 7.6 80 29.0 0.058 31.0 0.48

4.09 8.7 52 38.0 0.090 30.0 0.21

2.30 7.2 61 32.6 0.065 39.0 0.34

1.90 11.5 49 40.0 0.041 56.0 0.18

2.50 8.3 54.0 36.3 0.058 35.0 0.32

0.23 0.6 5.2 2.4 0.009 3.7 0.04

- 9.6 52.0 36.0 0.061 32.0 0.34

12 2.0 2.87 4.2

Nonventilated

60 33.0 0.027 34.0 0.35

13 2.0 2.83 9.3 63 35.3 0.027 37.0 0.27

14 3.5 2.10 11.9 53 52.0 0.044 33.0 0.27

15 2.0 2.24 8.0 77 56.0 0.042 24.0 0.32

16 1.5 2.60 9.2 44 42.6 0.063 22.0 0.41

17 7.0 2.05 10.2 60 39.5 0.056 32.0 0.38

18 2.7 1.90 8.4 82 59.0 0.033 42.0 0.27

19 1.0 2.60 7.7 67 35.4 0.036 35.0 0.28

Mean 2.70 2.40 8.6 62.0 44.1 0041 32.3 0.32

SEM 0.67 0.13 0.8 3.3 3.6 0.005 2.4 0.02

Expected - 9.6 55.0 36.0 0.061 29.5 0.34

TABLE II

ARTICLES 355

RESULTS OF INITIAL LUNG FUNCTION TESTS

silicone putty. The flow signal was integrated to give volume, and dynamic compliance and minute ventilation were calculated in the conven-tional manner from simultaneous recordings of

transpulmonaiy pressure and tidal volume during at least ten consecutive breaths while the infant was breathing quietly. It was not possible to obtain measurements of compliance in all the

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TABLE III

RESULTS OF LUNG FUNCTION TESTS AT FOLLOW-UP

Postnatal Weight

Tidal

Volume TGV

Sc, (ml/cm H20/

Raw

(cm H20/

SGaw

(sec I

No. Age (wk) (kg) (ml/kg) (ml/kg) ml TGV) liter/sec) cm H,O

Frequency (per mm)

1 43 7.4 7.5

Ventilated

28 34.5 0.035 28 0.14

2 37 8.9 5.3 34 34.0 0.040 21 0.16

3 29 8.1 4.7 37 30.7 0.072 22 0.18

4 36 7.7 5.2 30 34.6 0053 21 0.18

5 18 5.8 6.3 60 42.0 0.033 24 0.16

6 24 4.6 7.8 36 36.0 0.056 33 0.18

7 28 6.3 9.2 37 30.4 0.056 37 0.14

8 24 6.6 7.3 40 35.2 24 0.18

9 34 7.7 6.2 40 35.7 - 22 0.17

10 35 8.0 5.0 43 34.2 0.073 24 015

11 25 7.0 9.2 40 36.0 0.046 32 012

Mean 30.4 7.10 6.70 37.5 34.80 0.052 26.0 0.16

SEM 1.8 0.36 0.49 2.9 0.92 0.005 1.7 0.01

Expected 6.00 35.0 33.00 0.053 17.4 0.23

12 43 9.0 5.6

Nonventilated

35 31.8 0.040 12 0.29

13 32 9.5 6.8 42 22.0 - 22 0.22

14 28 6.4 6.9 45 34.5 0.072 17 0.28

15 22 7.0 6.4 37 34.7 15 0.27

16 32 8.1 8.6 40 34.5 13 0.27

17 39 10.0 4.2 48 33.4 - 10 0.30

18 31 7.7 5.8 60 33.2 0.036 15 0.25

19 26 7.7 6.2 35 33.1 - 13 031

Mean 31.6 8.2 6.30 42.0 32.30 0.049 14.8 0.27

SEM 2.4 0.3 0.44 2.9 1.52 0.011 1.2 0.01

Expected - 6.00 35.0 33.00 0.053 16.4 0.23

infants at the follow-up study since some of them were unable to tolerate the esophageal balloon at this age.

The expected values for normal infants, which

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ARTICLES

357

compliance based on the study of 38 normal

infants by Phelan et al. #{176}The values for TGV were

obtained by taking the numerically weighted mean of the results of Phelan et al.’#{176}and

Radford.11 The expected value for Raw of older infants is based on the work by Radford’9 who

used a very similar heating rebreathing system,

although his tap was less satisfactory than that now in use.

RESULTS

Clinical Status and Treatment

Although all infants were ill enough to require

supportive therapy and frequent monitoring of arterial blood gases, those that received IPPV

were more severely affected than the others and required more prolonged ventilatory assistance

and oxygen therapy. The difference in oxygen

therapy between the ventilated and

nonventi-lated infants was significantly different with regard to total duration (P = < .05), but not with regard to concentration. This was partly due to the relatively small sample but also reflects the fact that there was considerable overlap between the two groups, as can be seen in Table I.

Similarly, although the total time for assisted

ventilation and hence intubation with exposure of the airways to positive pressure was almost twice as long in the IPPV-treated infants when compared with those receiving CPAP alone, there was considerable individual variation

with-in each group.

At the time of the initial study all infants had attained normal blood gases and were breathing

spontaneously in air, only requiring regular

nursing management commensurate with their gestational ages. Routine follow-up X-ray films are not normally taken in this department once an infant has clinically and physiologically

im-proved.

Subsequent to discharge from the unit, all

infants were seen regularly in the special baby

clinic of this hospital up to the time of their follow-up studies. One of the IPPV-treated infants

(

No. 1) had recurrent episodes of wheezing,

necessitating admission to hospital on one

occa-sion. Her chest X-ray film continued to show areas of consolidation, but these were unlike the changes normally seen in BPD. One other

venti-lated infant had very mild wheezing from time to time. None of the other infants had suffered from any lower respiratory tract illnesses by the time of the follow-up studies. Chest X-ray films were taken of the first five IPPV-treated infants to be

studied at follow-up. None of these X-ray films

showed any pulmonary abnormalities and it was

therefore felt to be unjustified to carry out routine chest X-ray films on the remaining infants, all of whom were asymptomatic at the time of the follow-up study.

Lung Function Studies

The individual values for lung function at the initial study are given in Table II and those from the follow-up studies are given in Table III. The results for the oxygen-treated infants and the CPAP-treated infants were found to be very similar and have been combined for purposes of comparison with the IPPV-treated infants.

The most striking observations were: (1) Lung function was within the normal range in most in-fants at the initial study, regardless of treatment received. (2) At the time of the follow-up investi-gation there was a marked difference between the nonventilated group who were still normal and the ventilated group, all of whom showed a raised

Raw.

In the initial studies (Table II) the relatively high respiratory rate and large tidal volume is a reflection of the fact that the infants were not studied under basal conditions and were breath-ing through a pneumotachograph. Normal infants from the unit were found to have a similar minute ventilation.

Several of the nonventilated infants had some reduction in specific compliance (ScL equals compliance divided by TGV) andlor an enlarged TGV, which probably reflects the fact that they were studied at a much younger age when they were still showing slight residual changes from their acute illness. The mean ScL of this group was

significantly different from normal (P = < .02). Specific conductance (SGaW equals conductance

divided by TGV) was normal in all nonventilated

infants at the initial study but was low in two ventilated infants (No. 9 and 11). Infant 9 was initially studied at an older age than the other infants and may in fact have begun to show similar changes to those found in other IPPV-treated infants at follow-up.

At the follow-up examination (Table III), TGV, tidal volume, frequency, and compliance were similar in both groups and were all well within the expected normal range. The major

abnor-mality was seen in the Raw which was highly significantly increased (P < .0005) in the IPPV-treated group compared with the nonventilated infants who fell within the normal range. Since

there is a generally linear relationship between the reciprocal of resistance (conductance, Gaw)

and TGV, the values for each of the infants were plotted in Figure 1 and summarized in Figure 2.

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0.10

0.08

-0.06

-0.04

0.02

0

E

U

C-)

z

C-)

z

0

C-)

>-0

DISCUSSION

#{149}-oI.P. P.V.

#{163}--sC.

P.A. P. ‘-a 02

THORACIC GAS VOLUME - ml

0

FIG. 1. Relationship between Ga,, and TGV for individual

infants. Closed symbols represent initial studies; open

symbols represent follow-up studies.

The present study has shown that there was a consistent pattern of abnormally high Raw at about 7 months of age in infants who had been ventilated at birth, but not in those who had only received CPAP or oxygen therapy.

The significance of these findings depends

upon the reliability of the measurements and the

I I I 200 ‘ 300 ‘ 400 comparability of the infants treated in different

0 100 ways. Raw has generally been regarded as more

difficult to measure accurately than other

param-eters of lung function in infancy, and Radford’9 has shown that the accuracy is critically affected

by the temperature of the respired gas. Our present further refinement of the plethysmo-graphic technique, using better heating and an oscilloscope display for quality control, has resulted in a coefficient of variation of only 6.1% which is quite comparable with that for the well-established plethysmographic method of measur-ing TGV in infancy.

It is possible that the highly significant differ-ence in SGaw between the ventilated and nonven-tilated infants (P < .0005) at the age of 7 months was due to the original disease being more severe in the former group and persisting into later

infancy. If this were the case, one would have

expected to have found differences at the initial study, whereas the SGaw of all but two of the infants were normal at this time. In addition, it

has already been pointed out that there was considerable overlap between the IPPV-treated and CPAP-treated infants in terms of oxygen therapy and duration of assisted ventilation (e.g.,

infants 10 and 12). If the raised resistance were dependent on severity of the initial disease, one would expect to have found a far higher resistance in the infant who received 500 hours of oxygen therapy with 103 hours of ventilaton (No. 9) than in one who received less than 12 hours of IPPV (No. 11) and was not nearly so severely ill; whereas, in fact, their resistances were affected to a similar degree. Moreover, it should be noted that the infant who never had HMD but who was ventilated for 28 hours in air (No. 4) showed the same increase in Raw as all the other IPPV infants.

This shows the normal relationship of Gaa. and

TGV found

in the infants at their initial examina-tion, and the deviation from normal only in the ventilated infants at the time of follow-up. It can be seen that all infants except one showed an increase in conductance (decrease in resistance) with age, as would be expected from the growth of the lung during this period, but the rate of increase was far slower in the ventilated infants than in the others. The one infant who was found to have a lower conductance at follow-up than at the initial study had a severely stenosed nostril which no doubt contributed to the result.

The abnormality of resistance in the IPPV infants was seen in every case including the infant who had only been ventilated for four hours (No. 10) and the infant who did not suffer from HMD at birth but was ventilated for 28 hours in air (No. 4). In contrast, lung function was entirely normal in the infant treated wih CPAP for 72 hours (No. 12) who also received > 60% oxygen for 19 hours. It can be seen that infants 10 and 12 received almost identical treatment in terms of duration of oxygen therapy (118 and 120 hours respectively) and duration of assisted ventilation (67 and 72 hours respectively), the only difference being that

infant 10 received four hours of IPPV (the remaining assisted ventilation being given by

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0.08 -

Non-ventilated

0

E

C-) C-)

Q)

LU

L) z I-C-)

z 0 C-)

>-+

1

ARTICLES 359

0. 10

0. 06

0.04 -0. 02

0

-

Ventilated infants

-

Normal

control

-

+S.E.M.

0

50 Initial

Follow-up

.

0

A-a---- 0

I I

100 150

I

200

250 THORACIC

GAS

VOLUME

-

ml

FIG. 2. Relationship between and TGV showing mean results of ventilated, nonventilated, and normal infants.

Thus, the only clearcut factor that differentiated the ventilated infants from the others was the actual administration of IPPV to the former.

We believe that our findings can be explained

by damage to the airways by ventilation, causing

a failure to grow at the normal rate and, hence, the failure of Raw to decrease normally as lung

volume increased. If the brunt of the damage fell on the airways rather than on the alveoli, then one would not expect any major abnormality in either lung volume or compliance, and indeed these two parameters were normal in our venti-lated infants.

It is perhaps surprising that there was no correlation between increased resistance and duration of ventilation but, if we were observing a damaging effect on airway growth, this might well result from brief exposure to IPPV. The normal results found soon after recovery strongly argue against direct airway damage from pressure

which would be much more likely to be duration-related. The recent comprehensive review of the prognosis of ventilated infants by Reynolds et al.9

strongly suggests that improved techniques of ventilation rather than any reduction in oxygen therapy had led to a significantly reduced mci-dence of BPD. The improved technique which they recommend is virtually identical to that which we have been using in this unit, and may well account for the lack of overt BPD in our survivors. The difference between IPPV and

CPAP

as used in this department is that the peak airway pressure is approximately 25 cm of water in the former, and fluctuates by some 20 cm of water during the respiratory cycle, with the mean pressure being approximately 18 cm of water. CPAP pressure is about 10 cm of water and only fluctuates by 1 to 2 cm of water during each breath. The repeated trauma of rapidly changing pressure of IPPV may be the major etiological factor in airway damage, although the mean airways pressure may also be of some

signifi-cance.

The only similar study of which we are aware has recently been published by AhlstrOm,2’ in

which dynamic compliance and pulmonary

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0

0 0 0 0

0

o

0

I I I I I I I I

‘0 CsJ

E

C-)

0) (I,

C)

z

C)

z

0

C-)

>-C-)

C-)

C-,,

0.3

0.2 0. 1

0

0.3

0.2

0.

1

0

HOURS

OF VENTILATION

100

0 0

00

0

.c.

P.A. P.

o I. P. P. V.

I I I I I

.

0

.

0

20

40

60

80

100 HOURS

OF >60%

02

FIG. 3. Relationship of SGaw to duration of ventilation and high oxygen therapy.

ance were measured using a saline-filled esopha-geal catheter. His data show lower conductance values in ventilated babies initially and at follow-up compared with most of the CPAP-treated babies. However, he did not measure lung volume, which is an important determinant of airways conductance, and it is possible that the low value of conductance seen in two infants treated by CPAP was due to small lung volume and persistence of their initial disease. Serial lung function tests on ventilated and nonventilated

survivors of RDS during the first year of life have

also been carried out by Bryan et al.3 None of their nonventilated infants developed BPD and they had all returned to normal by 2 to 4 months. Three of the ventilated babies who had BPD survived and were found to have a low compli-ance and increased lung volume at 6 to 12 months, whereas the 18 ventilated infants without overt BPD had normal lung volumes and compli-ance at this age, as did our ventilated infants. However, they did not measure resistance which

seems to be the most sensitive parameter from our studies, and we can find no other data on serial measurements of resistance in infants surviving RDS. The fact that the pathological abnormalities seem to lie in the airways to such an extent in

BPD4-6-9

seems to suggest that the measurement of

Raw S probably the best way of assessing its

functional significance. Only in severe (and hence

probably overt) BPD would one expect to find hyperinflation and low compliance.

It is obviously important to know whether or not oxygen therapy, alone or combined with CPAP, can cause airways damage, and why some ventilated infants do not appear to have devel-oped BPD. Westgate et al.5 suggest that oxygen toxicity is responsible for lung damage in the

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ARTICLES

361

ventilated infants given prolonged high

concen-tration of oxygen than in ventilated infants given less oxygen.4-’ These infants either had gross radiological changes or had been diagnosed at autopsy. These studies and that by Bryan et al.3

include babies who had been ventilated but had not developed BPD; however, the lack of radiolog-ical and pathological changes does not necessarily exclude functional subclinical changes, such as we have found in the present study. A recent study by Philip22 describes the appearance of bronchopul-monary dysplasia in ten infants who had been ventilated with relatively low concentrations of oxygen and, although he concluded that the immature lung might be sensitive to these low concentrations, the data can be equally well interpreted as showing that ventilation but not oxygen was the primary factor in causing the lung

damage.

The majority of infants with overt BPD have received prolonged high oxygen concentrations in addition to ventilation, whereas our subclinically affected infants required less oxygen with their IPPV. It is possible that a spectrum of BPD exists which is caused by IPPV but whose severity is a function not only of the ventilation but also of the oxygen concentration. Since some of our nonven-tilated infants received more oxygen than some of the ventilated infants, we believe that careful administration of oxygen alone or combined with CPAP does not cause airway damage in the absence of ventilation. We can find no objective evidence to show that high oxygen concentration without ventilation can cause BPD.

The present results suggest that, although the better form of IPPV now in use in this and other large units has led to a decreased incidence in overt BPD, it is not without effect on the airways and should be reserved only for those infants who cannot be managed by CPAP and high concentra-tions of oxygen.

The normal results that we obtained in babies treated by CPAP are reassuring, and suggest that this should be the treatment of first choice in infants with RDS requiring assisted ventilation. It is not yet clear whether CPAP and a lower con-centration of oxygen is more desirable than higher oxygen concentrations alone, providing both methods maintain adequate arterial blood gas levels.

SPECULATION

Infants who require artificial ventilation fail to

increase their SGaw at the normal rate irrespective of the initial severity of their disease or the amount of oxygen received, while infants treated

with

CPAP

or oxygen increase their conductance at the normal rate. These data are consistent with the hypothesis that artificial ventilation results in trauma to the airways which delays their growth. Since this trauma is not evident with CPAP, it is possible that the rapid changes in pressure during

IPPV

cause barotrauma. It has yet to be proven that oxygen alone can cause BPD or even subclin-ical changes, but there is a need for further follow-up studies on infants who have received prolonged high concentrations of oxygen in the absence of IPPV.

REFERENCES

1. Auld PAM, Nelson NM, Cherry RB, et al: Measurement of thoracic gas volume in the newborn infant. JClin Invest 42:476, 1963.

2. Krauss AN, Auld PAM: Measurement of functional residual capacity in distressed neonates by helium rebreathing. J Pediatr 77:228, 1970.

3. Bryan MH, Hardie MJ, Reilly BJ, Swyer PR: Pulmonary function studies during the first year of life in infants recovering from the respiratory distress syndrome. Pediatrics 52: 169, 1973.

4. Northway WH, Rosan RC, Porter DY: Pulmonary

disease following respirator therapy of hyaline membrane disease: Bronchopulmonary dysplasia. N Engl J Med 276:357, 1967.

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KICKING THE HABIT

Hypnosis can help smokers quit-but only if they really want to kick the habit. Desire to stop was the main factor in success in quitting for at least a year by 73 patients in a study described at the International Conference on Lung Diseases at Montreal.

Since August 1972, 233 smokers completed the four-week course in the study, which was de-signed to determine the usefulness of hypnosis as a way to help smokers who had expressed a desire to quit. 180 of these had stopped smoking at the end of the sessions, at least for a while. When interviewed 12 to 29 months later, 73 were still off cigarettes.

A series of post-hypnotic suggestons designed to niake smoking unpleasant, eliminate uncon-scious smoking, reward nonsmoking behavior and to build willpower were given in the eight sessions of the four-week course. No fee was charged. Both individual and group treatment was offered, and self-hypnosis was taught during the first three sessions so that subjects could repeat the same suggestions to themselves several times a day.

All patients who had not cut down to five or fewer cigarettes per day by the fourth session

were subjected under trance to ideomotor ques-tioning to determine whether they were truly motivated, and to identify blocking factors. Once a patient was able to abstain from smoking for an entire day, post-hypnotic suggestions were changed to emphasize their identity as

“non-smokers.”

Motivation was the only factor which corre-lated with successful quitting. Age, sex, smoking history, smoking habits, earlier unsuccessful attempts to quit or the reason to quit were not associated with success. The main problem appeared to be separating those who were prop-erly motivated from those who were not. Some who said they “had to” quit really did not want to, and none succeeded.

Although it is possible that some might have given up smoking without hypnosis, it is felt that hypnosis is useful in providing help to those who really want to quit. Most such people believe they cannot stop without some sort of assistance.

GEORGE GiiYsoN, M.D.

Presented at the International Conference on Lung Diseases, Montreal, Canada

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1976;57;352

Pediatrics

Janet Stocks and S. Godfrey

Damage in Neonates: Assessment by Serial Measurements of Lung Function

The Role of Artificial Ventilation, Oxygen, and CPAP in the Pathogenesis of Lung

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