generalized pulmonary fallot's in neonate · generalized underventilation inrelation to...

Thorax (1975), 30, 452.

Generalized pulmonary hyperinflation and Fallot'stetralogy in a neonate investigated by pulmonary

physiological and radioisotopic methodsS. GODFREY, R. RONCHETTI1, JANET STOCKS,

and KATHERINE HALLIDIE-SMITH

Department of Paediatrics and Neonatal Medicine, Institute of Child Health, and Division ofCardiovascular Disease, Department of Medicine, Hammersmith Hospital, London W12 OHS

Godfrey, S., Ronchetti, R., Stocks, Janet, and Hallidie-Smith, Katherine (1975). Thorax,30, 452-460. Generalized pulmonary hyperinflation and Fallot's tetralogy in a neonateinvestigated by pulmonary physiological and radioisotopic methods. An infant is describedwho presented a complex cardiopulmonary problem which was evaluated with the helpof new physiological techniques. The infant was born at term after an emergencyCaesarian section for fetal distress and was found to have meconium aspiration. Heremained persistently tachypnoeic and hypoxic despite high ambient oxygen. Chestradiographs suggested cystic lesions at the lung bases, and lung function tests confirmedhyperinflation with delayed nitrogen washout. In addition the child had signs of Fallot'stetralogy, and this diagnosis was confirmed by cardiac catheterization. Because of per-sistent hypoxia and tachypnoea disproportionate to the cardiac condition, the possibilityof localized lung disease was considered. Regional lung function tests were carried outin the neonatal period and again at six months of age using radioisotopic "N given byboth inhalation and injection. These studies showed gross ventilation/perfusion im-balance in the lungs, particularly marked at the bases, but with enough generalizedabnormality to preclude the possibility of surgical intervention. The principles of themeasurement of lung mechanics in the newborn by whole-body plethysmography,nitrogen washout, and regional radioisotopic spirometry are outlined. The parLicularvalue of these techniques in the evaluation of complex disorders is discussed, especiallywhere both cardiac and pulmonary abnormalities are present.

The diagnosis of lung disease in a baby with con-genital heart disease or vice-versa can be verydifficult (Roberton, Hallidie-Smith, and Davis,1967) and taxes the skill of the clinician.Tachypnoea, hypoxia, and heart failure are com-mon in either condition. There is also an associa-tion between congenital lobar emphysema andcongenital heart disease (Lincoln et al., 1971)which further increases the difficulty of distin-guishing the major disorder when pulmonaryhyperinflation is present. The investigation ofpulmonary function may throw some light on theproblem since pulmonary compliance has beenshown to be abnormal in some infants with con-genital heart disease, while their lung volume

"Present address: Department of Paediatrics, University of Parma,Italy

and airways resistance usually remain normal(Howlett, 1972) whereas lung disease in infancyusually affects lung volume and resistance as well.We recently had cause to investigate an infant

with a complex cardiopulmonary problem, largelyas a result of which we developed new techniquesfor the detailed assessment of lung mechanics andregional lung function to help elucidate theproblem. The case report is presented first, andsome details of the techniques are given in theappendix.

CASE REPORT

The patient was a male infant, born at term inthis hospital on 5 January 1974, weighing 2880 g(lOth/25th percentile) to a primaparous Indian

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Pulmonary hyperinflation and Fallot's tetralogy in a neonate

mother, who had had an uneventful pregnancy.She was admitted to the obstetric unit in estab-lished labour, with meconium staining of theliquor. The fetal heart rate fell to 108 beats perminute and an emergency Caesarian section wasperformed under general anaesthesia. The babycried immediately after birth but was verytachypnoeic, and crepitations were heard overboth lungs. Inspection showed meconium in thelarynx and trachea, which was aspirated underdirect vision, but the tachypnoea persisted andthe infant was transferred to the neonatal inten-sive care unit. A chest radiograph at this timeshowed widespread patchy changes consistent withmeconium aspiration. The respiratory rate was100 to 120 breaths per minute, the infant becamecyanosed when disturbed, and there were crepita-tions in the lungs, but no other abnormalitieswere detected. At the age of 12 hours, radialarterial blood gases showed Po2 41 mmHg,Pco2 42 mmHg, and pH 7 40. An umbilical arterycatheter was inserted and the baby was nursedin 25% oxygen without an obvious change incolour. Antibiotics were given because of thepossibility of infection.The infant remained tachypnoeic during the

next four days; his arterial Po2 varied from 40 to

50 mmHg in air and was little influenced by in-creasing concentrations of ambient oxygen up to50%. There was an initial rapid weight gain of250 g in the first five days, accompanied by someslight hepatomegaly and oedema of the feet. Asystolic murmur was heard at the left sternal edge.The electrocardiogram showed right axis deviationand right ventricular hypertrophy: his chest radio-graph showed cardiac enlargement and an in-crease in the lung volume with some cyst-likeareas, especially at the bases. These changes be-came more marked later on and are shown inFigure 1. Haematological and biochemical investi-gations were normal.The possibility of heart failure due to lung

disease or combined heart and lung disease wasconsidered, and pulmonary function studies werecarried out in the whole-body infant plethysmo-graph, as described in Appendix 1. These wererepeated at intervals over the next three weeks.The results are given in Table I, together with theexpected values derived from studies in thislaboratory and elsewhere. There was gross tachy-pnoea, with a small tidal volume, and hyperinfla-tion with an approximate doubling of the thoracicgas volume. Airways resistance was relatively nor-mal for the baby's size, although it was raised in

FIG. 1. Chest radiograph taken at the age of 6 months showing hyper-inflation with areas of increased transradiancy, especially at the bases.

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S. Godfrey, R. Ronchetti, Janet Stocks, and Katherine Hallidie-Smith

TABLE IRESULTS OF PULMONARY FUNCTION TESTS

ExpectedAge Values Expected

during Values forNeonatal Age 5-6 kg

6 days 10 days 13 days 17 days 26 days Period" 6* mth Infant References

Tidal volume (ml) 7 0 7.5 7-5 8-0 10.9 19.0 40 0 34 0 A,B,C,D,EFrequency/minute 165 168 170 96 73 35 77 30 A,B,C,FMinute ventilation (ml/min) 1155 1260 1270 768 795 665 3080 1020 A,B,C,FThoracic gas volume (ml) 203 250 270 248 230 93 368 198 G,H,I,J,KFunctional residual capacity (ml)

(a) at 3 minutes 138 90 - - L,M(b) extrapolated 237 90

Dy'namic compliance (ml/cmH,O) 2*1 2-0 1.9 2-1 2-7 5 8 11-5 20-0 B,E,F,G,JAirway resistance (cmH,O/l/per sec) 31-0 32'0 26-5 28-6 41 02 35-0 26-0 10.0 N

'The expected values are derived from the weighted means of published data on normal infants of approximately the same weight.'Measured two days after cardiac catheterization.A Cross (1949) F Cook et al. (1957) K Klaus et al. (1962)B Swyer et al. (1960) G Chu et al. (1964) L Geubelle et al. (1959)C Strang (1961) H Lacourt and Polgar (1974) M Nelson et al. (1963)D Nelson et al. (1962) I Phelan and Williams (1969) N Radford (1974)E Drorbaugh et al. (1963) J Polgar and String (1966)

relation to lung volume, while dynamic compli-ance was low; however, this latter result is diffi-cult to interpret in the presence of such grosstachypnoea. Functional residual capacity after athree-minute period of rebreathing (measuredby a rebreathing technique as described in Ap-pendix 2) was considerably less than that of thethoracic gas volume measured by the plethysmo-graph, indicating the presence of trapped gas, andthe rate of nitrogen washout was inordinately slow(Fig. 2), indicating poor ventilation. When thenitrogen washout curve was extrapolated to givethe theoretical concentration at equilibrium, thecalculated functional residual capacity was thenvery similar to the measured thoracic gas volume(Table I).The infant was treated with digoxin and

diuretics, and his heart failure improved, but thetachypnoea and hypoxia persisted. The calculatedvenous admixture breathing air was 50%, andeven when the infant was given 100% oxygen, thearterial Po2 rose only to 117 mmHg, indicating aresidual right-to-left shunt of 24%. These resultssuggested that approximately half the venous ad-mixture was due to an imbalance of ventilationand perfusion in the lungs, the rest being due toanatomical shunting.By this stage it was clear that the infant had

both abnormal lungs and congenital heart disease,and a clinical diagnosis was made of tetralogy ofFallot with a possible patent ductus arteriosus.Cardiac catheterization and angiocardiographyconfirmed the presence of Failot's tetralogy witha marked bronchial arterial blood supply to thelungs, but the ductus was not patent. The babymade good progress over the next two weeks,with a normal weight gain, but remained tachy-

100

so \i 50::'

Patient

z

120 ,

Controls

10012 34 5 7Minutes

FIG. 2. Nitrogen washout cuirves on patient and twocontrol infants of similar size. The proportion ofnitrogen remaining in the lungs which could beexcreted until rebreathing equilibrium was obtainedhas been plotted against time on a semilogarithmicgraph.

pnoeic, and his chest radiograph still showed per-sistent hyperinflation, which was confirmed byrepeated lung function studies.The tachypnoea was felt to be disproportionate

to the relatively mild and well-compensatedFallot's tetralogy, and it was therefore importantto determine the extent of the lung disease. Atthe age of 5 weeks a radioisotope examination ofthe lungs was performed with '5N using the gammacamera as detailed in Appendix 3. The most ob-vious finding was that the area of radioactivity

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after injection of the isotope was much largerthan after inhalation, especially at the bases,showing the presence of large, poorly ventilatedbut perfused regions. The inhalation curve was ofpoor quality, but calculation of regional ventila-tion from the washout of injected activity showedgeneralized underventilation in relation to regionalvolume. It was concluded that the infant hadgeneralized pulmonary disease with gas trappingand poor ventilation, and that the changes wereprobably more marked at the bases. His a,-antitrypsin level was normal. Surgery was notconsidered possible in the light of the combinedheart and generalized lung disease.The baby was discharged on a maintenance dose

of digoxin and was followed up in the clinic. Hegrew along the 3rd percentile and reached hismilestones at appropriate times. However, he re-mained tachypnoeic with respiratory rates con-sistently recorded in the region of 80 breaths perminute. At the age of 6 months he was re-investi-gated. Lung function studies (Table I) showedpersistent hyperinflation of the lungs, with a raisedairway resistance and low compliance, indicatinggeneralized lung abnormality. The chest radio-graph (Fig. 1) showed progression of the lungdisease with obvious basal radiolucencies. A re-peat "N study was carried out using an improvedbolus technique and gave much clearer results,though essentially confirming the earlier findings.The whole lung activity was greater after infusionthan after inhalation and the wash-out after in-fusion was much slower than after inhalation be-cause the trapped gas was very slowly ventilated(Fig. 3). From these studies it was possible tocalculate indices of regional ventilation and per-fusion (Table II) which showed generalized poorfunction, most severe in the bases. The abnormali-ties appeared to be worse than in the previousstudy.The baby is still being followed at the time of

writing. Diagnostic lung biopsy is not thought tobe justified as the condition is clearly not amen-able to surgical or medical correction.

DISCUSSION

The initial course of this infant's disease suggestedbirth asphyxia followed by meconium aspiration.The evolution of the chest radiograph and thepersisting abnormalities then suggested a possiblediagnosis of congenital cystic adenomatoid mal-formation, especially since this has been describedfairly frequently in association with oedema(Merenstein, 1969). The development of heart

' I,',100 ,t 2 Innhlation "'2 inIusion

50 !

'E ilo,''s~~~~~~~~~...'0

2 .

1 -^^, ,. 60 1 2 3 4 5 6b 23456789Minutes

FIG. 3. Whole lung washout curves for radioactivityafter (a) inhalation of "N., and (b) injection of "N,.The counts have been expressed on a logarithmicscale as percentage of maximum. The very slow wash-out of radioactivity from perfused lung can be seenwhich indicates gross mismatching of ventilation andperfusion in the lungs. The regional variation inwashout is given in Table II.

TABLE IIREGIONAL LUNG FUNCTION AT 6 MONTHS OF AGE

(A) Distribution Indices (normal= 1 .0)

Zone Inhaled Gas Perfusion

Left lower 0-32 0-8lLeft upper 1 22 0 77Right upper 1-59 1 48Right lower 0.99 0-97

(B) Fractional Ventilation (I/minil) (expected= 3 0-5 0 for ventilatedlung and 2 0-40 for perfused lung)

Zone Ventilated Lung Perfused Lung

Left lower 179 055Left upper 2-63 0 57Right upper 3-43 0 71Right lower 2-97 0-61

failure was thought, at this time, to reflect theseverity of lung disease, which had been shown tobe present as a result of the lung function studies.However, it became clear that congenital heartdisease was also present, and a diagnosis ofFallot's tetralogy was confirmed. Finally, the im-portance of the combined lung and heart diseasewas recognized, since it was impossible to accountfor the persistence of the infant's symptoms on

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the basis of his relatively mild degree of heartdisease alone.The exact pathological diagnosis of the lung

condition remains speculative at the present time,but presumably it must be characterized by gen-eralized emphysematous changes, causing trappingof gas and maldistribution of ventilation and per-fusion within the lung. It may be a variety ofcongenital lobar emphysema distributed through-out the lungs, possibly like the polyalveolar diseasedescribed by Hislop and Reid (1970). The possi-bility of cystic adenomatoid malformations cannotbe excluded, and this has been described pre-viously in association with cardiovascular ano-malies such as an aberrant pulmonary bloodsupply (Hutchin, Friedman and Satltzstein, 1971),but this seems unlikely.The use of the techniques which have been

developed to enable detailed investigation of pul-monary function in the infant are of special in-terest in this case. Their contribution was veryconsiderable, and little headway could have beenmade in the interpretation of the problems with-out their aid. It is not proposed to discuss in detailthe theory and practice of these new types oflung function tests in this communication since afuller account is being prepared, but a few pointsare worthy of note. The whole-body infantplethysmograph provides a very useful non-inva-sive tool for measuring lung function in the new-born infant. In order to measure airway resistancewith this apparatus, it is essential to avoid thechanges in gas temperatures which occur duringnormal tidal breathing (Radford, 1974). Unfor-tunately, this has not been done in previous pub-lished studies and consequently there are nostandards available apart from those which wehave prepared in our own laboratory. However,this problem does not apply with respect to themeasurement of thoracic gas volume, and exten-sive data on normal infants now exist. On thisbasis there can be no doubt that the presentpatient had very considerable enlargement of theresting lung volume in relation to body weight.When lung volume is abnormally large, it is diffi-cult to calculate the expected values for airwaysresistance and pulmonary compliance, since theseare usually related to the size of the lung volumein normal subjects. His compliance was very low,but this is also difficult to interpret because of thefrequency dependence of compliance which wouldbe particularly relevant in this child with grosstachypnoea. Thus conventional total lung functionwas abnormal but gave no real indication of thepathophysiology.

The results from the simple nitrogen washoutmeasurement of functional residual capacity wereabnormal when compared with results that wehave obtained from normal healthy infants andwere very suggestive of poor gas mixing within thelungs. This rebreathing washout study gave anoverall estimate of lung function but could notdistinguish localized from generalized disease. Itwas only possible to make a full analysis ofregional lung function and thus detect the gen-eralized nature of the trapped gas and the verypoorly ventilated areas by using "N and thegamma camera. We know of no adequate datawith which to compare our "N studies, becausethey do not appear to have been carried out innormal infants. However, the study by Koch et al.(1973) using "'Xe in normal infants suggests a veryrapid clearance of activity after both injection andinhalation, although it is difficult to compare theirresults with ours because of the different tech-niques employed. We have studied one baby withcongenital absence of the right lung and an ap-parently normal left lung by the same technique.There was no evidence of abnormality in thesingle lung, and the washout of activity after bothventilation and injection fell by 90% in approxi-mately 0-2 to 0 4 minutes, with a uniformdistribution throughout the lung. In the artificiallyventilated monkey, Ronchetti et al. (1973) foundthat the ventilation calculated from the washoutcompared well with the imposed ventilation.Recent studies in a number of infants with otherconditions of a localized nature have shown verymuch more effective and even distribution ofventilation and perfusion to the non-involvedregions than was seen in any part of the lung ofthe present case and give fractional ventilationindices of 3 to 4 min-'.One problem in the interpretation of the present

results concerns the 24% right-to-left shunt whichmeant that this proportion of infused radioactivitybypassed the alveoli and was distributed to tissuesthroughout the body, including the lung tissueand thoracic structures within the field of thegamma camera. In fact only a very small propor-tion of this shunted activity would have enteredthe defined fields because the mass of tissue andits blood supply would be only a small proportion(probably under 10%) of the mass and blood sup-ply of the whole body. Thus only some 2'4% ofinfused activity would have entered lung tissue,and calculations show that this would have beenremoved over some five minutes. In fact we alwayscorrect the lung scan for tissue backgroundactivity measured continuously over a similar

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area in the camera field, usually over the abdo-men. Thus recirculation could not have affectedthe very slow washout of "3N seen in the presentcase (Fig. 3b). It is interesting to note that themean tissue count in babies without shunts whomwe have studied is about 1 6% of the peak lungcount, while that for the present patient was 3 1%.This demonstrates that excess shunting waspresent and, although unlikely to affect the lungscan much, it was worth correcting the curve aswe did with the computer.The technique of regional studies by means of

radioisotopic gas which was developed for thisinfant can provide useful information in selectedcases. It requires no collaboration on the part ofthe patient, and is rapid and simple to perform,although the calculation of the results generallyrequires computing facilities. The radioactivityadministered is generally less than that obtainedfrom simple diagnostic radiology. It would appearto be particularly useful when it is necessary toquantitate the regional extent or severity of asuspected abnormality. From our recent experi-ence this technique is very useful in small childrenwho are too old for the infant plethysmograph andtoo young for meaningful studies by standardmethods.

We wish to express our gratitude to our colleaguesfrom the Department of Medicine, Medical Physicsand the Cyclotron Unit for their major contributionto the development and use of the "N technique.

REFERENCES

Chu, J. S., Dawson, P., Klaus, M., and Sweet, A. Y.(1964). Lung compliance and lung volumemeasured concurrently in normal full-term andpremature infants. Pediatrics, 34, 525.

Cook, C. D., Sutherland, J. M., Segal, S., Cherry,R. B., Mead, J., Mcllroy, M. B., and Smith C. A.(1957). Studies of respiratory physiology in thenewborn infant. III: Measurements of mechanicsof respiration. Journal of Clinical Investigation,36, 440.

Cross, K. W. (1949). The respiratory rate and ventila-tion in the newborn baby. Journal of Physiology,109, 459.

Drorbaugh, J. E., Segal, S., Sutherland, J. M., Oppe,T. E., Cherry, R. B., and Smith, C. A. (1963).Compliance of lung during first week of life.American Journal of Diseases of Children, 105,63.

Dubois, A. B., Botelho, S. Y., Bedell, G. N., Marshall,R., and Comroe, J. H. (1956). A rapid plethysmo-graphic method for measuring thoracic gasvolume. Comparison with nitrogen washoutmethod for measuring functional residualcapacity in normal subjects. Journal of ClinicalInvestigation, 35, 322,

Geubelle, F., Karlberg, P., Koch, G., Lind, J.,Wallgren, G. and Wegelius, C. (1959). L'a6rationdu poumon chez le nouveau-n6. Biology of theNeonate, 1, 169.

Heckscher, Th. O., Larsen, 0. A., and Lassen, N. A.(1966). Clinical method for determination ofregional lung function using intravenous injec-tion of Xe"'. Scandinavian Journal of RespiratoryDiseases, Supplement 62, p. 31.

Hislop, A. and Reid, L. (1970). New pathologicalfindings in emphysema of childhood, 1. Poly-alveolar lobe with emphysema. Thorax, 25, 682.

Howlett, G. (1972). Lung mechanics in normal infantsand infants with congenital heart disease.Archives of Disease in Childhood, 47, 707.

Hutchin, P., Friedman, P. J., and Saltzstein, S. L.(1971). Congenital cystic adenomatoid malforma-tion with anomalous blood supply. Journal ofThoracic and Cardiovascular Surgery, 62, 220.

Klaus, M., Tooley, W. H., Weaver, K. H., andClements, J. A. (1962). Lung volume in the new-born infant. Pediatrics, 30, 111.

Koch, G., Heiskanen, T., Riihimaki, E., Lund, J.,Tahti, E., and Osterlund, K. (1973). Regionaldistribution of ventilation and perfusion in thehealthy newborn infant and in the idiopathicrespiratory distress syndrome. Bulletin de Physio-pathologie Respiratoire, 9, 1511.

Krauss, A. N. and Auld, P. A. M. (1970). Measure-ment of functional residual capacity in distressedneonates by helium rebreathing. Journal ofPediatrics, 77, 228.

Lacourt, G. and Polgar, G. (1974). Development ofpulmonary function in late gestation, I: Thefunctional residual capacity of the lung in pre-mature children. A cta Paediatrica Scandinavica,63, 81.

Lincoln, J. C. R., Stark, J., Subramanian, S.,Aberdeen, E., Bonham-Carter, R. E., Berry,C. L., and Waterston, D. J. (1971). Congenitallobar emphysema. Annals of Surgery, 173, 55.

Merenstein, G. B. (1969). Congenital cystic adenoma-toid malformation of the lung. AmericanJournal of Diseases of Children, 118, 772.

Nelson, N. M., Prod'hom. L. S., Cherry, R. B.,Lipsitz, P. J., and Smit': C. A. (1962). Pulmonaryfunction in the ne t burn infant, 1. Methods:Ventilation and :us metabolism. Pediatrics,30, 963.

in,-,- and (1963). Pulmonaryfunction in the n^-wborn infant: V: Trapped gasin the normal inifant's lung. Journal of ClinicalInvestigation, 42, 1850.

Phelan, P. D. and Williams, H. E. (1969). Ventilatorystudies in healthy infants. Pediatric Research,3, 425.

Polgar, G. and String, S. T. (1966). The viscousresistance of the lung tissues in newborn infants.Journal of Pediatrics, 69, 787.

Radford, M. (1974). The measurement of airwayresistance and thoracic gas volume in infancy.Archives of Disease in Childhood, 49, 611,

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Roberton, N. R. C., Hallidie-Smith, K. A., and Davis,J. A. (1967). Severe respiratory distress syndromemimicking cyanotic heart-disease in term-babies.Lancet, 2, 1108.

Ronchetti, R., Benci, S., Federici, E., Manfredi, M.,Crofetta, L., and Gentili, G. (1974). Theoretical basisfor the calculation of the regional ventilation/perfusion ratio (V/4) of the lungs in the newborn:Journal of Nuclear Biology and Medicine, 18,123.

- , , Schianchi, G., Manfredi, M., Federici, E.,Gentili, G., and Bevilacqua, G. (1973). VI4 distribu-tion in artificially ventilated monkeys studied by in-haled and continuously infused Xe133. Proceedings ofColloquium INSERM on 'Physiologie appliquee dela ventilation assiste chez le nouveau-ne', Pont-a-Mousson (Nancy). Ed. INSERM 129.

Ronchetti, R., Geubelle, F., Chantraine, J. M., andSenterre, J. (1971). Studio del rapportoventilazione/perfusione nel neonato mediante loXe"33. Minerva Pediatrica, 23, 1476.

Secker-Walker, R. H., Hill, R. I., Markham, J., Baker, J.,Wilhelm, J., Alderson, P. O., and Potchen, E. J.(1973). The measurement of regional ventilation inman: A new method of quantitation. Journal ofNuclear Medicine, 14, 725.

Strang, L. B. (1961). Alveolar gas and anatomical dead-space measurements in normal newborn infants.Clinical Science, 21, 107.

Swyer, P. R., Reiman, R. C., and Wright, J. J. (1960).Ventilation and ventilatory mechanics in the newborn.Journal ofPediatrics, 56, 612.

APPENDIX 1 MEASUREMENT OF LUNG MECHANICS

Studies of lung mechanics were carried outusing a specially constructed whole-body infantplethysmograph and applying the techniques des-cribed by Dubois et al. (1956). The plethysmo-graph has been developed by our group (Radford,1974) and recently modified so that the infant re-

breathes oxygen maintained at 37°C and fullyhumidified throughout the measurement. Thisensures that all pressure changes within theplethysmograph reflect changes in alveolar pres-sure and are not invalidated by additional changesdue to the heating or cooling of respired gas. Inthe technique for adults, the subject normallypants in order to minimize such errors, but thisis impossible for the infant, who must be allowedto breathe in his normal fashion.The infant was lightly sedated with chloral

hydrate (30 mg/kg) given immediately before a

feed and was studied soon after the feed was

completed. He slept quietly within the plethysmo-graph and was connected to the rebreathing sys-tem through a nasal adaptor or a face-masksealed in place with silicone putty. The infantwas initially allowed to breathe quietly for a few

breaths while a display of flow plotted againstbox pressure was watched on the oscilloscope toensure that they were in phase, thus indicatingthat the gas was at a uniform temperaturethroughout the system. The actual temperaturewas also measured by thermisters placed at stra-tegic points. When sufficiently flat loops were ob-tained, a record was made on a chart recorder,from which the results were subsequently cal-culated. The airway was then suddenly occludedat the end of an expiration by inflating a balloon,and a further record was obtained relatingplethysmograph pressure to airway pressure.Thoracic gas volume and airway resistance werecalculated from these two sets of measurementsin the conventional manner. The investigation wasrepeated two or three times to ensure reproduci-bility, and allowance was made for the deadspace(8 ml) and resistance (15 cmH2O/l per sec) of theapparatus when calculating the final results.

Tidal volume, frequency, and ventilation weremeasured using a pneumotachograph and inte-grator during free quiet breathing following theconclusion of the plethysmograph studies. Anoesophageal balloon of suitable proportions waspassed to mid-oesophagus so that dynamic com-pliance could be measured by relating changesin oesophageal pressure to changes in tidalvolume. The results of all these studies of lungmechanics in the patient described are given inTable I. The normal values included in this tablehave been derived from the literature and studiesin this laboratory as indicated. The mean expectedvalues which have been calculated have beenbased on the collected data for a 3-kilogram infantappropriately weighted for the number of subjectsinvolved in each study.

APPENDIX 2 MEASUREMENT OF FUNCTIONAL RESI-DUAL CAPACITY BY REBREATHING

Functional residual capacity was measured by arebreathing method which is a modification of themethod described by Krauss and Auld (1970). Theinfant rebreathed for about three minutes froma bag which initially contained a known amount ofpure oxygen (400 ml in this case). He was con-nected to the rebreathing bag through a masksealed in place with silicone putty. Serial samplesof gas were taken from the bag at intervals, afterthorough mixing, and analysed for carbon dioxide,oxygen, and argon (which is converted to anequivalent concentration of nitrogen) using a res-piratory mass spectrometer. In order to calculate

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functional residual capacity, it is necessary toknow the volume of the system at the time of N2measurement as this decreases due to continuingoxygen consumption and progressively decreasingcarbon dioxide excretion. It is also necessary tocorrect for the nitrogen removed from the systemby sampling during the rebreathing period. Asimple digital computer program was written toapply corrections for these various factors in thecalculations. The final nitrogen concentration wasused in the present case to calculate the functionalresidual capacity by simple proportions.With any washout system it is also possible to

obtain an equilibrium concentration by a graphicalmethod of solution, in which the difference be-tween the observed gas concentration and the ex-pected equilibrium value is plotted against timeon semilogarithmic paper (Ronchetti et al., 1974).Using this technique, it is possible to derive theultimate equilibrium concentration providedenough data points are available, even if thepatient has not reached equilibrium at the end ofthree minutes. In the present case this was quiteeasy because of the relatively slow equilibration,so that six points of rising N2 concentration wereobtained over the three-minute period. The resultof the calculated value for functional residualcapacity after a three-minute period of rebreath-ing and the alternative result calculated by extra-polating to the final equilibrium concentration areboth given in Table I. It can be seen that theextrapolated method gives a value which iscloser to the thoracic gas volume measured by thepurely physical principle of Boyle's Law. In nor-mal children studied in this way, the equilibriumis reached within one minute of rebreathing (per-sonal observations) so that their functional resi-dual capacity is constant when calculated fromsamples taken at any time after this, providingbag volume is measured at the same time. Serialsampling is, however, desirable, since it demon-strates whether equilibration has been completed,and in the present infant this was clearly not thecase even after three minutes of rebreathing.

APPENDIX 3 REGIONAL LUNG FUNCTION MEASUREDBY MEANS OF 13N

The regional distribution of lung function wasmeasured using a gamma camera with 13N as thetrace element. This isotope is very insoluble inblood and has a half-life of only 10 minutes. It isparticularly suitable for studies of lung functionbecause of its very low blood and tissue solubility

but it must be produced by a cyclotron close towhere the test is being carried out because of itsshort half-life.The technique used for the first study was that

developed by Ronchetti et al. (1971; 1973) modi-fied for use in the infant. The infant lay supineshortly after a feed, and sedation was unnecessary.A scalp vein needle was inserted just before theprocedure to provide a route for injection of thetrace isotope. The investigation was carried out intwo stages with a perfusion study and an inhala-tion study. When the infant was sleeping quietly,0 5 mC of 13N dissolved in 5 ml of isotonic salinewas slowly injected at a constant rate over a one-minute period. The thorax was scanned by thegamma camera throughout the period and overthe next five minutes during the subsequent wash-out of activity by ventilation. After a 20-minuterest the infant was allowed to breathe from aheadbox, into which a flow of air labelled with"3N in a concentration of 05 mC per litre wasdelivered at the rate of 10 litres per minute. Theinfant breathed the gas for one minute, duringwhich period he inhaled approximately 0 5 mC ofactivity. The thorax was scanned by the cameraduring inhalation and for the following fiveminutes. The data from the gamma camera wereprocessed by an on-line computer so that theactivity in any region of the lung corrected fordecay with respect to time and for tissue back-ground activity was obtained as a printout. Thedose of radioactivity received from the combinedinjection and inhalation studies was calculated tobe of the order of 200 mrads. This dose iscomparable to that received during diagnosticradiography.By the time the second study was performed we

had improved and modified the method. We foundthat the earlier studies did not give enough countson the camera to be reliable and also that a steadystate was almost impossible to achieve. For theseand other theoretical reasons the technique wasmodified so that rapid bolus doses of activity weregiven into the nasopharynx at the end of expira-tion and intravenously. Much better definition wasobtained. Because the latter part of the earliertype of study was effectively rendered a bolusstudy by flushing the lines, it was possible to treatboth studies in a single mathematical fashion withonly a small theoretical error. Regional distribu-tion of blood flow and ventilation was calculatedfrom the regional peak count rate corrected forscanned area (Heckscher, Larsen, and Lassen,1966), and regional ventilation per unit volume ofventilated or perfused lung was calculated from

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the peak count rate divided by the area under thewashout curve (Secker-Walker et al., 1973).

In a normal infant with an alveolar ventilationof 450 ml/min and a lung volume of 100 ml, thisventilation per unit volume for the whole lungshould be 4 5 min-' and in the supine position one

would expect this ratio to be evenly distributedthroughout the lungs.

Requests for reprints to: Dr. S. Godfrey, Departmentof Paediatrics and Neonatal Medicine, HammersmithHospital, Du Cane Road, London W12 OHS.

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generalized pulmonary fallot's in neonate · generalized underventilation inrelation to...

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