302
ceding the development of unequivocal diabetes. Using the best possible definition of prediabetes and selecting carefully matched controls, we failed to find any evidence to support theories that either hyperinsulinxmia or hypoinsulinmmia during oral glucosetolerance testing precedes the development of unequi-
apnœa,
regular breathing restarting with the reintro-
These observations suggest that respiratory drive in babies with provides mediated R.D.S., possibly through the Hering-Breuer inflation reflex.
duction of
C.P.A.P.
C.P.A.P.
a
Introduction
vocal diabetes mellitus. We thank the Gila River Indian community whose cooperation and participation made this study possible; Dr Stephen Kamenetzky, Dr Arthur Dorf, Dr Richard Sampliner, Dr Gordon Senter, and Dr Leonard Comess for the glucose-tolerance tests ; and Mary Barham, Linda Phillips, Carla Hendricks, Naomi Rankin, Janet Clark, and Vema Kuwanhoyioma for technical and secretarial assistance. Requests for reprints should be addressed to P. H. B., Epidemiology and Field Studies Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, 1440 East Indian School Road, Phoenix, Arizona 85014, U.S.A. REFERENCES 1. 2.
Colwell, J. A., Lein, Diabetes, 1967, 16, 560. Pyke, D. A., Cassar, J., Todd, J., Taylor, K. W. A.
Br.
med. J. 1970, iv,
649.
Cerasi, E., Efendic, S., Luft, R. Lancet, 1973, i, 794. Paulsen, E., Rechenderfer, L., Ginsberg-Fellner, F. Diabetes, 1968, 17, 261. 5. Jackson, W. P. U., van Mieghem, W., Keller, P. Lancet, 1972, i,
3. 4.
1040. 6. 7. 8.
9. 10.
11. 12.
M. S., Soeldner, J. S., Kyner, J. L., Gleason, R. E. Diabetes, 1974, 23, 684. Grodsky, G. M., Karam, J. H., Paveatos, F. Ch., Forsham, P. H. Lancet, 1965, i, 290. Siperstein, M. D., Unger, R. H., Madison, L. L. J. clin. Invest. 1968, 47, 1973. Bennett, P. H., Burch, T. A., Miller, M. Lancet, 1971, ii, 125. Reid, J. M., Fullmer, S., Pettigrew, K. D., Burch, T. A., Bennett, P. H., Miller, M., Whedon, G. D. Am. J. clin. Nutr. 1971, 24, 1281. Roth, J., Gorden, P., Pastan, I. Proc. natn. Acad. Sci. U.S.A. 1968, 61, 138. National Research Council. National Academy of Sciences publica-
Gottlieb,
tion no. 1146. Washington, 1964. 13. Classification of Genetic Diabetes Mellitus. Diabetes, 1967, 16, 540. 14. Savage, P. J., Dippe, S. E., Bennett, P. H., Roth, J., Gorden, P., Miller, M. ibid. (in the press). 15. Reaven, G. M., Shen, S. W., Silvers, A., Farquhar, J. W. ibid. 1971, 20, 416. 16. Ricketts, H. T., Cherry, R. A., Kirsteins, L. ibid. 1966, 15, 880.
EFFECT OF CONTINUOUS POSITIVE AIRWAY PRESSURE ON BREATHING PATTERN OF INFANTS WITH RESPIRATORY-DISTRESS SYNDROME * BRIAN D. SPEIDEL
PETER M. DUNN
Bristol Department of Child Health, Southmead Hospital, Bristol BS10 5NB
University of
The effect of continuous positive airway pressure (C.P.A.P.) on the breathing of ten newborn infants with respiratory-distress pattern has been studied using an impedance syndrome (R.D.S.) arterial pneumograph; oxygenation improved and respiration, previously disorganised, became regular in both rate and depth. Grunting usually ceased within 15 minutes of the start of C.P.A.P., and there was also on average a 30% increase in the respiratoryrate. The rapidity with which the breathing pattern changed suggests a reflex mechanism. Sudden reductions in airway pressure were frequently followed by
Sum ary
*
Based
on a
paper read to the Neonatal Society on Feb. 7, 1974.
Hospital, London,
at
St. Thomas’
INCREASING the transpulmonary pressure of infants with respiratory-distress syndrome of the newborn (R.D.S.) has led to a striking fall in mortality.1 The raised pressure may be applied either as a continuous positive airway pressure (C.P.A.P .) 2.3 or as a continuous negative pressure applied to the chest wall.4.5 Both methods increase arterial oxygen tension (Pao2) and reduce alveolar-arterial oxygen tension difference. The mechanism by which this increased oxygenation is achieved is not fully understood, though it is probable that the ventilation-perfusion relationship is improved by the expansion of atelectatic alveoli. 2,5 While investigating infants with R.D.S. we noticed that their breathing pattern, although at first disorganised in both rate and depth, rapidly became regular and even after the start of C.P.A.P. This does not seem to have been reported previously, although Gregory and his colleaguesmention that some of their infants with R.D.S. who had previously been
apnoeic developed regular respiration
on C.P.A.P.
Methods R.D.S. was diagnosed when increasing signs of inspiratory retraction, expiratory grunting, cedema, and poor alveolar air entry persisted for at least 4 hours after birth in conjunction with a characterstic chest X-ray. C.P.A.P. therapy, using a Gregory head box, was instituted in about a third of cases of R.D.S. because the Pa02 had fallen below 45 mm. Hg while breathing 40-80%
oxygen.6 Respiration was studied using a transthoracic impedance pneumograph made in the United Bristol Hospitals department of physics. A constant current of 150 µA at 10 kHz was passed between two electrodes, each 1 cm. in diameter, that were placed on either side of the chest in the midaxillary line. Variations in impedance were picked up by two more electrodes similarly placed on either side of the chest, and the signal was recorded on a Devices polygraph. Using a similar system, Olsson and Victorin 7 showed that the variation in transthoracic to the tidal volume of We confirmed their findings using reverse plethysmography.11 The respiratory-rate was taken from the impedance pneumograph record and checked by direct observation. Blood-gases and acid-base status were estimated on samples of blood obtained from the lower aorta via an umbilical arterial catheter which was also used for the measurement of the arterial blood-pressure. The thermal environment was adjusted to ensure that the abdominal skin temperature was maintained between 36 and 37 "C.
impedance
was
directly proportional
the newborn.
Results Ten infants with R.D.S. having a mean birth weight of 2075 g. (range 1120-3090 g.) after an average gestational age of 33 weeks (range 28-36 weeks) were investigated. Treatment with C.P.A.P. was started at an average age of 10 hours (range 2-24 hours) using a maximum airway pressure of 4-5 mm. Hg. After the application of C.P.A.P. for 2 hours, the
303
Fig. 1—Breathing pattern of infant with
R.D.S. before
on average from 38 to 62 mm. Hg, although the mean ambient oxygen had been reduced from 50 % The mean Paco2 fell to 38% during this period. from 53 to 52 mm. Hg during the first 2 hours on C.P.A.P., and thereafter fell to 45 mm. Hg over the next 10 hours. The respiratory-rate increased on average from 62 to 82 breaths per minute after treatment in C.P.A.P. for 1 hour, and to 85 per minute after 12 hours. The characteristic effect of C.P.A.P. on the pattern of breathing is illustrated in fig 1. This infant weighed 1120 g. after a gestation of 28 weeks, and severe R.D.S. developed rapidly. The upper trace was recorded at the age of 6 hours while breathing at atmospheric pressure, and shows the disorganised breathing typical of R.D.S., with irregularity in rate and depth and frequent sighs. The lower trace was made 22 hours later after 2 hours of treatment in C.P.A.P. 4 mm. Hg. Breathing had become even and regular. This alteration, which was observed in nine of the ten cases studied, happened at once or after a minute or two of C.P.A.P., and respiration was then maintained with remarkable regularity, sometimes without interruption for up to 30 minutes at a time. Grunting diminished and usually ceased within 15 minutes of
PaO2 rose
(A)
and after
(B) application
of C.P.A.P. 4
mm.
Hg.
When of the
C.P.A.P. was discontinued during the disease, respiration usually became irregular once more, grunting often recommenced, and the Pao2 fell. Similar but less striking changes in breathing also tended to occur when C.P.A.P. therapy was finally discontinued. In two of the nine infants deep sighs persisted although respiration became regular. In both these babies the Pao2 improved only a little with the introduction of C.P.A.P., as compared with that occurring in In the tenth infant, C.P.A.P. the remaining seven. seemed to have little effect on the breathing pattern, which remained irregular; the PaO2 also remained unchanged in this infant, who had severe Rh haemolytic
C.P.A.P. course
disease besides R.D.S. In one infant, the initiation of C.P.A.P. was associated with a period of apnoea lasting 3 minutes before spontaneous respiration was re-established, and breathing only became regular after a further 7 minutes. In two further cases in this series (and in several others we have seen) a sudden unintentional fall in airway pressure seemed to precipitate prolonged apnoea, sometimes necessitating the use of artificial ventilation. Fig. 2 illustrates an example of this. The infant, a boy, weighed 1600 g. at birth after a gestation of
Fig. 2—Apnœa, with bradycardia and raised blood-pressure, occurring in association with sudden loss of C.P.A.P.
304 R.D.s. for which he received This from the Hg age of 3½ hours. when 22 hours shows the made he was recording, old, effect of a sudden fall in C.P.A.P. from 5 to 0 mm. Hg. Breathing stopped immediately, and within 15 seconds the heart-rate began to fall while the blood-pressure rose. Within 1 minute, C.P.A.P. 5 mm. Hg was reintroduced and led rapidly to the return of normal respiration, heart-rate, and blood-pressure.
28
In
weeks, and developed
C.P.A.P.
5
mm.
Discussion which with rapidity respiration became regular once C.P.A.P. was started suggests a reflex mechanism. Furthermore, the development of apnoea after a sudden fall in airway pressure, and the re-establishment of regular respiration following the reintroduction of C.P.A.P., supports the belief that C.P.A.P. may provide some form of reflex respiratory drive. C.P.A.P. probably acts by promoting alveolar expansion in R.D.s. and improving pulmonary gas exchange. The
in PaO2 and PaCO2 may then influence the rate and depth of breathing via the peripheral and central chemoreceptors in such a way as to bring about more even and regular respiration, which may in turn further enhance pulmonary function. However, we do not think this is likely to be the main explanation for the changes observed. Although the use of C.P.A.P. was associated with a rise in P a02, we have also noted the characteristic changes in the pattern of respiration in infants with R.D.S. who were not hypoxxmic. Increased Paco2 is a powerful stimulus to breathing, but the mean level hardly changed in the first 2 hours of C.P.A.P. Furthermore, breathing remained regular and at a more rapid rate than previously during the next 10 hours, even though the PaCO2 fell from 52 to 45 mm. Hg during this time. Although in previous reports 2,5 raising the transpulmonary pressure led to a fall in respiratory-rate, in our study there was on average a 30 % increase. The explanation may lie in the timing of C.P.A.P in relation to the course of the disease or in the amount of pressure applied. Kilburn and Sieker9 also observed an increased respiratory-rate with the application of C.P.A.P. to normal adults. In addition, studies in the newborn 10 have demonstrated that occlusion of the airway at end-expiration stimulates the Hering-Breuer inflation reflex and is associated with an increased rate of respiration. This increase was especially striking in preterm infants. If the receptors of this reflex are in the airways, then when the alveoli are less compliant, a raised transpulmonary pressure will tend to stretch them more than usual, inspiration will be turned off earlier, and the rate of breathing will increase, though at a reduced tidal volume and with less breath-to-breath variation.11 A raised transpulmonary pressure tends to reduce the tidal volume, to lower compliance, and to raise the functional residual volume.2.5 These last two changes would favour the stimulation of the receptors for the Hering-Breuer reflex. While we can only speculate on the mechanism, the inflation reflex provides a possible explanation for the alteration in breathing pattern and the apparent respiratory drive observed in some babies with R.D.S. treated with C.P.A.P.
Consequent changes
some
of
our
cases,
expiratory grunting
and
breathing had become regular sighing persisted It therefore seems likely with the use of C.P.A.P. that the abolition of these features is mediated through after
a
different mechanism.
Thibeault
et
al.12 found that
the functional residual volume of
apparently, normal preterm infants was often reduced, probably due to atelectasis. They observed that the breathing of these infants tended to be periodic, and that even when regular it was frequently interrupted by deep sighs. This sighing, they suggested, might help the baby to overcome atelectasis. They also found that the application of continuous negative pressure both increased functional residual volume, reduced tidal volume, and appeared to make respiration more regular while abolishing both periodic breathing and sighing. These observations would suggest that sighing is associated with atelectasis. It is of interest that sighing persisted in the two cases in our study that exhibited the least rise in Pao2 after the use of C.P.A.P. The occurrence of apnoea in association with a sudden drop in airway pressure is clearly of immense clinical importance. Following our recognition of this hazard, we developed a pressure-monitoring module in 1971, capable of setting off an alarm should the pressure fall 1-2 mm. Hg below the intended level.6 We thank the Variety Club of Great Britain for the donation of monitoring apparatus and Mr A. C. Poole for technical assistance. REFERENCES 1. 2.
3. 4. 5. 6. 7. 8. 9. 10.
Lancet, 1973, ii, 244. Gregory, G. A., Kitterman, J. A., Phibbs, R. H., Tooley, W. H., Hamilton, W. K. New Engl. J. Med. 1971, 284, 1333. Dunn, P. M., Thearle, M. J., Parsons, A. C., Watts, J. L. Lancet, 1971, ii, 971. Chernick, V., Vidyassagar, D. Pediatrics, 1972, 49, 753. Bancalari, E., Garcia, O. L., Jesse, M. J. ibid. 1973, 51, 485. Dunn, P. M. Proc. R. Soc. Med. 1974, 67, 245. Olsson, T., Victorin, L. Acta pœdiat. scand. 1970, suppl. 207. Karlberg, P., Cherry, R. B., Escardo, F., Koch, G. Acta pœdiat. Stockh. 1960, 49, 345. Kilburn, K. H., Sieker, H. O. Circulatim. Res. 1969, 8, 660. Olinsky, A., Bryan, M. H., Bryan, A. C. J. appl. Physiol. 1974, 36, 426.
11. 12.
Comroe, J. H. Physiology of Respiration; chap. 8. Chicago, 1965. Thibeault, D. W., Wong, M. M., Auld, P. A. M. Pediatrics, 1967, 40, 403.
LYMPHOCYTE-DEPENDENT ANTIBODY CROSS-MATCHING FOR TRANSPLANT PATIENTS ALAN TING
PAUL I. TERASAKI School
Department of Surgery, of Medicine, University of California, Los Angeles, California 90024, U.S.A. Cadaver donor transplant patients who had a negative complement-dependent cytotoxicity cross-match test were tested in parallel with the specific donor at the time of transplantation by the lymphocyte-dependent antibody (L.D.A.) test. Transplants were performed on the basis of negative standard and long (2-5-hour) complement-dependent cross-match tests and the results of the L.D.A. test were withheld from the transplant centres. Of the 57 transplants tested, 49 had a negative L.D.A. result with 74% one-month function whereas 8 had a positive L.D.A.
Summary
ceding the development of unequivocal diabetes. Using the best possible definition of prediabetes and selecting carefully matched controls, we failed to find any evidence to support theories that either hyperinsulinxmia or hypoinsulinmmia during oral glucosetolerance testing precedes the development of unequi-
apnœa,
regular breathing restarting with the reintro-
These observations suggest that respiratory drive in babies with provides mediated R.D.S., possibly through the Hering-Breuer inflation reflex.
duction of
C.P.A.P.
C.P.A.P.
a
Introduction
vocal diabetes mellitus. We thank the Gila River Indian community whose cooperation and participation made this study possible; Dr Stephen Kamenetzky, Dr Arthur Dorf, Dr Richard Sampliner, Dr Gordon Senter, and Dr Leonard Comess for the glucose-tolerance tests ; and Mary Barham, Linda Phillips, Carla Hendricks, Naomi Rankin, Janet Clark, and Vema Kuwanhoyioma for technical and secretarial assistance. Requests for reprints should be addressed to P. H. B., Epidemiology and Field Studies Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, 1440 East Indian School Road, Phoenix, Arizona 85014, U.S.A. REFERENCES 1. 2.
Colwell, J. A., Lein, Diabetes, 1967, 16, 560. Pyke, D. A., Cassar, J., Todd, J., Taylor, K. W. A.
Br.
med. J. 1970, iv,
649.
Cerasi, E., Efendic, S., Luft, R. Lancet, 1973, i, 794. Paulsen, E., Rechenderfer, L., Ginsberg-Fellner, F. Diabetes, 1968, 17, 261. 5. Jackson, W. P. U., van Mieghem, W., Keller, P. Lancet, 1972, i,
3. 4.
1040. 6. 7. 8.
9. 10.
11. 12.
M. S., Soeldner, J. S., Kyner, J. L., Gleason, R. E. Diabetes, 1974, 23, 684. Grodsky, G. M., Karam, J. H., Paveatos, F. Ch., Forsham, P. H. Lancet, 1965, i, 290. Siperstein, M. D., Unger, R. H., Madison, L. L. J. clin. Invest. 1968, 47, 1973. Bennett, P. H., Burch, T. A., Miller, M. Lancet, 1971, ii, 125. Reid, J. M., Fullmer, S., Pettigrew, K. D., Burch, T. A., Bennett, P. H., Miller, M., Whedon, G. D. Am. J. clin. Nutr. 1971, 24, 1281. Roth, J., Gorden, P., Pastan, I. Proc. natn. Acad. Sci. U.S.A. 1968, 61, 138. National Research Council. National Academy of Sciences publica-
Gottlieb,
tion no. 1146. Washington, 1964. 13. Classification of Genetic Diabetes Mellitus. Diabetes, 1967, 16, 540. 14. Savage, P. J., Dippe, S. E., Bennett, P. H., Roth, J., Gorden, P., Miller, M. ibid. (in the press). 15. Reaven, G. M., Shen, S. W., Silvers, A., Farquhar, J. W. ibid. 1971, 20, 416. 16. Ricketts, H. T., Cherry, R. A., Kirsteins, L. ibid. 1966, 15, 880.
EFFECT OF CONTINUOUS POSITIVE AIRWAY PRESSURE ON BREATHING PATTERN OF INFANTS WITH RESPIRATORY-DISTRESS SYNDROME * BRIAN D. SPEIDEL
PETER M. DUNN
Bristol Department of Child Health, Southmead Hospital, Bristol BS10 5NB
University of
The effect of continuous positive airway pressure (C.P.A.P.) on the breathing of ten newborn infants with respiratory-distress pattern has been studied using an impedance syndrome (R.D.S.) arterial pneumograph; oxygenation improved and respiration, previously disorganised, became regular in both rate and depth. Grunting usually ceased within 15 minutes of the start of C.P.A.P., and there was also on average a 30% increase in the respiratoryrate. The rapidity with which the breathing pattern changed suggests a reflex mechanism. Sudden reductions in airway pressure were frequently followed by
Sum ary
*
Based
on a
paper read to the Neonatal Society on Feb. 7, 1974.
Hospital, London,
at
St. Thomas’
INCREASING the transpulmonary pressure of infants with respiratory-distress syndrome of the newborn (R.D.S.) has led to a striking fall in mortality.1 The raised pressure may be applied either as a continuous positive airway pressure (C.P.A.P .) 2.3 or as a continuous negative pressure applied to the chest wall.4.5 Both methods increase arterial oxygen tension (Pao2) and reduce alveolar-arterial oxygen tension difference. The mechanism by which this increased oxygenation is achieved is not fully understood, though it is probable that the ventilation-perfusion relationship is improved by the expansion of atelectatic alveoli. 2,5 While investigating infants with R.D.S. we noticed that their breathing pattern, although at first disorganised in both rate and depth, rapidly became regular and even after the start of C.P.A.P. This does not seem to have been reported previously, although Gregory and his colleaguesmention that some of their infants with R.D.S. who had previously been
apnoeic developed regular respiration
on C.P.A.P.
Methods R.D.S. was diagnosed when increasing signs of inspiratory retraction, expiratory grunting, cedema, and poor alveolar air entry persisted for at least 4 hours after birth in conjunction with a characterstic chest X-ray. C.P.A.P. therapy, using a Gregory head box, was instituted in about a third of cases of R.D.S. because the Pa02 had fallen below 45 mm. Hg while breathing 40-80%
oxygen.6 Respiration was studied using a transthoracic impedance pneumograph made in the United Bristol Hospitals department of physics. A constant current of 150 µA at 10 kHz was passed between two electrodes, each 1 cm. in diameter, that were placed on either side of the chest in the midaxillary line. Variations in impedance were picked up by two more electrodes similarly placed on either side of the chest, and the signal was recorded on a Devices polygraph. Using a similar system, Olsson and Victorin 7 showed that the variation in transthoracic to the tidal volume of We confirmed their findings using reverse plethysmography.11 The respiratory-rate was taken from the impedance pneumograph record and checked by direct observation. Blood-gases and acid-base status were estimated on samples of blood obtained from the lower aorta via an umbilical arterial catheter which was also used for the measurement of the arterial blood-pressure. The thermal environment was adjusted to ensure that the abdominal skin temperature was maintained between 36 and 37 "C.
impedance
was
directly proportional
the newborn.
Results Ten infants with R.D.S. having a mean birth weight of 2075 g. (range 1120-3090 g.) after an average gestational age of 33 weeks (range 28-36 weeks) were investigated. Treatment with C.P.A.P. was started at an average age of 10 hours (range 2-24 hours) using a maximum airway pressure of 4-5 mm. Hg. After the application of C.P.A.P. for 2 hours, the
303
Fig. 1—Breathing pattern of infant with
R.D.S. before
on average from 38 to 62 mm. Hg, although the mean ambient oxygen had been reduced from 50 % The mean Paco2 fell to 38% during this period. from 53 to 52 mm. Hg during the first 2 hours on C.P.A.P., and thereafter fell to 45 mm. Hg over the next 10 hours. The respiratory-rate increased on average from 62 to 82 breaths per minute after treatment in C.P.A.P. for 1 hour, and to 85 per minute after 12 hours. The characteristic effect of C.P.A.P. on the pattern of breathing is illustrated in fig 1. This infant weighed 1120 g. after a gestation of 28 weeks, and severe R.D.S. developed rapidly. The upper trace was recorded at the age of 6 hours while breathing at atmospheric pressure, and shows the disorganised breathing typical of R.D.S., with irregularity in rate and depth and frequent sighs. The lower trace was made 22 hours later after 2 hours of treatment in C.P.A.P. 4 mm. Hg. Breathing had become even and regular. This alteration, which was observed in nine of the ten cases studied, happened at once or after a minute or two of C.P.A.P., and respiration was then maintained with remarkable regularity, sometimes without interruption for up to 30 minutes at a time. Grunting diminished and usually ceased within 15 minutes of
PaO2 rose
(A)
and after
(B) application
of C.P.A.P. 4
mm.
Hg.
When of the
C.P.A.P. was discontinued during the disease, respiration usually became irregular once more, grunting often recommenced, and the Pao2 fell. Similar but less striking changes in breathing also tended to occur when C.P.A.P. therapy was finally discontinued. In two of the nine infants deep sighs persisted although respiration became regular. In both these babies the Pao2 improved only a little with the introduction of C.P.A.P., as compared with that occurring in In the tenth infant, C.P.A.P. the remaining seven. seemed to have little effect on the breathing pattern, which remained irregular; the PaO2 also remained unchanged in this infant, who had severe Rh haemolytic
C.P.A.P. course
disease besides R.D.S. In one infant, the initiation of C.P.A.P. was associated with a period of apnoea lasting 3 minutes before spontaneous respiration was re-established, and breathing only became regular after a further 7 minutes. In two further cases in this series (and in several others we have seen) a sudden unintentional fall in airway pressure seemed to precipitate prolonged apnoea, sometimes necessitating the use of artificial ventilation. Fig. 2 illustrates an example of this. The infant, a boy, weighed 1600 g. at birth after a gestation of
Fig. 2—Apnœa, with bradycardia and raised blood-pressure, occurring in association with sudden loss of C.P.A.P.
304 R.D.s. for which he received This from the Hg age of 3½ hours. when 22 hours shows the made he was recording, old, effect of a sudden fall in C.P.A.P. from 5 to 0 mm. Hg. Breathing stopped immediately, and within 15 seconds the heart-rate began to fall while the blood-pressure rose. Within 1 minute, C.P.A.P. 5 mm. Hg was reintroduced and led rapidly to the return of normal respiration, heart-rate, and blood-pressure.
28
In
weeks, and developed
C.P.A.P.
5
mm.
Discussion which with rapidity respiration became regular once C.P.A.P. was started suggests a reflex mechanism. Furthermore, the development of apnoea after a sudden fall in airway pressure, and the re-establishment of regular respiration following the reintroduction of C.P.A.P., supports the belief that C.P.A.P. may provide some form of reflex respiratory drive. C.P.A.P. probably acts by promoting alveolar expansion in R.D.s. and improving pulmonary gas exchange. The
in PaO2 and PaCO2 may then influence the rate and depth of breathing via the peripheral and central chemoreceptors in such a way as to bring about more even and regular respiration, which may in turn further enhance pulmonary function. However, we do not think this is likely to be the main explanation for the changes observed. Although the use of C.P.A.P. was associated with a rise in P a02, we have also noted the characteristic changes in the pattern of respiration in infants with R.D.S. who were not hypoxxmic. Increased Paco2 is a powerful stimulus to breathing, but the mean level hardly changed in the first 2 hours of C.P.A.P. Furthermore, breathing remained regular and at a more rapid rate than previously during the next 10 hours, even though the PaCO2 fell from 52 to 45 mm. Hg during this time. Although in previous reports 2,5 raising the transpulmonary pressure led to a fall in respiratory-rate, in our study there was on average a 30 % increase. The explanation may lie in the timing of C.P.A.P in relation to the course of the disease or in the amount of pressure applied. Kilburn and Sieker9 also observed an increased respiratory-rate with the application of C.P.A.P. to normal adults. In addition, studies in the newborn 10 have demonstrated that occlusion of the airway at end-expiration stimulates the Hering-Breuer inflation reflex and is associated with an increased rate of respiration. This increase was especially striking in preterm infants. If the receptors of this reflex are in the airways, then when the alveoli are less compliant, a raised transpulmonary pressure will tend to stretch them more than usual, inspiration will be turned off earlier, and the rate of breathing will increase, though at a reduced tidal volume and with less breath-to-breath variation.11 A raised transpulmonary pressure tends to reduce the tidal volume, to lower compliance, and to raise the functional residual volume.2.5 These last two changes would favour the stimulation of the receptors for the Hering-Breuer reflex. While we can only speculate on the mechanism, the inflation reflex provides a possible explanation for the alteration in breathing pattern and the apparent respiratory drive observed in some babies with R.D.S. treated with C.P.A.P.
Consequent changes
some
of
our
cases,
expiratory grunting
and
breathing had become regular sighing persisted It therefore seems likely with the use of C.P.A.P. that the abolition of these features is mediated through after
a
different mechanism.
Thibeault
et
al.12 found that
the functional residual volume of
apparently, normal preterm infants was often reduced, probably due to atelectasis. They observed that the breathing of these infants tended to be periodic, and that even when regular it was frequently interrupted by deep sighs. This sighing, they suggested, might help the baby to overcome atelectasis. They also found that the application of continuous negative pressure both increased functional residual volume, reduced tidal volume, and appeared to make respiration more regular while abolishing both periodic breathing and sighing. These observations would suggest that sighing is associated with atelectasis. It is of interest that sighing persisted in the two cases in our study that exhibited the least rise in Pao2 after the use of C.P.A.P. The occurrence of apnoea in association with a sudden drop in airway pressure is clearly of immense clinical importance. Following our recognition of this hazard, we developed a pressure-monitoring module in 1971, capable of setting off an alarm should the pressure fall 1-2 mm. Hg below the intended level.6 We thank the Variety Club of Great Britain for the donation of monitoring apparatus and Mr A. C. Poole for technical assistance. REFERENCES 1. 2.
3. 4. 5. 6. 7. 8. 9. 10.
Lancet, 1973, ii, 244. Gregory, G. A., Kitterman, J. A., Phibbs, R. H., Tooley, W. H., Hamilton, W. K. New Engl. J. Med. 1971, 284, 1333. Dunn, P. M., Thearle, M. J., Parsons, A. C., Watts, J. L. Lancet, 1971, ii, 971. Chernick, V., Vidyassagar, D. Pediatrics, 1972, 49, 753. Bancalari, E., Garcia, O. L., Jesse, M. J. ibid. 1973, 51, 485. Dunn, P. M. Proc. R. Soc. Med. 1974, 67, 245. Olsson, T., Victorin, L. Acta pœdiat. scand. 1970, suppl. 207. Karlberg, P., Cherry, R. B., Escardo, F., Koch, G. Acta pœdiat. Stockh. 1960, 49, 345. Kilburn, K. H., Sieker, H. O. Circulatim. Res. 1969, 8, 660. Olinsky, A., Bryan, M. H., Bryan, A. C. J. appl. Physiol. 1974, 36, 426.
11. 12.
Comroe, J. H. Physiology of Respiration; chap. 8. Chicago, 1965. Thibeault, D. W., Wong, M. M., Auld, P. A. M. Pediatrics, 1967, 40, 403.
LYMPHOCYTE-DEPENDENT ANTIBODY CROSS-MATCHING FOR TRANSPLANT PATIENTS ALAN TING
PAUL I. TERASAKI School
Department of Surgery, of Medicine, University of California, Los Angeles, California 90024, U.S.A. Cadaver donor transplant patients who had a negative complement-dependent cytotoxicity cross-match test were tested in parallel with the specific donor at the time of transplantation by the lymphocyte-dependent antibody (L.D.A.) test. Transplants were performed on the basis of negative standard and long (2-5-hour) complement-dependent cross-match tests and the results of the L.D.A. test were withheld from the transplant centres. Of the 57 transplants tested, 49 had a negative L.D.A. result with 74% one-month function whereas 8 had a positive L.D.A.
Summary
