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THE SEQUENCE OF EVENTS IN NEONATAL APNŒA
Saturday THE
OF EVENTS IN NEONATAL APNŒA
SEQUENCE
J. M. GUPTA M.D.
PHILIP
J.
Singapore (CLOTHWORKERS’ COMPANY) P. M. TIZARD J. M.A., B.M. Oxon., F.R.C.P., D.C.H.
NEATE RESEARCH FELLOW
PROFESSOR OF PÆDIATRICS
Nuffield Neonatal Research Unit, Institute of Child Health, Hammersmith Hospital, London W.12
From the
The state at birth of 1594 infants delivered at the Hammersmith Hospital is reported. Of 91 babies who were apnœic at one minute, 23 had cried before the onset of apnœa. On resuscitation, all but 1 left the delivery room with regular respiration. An attempt has been made to distinguish between primary and terminal apnœa in these babies. Adequate data was available in 60 cases; 42 of these were clearly in primary apnœa; the other 18 may or may not have been in terminal apnœa. The Apgar rating did not clearly distinguish between the two groups. Attention is drawn to the importance of three factors: (a) changes in heart-rate before resuscitation, (b) the sequence of events on recovery, whether gasping precedes an improvement in colour or vice versa; and (c) whether or not apnœa supervenes in a baby who has initially gasped or cried.
Summary
Introduction METHODS of resuscitation of the apnceic newborn baby have fluctuated; what is fashionable one year is out of date the next. The ready and credulous acceptance of new methods of resuscitation is understandable when one considers the course of events in experimental asphyxia of newborn animals. Whatever the asphyxiating influence or the species of animal the course of events is much the same. Fig. 1 (Davis 1961) illustrates the effect of immersion in pure nitrogen of a newborn rabbit. At first there is a period of dyspnoea lasting about half a minute. Respiration then ceases; the animal becomes limp and heart-rate and bloodpressure fall abruptly. Heart-rate and blood-pressure then rise, followed by a second decline which is slow and gradual. After several minutes of apnoea the animal gasps spontaneously for several minutes. This is followed by a second period of apnoea, the animal dying when the heart-rate and blood-pressure have fallen to zero. There are thus in experimental asphyxia two periods of apnoea, and while an animal can recover during either period, the measures needed to ensure resuscitation are very different. During the first period of apncea (primary apnoea) almost any stimulus, physical or chemical, will cause the animal to gasp, will in other words expedite the onset of the first spontaneous gasp and if the asphyxiating influence has been removed (e.g., if an atmosphere of nitrogen is replaced with oxygen or air) the animal will recover, gasps being 7506
8
July 1967
by regular respiration. Indeed in such circumstances no stimuli are necessary since spontaneous gasping will eventually take place. In terminal apncea, however, the situation is very different; no mechanical or chemical stimulation will cause gasping or any other movement, and recovery can only be brought about by increasing p a02 by artificial respiration (Cross et al. 1964). The apparent success of many widely differing methods of resuscitation-physical, such as the time-honoured slapping or rocking (Millen and Davies 1946) or phrenic-nerve stimulation (Cross and Roberts 1951), chemical, such as nikethamide or ethamivan (Barrie et al. 1962), or inefficient methods of administration of oxygen such as intragastric (Akarren and Furstenberg 1950), hyperbaric (Hutchison et al. 1963), or even simple neglect-could be readily explained if most apnceic newborn babies were in a state of primary rather than terminal apnoea. Anyone experienced in the resuscitation of the apnoeic newborn baby knows that a relatively fast rather than a slow heart-rate, cyanosis rather than pallor, and some flexural tone and spontaneous movement rather than limpness and immobility are all favourable signs. But, assuming the concept of primary and terminal apncea holds good for the apnoeic newborn baby, can one confidently distinguish between these states on clinical examination-i.e., distinguish those babies who will recover spontaneously, whatever is done, from those for whom artificial respiration is succeeded
essential ? Methods
Apgar (1953)
was
the first
to
systematise
the
recording of
heart-rate, respiration, reflex irritability, muscle tone, and colour of the newborn baby. 0, 1, or 2 points were awarded for each of these items and added together to produce a score (table i). At this hospital we have departed from her assessment in
some
not
respects and added
produce
a
single-figure
Fig. 1-Sequence of tion (Davis 1961).
events
in
two
score,
further items (fig. 2). We do believing that this may result
experimental asphyxia and
Diagrammatic representation of the aged 2-4 days.
newborn rabbits
resuscita-
response to acute anoxia in
56 TABLE I-METHOD OF SCORING IN EVALUATION OF NEWBORN
INFANT*
*
Evaluation 60 seconds after complete birth of infant (disregarding the cord and placenta). t Modified from Apgar (1953) and Apgar et al. (1958).
in
loss of information. We distinguish between pallor and cyanosis of the trunk since this may be of importance: we do not regard cyanosis of the extremities as being of great significance since this may be observed in otherwise healthy babies for twenty-four or forty-eight hours. We have coded the items " Did the baby cry before the age of one minute ", since this may be so in some babies who are apnceic at one minute and " Is the baby brown-skinned " since this adds to the difficulty of assessment of cyanosis (Tizard 1964). Most of the assessments were made by the midwifery staff with whom we held many discussions before the system was introduced and during the trial period. The clock on the resuscitation trolley (fig. 3) was started on the completion of delivery without reference to severance of the cord. The midwives were asked to make the assessment whenever possible between sixty and seventy-five seconds after complete delivery by counting the heart-rate by ausculation for fifteen seconds, the other observations either being made during or before this a
The actual heart-rate was examined in 200 consecutive normal deliveries requiring no resuscitation. The mean rate was 132; only 9 babies had heart-rates below 100 and only 2 had rates above 160. Table ill shows the numbers of babies who were in the best state in four or more of the six items (heart-rate, respiration, cry before one minute, muscle tone, response to catheter stimulation, and colour). Table IV gives a further breakdown of the 281 babies who were in the best state in five out of six items. The percentage figures give some idea of the reliability of each item as an index of asphyxia. For instance, if respiration was regular, there had been a cry before one minute, muscle tone and reflex movement were normal, and the trunk was pink, less than 0-1"had heart-rates below 100, whereas nearly 8% of these babies were blue when all the other items recorded were best.
Fig. 3-Resuscitation trolley.
shows the assessment of 91 babies who were minute. It should first be noted that in more than two-thirds of these babies the delivery was abnormal and the one-minute assessment was therefore made by one of the resident paediatricians. In rather less than a third, the apnoea was unexpected and therefore the one-minute assessment was made by the midwife. Of the 26 unexpected cases of apnoea, 1 baby had a diaphragmatic hernia and 7 had cords tightly wound round the neck. In the remaining 18 there was no obvious cause Table
apnoeic
Fig. 2-Standard form used in modified Apgar scoring.
period. We were careful not to insist that each record should be complete, believing that to insist on completion is to court inaccuracy. In this paper a distinction is made between complete records " and " incomplete records " in which one item was missing. Records have been discarded when more "
than one item was missing or when the observations were made after one minute. However, for abnormal deliveries, one of the two residents in neonatal paediatrics was always present, in case resuscitation was necessary, and the assessment of the baby was therefore made by the pxdiatrician who also wrote careful notes recording the course of events in all cases. Abnormal deliveries are defined here as premature births, abnormal presentations, fcetal distress, delivery by forceps, and cassarean section. Results deliveries with Table 11 relates to 1594 " normal or as defined records, above, and incomplete complete shows what can be expected in a population of babies with unexceptional births. It is clear that there is no real correspondence between the worst, medium, and best states in the different categories. For instance, whereas 95of all babies had a heart-rate of more than 100 at one minute only 69 °were pink (complete records). "
v
at one
TABLE II-NORMAL DELIVERIES
(STATE
AT ONE MINUTE AFTER
BIRTH)
I
i
57 TABLE III-STATE AT ONE MINUTE AFTER NORMAL DELIVERY IN BABIES
1224
(COMPLETE RECORDS)
signs of immediate danger. Of the 11 babies white 5 were intubated. Incidentally, it is clearly unprofitable to attempt to class apnoeic newborn babies into the old-fashioned categories of blue and white asphyxia (table vi).
regarded who
as
were
Sequence of Events
TABLE IV-INTERRELATION BETWEEN HEART-RATE, CRY BEFORE ONE MINUTE, RESPIRATION, MUSCLE TONE, RESPONSE TO CATHETER STIMULATION, AND COLOUR (TAKING ONE ITEM AS A VARIABLE, AND THE OTHER FIVE CONSTANT IN THE BEST
STATE)
in Neonatal Apnaa From the above results it would seem that a single clinical assessment at one minute is of little value in distinguishing between primary and terminal apnoea and therefore of little immediate prognostic significance. Apgar came to the same conclusion in respect of her score (Apgar et al. 1958). If, however, the findings in experimental asphyxia are applicable to the apnoeic newborn baby it might be possible to define the stage of apncea by following two sequences of events; firstly, changes in heart-rate before resuscitative measures are started and, secondly, the time at which colour improves in relation to the time of onset of respiration with or without active resuscitation. If resuscitative measures led to a gasp or regular respiration before an improvement in colour it would be reasonable to assume that the baby had been in the stage of primary apncea-and incidentally would have recovered TABLE VI-BABIES APNCEIC AT ONE MINUTE
(COMPLETE RECORDS)
Nearly all these mothers had been given but it is difficult to assess their role in normal onset of respiration. It is of interest that 23 of the 65 babies with abnormal deliveries had cried (usually feebly) before the age of one minute only to be apnoeic at one minute and for a variable time afterwards. The majority of these 23 babies had cssarean or instrumental deliveries, their mothers having inhalant anaesthetics. The supervention of apncea after an initial cry may be an example of the Fink effect-hypoxia caused by rapid diffusion of volatile anaesthetic gases from the blood into the alveoli (Fink 1954). Endotracheal intubation was carried out in only 2 of these 23 babies. A high proportion of all apnceic babies had heart-rates of less than 100 per minute, and were limp, motionless, and unresponsive to catheter stimulation, but only 12% were judged to be white rather than blue. Since respiration was re-established in all but 1 of these 91 babies and since only 25 (5 normal, 20 abnormal deliveries) were intubated it is clear that low heart-rate, hypotonia, and absence of reflex movement cannot be for apncea.
analgesics, preventing
TABLE V-BABIES APNCEIC AT ONE MINUTE
(COMPLETE RECORDS)
spontaneously without resuscitation-intubation, and so on, having simply expedited the first gasp. On the other hand, in the stage of terminal apncea, one would expect that a rise in P a02 would be necessary before respiration could be initiated and that an improvement in colour would therefore precede the first breath. Moreover, while it is clear that bradycardia develops in both primary and terminal apnoea, a rising heart-rate would indicate primary apnoea and a falling heart-rate (fig. 1) would suggest the terminal type. We therefore re-examined our case-records for those in which clear statements about these two sequential changes had been made. The results are shown in table VII. In respect of the order in which colour changes and respiration took place we found information in 60 of the 91 cases (6 normal deliveries, 54 abnormal deliveries) and a note, as to
58
pulse-rate was slowing or accelerating before resuscitation, had been made in 33 records (3 normal deliveries, 30 abnormal deliveries). Two main conclusions can be drawn from table VII. Firstly, the usual sequence of events when an apnoeic newborn baby is resuscitated is for onset of respiration to precede an improvement in colour. (It should be noted that the reverse never happened in babies who had normal deliveries.) Secondly, most of the babies who became pink before breathing were intubated. This probably means that they were in secondary apnoea and therefore needed intubation, but it could be argued that some were really in primary apnoea and that while the physical stimulus of intubation had been insufficient to expedite the first gasp, expansion of the lungs and administration of oxygen by intermittent positive pressure had effectively raised Pao2. On the other hand, it seems reasonable to assume that all the babies who gasped before becoming pink were in primary apncea. It should be noted that 5 of the 18 babies who became pink before breathing were not intubated, but in each case intermittent positivepressure oxygen was supplied by face mask. In practice we regard endotracheal intubation as a more effective means of expanding the hitherto unexpanded lung. However, if the face mask is tightly applied with the cricoid cartilage firmly pressed back towards the spine, to occlude the oesophagus, intermittent, positive pressure on a small anaesthetic bag is sometimes sufficient to cause expansion
whether the
of the chest-as it
was
in these
TABLE VIII-INTERRELATION OF APNCEIC BABIES TO APGAR
cases.
SEQUENCE
It should be added
OF EVENTS IN RECOVERY OF
SCORE, HEART-RATE, AND COLOUR
AT ONE
MINUTE AND CHANGE IN HEART-RATE BEFORE RESUSCITATION
TABLE IX-RELATION OF GASPING AND PINK COLOUR TO APGAR SCORE
TABLE
X-RELATION
OF
GASPING
AND
PINK
COLOUR
TO
CHANGING
HEART-RATE
that 2 of these 13 babies who were intubated and 2 of the 5 who were resuscitated by face-mask oxygen had cried before becoming apnceic at one minute and that their lungs were presumably partly expanded. Of the 42 apnoeic babies who gasped before becoming pink, 16 had cried before one minute. Table vin shows the relation of the sequence of events in recovery to the Apgar score, the heart-rate at one minute, colour at one minute and change in heart-rate before resuscitation. (In adding up the Apgar score we have followed Dr. V. Apgar’s system except that we have necessarily had to score the first two compartments of trunk colour as 0 and the third as 2.) Of the 60 babies about whom we had information concerning the sequence of recovery three (all normal deliveries) had an Apgar score of 4 and all the rest had a score of 3 or less. Only 1 of 18 babies who became pink before breathing had an Apgar score of 3, whereas 15 out of 42 babies who gasped first had scores of 3 or 4. But it is clear that the Apgar score does not provide sufficient evidence to distinguish these two groups. There was no evident correlation between the sequence of events and trunk colour or heart-rate above and below 100 at one minute. Examination of the actual heart-rates of individual babies at one minute did not help to distinguish the two groups. In particular, in the gasp first group 3 had heart-rates of 40 and 12 others were 60 or less (total 42). On the other hand, the sequence of recovery and changes in heart-rate before resuscitation did seem to be related. In none of the babies who became pink before gasping was the heart-rate increasing in contrast to 18 out of 24 babies’s who gasped first. It should be noted that the heart-rate might be accelerating or slowing in primary apnoea but only slowing in terminal apnoea (fig. 1). These relations are shown more simply in tables ix and x. Discussion be due to intrapartum hypoxsemia, Apnoea respiratory depressant drugs administered to the mother, or head injury. If the sequence of events after experimental asphyxia of newborn animals is applicable to the human infant it is clear from our results that the majority of apnoeic newborn babies are in primary apnoea. It is doubtful if any resuscitative measures are necessary in this situation although a large variety of stimuli will initiate the first gasp. But we do not believe that the clinician can confidently distinguish, in every case of neonatal apnoea, between the primary and terminal stages in time to influence his course of action. For practical purposes we at
birth
can
59 therefore act on the assumption that all apnoeic newborn babies are in the state of terminal apnoea, and proceed to intubate. But in retrospect we are usually aware that this procedure was unnecessary since its effect has simply been to initiate the first gasp-presumably as a result of evoking Head’s paradoxical reflex, (Cross et al. 1960). Only perhaps when the heart-rate is clearly accelerating is it reasonable, having cleared the air-passages, to await spontaneous gasping. In contrast, when the heart-rate is very low or the baby is pallid, it is our practice to intubate at once without even waiting to observe possible changes in heart-rate and this accounts for gaps in the data we have collected. However, quite apart from the indications for resuscitation it is clearly of some importance to try to make a retrospective distinction between primary and terminal apnoea. On the one hand the efficacy of any new method of resuscitation should only be judged with reference to babies in terminal apncea and on the other hand, if the human infant resembles in this respect the Rhesus monkey, anoxic brain damage is only likely to be a consequence of secondary apncea (Dawes 1967). It seems clear from our investigation that babies whose heart-rates are accelerating before resuscitative measures are started and babies who respond to resuscitation by gasping before an improvement in colour are in primary apncea. On the other hand, we cannot say with confidence that babies whose hearts are slowing or those who respond to resuscitation by becoming pink before gasping are necessarily all in terminal apnoea. That the heart-rate both accelerates and slows in primary apncea has been referred to above: as regards the sequence of events of resuscitation the effect of drugs administered to the mother might be relevant. Most mothers of our apnoeic babies had received drugs which are potentially respiratory depressants, generally pethidine, and Moore and Davis (1966) have shown that in experimental asphyxia morphine prolongs the period of primary apncea at the expense of that of gasping. General anaesthesia may have the same effect, and Purves (1966) has shown that in the lamb the onset of the first breath is determined by the total sensory input. It is therefore possible that some of our babies who responded to artificial respiration by an improvement in colour before the onset of spontaneous breathing may have had their gasp reflex depressed by drugs. Of the 60 apnoeic babies about whom the relevant observations were available no less than 18 responded to artificial respiration by becoming pink before gasping and it is difficult to believe that 30% of our apnceic babies were in terminal apnoea. Nevertheless it is in this group that the efficacy of new methods of resuscitation should be tested and in this group in which careful follow up for possible brain damage is particularly important. The efficacy of endotracheal oxygenation in the resuscitation of newborn animals after the last gasp-i.e., in terminal apnoea-is beyond question (Cross et al. 1964). All the apnoeic babies in our series, except 1 who had multiple congenital abnormalities, established regular before leaving the delivery room. Besides the changes in heart-rate before resuscitation and the sequence of events on resuscitation one further point is of particular importance, whether or not the baby had gasped or cried before the supervention of apnoea. In our series nearly all such babies were clearly in primary apnoea but whatever the interpretation of this condition it is clear that initial spontaneous respiration or partial
respiration
expansion of the lungs will influence the ease with which artificial oxygenation can be achieved. Thus in this situation exposure to high or hyperbaric oxygen tensions might allow effective apnoeic oxygenation (Hutchison et al. 1963). We thank the Sir William Coxen Trust Fund for provision of facilities and equipment ; Dr. J. A. Davis for fig. 1 and advice on the preparation of the manuscript; Miss B. W. Rowles the midwifery superintendent, Sister M. Tucker, and the midwifery staff for their cooperation in this project. Figs. 1 and 2 and tables v and vI are reproduced from Pediatrics, 34, 771 (1964). Requests for reprints should be addressed to J. P. M. T. REFERENCES
Apgar, V. (1953) Curr. Res. Anesth. Analg. 32, 260. Holaday, D. A., James, L. S., Weisbrot, I. M., Berrien, C. (1958) J. Am. med. Ass. 168, 1985. Åkarrén, Y., Furstenberg, N. (1950) J. Obst. Gynœc. Br. Emp. 57, 705. Barrie, H., Cottom, D., Wilson, B. D. R. (1962) Lancet, ii, 742. Cross, K. W., Dawes, G. S., Hyman, A., Mott, J. C. (1964) ibid. ii, 560. — Klaus, M., Tooley, W. H., Weisser, K. (1960) J. Physiol., Lond. 151, —
551.
— Roberts, P. W. (1951) Br. med. J. i, 1043. Davis, J. A. (1961) J. Physiol., Lond. 155, 56P. Dawes, G. S. (1967) Foetal and Neonatal Physiology. Chicago. Fink, B. R. (1954) Acta anœsth. belg. 5, 42. Hutchison, J. H., Kerr, M. M., Williams, K. G., Hopkinson, W. I. (1963) Lancet, ii, 1019. Millen, R. S., Davies, J. (1946) Am. J. Obst. Gynec. 52, 508. Moore, W. M. O., Davis, J. A. (1966) Br. J. Anœsth. 38, 787. Purves, M. J. (1966) Paper presented to the Neonatal Society, London. Tizard, J. P. M. (1964) Pediatrics, Springfield, 34, 771.
CADAVERIC RENAL TRANSPLANTATION PRISCILLA KINCAID-SMITH M.B., B.Sc. W’srand, M.R.C.P., M.R.A.C.P., D.C.P. V. C. MARSHALL T. H. MATHEW M.B. Melb., F.R.A.C.S. M.B. Melb., M.R.A.C.P. R. B. BROWN JENNIFER EREMIN M.B. Melb. M.B. Melb., F.R.C.S., F.R.A.C.S. R. R. H. LOVELL N. JOHNSON M.S. Melb., F.R.C.S., M.D., M.Sc. Lond., F.R.A.C.S. F.R.C.P., F.R.A.C.P. D. G. MCLEISH K. F. FAIRLEY M.S. Melb., F.R.C.S., M.D. Melb., M.R.C.P., F.R.A.C.S.
F.R.A.C.P.
E. A. ALLCOCK
M. R. EWING M.B., M.Sc. Edin., F.R.C.S.E., F.R.C.S., F.R.A.C.S.,
M.S. Minn., B.D.S. Manc.,
F.D.S.R.C.S., F.R.C.S., F.R.A.C.S.
From the
F.A.C.S.
Medicine and
Departments of Surgery, University of Melbourne, and the Department of Surgical Metabolism, Royal Melbourne Hospital, Australia 20 out of 24 patients who received a cadaveric renal transplant over the past two years have satisfactory function in the grafted kidney. None of the 20 living patients received more than one graft. Stable renal function has been maintained in 5 out of 7 patients who received a graft over a year ago, and in 11 out of 14 patients who received a graft over six months ago. Patients were prepared for grafting by means of Kiil dialysis according to the methods advocated for long-term hæmodialysis. Cadaveric renal transplantation at present seems to offer a more practical solution to the treatment of chronic renal failure than recurrent hæmodialysis. Summary
Introduction THROUGHOUT the world doctors are faced with the problem of the management of terminal renal failure. Patients and their relatives are increasingly aware that a kidney transplant or an artificial kidney can take over the function of diseased kidneys.
OF EVENTS IN NEONATAL APNŒA
SEQUENCE
J. M. GUPTA M.D.
PHILIP
J.
Singapore (CLOTHWORKERS’ COMPANY) P. M. TIZARD J. M.A., B.M. Oxon., F.R.C.P., D.C.H.
NEATE RESEARCH FELLOW
PROFESSOR OF PÆDIATRICS
Nuffield Neonatal Research Unit, Institute of Child Health, Hammersmith Hospital, London W.12
From the
The state at birth of 1594 infants delivered at the Hammersmith Hospital is reported. Of 91 babies who were apnœic at one minute, 23 had cried before the onset of apnœa. On resuscitation, all but 1 left the delivery room with regular respiration. An attempt has been made to distinguish between primary and terminal apnœa in these babies. Adequate data was available in 60 cases; 42 of these were clearly in primary apnœa; the other 18 may or may not have been in terminal apnœa. The Apgar rating did not clearly distinguish between the two groups. Attention is drawn to the importance of three factors: (a) changes in heart-rate before resuscitation, (b) the sequence of events on recovery, whether gasping precedes an improvement in colour or vice versa; and (c) whether or not apnœa supervenes in a baby who has initially gasped or cried.
Summary
Introduction METHODS of resuscitation of the apnceic newborn baby have fluctuated; what is fashionable one year is out of date the next. The ready and credulous acceptance of new methods of resuscitation is understandable when one considers the course of events in experimental asphyxia of newborn animals. Whatever the asphyxiating influence or the species of animal the course of events is much the same. Fig. 1 (Davis 1961) illustrates the effect of immersion in pure nitrogen of a newborn rabbit. At first there is a period of dyspnoea lasting about half a minute. Respiration then ceases; the animal becomes limp and heart-rate and bloodpressure fall abruptly. Heart-rate and blood-pressure then rise, followed by a second decline which is slow and gradual. After several minutes of apnoea the animal gasps spontaneously for several minutes. This is followed by a second period of apnoea, the animal dying when the heart-rate and blood-pressure have fallen to zero. There are thus in experimental asphyxia two periods of apnoea, and while an animal can recover during either period, the measures needed to ensure resuscitation are very different. During the first period of apncea (primary apnoea) almost any stimulus, physical or chemical, will cause the animal to gasp, will in other words expedite the onset of the first spontaneous gasp and if the asphyxiating influence has been removed (e.g., if an atmosphere of nitrogen is replaced with oxygen or air) the animal will recover, gasps being 7506
8
July 1967
by regular respiration. Indeed in such circumstances no stimuli are necessary since spontaneous gasping will eventually take place. In terminal apncea, however, the situation is very different; no mechanical or chemical stimulation will cause gasping or any other movement, and recovery can only be brought about by increasing p a02 by artificial respiration (Cross et al. 1964). The apparent success of many widely differing methods of resuscitation-physical, such as the time-honoured slapping or rocking (Millen and Davies 1946) or phrenic-nerve stimulation (Cross and Roberts 1951), chemical, such as nikethamide or ethamivan (Barrie et al. 1962), or inefficient methods of administration of oxygen such as intragastric (Akarren and Furstenberg 1950), hyperbaric (Hutchison et al. 1963), or even simple neglect-could be readily explained if most apnceic newborn babies were in a state of primary rather than terminal apnoea. Anyone experienced in the resuscitation of the apnoeic newborn baby knows that a relatively fast rather than a slow heart-rate, cyanosis rather than pallor, and some flexural tone and spontaneous movement rather than limpness and immobility are all favourable signs. But, assuming the concept of primary and terminal apncea holds good for the apnoeic newborn baby, can one confidently distinguish between these states on clinical examination-i.e., distinguish those babies who will recover spontaneously, whatever is done, from those for whom artificial respiration is succeeded
essential ? Methods
Apgar (1953)
was
the first
to
systematise
the
recording of
heart-rate, respiration, reflex irritability, muscle tone, and colour of the newborn baby. 0, 1, or 2 points were awarded for each of these items and added together to produce a score (table i). At this hospital we have departed from her assessment in
some
not
respects and added
produce
a
single-figure
Fig. 1-Sequence of tion (Davis 1961).
events
in
two
score,
further items (fig. 2). We do believing that this may result
experimental asphyxia and
Diagrammatic representation of the aged 2-4 days.
newborn rabbits
resuscita-
response to acute anoxia in
56 TABLE I-METHOD OF SCORING IN EVALUATION OF NEWBORN
INFANT*
*
Evaluation 60 seconds after complete birth of infant (disregarding the cord and placenta). t Modified from Apgar (1953) and Apgar et al. (1958).
in
loss of information. We distinguish between pallor and cyanosis of the trunk since this may be of importance: we do not regard cyanosis of the extremities as being of great significance since this may be observed in otherwise healthy babies for twenty-four or forty-eight hours. We have coded the items " Did the baby cry before the age of one minute ", since this may be so in some babies who are apnceic at one minute and " Is the baby brown-skinned " since this adds to the difficulty of assessment of cyanosis (Tizard 1964). Most of the assessments were made by the midwifery staff with whom we held many discussions before the system was introduced and during the trial period. The clock on the resuscitation trolley (fig. 3) was started on the completion of delivery without reference to severance of the cord. The midwives were asked to make the assessment whenever possible between sixty and seventy-five seconds after complete delivery by counting the heart-rate by ausculation for fifteen seconds, the other observations either being made during or before this a
The actual heart-rate was examined in 200 consecutive normal deliveries requiring no resuscitation. The mean rate was 132; only 9 babies had heart-rates below 100 and only 2 had rates above 160. Table ill shows the numbers of babies who were in the best state in four or more of the six items (heart-rate, respiration, cry before one minute, muscle tone, response to catheter stimulation, and colour). Table IV gives a further breakdown of the 281 babies who were in the best state in five out of six items. The percentage figures give some idea of the reliability of each item as an index of asphyxia. For instance, if respiration was regular, there had been a cry before one minute, muscle tone and reflex movement were normal, and the trunk was pink, less than 0-1"had heart-rates below 100, whereas nearly 8% of these babies were blue when all the other items recorded were best.
Fig. 3-Resuscitation trolley.
shows the assessment of 91 babies who were minute. It should first be noted that in more than two-thirds of these babies the delivery was abnormal and the one-minute assessment was therefore made by one of the resident paediatricians. In rather less than a third, the apnoea was unexpected and therefore the one-minute assessment was made by the midwife. Of the 26 unexpected cases of apnoea, 1 baby had a diaphragmatic hernia and 7 had cords tightly wound round the neck. In the remaining 18 there was no obvious cause Table
apnoeic
Fig. 2-Standard form used in modified Apgar scoring.
period. We were careful not to insist that each record should be complete, believing that to insist on completion is to court inaccuracy. In this paper a distinction is made between complete records " and " incomplete records " in which one item was missing. Records have been discarded when more "
than one item was missing or when the observations were made after one minute. However, for abnormal deliveries, one of the two residents in neonatal paediatrics was always present, in case resuscitation was necessary, and the assessment of the baby was therefore made by the pxdiatrician who also wrote careful notes recording the course of events in all cases. Abnormal deliveries are defined here as premature births, abnormal presentations, fcetal distress, delivery by forceps, and cassarean section. Results deliveries with Table 11 relates to 1594 " normal or as defined records, above, and incomplete complete shows what can be expected in a population of babies with unexceptional births. It is clear that there is no real correspondence between the worst, medium, and best states in the different categories. For instance, whereas 95of all babies had a heart-rate of more than 100 at one minute only 69 °were pink (complete records). "
v
at one
TABLE II-NORMAL DELIVERIES
(STATE
AT ONE MINUTE AFTER
BIRTH)
I
i
57 TABLE III-STATE AT ONE MINUTE AFTER NORMAL DELIVERY IN BABIES
1224
(COMPLETE RECORDS)
signs of immediate danger. Of the 11 babies white 5 were intubated. Incidentally, it is clearly unprofitable to attempt to class apnoeic newborn babies into the old-fashioned categories of blue and white asphyxia (table vi).
regarded who
as
were
Sequence of Events
TABLE IV-INTERRELATION BETWEEN HEART-RATE, CRY BEFORE ONE MINUTE, RESPIRATION, MUSCLE TONE, RESPONSE TO CATHETER STIMULATION, AND COLOUR (TAKING ONE ITEM AS A VARIABLE, AND THE OTHER FIVE CONSTANT IN THE BEST
STATE)
in Neonatal Apnaa From the above results it would seem that a single clinical assessment at one minute is of little value in distinguishing between primary and terminal apnoea and therefore of little immediate prognostic significance. Apgar came to the same conclusion in respect of her score (Apgar et al. 1958). If, however, the findings in experimental asphyxia are applicable to the apnoeic newborn baby it might be possible to define the stage of apncea by following two sequences of events; firstly, changes in heart-rate before resuscitative measures are started and, secondly, the time at which colour improves in relation to the time of onset of respiration with or without active resuscitation. If resuscitative measures led to a gasp or regular respiration before an improvement in colour it would be reasonable to assume that the baby had been in the stage of primary apncea-and incidentally would have recovered TABLE VI-BABIES APNCEIC AT ONE MINUTE
(COMPLETE RECORDS)
Nearly all these mothers had been given but it is difficult to assess their role in normal onset of respiration. It is of interest that 23 of the 65 babies with abnormal deliveries had cried (usually feebly) before the age of one minute only to be apnoeic at one minute and for a variable time afterwards. The majority of these 23 babies had cssarean or instrumental deliveries, their mothers having inhalant anaesthetics. The supervention of apncea after an initial cry may be an example of the Fink effect-hypoxia caused by rapid diffusion of volatile anaesthetic gases from the blood into the alveoli (Fink 1954). Endotracheal intubation was carried out in only 2 of these 23 babies. A high proportion of all apnceic babies had heart-rates of less than 100 per minute, and were limp, motionless, and unresponsive to catheter stimulation, but only 12% were judged to be white rather than blue. Since respiration was re-established in all but 1 of these 91 babies and since only 25 (5 normal, 20 abnormal deliveries) were intubated it is clear that low heart-rate, hypotonia, and absence of reflex movement cannot be for apncea.
analgesics, preventing
TABLE V-BABIES APNCEIC AT ONE MINUTE
(COMPLETE RECORDS)
spontaneously without resuscitation-intubation, and so on, having simply expedited the first gasp. On the other hand, in the stage of terminal apncea, one would expect that a rise in P a02 would be necessary before respiration could be initiated and that an improvement in colour would therefore precede the first breath. Moreover, while it is clear that bradycardia develops in both primary and terminal apnoea, a rising heart-rate would indicate primary apnoea and a falling heart-rate (fig. 1) would suggest the terminal type. We therefore re-examined our case-records for those in which clear statements about these two sequential changes had been made. The results are shown in table VII. In respect of the order in which colour changes and respiration took place we found information in 60 of the 91 cases (6 normal deliveries, 54 abnormal deliveries) and a note, as to
58
pulse-rate was slowing or accelerating before resuscitation, had been made in 33 records (3 normal deliveries, 30 abnormal deliveries). Two main conclusions can be drawn from table VII. Firstly, the usual sequence of events when an apnoeic newborn baby is resuscitated is for onset of respiration to precede an improvement in colour. (It should be noted that the reverse never happened in babies who had normal deliveries.) Secondly, most of the babies who became pink before breathing were intubated. This probably means that they were in secondary apnoea and therefore needed intubation, but it could be argued that some were really in primary apnoea and that while the physical stimulus of intubation had been insufficient to expedite the first gasp, expansion of the lungs and administration of oxygen by intermittent positive pressure had effectively raised Pao2. On the other hand, it seems reasonable to assume that all the babies who gasped before becoming pink were in primary apncea. It should be noted that 5 of the 18 babies who became pink before breathing were not intubated, but in each case intermittent positivepressure oxygen was supplied by face mask. In practice we regard endotracheal intubation as a more effective means of expanding the hitherto unexpanded lung. However, if the face mask is tightly applied with the cricoid cartilage firmly pressed back towards the spine, to occlude the oesophagus, intermittent, positive pressure on a small anaesthetic bag is sometimes sufficient to cause expansion
whether the
of the chest-as it
was
in these
TABLE VIII-INTERRELATION OF APNCEIC BABIES TO APGAR
cases.
SEQUENCE
It should be added
OF EVENTS IN RECOVERY OF
SCORE, HEART-RATE, AND COLOUR
AT ONE
MINUTE AND CHANGE IN HEART-RATE BEFORE RESUSCITATION
TABLE IX-RELATION OF GASPING AND PINK COLOUR TO APGAR SCORE
TABLE
X-RELATION
OF
GASPING
AND
PINK
COLOUR
TO
CHANGING
HEART-RATE
that 2 of these 13 babies who were intubated and 2 of the 5 who were resuscitated by face-mask oxygen had cried before becoming apnceic at one minute and that their lungs were presumably partly expanded. Of the 42 apnoeic babies who gasped before becoming pink, 16 had cried before one minute. Table vin shows the relation of the sequence of events in recovery to the Apgar score, the heart-rate at one minute, colour at one minute and change in heart-rate before resuscitation. (In adding up the Apgar score we have followed Dr. V. Apgar’s system except that we have necessarily had to score the first two compartments of trunk colour as 0 and the third as 2.) Of the 60 babies about whom we had information concerning the sequence of recovery three (all normal deliveries) had an Apgar score of 4 and all the rest had a score of 3 or less. Only 1 of 18 babies who became pink before breathing had an Apgar score of 3, whereas 15 out of 42 babies who gasped first had scores of 3 or 4. But it is clear that the Apgar score does not provide sufficient evidence to distinguish these two groups. There was no evident correlation between the sequence of events and trunk colour or heart-rate above and below 100 at one minute. Examination of the actual heart-rates of individual babies at one minute did not help to distinguish the two groups. In particular, in the gasp first group 3 had heart-rates of 40 and 12 others were 60 or less (total 42). On the other hand, the sequence of recovery and changes in heart-rate before resuscitation did seem to be related. In none of the babies who became pink before gasping was the heart-rate increasing in contrast to 18 out of 24 babies’s who gasped first. It should be noted that the heart-rate might be accelerating or slowing in primary apnoea but only slowing in terminal apnoea (fig. 1). These relations are shown more simply in tables ix and x. Discussion be due to intrapartum hypoxsemia, Apnoea respiratory depressant drugs administered to the mother, or head injury. If the sequence of events after experimental asphyxia of newborn animals is applicable to the human infant it is clear from our results that the majority of apnoeic newborn babies are in primary apnoea. It is doubtful if any resuscitative measures are necessary in this situation although a large variety of stimuli will initiate the first gasp. But we do not believe that the clinician can confidently distinguish, in every case of neonatal apnoea, between the primary and terminal stages in time to influence his course of action. For practical purposes we at
birth
can
59 therefore act on the assumption that all apnoeic newborn babies are in the state of terminal apnoea, and proceed to intubate. But in retrospect we are usually aware that this procedure was unnecessary since its effect has simply been to initiate the first gasp-presumably as a result of evoking Head’s paradoxical reflex, (Cross et al. 1960). Only perhaps when the heart-rate is clearly accelerating is it reasonable, having cleared the air-passages, to await spontaneous gasping. In contrast, when the heart-rate is very low or the baby is pallid, it is our practice to intubate at once without even waiting to observe possible changes in heart-rate and this accounts for gaps in the data we have collected. However, quite apart from the indications for resuscitation it is clearly of some importance to try to make a retrospective distinction between primary and terminal apnoea. On the one hand the efficacy of any new method of resuscitation should only be judged with reference to babies in terminal apncea and on the other hand, if the human infant resembles in this respect the Rhesus monkey, anoxic brain damage is only likely to be a consequence of secondary apncea (Dawes 1967). It seems clear from our investigation that babies whose heart-rates are accelerating before resuscitative measures are started and babies who respond to resuscitation by gasping before an improvement in colour are in primary apncea. On the other hand, we cannot say with confidence that babies whose hearts are slowing or those who respond to resuscitation by becoming pink before gasping are necessarily all in terminal apnoea. That the heart-rate both accelerates and slows in primary apncea has been referred to above: as regards the sequence of events of resuscitation the effect of drugs administered to the mother might be relevant. Most mothers of our apnoeic babies had received drugs which are potentially respiratory depressants, generally pethidine, and Moore and Davis (1966) have shown that in experimental asphyxia morphine prolongs the period of primary apncea at the expense of that of gasping. General anaesthesia may have the same effect, and Purves (1966) has shown that in the lamb the onset of the first breath is determined by the total sensory input. It is therefore possible that some of our babies who responded to artificial respiration by an improvement in colour before the onset of spontaneous breathing may have had their gasp reflex depressed by drugs. Of the 60 apnoeic babies about whom the relevant observations were available no less than 18 responded to artificial respiration by becoming pink before gasping and it is difficult to believe that 30% of our apnceic babies were in terminal apnoea. Nevertheless it is in this group that the efficacy of new methods of resuscitation should be tested and in this group in which careful follow up for possible brain damage is particularly important. The efficacy of endotracheal oxygenation in the resuscitation of newborn animals after the last gasp-i.e., in terminal apnoea-is beyond question (Cross et al. 1964). All the apnoeic babies in our series, except 1 who had multiple congenital abnormalities, established regular before leaving the delivery room. Besides the changes in heart-rate before resuscitation and the sequence of events on resuscitation one further point is of particular importance, whether or not the baby had gasped or cried before the supervention of apnoea. In our series nearly all such babies were clearly in primary apnoea but whatever the interpretation of this condition it is clear that initial spontaneous respiration or partial
respiration
expansion of the lungs will influence the ease with which artificial oxygenation can be achieved. Thus in this situation exposure to high or hyperbaric oxygen tensions might allow effective apnoeic oxygenation (Hutchison et al. 1963). We thank the Sir William Coxen Trust Fund for provision of facilities and equipment ; Dr. J. A. Davis for fig. 1 and advice on the preparation of the manuscript; Miss B. W. Rowles the midwifery superintendent, Sister M. Tucker, and the midwifery staff for their cooperation in this project. Figs. 1 and 2 and tables v and vI are reproduced from Pediatrics, 34, 771 (1964). Requests for reprints should be addressed to J. P. M. T. REFERENCES
Apgar, V. (1953) Curr. Res. Anesth. Analg. 32, 260. Holaday, D. A., James, L. S., Weisbrot, I. M., Berrien, C. (1958) J. Am. med. Ass. 168, 1985. Åkarrén, Y., Furstenberg, N. (1950) J. Obst. Gynœc. Br. Emp. 57, 705. Barrie, H., Cottom, D., Wilson, B. D. R. (1962) Lancet, ii, 742. Cross, K. W., Dawes, G. S., Hyman, A., Mott, J. C. (1964) ibid. ii, 560. — Klaus, M., Tooley, W. H., Weisser, K. (1960) J. Physiol., Lond. 151, —
551.
— Roberts, P. W. (1951) Br. med. J. i, 1043. Davis, J. A. (1961) J. Physiol., Lond. 155, 56P. Dawes, G. S. (1967) Foetal and Neonatal Physiology. Chicago. Fink, B. R. (1954) Acta anœsth. belg. 5, 42. Hutchison, J. H., Kerr, M. M., Williams, K. G., Hopkinson, W. I. (1963) Lancet, ii, 1019. Millen, R. S., Davies, J. (1946) Am. J. Obst. Gynec. 52, 508. Moore, W. M. O., Davis, J. A. (1966) Br. J. Anœsth. 38, 787. Purves, M. J. (1966) Paper presented to the Neonatal Society, London. Tizard, J. P. M. (1964) Pediatrics, Springfield, 34, 771.
CADAVERIC RENAL TRANSPLANTATION PRISCILLA KINCAID-SMITH M.B., B.Sc. W’srand, M.R.C.P., M.R.A.C.P., D.C.P. V. C. MARSHALL T. H. MATHEW M.B. Melb., F.R.A.C.S. M.B. Melb., M.R.A.C.P. R. B. BROWN JENNIFER EREMIN M.B. Melb. M.B. Melb., F.R.C.S., F.R.A.C.S. R. R. H. LOVELL N. JOHNSON M.S. Melb., F.R.C.S., M.D., M.Sc. Lond., F.R.A.C.S. F.R.C.P., F.R.A.C.P. D. G. MCLEISH K. F. FAIRLEY M.S. Melb., F.R.C.S., M.D. Melb., M.R.C.P., F.R.A.C.S.
F.R.A.C.P.
E. A. ALLCOCK
M. R. EWING M.B., M.Sc. Edin., F.R.C.S.E., F.R.C.S., F.R.A.C.S.,
M.S. Minn., B.D.S. Manc.,
F.D.S.R.C.S., F.R.C.S., F.R.A.C.S.
From the
F.A.C.S.
Medicine and
Departments of Surgery, University of Melbourne, and the Department of Surgical Metabolism, Royal Melbourne Hospital, Australia 20 out of 24 patients who received a cadaveric renal transplant over the past two years have satisfactory function in the grafted kidney. None of the 20 living patients received more than one graft. Stable renal function has been maintained in 5 out of 7 patients who received a graft over a year ago, and in 11 out of 14 patients who received a graft over six months ago. Patients were prepared for grafting by means of Kiil dialysis according to the methods advocated for long-term hæmodialysis. Cadaveric renal transplantation at present seems to offer a more practical solution to the treatment of chronic renal failure than recurrent hæmodialysis. Summary
Introduction THROUGHOUT the world doctors are faced with the problem of the management of terminal renal failure. Patients and their relatives are increasingly aware that a kidney transplant or an artificial kidney can take over the function of diseased kidneys.