·No text on this page.

·The Metabolic Response
to Neonatal Surgery
PP RICKHAM, MS (London), F RCS, DCH
Consultant Paediatric Surgeon, Royal Liverpool Children's Hospital
and Alder Hoy Children's Hospital, Liverpool, England
Arts and Gale Lecturer
Royal College of Surgeons of England, 1956
of
Published for The Commonwealth Fund
BY HARVARD UNIVERSITY PRESS
Cambridge, Massachusetts, 1957

·No text on this page.

·To Isabella Forshall

·No text on this page.

·Preface The problems associated with the pro- and Professor N B Capon, Director of the post-operativo managemont of newborn Department of Child Health of the Uniinfants have interested me for a number of versity of Liverpool, has given me most years ars This interest was further stimulated valuable encouragement during the course by a visit to the United States, which I of the investigations undertook five years ago with the aid of DIE G Hall, Pathologist to Alder Hey a spedal fellowship from the Common Children s Hospital, has been closely conwealth Fund in New York. My studies nected with this study from its inception convinced me that the pro and post-operato its completion. He helped to draw up tive treatment of neonates was mainly the original plan of research, was largely based on clinical experience I therefore responsible for supervising the technical attempted to put our treatment on a scien side of the investigation, and has been of tific basis by Investigating the metabolic the greatest assistance in preparing this changes brought about by operation. manuscript. He specfically concerned This research was carried out on new himself with the investigation of the body born infants admitted under the care of fluids, and is responsible for that part of Miss I Forshall and myself to the Noo Chapter o describing our methods Withnatal Surgical Unit of Alder Hey Chil. out his knowledge and enthusiasın this dren's Hospital, Liverpool, under the aus. work would never have been completed. pices of the Department of Child Health. It would be impossiblo to carry out such Financial aid was provided by a grant an investigation without the help of a biofrom the Research Committee of the chemist. We have indeed been fortunate United Liverpool Hospitals In enlisting the collaboration of Mr JT I should like to thank all my colleagues, Ireland, Senior Biochemist to Alder Hey who gavo me so much of their time in help- Childrens Hospital Mr Ireland s ingenuing and advislog me during the progress of ity in modifying existing ultra micro tests for blood analysis and in devising new ones [vii] this report.

·No text on this page.

·Contents
PACT
vil
PREFACE
CHAPTER I
Introduction and Historical Notes
1
CHAPTER I
Subjects and Methods
5
CHAPTER HI
Investigation and Results
13
CHAPTER IV
General Discussion
CHAPTER V
Practical Applications
72
APPENDEK
81
MIBLIOGRAPHY
83
[b]

·No text on this page.

·CHAPTER Introduction and Historical Notes Neonatal surgery, one of the nowest branches paratively crude. In 1839 the Alsatian choma of general surgery, has made great advances ist ] -B Boussingault had carried out the first during the last twenty years - mainly under scientifically accurate metabollo study The the impetus of the studies conducted in Bog. "patient" thus analysed for the benefit of ton by Professors Ladd and Gross (1841) future generations was a lactating cow and, The fact that the operative mortality - Onco significantly, the results of the investigation forbiddingly high-has gradually fallen can were recorded, not in a medical or veterinary not be ascribed to improvements in the actual publication, but in a surgical journal. Meanforgical technique, as there have been few while, Justus von Liebig's studies in organic technical advances during the last ten years. chomistry had led him to recognize the proc- It should be crodited, rather, to more ef ess of metabolism which he defined as "tho ficient pro- and post-operative management. sum of chemical changes of materials wder Until recently pro- and post-operativo treat the influence of living cells” (Liebig, 1842) ment of neonates has been largely empirical. This definition has nover been improved Since the normal physiology of nowborn in upon fants is as yet little indorstood and there is Throughout the nineteenth century the considerable disagreement among the author obvious metabolic responses produced by Itles about oven such a fundamental problem cholera stimulated scentio interest in the us the function of the kidney during the new preciso nature of the changes. As early as born perlod, it is not surpristng that fow data 1831, W B O'Shaughnessy, a British meditare available on the noonatal response to cal practitioner reported the fundamental rurgery observation that cholera deprives the body of Tho large amount of research carried out water and chlorides and suggested that roduring the last fow docades on motabolic covery from the disease was facilitated by the reactions of older children and adults some restoration of water and salt. O'Shaugh ttmas obscuros the fact that much of the fun Detry s observatons led another British docdamental experimentation was accomplished tor, Thomas Latta, to effect an encouraging during the nineteenth century even though improvement in an elderly cholera patient by the methods of pathological and blochemical administering the maline solution Intra investigation avallable at that timo were com venously, rather than orally In 1850 a Ger [1]

·No text on this page.

·INTRODUCTION AND HISTORICAL NOTES dangerous than those that occur in the later practical, and especially a financial, impossiuge groups. This view is supported by the billity fact that, if certain procautions are taken, Therefore two considerations must be kept these Infants stand extensive operations ex in mind. One is that the number of cases fotraordinarily well vestigated is probably too small to bo statisti- By undertaldog this research we hopod to cally significant. For this reason it must be ovalve & pre- and post-operativo régime clearly understood that in discussing the robased on laboratory as well as clinical evi sults of our experiments and in trying to do dence, and also to throw somo light on tho duce some generalizations, our report deals way in which neonates differ from adults in only with trends and cannot be dogmatic their metabolic response to surgery To fa about any single finding The other consider alltato comparison, wo consciously modelled ation concerns the fact that many surgeons our studies and the presentation of our results have Deither the facilities nor the time to on the report on the metabollo response of perform extensive metabolic studies on their adults to surgery published in 1952 by Moore patients. Throughout our investigations we and Ball were aware that wless our studies helped At the outset of our study we wero handi us to evolve a pre- and post-operative régimo capped by the lack of precedents. At first that was as satisfactory from the clinical as We encountered many technical difficulties from the laboratory point of viow, wo had, at and theso were only gradually overcome The best, been engaged in an academic exercise. procedures that we finally found most satis In the last chapter of this report we have factory for our purposes are described in therefore attempted to correlate the labora- Chapter 1L Bocause these ultra micro meth tory findings with the clinical opinions and ods are time-consuming and the supervision bave described the pre- and post-operative of the infants during the studies must be régimo that seems indicated. motículous, we were ablo to observe only Whilst we have studied in detail only nine nino casos over a period of nearly three years pationts during our metabolic investigations, Tho study of thero nine cases entalled over our clinical experience over a five-year period 8,500 chemical analyses, and although somo comprises more than three hundred conatos of tho standard tests have been greatly simpli suffering from urgent surgical conditions. As filed by the invention of the flame photometer & result of the pro- and post-operative régime (Barnes ot al, 1945), it was difficult to fit this established in accordance with the findings extra work into the laboratory routine of a of our study, the mortality for major surgical busy hospital. In the United States special procedures on neonatos fell from 76 per cent motabollo research laboratories have been rot in 1940 (Rickham, 1952) to about 25 per up for this purpose. Even #0 we noted that cont in 1952, and is still falling The mortality Moore and Ball and their aumerous collabo rato for neonates with fntestinal obstruction rators required three yean to study thirty alono has fallen from 78 per cent fa 1949 to adult cases - by far the largest stady yet at 28 percent in 1952 (Fonhall and Rickham, tempted. Most other detalled metabolic in 1953) Although perfection of the anaes vestigations, especially those concernod with thenia used for neonatal rurgery is undoubt- Infanta, deal with only a few cases - oftom do odly pertly responsible, we are convinced more than two or three. It is difficult to sco that the chief cause of the decrease in opora how this situation could be remedied unless tve mortality has been the improvement of armies of fuvestigators could be raised - a pro and post-operative management. It is [3]

·No text on this page.

·CHAPTER II Subjects and Methods SELECTION OF PATIENTS Infants studied by us was therefore grossly All the patients studied in this investiga premature, the smallest (Esther O) weightion wero admitted to the Noonatal Surgical ing 1902 gm. However, metabolic studies Uolt at Alder Hey Children s Hospital, carriod out by other investigators on pre- Liverpool mature babies and certain clinical impressions of our owa do make it possiblo to discuss Ago some aspects of the premature infants met All patients were under four weeks of age. abolic response to surgery Most of them were only a fow days old. On Sex the basis of clinical caporience we had formed the opinion that there is a distinct With one exception (Esther O) the pa difference in response to major surgical pro tients have been boys This selection was cedures between infants a fow days old and made because of the great difficulty in colthose over two weeks old. We therefore in lecting all urine passed by baby girls without duded threo Infants three weeks old in this resort to continuous catheterisation. favestigation fin order to compare the labora Type of Cases tory data. The patients were selected according to Prematurity the following criteria Since tho metabolism of prematuro infants 1 To study the effect of operativo trauma has been the subject of many studies during alone, on Infants who had been fed prorecent years, it would have been of great operatively and whose fluid and electro- Interest to investigate the metabolic response lyto balances were undisturbod -le, a of such Infants to surgical procedures. We asion of tumours from otherwise normal felt, howover that the added risk of pro babies (3 cases) maturity to infants undergoing extensive 2 To study the effoct of operative trawda operations made it inadvisable to carry out upon bables who had had do previous our studies on infants of this age group, as fluid and food intako and had had do abany further intaferen.co with them might normal losses - Le, operations on infants turn the scales against survival. None of the with oesophageal atresla (2 casos) [8]

·No text on this page.

·16-17 2 1 MICUNE 2. (right) To facilitato the collection of foecos tho ffant is mured on a rubber sheet throughout the period of Investigation. Urloo is collected in a storllo bottle as shown Wound diecharge is mhailmlzod by sealing the opening with plastio glue. Vomiting to provented by coothnous guirlo niction. Intra verous infudon is given by way of a scalp veln tho needlo betog fixed to the scalp with plaster of Parks. FICURE 1 (loft) Alessuring burette of 50 ml capacity (accurate to 1 ml) which brouttely employed for all neonates recetvtag intravenous Infusion

·No text on this page.

·1 boogid od A tut acth * SUBJECTS AND METHODS was eventually found that lost 20.5 gm of water bourly per square meter i shart length of Panls colostomy tubing, of body surface. Darrow (1948) estimated 'which can be wbtained in a variety of di that the imperceptiblo water loss from lungs motors could bospulled over any size of and skin was '44 gm for every 100 calories porta, food with amapping, and comectod to metabolized, and Darrow et al. (1948) comi receiving bottleThis mothod is practically puted that this water loss in Infants was bofootproof, and 'ua nont place of tubing is tween 50 and 100 ml per kg of body weight. applied each day, there is no loak and the in Pointing out that infants lose a lot of insen fants aktaidoes not bocomo, inflamed (Ed. sible water becauso of the relatively largo mund1980), surface area of their bodies, Butler and Tal- Tour Vomiting is very common in in bot (1944) computed that the daily loss of fants with murgical conditions, but collection an infant weighing from 2 to 10 kg would of the vomitms, presento e dificult problem. range from 75 to 300 gm. Thoy also statod In order to provent vomiting, infants oper that the insensible water loss increases by atod upon for intestinal obstruction were 100 per cent after operation. On the other However, if the baby vomited in curately the insensible water loss of nowborn spite of all procetitions, the nurso immedi Infants nursed at a constant temperature of ately pocked up the vomitus with pipettes 31° C. in a supersaturated atmosphere of and stored it in glass containers to the re water mist - Le under conditions identical frigerators no materials were used which with those of the incubators in which our could absorb the spilled fluid, it was combabies wero nurod. Under these circumaparatively easy to suck up thoʻvomitus from stances, the daily total insensible water loss the baby's skin or the rubber sheeting was 18.8 gm per kg of body weight, 3.8 gm Urine, fuoces, and aspirations were stored represented water lost from the lungs and In the refrigerator and pooled every twenty- 10 gm water lost from the body surface. This total was not quite half the amount of in- WOTNO BOCHARGE. To provent discharge, sensible water lost by bables nursed in room tho wounds were sealed off with a quick afr As Darrow pointed out in 1850 the only drying cestio plastic glue (Portex) Wo thus way to provent inaccuracies due to insensible circumvented tho difficulty that other investit water loss in metabolic balance studies on malori had experienced in collecting wound Infants is to nurse them at a constant temper discharge from absorptive dressings ature of 80° to 820 p in an atmosphere of DIZALI WATDA LOS Losses of water and constant high humidity Happíly, our routino doctrolytes through the abdn are hard to do method of nursing Doonates post-operatively termine with any accuracy and have there in Incubators closely follows the criteria laid foro boem ignored in many balanco studies. down by Darrow Water losses can be estimated to a certain In discussing the loss of clootrolytes extent from the wolght changes, but the loss through the skin Conn (1949) estimated that can only be measured with sweat contains between 15 and 60 mog of great dificulty (Gamblé et al, 1951) Burch sodium chloride per litre. However, the and Winsor (1945) found that adult males podium chlorido content of infants sweat is much lower than adults (Cooko et al, 1950) There was con escoption. The world of Cowo corered by abecepttrodroming vod a certain amount An infant weighing 2.5 kg loses only 0.21 mm of wood lakapo occurred. of chlorido per day (SWANSON and Iob, 1833) four hours for analysis . of electrolytes 172

·No text on this page.

·SUBJECTS AND METHODS with 0.2 ml of the ono-In-ten plasma di function of noonates undergoing opera Intion. The final back Hitration was tions Wo used the stain Introduced by carried out with a 0.5 ml micro-buretto Randolph (1949), Phlodne and moth- (Agla micromoter syringe) ylene blue dissolved in equal parts of 7 Plarma sodium and potassium were esti propylene glycol and water, for countmated by flamo photometry, using 0.2 m) Ing the posinophils in the chamber and 1.0 ml, respectively of the one-in Eosinophil counts in normal newborn ton plaçana dilation Infants vary widely According to Klela and Hanson (1950), the range for 80 in 8 The plasma carbon dioxide mturation fants on the first day of lifo was 78 to capadty was determined with a micro manometric gasometer of the Natalsom 288, the range for 33 Infants on the sec type (1851), using 003 ml of plasma. ond day of life was 75 to 1,100, and the 9 The lower layer of plasma and the upper average range for these two days was 350 + 47 and 420 = 43, respectively layer of calls were drawn off by a Pasteur pipette and used to determine blood Estimation of Body Fhalds urea concentration (from 005 to 01 ml, Although dotermination of the metabolic according to the amount available) by direct nesaderization of protein freo il balance during the post-operativo period was trate after incubating with urease (micro the primary object of our buvestigation, we modification of King. 1951) thought that pro-operativo date on the plasma, atra-cellular fluid, and total body water 10 The remaining cells were then packod volumes would also be weful. Techniques by spinning for half an hour at 3,000 that would be applicable to capillary blood Ip.m The rest of the plasma and the samples were therefore elaborated, but as wo whole top layer of cells were then drawn considered that they carried somo risk to the off and used to increase the amount avail infants, they were not performod in all cases, able for urea estimation (itern 9 above) nor did wo repeat them in the post-operativo The lower layer of packed cells was then drawn up to the mark in a 0.2 ml pipette, justifiable to subject normal infants to mmperiod. Furthermore, we did not consider it the outside of the pipette carefully wipod, and the cells opellod fnto 1.8 ml of nocessary manipulations in order to obtain control velaes For these reasons the deterglass-distillod water After ten minutes the tube was spun and the supernatant minations of plasma, atre-cellular fluid, and fluid transferred to a clean dry tubo. Ali total body water volumes, although of conalderablo interest, are not submitted as an quots of the ono-in-ten dilution of calls were then used (after further dilution Integral part of the investigation. The techwhere necessary) to determine the soniques that wo employod aro described below dium, chlorido, and potassium contents of cells by methods stmilar to those do BLOOD VOLUIE. Estimation of plasma vol talled above, uno has been commonly carried out with T.1894 (Evans Bluo) Other dyes such as 11 Tho hacmoglobin content of the wholo Vial Red (Kalth et al, 1015) and more blood was estimated with a M.R.C grey wedge photometer (Klog et al., 1948) recently Blue Geigy 538 (Welss et al. 1959) have also been used, but their efficacy is not 12. Eosinophil counts were made in order yet generally accopted. to study the changes in adreno-corticoid A micro version of the Evans Bluo method [9]

·No text on this page.

·1 SUBJECTS AND METHODS fuld volume. Wo used the thiosulphate toch oured solution containing 004 gm of NAAP nique of Cardozo and Edelman (1852), was injected by similar tochnique over a modified as follows minute period. Tho drip was run at a madmu rate of 5 ml per hour durtag the ensuing A sterilo 10 per cent solution of sodium 6 bours, and heparinized capillary blood samthiosulphate containiog a Hitlo Evans Blue was prepared. Approximately 4.5 ml of this ples were taken at 3, 4%, and 8 hours. Using 0.2 ml fostead of 2 ml plasma samples, wo solution was introduced through the drip tube, in a manner similar to that described analysed these by the techniqoo of Brodio ot al (1951) above, as soon as tho second fontanello sam plo had been taken. Tho actual amount in- The results obtained by the above threo fected was dotermined by weighing the syrtechniques were corrected for the amounts inge and poedle before and after injection, of fluid injected and removed during the tests and also weighing an accurately measured A good basis for comparison was afforded volume of the solution. The latter was used by the extensive studies of Friis-Hansen and to mako op the standard solutions required his colleagues Using deutorlum ouide and in the subsequent analysis of plasma spoci antipyring, Friis Hansen et al (1951) found mens. The coloured thiosulphate solution was that the total body water of premature and full term neonates was between 70.2 and 83 infoctod at a steady rate, over a period of about 10 minutes, and then fushed through per cent of the total body wedght, and Edal with 2 or 3 ml of glucote water The addod man ot al. (1952) determined that the prodye indicated when the polythene tube was portion was 76 7 cent. The summo investi par clear of the thiosulphato solution Flvo capil gators found a relationship of 121 L/m belary blood samplos of hepartatzed blood were tweon total body water and body sufaca. taken at 10-minute latervals over a period of 20 to 70 minutes after the start of the injec- PRESENTATION AND CHARTING Hon TOTAL BODT WATER VOLUME. This can be Balance Charts measured elther by isotopo dlution (F D Accurate balance data were compiled in Moore, 1946, Schloerb ot ch 1950) or by in tabular form, but have not boen Included in travenous infection of antipyrino (Davies, the present report. Whilst these data are the 1837) Antipyrine is, howovor pot considered wat results of our investigations, they are to be an ideal agent for the measurenent dificult to comprehend and to visualizo. A of total body water, as it is bound to plasma much more comprehensible, although slightly proteins to the atent of about 10 per cent. less accurate, representation can be achieved N-acetyl-4-amino-antpyrine (NAAP) was by graphic moans (see Charts 1-0) found by Brodie and Arelrod (1850) to bo Numerous methods of chartlog have been distributed in the tissues in proportion to tused by different investigators. We have used thefr water content, being noguglbly bound a slight modification of the method described to proteins and not metabolized to any ap by Moore and Ball (1952) not only because prodablo degree. This substance wes used this method served our purposes well but also by Brodio et al. (1951) La estimating the because the pattern of our research closely totul body water, and we adopted their follorved that of the Boston investigators, mothods with somo modifications. although concerned with Dowborn infants A few minutes after the completion of the rather than adult patients thiosulphate injection 2 ml of a sterile, cal The daily nitrogen, chloride, sodium, and [11] ·п ·CHAPTER III Investigation and Results Introductory Note CASE 1 (GEORGE 8 ) History As stated in Chapter I tho patlents studied in this investigation were admitted to the Neo 23rd May 1953 DATE OF BIRTH natal Surgical Unit at Aldes Hoy Childrens 23rd May 1953 ADMITTED TO THE NEONATAL Hospital, Liverpool SURGICAL UNIT Throughout thelr stay in the hospital, the WEIGHT 2,016 gm. Infants war nursed in incubators in which DIAGNOSIS Exomphalos. tho oxygen content of the atmosphere was kept at 50 per cent, the humidity at 100 per EXALONATTON The infants general condicont, and the temperaturo at 85°F One Infant Hon was satisfactory Hydration was ado- (Caso 6) was nursed at a temperature of quata. A loop of intestino could bo soen 90°F During operation the infants were not through the thin membrano covering the protected against heat loss in any way, and comphalos (diam. about 1 in.) Tholr body tomperaturo often dropped quito 94h May 1953 OPERATION (Hmo 1 hour) considerably They were returned to the in The exomphalos was found to contain a cubator immediately after operation. largo Meckel's diverticulum, which was Antibiotic therapy was routinely trstituted resected. baforo operation. In cach caso penicillin 25th May 1853 The childs condition was (250 000 units daily) and streptomycin (150 very good. Intravenous infusion was dismg delly) were given parenteraly Cases 4 continued, and oral feeding with glucose and 7 received additional antibiotic therapy salino was started. Gastric fiction stopped. An intravenous infusion was set up pro 28th May 1853 Condition stationary: fced operatively, and, oxcopt In Cases 4 and 5 contimuous gastric suction was started pre-operi ing with half-strength milk mituro started. tively to provent vomiting, 27th May 1953 Finst milk stools passed. In each case, sedation was accomplished 28th May 1853 Feeding with full-strength by atropine (1/400 g), and anaesthesia mtuturo started. Antibiotic stoppod. was toduced by ondotracheal administration 31# day 1953 Child very well, stitches reof oxygen and nitrous oxide, with minimal moved cther Sucdnylcholine was given intravo 13th Juno 1958. Child very well and gaining nously satisfactorily, discharged home [ 18 ] ·r ·INVESTIGATION AND RESULTS of kooping newborn infants cool during oper over, be added that tho Leonates in Thomsons etlom (300 Chapter iv, p 68) No artificial study had, on the whole, a lower floid fatako methods of cooling were employed, but we than the baby under discusion. did not tako precautions against loss of heat, Except on the second day, when only about by the use of clothing, blankots, hot water per cont of the fluid intako was retalnod, bottles, etc. the percentage of water retainod was rather WEICHT The birth weight was slightly bo greater than the normal values given by low average and dropped by 100 gm after Thomson. Thereafter, the amount of water operation. It then remained practically steady, retained remained fairly constant, between and during the fint week after operation 200 and 340 ml. This would explain the abthere was a net gain of 58 gm. This is Intern sence of the usual post natal drop to weight. estlog in vlow of the fact that most infants CALORIES. Tho calorio latako rosa steadily lose between 5 and 10 per cent of their weight from around 20 calories on the first day to during the first Ave days of lifo (Yomg otal, roughly 200 calories from the fifth day on 1950) wards. This calorio intako was somewhat LOSINOPHIL COUNT On the day of opera lower than the 80 calories per Hilogram of Hon the cosinophill count was 297/mm., body weight usually allowed for full term which is within normal limits. Following oper babies (Smith, 1951), but it wu adequate atlon tho coumt dropped steadily until the for the imunediate post-operative period. stath day of the study, when a slight rise NITROGEN BALANCE During the first two occurred. On the seventh and eighth days days of our study the nitrogen intake was nil values below 50/mm' were recorded. The de The nitrogen output was very small on the creado continued while the child was making first day but was greatly increased during an interrupted recovery the second day – 520 mg being excreted, FLUD DALANCE. The fluid intako, rising 425 mg to the urine. The urinary nitrogen from 128 ml on the first day to 480 ml on the concentration was 354 mg per cent. This con Bfth day, was more than adequato for a child centration was considerably higher than that less than one week old Practically tho whole found dumg the following week but sul fluid intako on the first day and 42 ml of the below the average (orceeding 700 ml per latake on the socond day consisted of intra cent) found in normal infants urine at similar venously infusod 5 per cent głucose cline Ages (Barlow and McCanco, 1948) The low Tho urinary output was only 7 ml on the day concentration during the following week can of operation - almost all the water being ro bo explained by the relatively largo fluid outtained. It is difficult to decide whether the put. very low urinary output should be attributed As stated above, a relatively large amount to primary water rotention, which Lo Queste of nitrogen pas excreted on the second day (18514, b) observed post-operatively in to spite of a zero intake. From then onwards, adults, or to the fact that infants secreto very with increasing Intake, the positive balance little during the first few days of life - 20 ml becamo rapidly larger From the fifth day on being given by Thomson (1844) as an aver wards, roughly between 700 and 1,000 mg of ago for the first two days. The urinary and nitrogen were retained each day- or from hence the total Auld output vas within not. 230 to 330 mg per kg of body weight, which mal limits, except during the first three days Is considerably higher then the daily average after operation, when it was rather higher of 160 mg per kg of body weight retained by than the value recorded for normal full-teran breast fed infants during the first month of infants by Thomson (1944) It must, how lfo (Beach et al, 1941) Accordlag to Moore [15]

·No text on this page.

·PLAMA ALKALI HAVE AND QILORIDI: INVESTIGATION AND RESULTS and Hoffman et al. (1949), for premature bonate for premature infants to be 188 babies, noticed a retention of potassium meq/L. - Youmg et al (1941) found that the greatly in acess of that required for the chlorido level in premature mfants between formation of normal tissues Wallace (1952) 8 and 18 days old was 109 meq/I, and Dar estimated the K N ratio in normal infants to row (1946) found that it might rise to a be between 41 and 6,8 meq/gm. maximum of 114 mea I, unless the infants were fed with sodium bicarbonate. Blood Studios (Tabło 1) The plasma alkali reservo in the infant under discussion was slightly below the flg LEVEL Throughout the whole period of ob ures quoted above As has been noted before servation, the alkali reserve was remarkably (Hoffman ot al, 1949), there was no clinical low There was a steady increase in the evidence of acidosis. The infant was very acldosis after operation and only on the ixth well and apparently thriving. The addosis day was thero a slight upward trend of the and hyperchloraemia subsided very slowly, curve. As was to be expectod, the plasma but blood tests performed three months later chlorido lovel was very high, except on the showed that the blood chemistry had ro- Afth and slath days, when it was below turned to normal. There is little doubt that normal the acidosis was produced by retention of It has been known for somo time that chloride in excess of sodium, as in cases normal infants often develop acidosis with previously reported by Darrow (1948) high plasma chloride lovels Branning (1942) PLASMA SODIUM AND POTASSIUM LEVELS The reported the average level of plasma bicar plasma sodium concentrations were well Tablo 1. Blood, Body Flulds, and Other Data 14 03 23.5 - 42 18 20 27 16.7 104 188 8.8 03 Day Hb-gm % Hct. % cells Blood urea mg % Palk. rer. meq/L P a meg P No mog/L P Imoql P prot. gmn * Coll N, gm % Cela mogli Cell Nameq/L Cell K meq/l Weight (gm) Eot po mm PV (ml) ECF (ml) TBW (ml) 22.0 64.3 50 13.3 107 144 4.7 6.5 9.1 6:0 2227 84.1 n Tich 100 23.1 20.8 18.8 19.5 19.2 68.1 641 18.2 587 34 32 36 34 35 13.5 117 117 13 13 6 14 116 118 89 853 1097 134 152 144 123 180 143 158 0.7 6.1 8.0 54 61 70 0.85 60 5.65 8 85 8.2 90 7.8 7.5 10.2 104 548 40.8 647 790 49.2 23.2 187 24.8 22.0 31.3 90.5 79 0 800 79.8 895 79.5 2,820 4,824 2,840 2,839 2,839 2,809 2,876 2,863 200 107 138 34 43 5.3 5 78 60 - - 2,916 297 1 [17]

·No text on this page.

·para + - t 1 + KATAL SURGICAL UNIT INVESTIGATION AND RESULTS CASE'S (CHRISTOPHER B) Balance Study (Chart I and Tablo 3) History This study was undertaken in order to in 21 October 1953 DATE OF BIRTH vestigate the metabolic response of an Infant Ulth Nooomber 1959 ADMITTD TO THE NED undergoing operation for cystic hygroma at the age of about three weeks. Shortly after birth the infant had been given blood trans- WLIGHT 3,880 gm. faslons to counteract anaemia resulting from MAQNOOTS Cystic hygroma of right awlla. haemorrhagic disease, but prior to operation HISTORY The child was bom by a difficult he had been well for over two weeks and forceps delivery He muffered from her steadily gaining wolght on adequate milk morhagic disease of the newborn and bad feeds As the hygroma was very large, been treatod with vitamin K and blood the operation was of considerable magnitude transfusions A swelling in the right axilla and resulted in a blood loss of over 70 ml. wau noticed at birth and had since in Convalescence was rapid and successful. creased in size TEMPERATURE. The temperature was not KAMINATION Tho infants general condi mal, caccept on the third day, when there was Hon and colour were good. The haemo a slight pyrarla, but this rapidly subsided. globln concentration was 10 9 gm per cent. WMGHT The patient was a big baby Thero There was a very large, cystic, multilocular was a weight loss of over 250 gm on the first swelling over the right dde of the chest, post-operative day The tumour contained a extending to the right axilla and the right farge amount of Auid, which could not be side of the Dock adequately measured during operation, and 14th November 1953 OPERATION (timo 1 its removal was undoubtedly the main causo hour, 30 minutes) When the hygroma was of weight loss. Unfortunately, becauso of ditrectod out, it was found to catend undersome leakage from the wound, it was impose Death the right pectoralis major and minor, sible to weigh the infant without dressings, which had to be divided. The tumour was except on the fourth day and on the day fol closely adherent to the adllary vessels and lowing cessation of the study had to be dissected off the vessels and EOSINOPHIL COUNT Tho eosinophill count 15th Novombor 1953 The child's general conwas much higher Initially than in Case I It ditlon was good. The intravenous Infusion dropped to practically zero two days after and gastric suction were discontinued and operation and then gradually roso to a lovel above the pro-operative figure. The responso oral feeding with glucose water, and later closely resembled that reported for adults with balf-strongth milk mixture, WAS following operative trauma (Laragh and started Almy, 1948) 18th Nooember 1959 Some oedema was FLUID BALANCE. The fluid intake was adonoted over the right deltoid and a pressure quate, throughout the investigation, 268 mi dressing was applied. Feeding with full of fluid were given intravenously during tho strongth milk mixture was startod. Ant first day 78 ml during the second day Tho urinary output was high, oven on the day of 25th November 1953 Wormd healed, stitches oporation, and the size of tho positive fuld removed balanco was very similar to that found in 3rd December 1953 Chid very well, dis Case I, who was considerably younger and charged home smaller [ 10 ] nerver blotics stopped

·No text on this page.

·t INVESTIGATION AND RESULTS, values were about the amo as those expected THE IN RATIO During the first two days, *t normal babies. On the fifth and sixth days, when the nitrogon and potassium balances the sodium balances were almost zero The were both Degativo, the IN ratio was 7.2 absenco of early sodium retention and the meq/gm, which was considerably in excess relatively small late retention wero unusual, of the K N ratio associated with breakdown but similar atypical findings have been to of loan muscle tissue. Here again the values ported for adults (Moore and Ball, 1952) differed from those fomed in Case 1 and resambled those found in adults. Because tho POTASSIUM MALANCE. It was in the potassium balance that Caxo 2 differed most obviously two balances had different signs from the from Case 1 In spite of the high potassfum third day onwards, it was impossiblo to cal Intake, the balance was continuously and culate the K N ratio for the succeoding dayı markedly negative throughout the six days of the study, except on tho third day, when a Blood Studios (Tablo :) minimal positivo balance accompanied a very PLASMA CHLORIDE AND SODIUM LEVELS. These large intake. The infant therefore closely resembled an adult undergoing atensive surg were more or less normal and showed only ry In tho absence of vomiting and diarrhoea insignificant changes. the potassium losses were truly formidable. PLASMA POTASSIUM LEVELS The plasina po- Surprisingly, tho faecal losses were nearly as tanium concentrations showed wide variagreat as the urloary losses. Hons. Twice, on the third and Afth days, Tablo 2. Blood, Body Fluids, and Other Data 1 54 od 74 D Hh. go Het % 12 11.5 14.9 11.2 11.8 11.8 128 ܝܠܐܗ. 82.8 85.8 30.9 857 38.2 38.0 16 60 40 13 40 22 21.5 204 191 23.1 25.0 104 1025 104 98 83.6 98.8 149 140 141 186 130 188 8 6 47 87 7 8.5 8.95 8.9 6.76 6.8 8.75 1.76 57 4.9 Blood ure mg % P nik res, meqſt P a meal P Ne mog/L P I nogl P prot. ga % Call N go % Call a meg. Cell No megl Col Imag Weight (go) Eos per mm PV (ml) ECF (ml) TBW (ml) 75 70 049 1 48.4 48.4 48.4 12 17 19 10 18 33 90 08.7 89.8 73.8 92.8 3,880 857 3,821 8,832 248 16 849 858 249 1,625 2,955 [21]

·No text on this page.

·1 INVESTIGATION AND RESULTS, lod of potassium depletion would pro Balance Study (Chart 3 md Tabl. 8) ably have been followed by potassium It was thought that the difference in the ntion to mako up for post-operative losses. metabolic response between Case I and Case anum low accompended by sodium gain 2 might have been due, not to tho difference found in the red blood corpuscles. In ago, but to the fact that the magnitude of the chloride and sodium balances wero the operation to Case 2 was much greater 1er atypical, as the early retention was than in Case 1 Consequently, it was do ent and late retention was not very dided to favestigate the metabolic responso kod to surgery of another three-wook-old infant, his infant, then, showed nitrogen and who required a comparatively minor operatrolyte balances as well as an eosinophil ton. As Case 3 had only a small meningocele, ponse rather different from those found with a narrow stalk and no neurological in Case 1 and very similar to those found in volvement, the operation could be scheduled It patients. for a convenient time. He was therefore a good subject for this study He stood the CASE & JOAN D) operation well, and convalescence was un- Istory eventful. h August 1954 DATE OF BIRTH TELPERATUAL The temperaturo remained h Soptomber 1854 ADMITTED TO THE NEO slightly below normal during the whole period KATAL SUBCICAL UNIT of observation. There were no wldo varla- EFMHT 3,774 gm. tons. DIAGNOSIS Memingocolo. WEIGHT Tho patient was a big baby There EXAMINATION Tho child's general condi was a welght drop of 80 gm on tho second Hon was good. A small, lumbar meningo day, which could not be accounted for by celo, with a very thin manbrano cover the amount of tissue removed, which weighed Ing it, was noted. There was no paralysis only 18 gm. As a considerable amount of and no hydrocophalus water was retained during the first day, the th Soptember 1954 OPERATION (timo 35 weight loss must have boon mainly due to minutes) When the meningocelo was or Hissuo breakdown. On the basis of Lusks clsed it was found to have only a very (1908) coefficient (38 gm of whole tissuo DANTOW communication with tho sploal equals 1 gm of nitrogen), the amount of protheca. The narrow stalk was ligated. Post teln tissuo lost was in the neighbourhood of operatively tho fotravenous infusion and 10 gm. The rest of the tissue broken down gastrio ruction wore discontinuod and oral was presumably fat. By the third day the feeding with glucose water was started. weight loss had been mado good, and be ith Septembor 1954 The child's condition tween the second day and seventh day thero was very good. Oral fooding with milk mis was an over all weight gain of more than tures was started. In order to provont any vomiting, the stomach was aspirated beforo POSINOPHIL COUNT On the first day the each feeding oosinophil count was unusually low for a Tho chid continued to make a satisfactory baby of three weeks, but, as discussed before, recovery during the not fow days. there edst wide individual variations. The la Septomber 1954 Wound healed, stitches count dropped to a very low lovel on the secremoved. Antibiotics stopped. ond day After a sharp riso on the third day, 5th September 1854 Chid discharged home. It altemately rose and fell but never reached [ 23 ] 130 gm.

·2
མ
Tomme
**PINAWEZVOLD"
mo

·PLASMA ALKALI RISCRVI AND CHLORIDE AND INVESTIGATION AND RESULTS and acrotion were high, thero was consid was therefore impossible to calculate the arable retention. K N ratio on a daily basis. The over all po- POTASIUM BALANCE. As in Case, the po tasdum and nitrogen balances during the testum scretion was very high In spite of last ste day were positive, and tho K N nato considerable Intake of potegloon the balance for this period was very low, approdmately was nogative except on the second and sixth 09 days During the seven-day period of obser vation only about 8 meg of potassium were Blood Studies (Tablo 3) retained. (In other words, there was a marked potasslum excretion in spite of a very high SODIUM LEVELS These were slightly clovated potassium intako, nearly 80 per cent of the on the first day but remained more or less potassium loss Occurring in the urine ) The normal during the rest of the study minimal potassium retention took place in PLASMA POTASSIUM LEVEL. This remained the presence of a high nitrogen retention, within high normal limits. about 75 gm of nitrogen being retained dur OTHER BLOOD INVESTIGATIONS Theso werd ing the same period. within normal limits for a threo-weak-old THE X N RATTO During the short negative infant phaso on the day of operation, when no nitro BODY GLUDThe estimated plasma volume gen or potassium was given, the K N ratio was 269.5 ml, but this figure is probably in was 9.3 mol/gm-a igure greatly in excess accurate, as ft would correspond to 114 ml of that found in lean muscle tissue During of blood per kg of body weight. The extra the remainder of the period the two daily callular fhuid volume was 1,543 mi, or 40.9 balances usually had different signs, and it per cent of the body weight, and the total Tablo 3 Blood, Body Fluids, and Other Data I och 169 183 40 . 14.5 408 13.5 407 40.9 15.3 40.8 3:0 19.8 100 129 20 6 81 8 18 92.7 IOLS 130 4.9 6.63 105.1 03.6 Day Hb gm % Kct. % cells Blood uron mg % Palk, red, meg L p a meq/L P Na moq/L P K megL P prot. gm % Cell N. ym % Cell a mogl Call Na mogli Cell Kmeq/ Weight (go) Eos, par mm PV (ml) ECF (ml) TBWV (ml) 12.6 121 32 21.2 102.5 132 4.8 015 1 79 133 24 24.6 112.1 147 50 6.05 1.89 51.2 18 805 9774 147 2895 1,513 2,820 27 16.8 101 190 4.9 8.85 1.89 574 25.5 B41 3,788 100 sd 13 1 43.5 52 21.5 102.9 132 4.7 0.2 1 75 KOO 21 89 8,798 139 49 59 1 76 577 22 80 3,844 574 83 83 52 04 1.81 801 21 80 6.25 1.85 5.1 23 822 3,828 63 31 80 3,883 3,819 59 - [23]

·No text on this page.

·TAUP F Stiga WEIGHT A. 2000 2000 POST MORTE DAVINATION 2010 02. 100 200 INVESTIGATION AND RESULTS #th March 1959 Messivo collapse of the right assumed that such a continuous low body lung occuorod. The right bronchus was temperaturo has some influence upon mo- Fucked out and the lung ro-opended. An tabolism. It is, of course, known that the intravenous infusion was set up. basal motabolic rate and the tissue oxygen 7th March 1853 Another tension pneumo requirements are diminished when the body thorax developod, and an intercostal drain tarperature is lowered, but the effect of was inserted into the right pleural cavity these conditions upon the nitrogen and elec- 8th March 1953 The infants condition was trolyte balances have, as yet, not been fully satisfactory Tho intravenous infusion was Investigated. discontinuod. Peniallin and streptomycin WACHT The birth weight of just over 2,700 were discontinued. Aureomycin (20 mg) gm was considerably below average, although was given orally every six hours 9th March 1953 Oral feeding with glucose water was begun. Howover, the child had a sudden attack of cyanosis and dyspnoea. Resuscitation was of no avail, and the infant died soon after There was found to be a leak from the oesophageal anastomosis, widespread bilateral bronchopneumonla with an early bilateral empyema was noted. CAUSE OF DEATH Bronchopneumonia. FLUID ML 100 Balance Study (Chart 4 mod Tablo 4) This study was undertaken to order to in vestigate the metabolic response of a now CAL bora Infant undergoing an extensive chest operation for oesophageal atresia. There had been no fluld or food intako prior to admis slon. In additon, tho baby had had some resptratory distress before the study commenced. The initial post-operative period was satisfactory, but a modlastinal leak de A MED veloped which finally led to the infants death six days after operation. TERPERATURE. Throughout the investiga gation the temperaturo was subnormal, its lowest point being 90° F during operation. Ha WLED A subnormal body temperaturo in neonates undergoing surgery has been given a grave prognosis by some surgeons (Santull, 1854) It is, however, ou impression that youg in K KLET fants, like yotg animals, wually stand low body temperatures very well Indeed (see also Churchill-Davidson et al, 1959) It must be Chart Metabollo Balance Data [27] 0 -100 100 0 BOO to XL 0 -500L 1000 07.3 79 10 ..2 0 15 6.45 10 F n. 0 3 ore TION 1 2 5 ·一 ·INVESTIGATION AND RESULTS first four days, the differenco fin the potassium comparable age. It must be remembered that balance being mainly due to varying amounts the patient received no milk feeds. of potassium excretod in the stools. PLASMA SODIUM AND CHLORIDE LEVELS Tho THEY N RATIO During the soven-day period curves ran parallel, rising above normal on tho K N ratio was 2.78 meq/gm, which is the third day when the balance of these lons very close to the figuro for loan muscle tissue. and water was negative, then dropping bo- This suggests that during the operative and low normal on the fifth day at the time of post-operative period the infant lost potas mardmum chloride, sodium, and water reten sum at a rate corresponding to the break Hon, and finally rising again to normal levels down of Hssue protein The high post-opera at the time of death. (The autopsy blood Hvo KN ratio found in adults and older samplo was taken by means of cardiac ventri children was not reachod. Excessive potascular puncture a few minutes after the child slum loss did not occur, in spite of the very diod.) ostanstvo, long, and shock producing surgical procedure and fatal post-operative complica PLASMA POTASSIUM LEVAL In general tho tions. curve followed the remo trend as the sodium curvo. it dropped below normal on the sixth Blood Studios (Tablo 4) day PLASMA ALKALI ARSERVE This was slightly OTHER BLOOD INVESTIGATIONS The blood lower than the normal range for Infants of urea rose steadily, except for a slight drop on Tablo 4 Blood, Body Fluids, and Other Data Dey 13 3n KA P.M 21.4 24.6 72.1 48 20.05 74.9 24.8 68.6 77 64 89 04.2 104 22.0 83.2 37 10.5 103 13.0 8.2 160 109 171 108 141 6.8 16.4 103 130 17 6 94 149 128 6.9 54 8.0 22.7 71.4 74 180 02 125 4.7 6.5 5.99 67 1.5 88.8 2,801.5 119 0.8 нь. gm % Het. % calls Blood urca mg % p alk. ros moq P a moq 1 P Ne mog/L P I meals P prot gm % Call N gm % Cel a meg Cell Ne meg Call Kmeg Weight (go) Eos per mm PV (ml) ECF (ml) TBW (ml) 8.9 6 0.3 104 137 8.8 6.35 5.98 68 7.8 5.02 00 8.0 4.94 54 49 41 57.5 8.17 75 2 16 83.8 2 848 15 823 2,482 19 93.1 82_5 2,758.75 176 85.8 - 40 28 ( 29 )

·No text on this page.

·100 N00 Doo INVESTIGATION AND RESULTS foods wall. There was some infoction of 100 the wound, and the infants lips and left TEX "F cyo were inflemed. His penis had bocome mflamed from the continuous also of strep MESUT ping to fix the rubber tube for collecting trine. Hh Nooombor 1953 Tho infants general condition was good. There was still some skin infection. The motabolic balance expert E02. ment was stopped la Decembor 1959 Tho Infant had been gatning steadily, and the wound had healed well. Although x ray examination with bart om swallow did not show & stricture at the FULD site of tho anastomosis, there was a slight ML temporary hold up of the feeds at the anastomotic site. The child was discharged homo. BOO 400 200 100 0 200 100 CAL 0 LEDO 1000 un 100 0 10 19 10 0 3 12.07 0 Balanoo Study (Chart 5 and Tablo 5) This study was undertaken in order to fovestigate tho metabolic response of a non born infant who was operated upon for NHC oesophageal atresia. There wero certain dif ferences between this case and the proceding ono. The infant under discussion was prematuro and was admitted when four days A MER old, during which time he did not havo any fuld or electrolyte intake. Clinically he was dehydrated, but not to a marked degree Although the pro-operative conditions were He MED therefore not favourable, this infant mado ad uninterruptod recovery TEMPERATURE. The temperature remained normal or slightly below normal almost to I oreaktion the end of the investigation, which had to be K HER discontinued because the infant doveloped multiple small skin infections. WEZIT The birth weight was reputed to Chart & Metabolio Balance Data be 5 lb, 6 oz (2,440 gm) On admission the baby weighed 2,382 gm. Post-operatively bo gained steadily and weighed 2009 gm on the mm) Unfortunately, no count was perclighth day of the study formed before operation. Whilst the child EOSINOPHIL. COUNT Tho post-operative ea was rapidly recovering the count fall consinophill count was surprisingly high (834/- timously On tho dghth day It was 88/mon ( 31 ) 10 6- 0 132 T DAY! 1 2

·No text on this page.

·INVESTIGATION AND RESULTS Infants over a three-day period (Hoffman et gard as normal for an infant of the prematuro al., 1949) age group THE IN RATTO During the first two days, PLASMA SODIUM AND POTASSIUM LEVELS. The when the nitrogen and potassiun balances plasma sodium lovel, like the chloride lovel, were both negative, the N ratio was 2.28 showed a post-operative rise. On the sixth m0q/gm. Again we see that this corresponds day the concentration fell to 125 meq, from to the K N ratio of lean muscle tissuo. Later the soventh day onwards it remained at 127 on, rotention of potassiun was marked, meq The potassium remained constantly bo whereas the nitrogen balance was nearly tween 5 05 and 53 meq/L, which is slightly zero Potassium retention is difficult to a higher than the range we have come to regard plain, in the absence of previous excessive as normal for premature infants. potassium loss, but it also occurs in premature OTHER BLOOD INVESTIGATIONS The blood infants who have not undergone operations urer was over 120 mg per cent at the begin (Hoffman et al., 1949) ning of the study With increasing hydration it fell to normal levels. There was a slight Blood Studios (Tablo 5) upward trend on tho eighth day, without any PLASMA ALCALI RESERVE AND SODIUM AND apparent cause. CHLORIDE LEVELS. The alali reserve rose to The plasma protein concentration was also 198 moq on the fourth day and tho plasma continuously above normal. chloride level to 110 me on the third day; The haematocrit and bacmoglobin lovels, thereafter both settled down to what we ro on the other hand, remained constantly be Tablo 3 Blood, Body Fluids, and Other Data Day & 02 la 19.2 18.3 198 157 48.8 130 10.3 110 145 3.1 14.8 461 84 IKO 85 407 40 19.1 147 401 50 171 97 127 90.0 14.8 5.9 110 19.8 103 137 51 0.9 5.04 79 72 191 8:8 127 5.3 5.0 46.0 100 17.1 08 133 5.07 72 8.32 125 Hb gm 46 Hot. % cells Blood uron mg% P neresmoq/L Pameq/L P Ne moq P moq/L P prot go Call N gm % Call a meal Coll Nameque Cell Kmet Welght (g) Eo per mom PV (ml) ECF (ml) TBW (ml) 5.07 167 105 134 605 0.9 776 08.7 54 84 2,382 81 94 5.2 127 6.3 3.9 5.08 6.6 60 67 8.79 87 35 43.5 64 43 824 52 77 71.6 80 91 1 60 73.7 2,498 789 115 4,150 834 2,569 117 639 2,599 88 188 244 820 1,538 1 - [33]

·No text on this page.

·z 2 1 INVESTIGATION AND RESULTS teristic features of a Mongol. She appeared stenosis at the ampulla of Vater The dooto be mildly dehydrated. There was somo deno-jejunostomy was patent and thore opigustrlo distension and visible peristalsis was no leak. Somo fatty degeneration of was noted. X ray examination of the abdo the liver was noted and the mucose over mon (with the child held in the upright the tdgono of the bladder was hacmorposition) showed typical duodenal ob thagia. struction. An indwelling catheter was CAUSE OF DEATH Pneumonia and premapessed into the bladder turity 37# January 1953 OPERATION (time 1 hour, 50 minutes) The abdomen was opened Balance Study (Chart 8 and Tablo 6) through a transverse supra umbilical t This study was undertaken in order to indision. There was a small amount of free vestigate the motabolic response of a properitoneal fluid. Duodenal stenosis was mature Infant undergoing a severo operation found and a duodeno-jejunostomy was two days after birth. As the infant sufferod performed from high intestinal obstruction, in addition la Fobruary 1953 The chillds condition was to having been starved, she had lost a consatisfactory siderable quantity of fluid and electrolytes And Fobruary 1953 The intravenous infusion by coplous vomiting during the two days be was stopped and oral foeding with glucose foro operation. Although her condition was water was started. fair immediately after operation, sho soon Srd February 1953 Tho child s general con doveloped bronchopnoumonia, from which diton remained atisfactory There was she died somo hacmaturla. Feoding with half As has been mentionod before, this patient strength Ostermilk no. 1 was started. was the only girl to our series and she was a 5th Fobruary 1853 Tho child s general com Mongol. Whilst we believe that the fact that dition was unchanged. There was some she was a Mongol had little, if any, Influence regurgitation of feeds and continued has upon her metabolic response, it must be maturla. added that, in our experience, such babies die oth Pobruary 1859 The child had some res very frequently during the post-operativo piratory distress and her general condition perlod, as they seem to be particularly sushad deteriorated. Haematula and regurgi coptiblo to bronchopneumonia. Esther O tation of feeds continued. An intravenous was no exception in this rosport, she had tho additional disadvantage of being six weeks 7th February 1953 Tho child's condition pramature. was very poor, she was cold and limp She TEMPERATURE The temperature was perdiod in the afternoon. ristently subnormal, swinging betwoen 840 POST MORTZA DIAMIRATION The laryns, and 88° F In our experience, this low body trachea, and bronchl were found to con tamperature is the rule with premature babies tain blood-stalood, frothy material. Both after operation. pleural cavities containod an excess of WEICHT The infants birth weight was rofuld and both lungs showed diffuse areas of consolidation. There was an excess of puted to bo 4 lb, 10 oz. (2,091 gm) On adblood-stained fluid in the peritoneal cavity mission her weight was slightly over 1,900 Tho stomach and the proximal part of the gm. In spite of tho fact that her condition duodau were dilated. There was . was rapidly deterforatiog durtag the postoperative period, sho steaddy galnod weight [85] Infusion was set up.

·No text on this page.

·No text on this page.

·No text on this page.

·1 INVESTIGATION AND RESULTS foods. There was gradually increasing ab both lungs and an early bilateral empyerna dominal distension. were found. The pharynı, oesophagus, FLAMINATION The child s general condi and stomach showed multiple ulcerations. Hon wu stisfactory Hydration was ado The other intra abdominal organs appeared quate. X ray examination of the abdomen normal and the operation site was soundly (with the child held to the upright post healod thon) showed multiple fuld lovels in the CAUSE OF DEATH Septicaenia. small intestine. X ray cxamination with bertum enama showed typical Hirsch Balance Study (Chart 7 and Tablo 7) sprungs disease the grossly dilated colon In this study wo lavestigated the motabolio narrowod suddenly at the functure of the response to surgery of a newborn infant sufdescending and dgmold sections of tho fering from low intestinal obstruction. Uncolon. like Case 6, this infant was a full term baby 7th May 1953 OPLBATTON (thmo 2 hours, 35 As the obstruction was in the large intestino, mloutes) The abdomen was opened the child had vomited only small amounts through a transverse infra ambilical Instprior to admission and there wero no clinical sion. The splenic flexure, the descending signs of dehydration. There was, howover, and sigmoid sections of the colon, and the gross abdominal distension, and although roctum were mobilizod and a pull through this distension was, in the main, due to gas, recto-sigmoidectomy was performed. there must have boon somo accumulation of 8th May 1853 No bowel sounds. Urino fluid in tho tntestino. passed. Although the child stood the very attenslye 9th May 1853 Mocontum passed operation quite well, he subsequently devel 10th May 1959 The child looked pale. His oped septic complications from which he tongue was swollen, and there was bleed died. Maximal trauma and maximal posttng from the mouth. Dodoma of the scalp operative stress therefore, were involved in and the extremities was noted. No bowel this case. sounds were heard. TEMPERATURE. Except on tho first day, Ulth May 1953 Tho child's condition was when there was a slight elevation, the tem poor His abdomen was distended but soft. peraturo was normal or slightly subnormal, No bowel sounds were heard. There was in spite of the septicaemia. In this respect generalized oedoms. There was bloedlog the patient differed from the prematuro in from the mouth, and blood appeared in fant with high intestinal obstruction disthe urine. It was decided to discontinuo cussed proviously penicillin and streptomycin. Terramycin WEICHT The birth weight was reputed to (50 mg) was given intramuscularly overy six bo 7% lb (3,402 gm), but as in the previous hours 19th day 1853; The child's condition was cases, the accuracy of the birth weight is somowhat doubtful. On admission, the child very poor Ho suddenly collapsed and weighed 3150 gm. After operation he was given intravenous fluids continuously until POST MORTO ALIINATION There was his death, and it was therefore impossible to pepticucmia, presumably secondary to a weigh him again. septic pyelophlebitis of the right internal saphenous vefn, which had been used for EOSINOPHIL COUNT The eosinophil levels the first transfusion. Multiple abscesses in was extremely low throughout the period of investigation the lowest were reached the [59] died.

·No text on this page.

·INVESTIGATION AND RESULTS considerably higher than the potassium con ma chloride concentration was also above centration found in adult intestinal contents normal, acept on the fourth day during lleus (Lesser and Pareira, 1953) PLASMA BODY AND POTASSION LUSS In THE IN RATIO The KN ratio for the general, these mfrrored the chloride curves. whole period of investigation was 288 But whilst the odlum curve continued to rise meq/gm. This means that the potassium on the sixth day, the potassium lovel remained lose was not excessive, even though the bal below normal. Ance remained nogative and even though OTHER BLOOD INVESTIGATIONS. Blood uroa, the child had vomited pre-oporatively for plasma protein, and hromatocrit levels were three days, was subjected to sovere operative abovo normal at the beginning of the investi stress, and died of its after-effects. gation, but the two latter curves fall below normal during the later part of the study Blood Studies (Tablo 7) BODY FLUIDS On the first day the plasme valume was 178 ml With a haematocrit LIVEL. The plasma alkali reserve was con reading of 49 per cent, the blood volume was Hnuously above normal. The initial alkalosis calculated to amount to 310 ml, or 88 4 ml was not surprising in view of the fact that the per kg of body weight Figures for extra child had vomited pro-operatively During cellular fluid volume were not obtained for the post-operative period of continuous gastrio suction, the aspirated material con The total body water volume was 2,016 ml, sisted mainly of mucus, the content of baso or over 60 per cent of the body weight. This slightly aceeding that of chlorido. The plas- Agure, which is below the normal range for PLAVA ALKALI BATERY AND CHLOHLS this patient Table 7 Blood, Body Fluids, and Other Data 1. 10.3 14.5 16.0 60.8 17.8 45 0 49 38 34.7 43 21.0 14.6 49.85 56 18.9 101 68 23.8 103.5 141 21.0 21.8 110 145 2.1 128 136 17.8 57 41 23.8 111 158 8.9 77 4.6 674 360 100 114 141 34 40 Dey Hb. gm % Hct. % cells Blood uron mg % P ak res, meq/L P a meg P Na meq/L P Kmoq P prot gm % Cell No gm % Call a moql Call Na meg/L celli meq/L Wdght (gr) Eos. per PV (mal) ECF (ml) TBW (ml) 5.8 8.7 3.0 50 4.15 70.2 88.0 81.0 6.1 4.5 717 88.0 51.0 56 59.9 59.9 23.2 100 3,150 39 5.85 519 250 94.3 40.0 87 0 11 29 82 12 35 178 2016 [ 41 ]

·No text on this page.

·INVESTIGATION AND RESULTS the last twenty four hours the vomitas hed vomited for prolonged periods and were bocomo bilo-stained. markedly dehydrated. Our patient also dif- BLAMINATION Tho child's general condi fered in that he had a low intestinal obstruc- Hon was fair He was moderately dehy Hon duo to an intussusception, a very rare drated. His abdomen was distendod. X cause of obstruction in the neonatal age ray examination showed multiple fuld group (Koop 1853) levels in the small intestine. There was no TELIPERATURE. This showed little variation. air in the large intestino. It was slightly below normal during the tm- 29th January 1954 OPERATION (timo 40 min mediate post-operative period. utes) Tho abdomen was opened through a WEIGHT The infant weighed 2,426 gm on transverse supra unablical incision The admission. By the third day, the welght had johumum and illum were found to be di fallon to 2,209 gm it rose to 2,574 gm on the lated. There was a small lico-ileal intus fourth day and then romafned roughly ste soscoption, which was easily reduced. Honary 30th January 1954 No bowel sounds. No EOSINOPHIL COUNT Unfortunately, a prostool passed operative count was not taken. On the sec- 31st January 1954 Numeroas bowel sounds ond day the count was very low indeed. It were heard. Intravenous infusion and gas rose to over 400/mm on the fourth day tric ruction were discontinued and oral Slight drops occurrOd on the fifth and stxth feeding with glucose water was started. days, coinciding with some Inflammation of The infant passed a watery stool the wound. 1st February 1954 Feeding with full-strength FLUID BALANCE. The patients fluid intako milk mbituro startod. during the first four days was roughly half 4th February 1954 Wound edges slightly in the amount theoretically required for a child flamed. of his age. Dortog the first two days all fulds 7th February 1854 The Infant was taking were given intravenously From the fifth day feeds well and gaining, wowd was healed. onwards there was an adequate fuid intake. Antblotics stopped. The fluid output was somewhat diminished 9th February 1954 Discharged homo. during the first two days, especially on the second day It then ramainod roughly con- Balanco Stady (Chart 8 and Tablo 8) stant mull the last day of the study when an This study was undertaken in order to ob Increased intake was accompaniod by a reserve the effect of an operation for intestinal duced output. The relatively largo positive obstruction upon an infant twenty five days flwd balance during the last four days may old - Lo., considerably older than the two have indicatod a certain amount of dehydrapatlcats suffering from intestinal obstruction tion during the earlier periods of the investidescribed in Cases 6 and 7 In the present gation. case it is quite possible that the obstruction CALORIES. Tho caloric intake was inado did not becomo complete until the last day, quate during the first four days, but later it when the patient started to vomit bllo. On approached 80 calories per kg of body weight. admission the baby's goneral condition was NITROGEN BALANCE. When the nitrogen in quite good, and ho was only mildly dehy take was nil and the output stall, the balanco drated. In this respoct he differed from the was negative. As soon as milk was given, tho two infants of similar ago studied by Danow nitrogen balance became positive although skil et al (1850), us these patients had the output Increased. During the last four [ 49 ]

·No text on this page.

·ܝܙ ( INVESTIGATION AND RESULTS Blood Studios (Table 8) loric stenosis but were at variance with our PLASMA ALKALINLAYS AND CHLORIDE LEYA. findings for the two younger Infants with fn- Tho plasma alkall reservo was slightly abovo testinal obstruction (Cases 6 and 7) normal at the start of the observation and tho OTHER BLOOD INVESTIGATION! Blood urea chloride concentration slightly below normal. and plasma protein concentrations were par This might well have been caused by premal" The haematocrit and haemoglobin operativo vomiting Later on, the alkali re levels were lower than in the preceding cases, servo quickly fell to normal, thero was marked as would be expected, considering the age chloride retention, and the plasma chlorido of the patient. Neither of these findings was lovel rose considerably suggestive of marked dehydration, which is PLASMA SODIUM AND POTASSIUM LEVELS. Tho somewhat surprising in view of the history plasma sodium curve showed the same trend of pre-operativo vomiting and the low fluid as the chlorido curvo, starting below normal intako during tho early post-operative period. and gredoally reaching a normal lovel dur CELL ELECTROLITE LEVELS. Tho red cell Ing the second part of the investigation. The chloride content was normal, acopt during mane configuration can be observed when the last two days, when it was slightly instudying the plasma potassium curve. The creased. hypokalsamic indings in the early post- The cell sodium loval was persistently operativo perlod (eg, 2.6 meq/L on the above normal but remained more or less con third day) resemblod those reported by stant. The cell potassium lovel was especially Danowski et al (1950) for infants with py low on the first day and, as in the proceding Tablo 8. Blood, Body Fluids, and Other Data LX n 5. ou To 154 12.8 11.5 11.8 18 409 13 88.8 389 99.2 120 41 4 24 21.7 17 12.8 40.0 28 18.9 89 1 128 24 91.1 93.1 193 26 11.2 404 28 174 1109 188 1000 180 174 102.5 131 2.9 US De Hbgm % Het. % cells Blood uren mg % P all. res. mog/L P a moql P Na moq/L P K mogL P prot go % Coll N. m % Call a mel Call Na noql Call Kmeq/L Weight (gr) Eos. par mm PV (ml) ECF (m) TBWV (m) 8,8 50 03.1 191 84 5.8 57 52.6 88.2 677 2,428 17 174 1043 128 20 4.7 5.7 577 39.6 790 2,374 402 3.0 6.8 3.1 83.0 29.8 81.3 49 1.8 S. 17.3 115.9 139 4.3 5.8 18 68.1 80.8 91.2 2,338.5 803 537 36.8 78.7 2,200 181 K4 3.9 701 484 844 2,380 518 3.7 240 83.0 2,342 245 - 83 1 2,353 183 87 [45] - K

·No text on this page.

·T nu INVESTIGATION AND RESULTS And February 1954 Tho intravenous infu- - 13th February 1954 No more totany The sfon was continued. Oral feeding was tried child was taking foods well. Caldum glu- Again, but had to be discontinued because conate was given intramuscularly of vomiting X ray examination of the ab 18h Fobruary 1954 The child was well and domen showed do afr beyond the duode taking his feeds well. There was slight rogurgitation. Intravenous infusion stopped. End February 1954 SECOND OPERATION ( time 18th February 1954 The child s general con 1 boor) When the abdomoon was 18 dition was good. A blood transfusion was opened, the anastomosis was found to be glvon. intact, but the bowel was kinked and ob SUBSEQUENT COURSE The child's general structed by numerous adhesions The ad conditori remained satlsfactory, but he dobesions were divided and the gut was veloped an obstructive Jaundico A third straightened. operation was performed on 15th March 3rd February 1954 The intravenous infusion 1854 to raliove the faundice At operation was continuod. Bllo-stained fluid was con It was found that the common bilo duct Hinuously asptrated from the stomech. was obstructed by numerous fibrous ad- 4th February 1954 There were numerous hesions. A cholecysto-duodenostomy was bowel sounds, the bowel openod. The in performod Following this operation the travenous infusion was discontinuod and jaundice quickly disappeared. The child oral feeding with glucose water was started. improved steadily and was discharged on 5th February 1954 Considerablo quantities 29th March 1954. of bilo-stained flod were again aspirated from the stomach. The intravenous Infu Balance Study (Chart 9 and Tablo 9) sion was sot up again. Tho study was undertaken for order to ob- 6th February 1954 Only small amounts of servo the motabolic response of another influid wero aspirated from the stomach. The fant operatod upon for Intestinal obstruction Intravenous Infusion was stopped and oral a fow days after birth. After an apparently feeding with dillutod milk mixture was satisfactory recovery, the child again de begun. veloped a mechanical obstruction on the third 7th February 1854 There was still some post-operative day vomiting The feedings were increased. Treatment by gastric suction and intre 8th Pobruory 1954 No change child still venous infusion was of no avail, and a second vomiting Stomach was washed out. operation had to be performed ive days after 9th Februory 1954 General condition im the first, in order to relieve this obstruction proved, no vomiting Antibiotics stopped. The infants condition was fair before the 10th February 1954 Again copious vomiting. first operation but poor before the second Oral feeding was contnued but stomach was aspirated periodically The metabolic study was continued. It Dow Uth February 1954 The child had repeated doveloped into a study of the effects of ro tetanic convulsions. An intravenous infu pested operativo trauma opon a newborn slom was started again and ammonium infant Following the second operation there chlorido was given intravenously doveloped a period of lotestna) Deus necesi 12th February 1954 The child had further tating prolonged gastric suction and intra attacks of tetany More ammonium chlo ride was given intravenously venous therapy Even when oral feeding was commenced, the infants general condition did [ 471 one.

·No text on this page.

·INVESTIGATION AND RESULTS not mprove, and, to our surprise, he devel slight fluctuation during the rest of the taves opod severe metabolic disturbances culmi Hgation period. nating in attacks of tetany lasting for nearly EOSINOPHILL COUNT Unfortunately, no cosin forty-eight hours after milk feeds had boon ophil counts were performed during the first started. As the child's life was endangerod, three days The count was 252./mm on the we attempted to relieve the attacks by in fourth day and 211 mm on the fifth day By travenous ammonium chloride. In spite of the soventh post-operative day (two days many technical difficulties, we wero able to after the socond operation) tho count dropped continue our balance studies throughout this to 100/mm' and, scept for a slight rise on period, until the baby s clinical condition and the following day, did not rise above blood chemistry had ceased to give cause for 100/mm' during the rest of the camination andety Altogether, we proceeded with tho period. In studying adult patients Moore balance studies for nineteen days and were (1850) reported that the eosinophils usually thus able to record the metabolic changes fol decreased after a second operation, provided lowing repeated trauma, as well as electrolyte it took place within ten days of the first oper deplotion of great severity ation. Hence it was not surpristag to find a In retrospoct, it may soom surprising that low count for our patient while he was still this child should have survived tho ordeal. under stress from the second operation. The Tho case gave further proof, if proof were noteworthy point in the record was that tho needed, of the astonishing stamina of now cormt remained low during the last four days, born infants. It also provided us with a mass when the child was showing clinical signs of of most useful data. The Infants subsequent rocovery dovelopment of faundice, which had to be FLOID BALANCE. In view of the fact that the treated by yot a third operation, did not ma chid had vomited copiously prior to admisterially affect our study as the faundice did sion, the fluid intako was toadequate during not appear until after the investigation had the first four days From then onwards, the been completed. intake was adequate Although small oral TEMPERATURE. In general, the temperature foods were occasionally given, intravenous Wus normal ar slightly subnormal. On the day infusions were used almost exclusively for six after the first operation and, later, at the days on the seventh post-operative day (two time when convulsions occurred the tempera days after the second operation) oral feeds turo was slightly elovatod. were tried - the stomach being suckod out WEICUT Tho infant was said to have before feods. However as most of the fluid weighed 8 lb, 11 oz (9,024 gm) at birth. On was recovered by aspiration, wo returned to Admission he weighed 27105 gm. Since bis intravenous infusion on the eighth day Milk general condition was fair, it seems strange feods at half strength were started on the that he should have lost such an appreciable ninth day During the period of lovestigation amount of welght in so short a time, and the three blood transfusions and Avo plasma Inaccuracy of the initial weighing may be fusions were administered. On the eighth day doubted. Ho was not weighed again until tho wo gave somo N/2 maline instead of the usual day of the second operation (four days after N/5, and on the fourteenth and fifteenth days the first operation), when a gain of over 100 M/B ammonium chlorido solution was fogm was recorded. Within tvo days of the soc fused. ond operation the weight had dropped almost Urinary output was low throughout tho to tho 2,500 gm marh, where it remained with period of observation, and at times (on the [ 49 ]

·No text on this page.

·INVESTIGATION AND RESULTS in the gastrio aspirations. From tho ninth day workers found that, in adults suffertag from awards, when adequate amounts of potas- lleus, large quantities of fluid and electrolytes slum were given in the milk, the balance was accumulated in the gut and were temporarily positivo oncept on the eighth day Potassium lost to the body Progressive alkalosis in our retention was, however, never very markod patient could therefore be eaplained if the und did not excood the values for normal in milk feeds remained either partially or wholly fants of the samol age. During this period pooled in tho coils of the intestine. some potassium was still lost in the aspira On the fourteenth and fifteenth days, when Homs. the alkalosis was at its height and the child THE I N RATIO During the first elght days, was suffering from totany, we tried to romody when the balances were negative, the KN the condition by infusing M/8 ammonium ratio was 87 mog/gm - l.e., considerably in chloride -- Doriadis, Goldfinch, Holt ances of the K N ratio of lean muscle tissue. (1953) having usod this method in treating Lo Querde (1854a) stated that the K N ratio Infants suffering from alkalosis due to vomitshould be calculated from the relativo con ing in pylorio stenosis. centrations of potassium and nitrogen in the Assuming that two-thirds of the body urlno. When calculatfog tho urinary K N ratio weight was water, Forbes and Ergantan during the flost eight days, we arrived at a (1946) had calculated that I ml of M/8 am value of 4.5 moq/gm. It seems to us, however, monium chloride per kg of body weight that when dgnificant losses are occurring by should lower the plasma alkall reserve by 0.25 routes other than the renal - In this case the moq/L. On the basis of Gambles assumption gastro-intestinal tract – they should be taken (1951) that the extracellular fuld volume is into account equivalent to 25 por cent of the body weight, From the eloventh day onwards the nitro Dordadis et al (1853) calculated that I ml of gen and potassium balances were both posi M/B ammonium chlorido per kg of body tve. The over-all positive balance showed & weight should be oquivalent to 0 67 moq/L K N ratio of 37 meq/gm. Rather surprisingly of alkali reserve. It would seem, howover, that this ratio was only slightly above the ratio for this valuo was too high in vlow of the demon lean muscle tissue. It is possible that complete stration by Deane ot oL (1852) that ono-third potassium restitution bed not occurred by the of the total body chloride is intra-cellular If timo our studios wero terminated. the calculation is correctod for this factor Blood Studies (Tablo 9) 1 ml of M/B ammonlum chlorido per kg of body weight should be equivalent to O 45 meq/L of alkali reserve. Actually, Darladis LEVEL Tho excessive chlorido loss in the gas and his co-workers found that for overy ml tric aspirations produced a steadily increas of M/8 ammonium chloride per kg of body ing alllosis. Even after milk feeds had com weight which they infused, the alkali reserve menced and chlorido retention had become fell by 0 43 meq/L marked, tho alkalon's remained and the plas Basing our procedure on their calculations, ma chloride level continued to drop At the wo Injected 50 ml of M/8 ammonium chlo- Hmd we were at a loss to explain this condi tion. We think now that the explanation may rildo intravenously on the fourteenth day Much to our surprise, the alkall reservo fell lio to the existence of a third Auld spacó only about 1 moq/l. On the following day described by Randall (1852) and Kreiger we therefore Injected 59 ml of M/6 ama al. (1854) As mentioned before, these monlum chloride, but the alloall PLASILA ALYALI ASEAVE AND CHLORIDE

·No text on this page.

·INVESTIGATION AND RESULTS dropped only about 2 meq/L. It is difficult mal until the last two days, when it roso above to aplain the difference between the re the normal level. The call sodium concentra sponse found in our patient and that found tion was above normal throughout the wholo in the infants described by Doriedis et al. period and roso to very high lovels on the (1853) It might bo explained partly by the seventh and eighth days. The cell potasshum fact that in new born infants the extra-cellu concentration was normal at the start It was lar fuld space is not 25 per cent of the body very low between the sixth and eighth days weight, as they assumed, but over 40 per cent and the rose gradually towards the normal Flane et al, 1947), and partly by our pa level at the end of the period of observation. tients inability to convert the injected am The Inverse relationship of cell sodium and mooia quickly into ures, as we still found cell potassium was again clearly shown. free ammanla in the plasma two days after the intravenous infusion. The final fall in the Summary and Discussion akali reserve on the edghteenth and nine In this study we were able to observe a teenth days may have been partly due to the delayed action of the infected ammonlum very young Infants metabolic response to rochloride, but were more likely due to absorp peated surgical trauma. The child not only Han of chlorides from the intestine. vomited copious amounts prior to admission, but his Auld and electrolyte stores were fur PLASMA, SODIUM AND POTASSIUL LEVELS The plasma sodium concentration was low at ther depleted by gastric aspiration over a tho beginning of the study rose on the third long period. In order to determine whether post-operative day and then fall gradually, such a gross depletion of electrolytes, and paralled to the chloride concentration curve, especially of potassium, would bring about a until it dropped to 115 meq/L between the potassium shift, do solutions containing potastouth and the thirteenth day It then rose slum were given intravenously, with the ex quickly to tho normal value on the nineteenth ception of the mall blood and plasma transday fusions containing a little potassium. Under Tho plasma potassium concentration rethis prolonged maximal stress, which was mained nearly normal until the fourth post much fu ccess of anything a newborn Infant operativo day with the onset of the intestinal had ever been subjected to in our practice, obstruction which necessitated the second thoro developed a gross alkalosis culminating operation, it rapidly dropped to the hypoin tetany and a degree of hypokalaemla The kalaemic lovel of just over 2 meq/L on the data in this case are very similar to those fifth day after milk was given, the level rose found by Fourman (1954) in a case of potassteadily. It was above normal on the last day sium deplotion tetany During the first eight days the intake of OTHER BLOOD INVESTIGATIONS. The blood nitrogen and potassium was very small or urea and plasma protein lovels were above zero The output was considerable and the normal on the third and fourth days, owing K N ratio greatly in cicess of that of lean to dehydration. On tho Afth day thoy fell to muscle tissue. A considerable part of the normal. Tho blood area and plasma proteins nitrogen and an even greater part of the then remained at normal lovels whilst the potassium wero lost in the stomach aspira haematocrit and haemoglobin gradually fell. tions. With increasing intake, retention of CILL ELECTROLITE LEVELS. The red call both nitrogen and potassium increased, but chlorido concentration remained below not the nitrogen retention was more marked than ( 53 ) of the investigation.

·No text on this page.

·CHAPTER IV General Discussion Before analysing the results obtained in the Phase I balance studies described in the provious In Phase 1 which lasts apprordmately three chapter, two major problems must be consid days and which Moore calls the adrenergiccred. These are, first, the metabolic response corticoid phase, the following changes were to surgery found in adult patients, and sec notod ond, the normal metabolism of newborn in- CLINICAL OBCHVATION Listlessness and loss fants. Both these problems have been exten of appetite, slightly elevated temperature, sively studied during the last decade, and vasoconstriction, and ileus are characteristic. It Is fmpossible to give more than a brief do- In certain types of patients – 10., those suf fcriptlon of the more important work which fering from cancer of the stomach - post-ophas been done. erative lothargy, anorexia, and ileus are espe In the light of this review, we shall discuss cally noticeable (Ariel et al., 1843) Such uomo of tho metabolic changes that we have observed in Deonates and suggest possible patients suffer from pronounced hypochlo raconia and hypoproteinaemia and aro much tunderlying causes for them. improved by giving large amounts of protein pro-operatively In this connection, it must be remembered that it has been known for some SUICICAL CONVALESCENCE time that the retention of fluids and crystal- OF OLDER AGE GROUPS loids in the circulation depends to a large er- When discussing individual cases in the tent, upon the concentration of the proteins previous chapter, mention was made of some (Lepore, 1831, Jones and Eaton, 1939) of the work on metabolism in older age WEIGHT The weight drops after operation groups. In addition, the earlier studies on more rapidly than can be accounted for by the subfoct were mentioned in the introduc the loss of nitrogen and water, suggesting tion. It now remains to summarize some of that fat is metabolized. Whilst this observa the more recent published work tion holds good if the first three or four days Bloore (1853a) has divided the body are taken together, there is no doubt that durchanges in surgical convalescence into four ing the first twenty four hours following op phases. eration the weight tends to increase quito [55]

·No text on this page.

·1 GENERAL DISCUSSION bat Miller and Darrow (1940), Derrow The cause of potassium loss from the cel (1045), and Encinton # oh (1948) showed following trauma is thought to be mainly that potratum can leave the call to sgnifi hormonal in origin, as will be discussed later ant amounts if it can be excreted and that on, but Winfeld et al (1951), performing large amounts of sodium can enter the cell muscle biopsies at the start and end of opera and replace the potassium oven if there is no Hons, found that the muscles to tho neighintelo of sodhim bourhood of the operation field lost up to 50 Further proof that increased potassium per cent of their potassium, whilst the muscles escretion is not entirely derived from do in distant sites lost only 10 per cent. They stroyed tasues was brought forward by BLE suggest that the high concentration of potasreokrono-Millor (1949), who showed that, sium in the urine may be due to the liberawhilst potassium ocrotion Increases mark Hon of potassiun from traumatized mascles. odly dx hours after operation, mardmum po Once potasslum leaves the call, sodium trastorn and nitrogen excretions do not colo enters to replaco It (Eldnton et al, 1948) ode. These findings make it very likely that but this roplacement compansates for only the access potissiun is, to fact, derived from two-thirds of the lost potassium. The remain the Intre-colular fluid (Willdason of che ing third of the potassium is said to be ro- 1850) placed by hydrogen lons (Cooke and Crow Further studios of the excessive amount of ley, 1852) In potassium depletion wo may potaalum lost by adults and children follow therefore meet the paradox of Intre-cellular bug surgery were made by Evans (1850) and acidosis in the presence of extra-cellular alka Lowo et al. (1950) Elman ot al. (1952) losis (Black, 1853) potnted out that, although most of tho pa Darrow ot ch (1948) found that in rats the tassium loss occurs in the uring, some is lost serum bicarbonate concentration varied di ta tho gastro-intestinal secretions. In adults rectly with the intra-cellular sodhim and in definite symptoms occur only when there is a directly with the intra-cellular potassium. deficiency of 200 meq or more Hypochloraonic alkalosis is thus a powerful Moore (1853a) found that the potassium stimulus for tho shift of potasstum – in effect concentration was usually normal during producing a hypokaleemlo alkalosds (Randall Phase 1 of the post-operative period, but ot ah, 1949 Arial, 1954) Stowart and Rourko (1838) found that it When potassium has passed into the extradecronsod. That the sodium and potassium cellular space it is rapidly screted by the concentrations accurately reflect the concen kidney (Tarall and Elkinton, 1949) The extration of the base in the extra-cellular fluid coss is not only discharged by the glomeruli was shown by Hastings et al. (1927) but also by the tubules (Madge et oh, 1948) It is known that some of tho call potasium It is, however, not true that the kidnoy can Is bound to proteta fa characteristic ratio to not conserve potassium. It can, fo fact, excoto the cell nitrogen (Hastings and Eichelberger, urino of lower potassium concentration than 1839), but it is not know how the call ac that found in plasma (Fourman, 1952) quires a higher concentration of potassium than tho extra-cellular fuld (Danowild, The suggestion that a potassium shift could be caused by increased excretion of potassium 1849) Potassium is, however, not the only by the kidney was discounted by Darrow latracellular base, but reprosents only 88 ot al (1948), but Burnott, ot al. (1950) per cent, tho remainder being mainly mado brought forward some evidence that inup of magnesium (Black, 1953) creased urinary excretion has an important [57]

·No text on this page.

·1 SCHUM BIL TRUBIN detail by Lo Quero (1854) Ho found that The hormonal control of post-operative sodium retention will be discussed below on the first post-operativo day sodium retene Hon was accompanied by water retention, Here, it suffices to state that the retention and thet the podium concentration of the appears, in part at least, to be due to the in urine wu thereforo paradoxically high. Late flammatory reactions to injury (Wilkinson podtum rotention is characterized by unal ot oh, 1850) There is some evidence that tered planna chloride concentration, lowered sodium and chloride are concentrated in the urinary sodium concentration and, as a result damaged tissues and mobilize in the undamof the sodium retention, secondary water ro aged tissues of the same person (Fax and tention. This lasts from four to six days, do Baer, 1947) pending upon the severity of the operation. BLOOD UREA CONCENTRATIONS Tho blood Tho chloride retention is similar to the sodi vrea concentration rises after operation. This um retention, but occasionally the chloride might be due to increased catabolism, but it retention is in arcess of the sodium retention. Is more likely due to a temporarlly impaired Potassium defiderscy por e can cause sodium function of the kidnoy (McCance and Wid retention, as shown by Black and Milno dowson, 1838) This viow is supported by the (1852) fact that in dogs reduction of the blood sup- Coller ot al (1936) and Coller and Mad ply to the kidney produces a transient ronal dock (1040) have shown that the kidneys impairment and rise in the blood urea (Van can conservo sodium chloride to a remarkable Slyko and Hiller 1947) degreo and Imder certain conditions may ex- CONCENTRATION Tho croto as Hulo as 0 1 gm per day, except on the serum bilirubin concentration rises after opday of operation, when the urlnary chloride eration. This is partly due to translent impairconcentration is usually high (Lo Quesne, ment of liver function lasting for about a 1954) week (Tagnon ot al, 1948), but it may also The post-operative sodium and chlorido be due to blood transfusions, as 2 per cent of balances are further complicated in patients the red blood corpuscles are destroyed within who vomit before or after operation or who the first three hours (Strumla ot ah, 1947) are on gastric or intestinal suction. McCann (1918) fouod that pylorio obstruction pro During and immediately following operation duced an allalosts due to the fact that moto the plasma volume decreases in size, al chloride than sodium was lost in the gastric though the haemoglobin may show little secretions According to Moore (1949), in change (Nelson ot ch, 1950) This fact is of high intestinal obstruction the loss of sodium great importance when operating upon pa for outwedghs the loss of potassium. Randall tients with chronic disease, many of whom et al (1950) have pointed out that sodium have a reduced blood volume in spite of norand chlorido can be rapidly lost in peritonitis, mal haamoglobin and bacmatowit readings and Cave (1946) has stressed the outpouring (Beling et al., 1948) This drop in the plasma of sodium, chlorido, and potassium from volume is followed by drops in the haemato Ileostomies. Marked sodium and potassium alt and plasme protein concentrations (Arla, defidances therefore often develop aftor gas. 1854) Wilkinson ot al. (1851) found that tro-intestinal operations needing prolonged the plasma proteins fell as the plasma alstuction, whilst thoy seldom occur after bumin fell and the plasma globulin concenthoracic surgical procodares (Aronstam et al., tration rose. They suggested that the drop in 1953) the plasma volume is due to transudation of ( 59 ) CHANGES IN ICF AND IN THE EOF VOLUME

·No text on this page.

·Photo DI GENERAL DISCUSSION cosinophil count returns to normal. If normal Pheso , called the corticold withdrawal diet is now started, Phase na commencos. phase by Mooro (1853a), starts roughly on Phase M the fourth day after operation and usually Lasts from two to three days Phaso L, called by Moore (19582) the i Clinically, this phase is characterized by spontaneous anabolic phase, is characterized as follows the petients becoming more lively and peristalsis commendng The patient does, L Clinically, the patient is still weak. Howhowever, easily tre. The wound now heals evet, ho eats well and feels strong despite and has to be cut if one wants to re-open his actual weakness. The caloric intake is it. In this connection it should be remom high bered that the taste falds adjacent to the 2 The potassium balance is weakly positive. wound usually have a high potassium con- It has been showo, both in animals (Cancentration (Menkdn, 1838) Even if the non ot ah, 1852) and for humans (Beal concentration is low, there is no delay in et al., 1953) that protein restoration can wound healing, as fibroblasts can grow in not occur without adequate provision of very varied concentrations of potassium potasslum for the synthesis of tissue. (Findlay and Lowes 1850) 3 The nitrogen balance remains steadily 2. The weight drops further, but there is now a close relation to the water and positive at the rate of 3 to 5 gm per day for a 70 kg man. The weight gain is cornitrogen balances related with the positive nitrogen balance. 3. The nitrogen losses are less acuto, but es only small amounts of nitrogen are usu- 4. The K N ratio is normal - 2.7 meq of ally given, the balanco remains negative. potassium per gm of nitrogen. 4. Potasshom acrotion is less marked than in 5 The sodium and chloride balances are Phase I, and even after a small intake the approximately zero balance becomes positive, always pro 6 The total body water Increases as the lean vided that there is no further vomiting or Hissue increases. gastric aspiration. 7 The cosinophil count is normal. & Sodium and chloride intake is increased, and there is a marked acration of these Phase IV electrolytes. The serum sodium returns to Phase ry differs from Phero I In that fat normal in spite of increased excretion gain has began. Tho weight gain continues, & Tho plagna and extra-cellular fluid vol with zero nitrogen and electrolyto balances times return to normal, as has been do the eosnophil count remains normal, and the scrlbed bofore, but the total body water total body water volume remains constant. very slightly decreased. ? The cosinophil comt rises above the THE METABOLISI original level and then drops bach to OF NEIZBORN INFANTS normal. Tho Dowborn infants motabolism differs in Tho and of Phase I is reached whan remany respects from that of adults and older tention of potassium ceases, the urinary conchildren. Some of the factors involved will centration of sodium increases, and the now be discussed: [61]

·No text on this page.

·. 3 GENERAL DISCUSSION oglobulty of urte hicroused us more podiun, has been challenged by Thomson (1951), potutom, chlorido, and nitrogen were ex who found no relation between the pH of creted, the sun concentration of these sub the gastric juice and the birth weight. This Kuco more. The highest blood ure, readiog investigator determined the volume of gasto thote sedles was, horrover, only 88 mg per tric fulce by aspirating the stomach shortly cent. They deduced that premature infants after birth. It manged from 04 to 12.25 ml are not protected from the effects of dehydra and averaged 2.85 ml tion by reason of their largo volume of total The cosinophil count varles greatly in now body water They also noticed as an inch born infants but is always very much lower dental finding that in infants of less than than in adults, it rises quickly during the first thirty-six weeks maturity the total excretion few weeks of life. The smaller and more proof electrolytes was two or three times that of mature the baby, the lower as a rule is the full-tarm infants cosinophil count (Burrell, 1952, 1953) Full- Tho minimal water requtrements of now term neonates show a less markod drop in the born infants depend upon the renal concent cosinophil count after the injection of ACTH trating power An infant with an intake of than do adults, and premature bables, even 800 calories and a urlasry specifio gravity of less than full-term infants, Wolman (1852), 1,005 noods 171 ml per kg of body weight performing the Thorn test on twenty four With a urinary specilho gravity of 1,025, how full-term infants on the day of birth, found over, the minimal water requirements are 94 that eight did not respond. Six of those sight, mal per kg of body weight (Dill et al., 1938) weighing under 6% pounds, responded on the The composition of the gastric falce in nor second day of Ilfe. Similar findings were romal doonates is of considerable interest to ported by Bergstrand ot al (1952) Klein as most of our babies vomited or and Hanson (1850) suggested that the feeblo Here on gastric section for some time during response to ACTH Indicatod a diminished the post-operativo period. Szydlowski (18924, activity of the suprarenal gland in neonates b) was the first to investigate the gastric The response Improved remarkably after the acidity of mfod nowborn infants and Toogl first or second week of life. (1908) the first to determine the pH. Millea Kidney fuction in the Dowborn has been (1941) found that the gastric acidity was much debated, and it is possible here to high during the first days of life – 172 ml of N/10 HC per 100 ml of gastric fuice. It mention only a fow of the major contributions to this subject roso to a maximum of 21.6 ml N/10 HC The newborn Kidney is histologically imduring the first forty-eight hours, equal mature (Gruenwald and Popper, 1840) Ung the gastric acidity of the healthy adult. Clara (1836) showed that the visceral layer It then dropped sharply and on the fifth day of lifo was only 07 ml N/10 HC per 100 ml of Bowmans capsule is cuboidal at birth and that the size and number of the capillary of gastric juice. Allar (1941) postulated loops in the glomerull are small. The number that this high acidity might be due to the toilgence of a maternal gastrogenic hormono of nephrons does not fncrease after birth, tho which reached the foetus through tho placenmain port natal dovelopment of the kidaoy consists of an increase in the tubular Ussuo. ta and which rapidly decreased in offoctivo- Dess after birth. Ho also stated that the birth The loop of Honle is short in infancy and Weights of infants are closely related to the increases in length with ago (Poter, 1927) amount of acid secreted, a statement which One of the difficulties confronting favestigators is the problem of how to compare the [89] this study,

·No text on this page.

·1 GENERAL DISCUSSION ituenced by Doo renal factors and that valid kddneys of children with congenital cerebral comparison with adalt values are therefore defects are sunal] when compared with those not yet posubla Prematuro infants excrete of normal children and that there is retarda potassium through the glomerull and tubules Hon of glomerular and tubular differentiation. (Todred ot el 1854) As the kidneys often Both thoso authors, however, point out that boso de much as 50 per cent of the amount of these differences are most apparent in older potassium intako (Elman et al, 1952), there children (five years of age and over one year, I no greater danger in giving potassium to respectively) On the other hand, Vesterdal presture infants than in giving it to full and Tudved (1949) studied the glomerular terud on. Altration rate in infants under three months The kidney function of neonates should of age and found that two Mongols had clearnot be judged by the blood ure. Increased ances comparable with those of normal in oltrogen inteko (Barnett and Vesterdal, fants. Calcagao and Rubin (1851), oo study- 1859), tissue breakdown (McCance and Wid ing the effect of dehydration upon the renal dowson, 1947), reduction in area clearance function lo soven infants, of whom four were due to dehydration (Black et al 1944), and Mongols and two mental defectives, found variation in the rate of urino flow (Barnett that the normal baby in the series behaved and Vesterdal, 1953) can all cause a rise in like the others. We thereforo felt justified in blood urea. Starvation probably explains in including the Mongol baby in our lovestiga part the borw nitrogen arcretion of nowbom Hon. infants, but the need for nitrogen to build up tissues is chiefly responsiblo (Barlow and RESULTS OBTAINED McCance, 1948) IN THE PRESENT INVESTIGATION Whilst the above description appears to show that the newborn infants Idney is In discussing our results and comparing rather immature, it must bo remembered that the metabolic response to surgery in newborn in all the above lavestigations the basis of infants with that roportod for adults, stress comparison was surface area. On the basis will be laid on those points whore the two of total body water, McCance ot oL (1954) responses are dissimilar found that the human infants kidney is moro Our investigations were of pecessity short mature than those of antmaals. They also and usually covered only Phaso I and part poted that, when given large doses of water, of Phase I of Moores (18522) classification Infants excreto urine as rapidly as adults the of convalescence. As the most important wine is equally diluta, and the glomerular changes occur durlog these phases, this curinoltration to the same lafants differ front Gallment of our studies is perhaps not too adults in that the volume of wine excreted serious. by them within a period of four to five and From the clinical point of view newborn 00o-half hours falls short of the test dose. In Infants stand prolonged operations extraorother words, altbough the neonatal kidney is dinarily well and wually are very lively a formatore, it is not so under developed as fow hours after operation. It is difficult to say anythiog definite about their appolite, but There might be somo afticism about in there is no doubt that they are very likely to chydig & Mongol in the present series to vomalt for several days following operation view of tho opinion expressed by Benda (1046) and Roosen-Runge (1949) that the This tendency and the subsequent danger of aspirating the vomitus are undoubtedly tho [3] was formerly thought

·No text on this page.

·GENERAL DISCUSSION purpose of maintaining a pormal plasma balance during the first few days of life. But volume and restoring the plasma protein calculation of the K N rato during the noga concentration tive phase, excluding the meconlum, gives It must be remembered that in starvation, lower valua than those obtained from the sich u occured post-operatively in most of total balanco. It appears, therefore, that in Our com, tho plesne volume decreases before general these newborn infants lost nitrogen the plasma protein concentration falls (Mad and potassium because thoy were starving do o ch, 1940) When the plasma protelas and that no other mechanism camo lato play fall, plastike fofusion will rostore the con An entirely different response to surgical contration to normal (Allon et al, 1948) trauma was shown by Cases 2 and %, who Once there is an adoquato nitrogen Intake were operated upon when they were moro by mouth, nitrogen retention occurs. The than three weeks old and whose reactions ochmal newbom bufant retains pitrogen to followed the adult pattern It would there e marked atent and behaves in this respect fore seem that ability to maintain a normal liko an adalt in Phaso o (Moore, 1955a) of K N ratio after surgery does not last for very the post-operative state, long after birth. That this is not invariably The blood trea, both before and after truo is shown by the data on Case 8 Although operation, tends to rise to comparatively high this infant was over three works old at the levels, although there is little or no dehydra time of operation, the KN ratio followed Hom, and one has to husum, that increased the neonatal pattern described above. This protoin breakdown and variation in the renal pattern is somewhat similar to that of do fonction play * part. pletod adult patients who have been II for a In adults the "potassium shift" described long time before surgery and who also tend above represents the characteristic change to maintain a KN ratio which approximates to the K.N ratio during the post-operativo the values of lean muscle tissue (Moore and period. As a result, more potassium leaves Ball, 1952) However the immediato posttho cell than is liberated by Hissue breakdown operative progress of the neonate, unlike that and excreted by the kidnoy, which cannot of the depleted adult patent, is usvally very retain it to any marked degree. The post good. operativa L.N ratio is therefore considerably There are four possible explanations for in excess of the value for normal lean muscle this phonomenon fa nowbom infants The teste. In this respect our most significant infants muscle may be depleted of potassium Anding was thet none of the six infants at birth, the potassium may be bound more who were operated upon shortly after birth firmly to the footal protein, the foetal bdney host an excessive amount of potassium, despite may bo incapablo of excreting the potassium the fact that tho majority had required or lost from the muscles, or tho hormonal contepalva rergery and were seriously ill posttrol and hence the metabolic changes in operatinedy Indeed three were so l that noodates may differ from those of adults and they failed to recover Nevertheless, in the older children post-operative negative phase all sta Infants showed . I N ratio within the range for loan The first possibility can be discounted. muscle tone. It might be objected that po McCauco et al. (1954) have shown that netborn infants muscles contain potassium tendon and nitrogen present in the meconi Uts, which are not derived from post natal sughtly in arcoss of that found in adults. Wo these breakdown, were included in the total found that the red blood corpuscles of dowborn babies had potresdun concentrations a [67]

·No text on this page.

·GENERAL DISCUSSION purpose of maintaining e normal plasma balance during the first few days of life. But volume and restoring the plasma protein calculation of the K N ratio during the negaconcogtration tive phase, excluding the meconium, gives It must be remembered that in starvation, lower values than those obtained from the auch us occurred post-operatively in most of total balance. It appears, therefore, that in our cases, the plastoa volumo decreases before general these nowborn fofants lost nitrogen tho plasma protein concentration falls (Mad and potassium because they were starving dem et ch, 1940) When the plasma proteins and that no other mechanism came into play fall, plasma fofusion will restore the con An entirely different response to surgical centration to normal (Allen of al, 1948) trauma was shown by Cases 2 and 3, who Once there is an adoquate nitrogen intake were operated upon when they were more by mouth, nitrogen retention occurs. The than three weeks old and whose reactions normal dowbom infant retains nitrogen to followed the adult pattern. It would therea marked atent and behaves in this respect fore seen that ability to maintain a normal like an adult in Phase o (Moore, 1953R) of K N ratio after surgery does not last for very tho post-operative state. long after birth. That this is not invariably The blood ures, both before and after truo is shown by the data on Case 8 Although Operation, tends to rise to comparatively high this infant was over three weeks old at the Lovels, although there is little or no dehydra time of operation, the K N ratio followod thou, and one has to assume that increasod the neonatal pattern described above This perotot breakdown and variation in the renal pattern is somewhat similar to that of do function play & part. pleted adult patients who have been ill for a In adults the "potassium shift" described long timo before surgery and who also tend above represents the characteristic change to maintain a K N ratio which approximates to the K N ratio during the post-operative the values of lean muscle tissue (Moore and period. As a result, more potassium leaves Ball, 1952) However, the immediate posttho cell than is llberated by disrue breakdown operativo progress of the neonate, unliko that and excreted by the kidney, which cannot of the depleted adult patient, is usually very retain it to any marked degree. The post- good. operative & N ratio is therefore considerably There are four possible explanations for In acest of the value for normal lean muscle this phenomenon in newborn infants The Horno. In this respect our most significant Infants muscle may be depleted of potassium finding was that none of the sts infants at birth, the potassium may be bound moro who were operated upon shortly after birth firmly to the foetal protein, the foetal kidnoy lost un arcessive amount of potassium, despite may be incepablo of escroting the potassium tho fact that the majority had required er lost from the muscles, or the homonal contensive surgery and were seriously ill posttrol and hence the metabolic changes in operatively indeed three were so all that neonatas may differ from those of adults and they failed to recover Novertheless in the older children post-operativo Degative phase all six Infants showed . K N ratio within the range for lean The first possibility can be discounted. McCance et al. (1954) have shown that now musclo tave. It might be objected that po born infants muscles contain potassium tantum and nitrogen present in the meconi ton, which are not derived from post natal alightly in excess of that found in adults. Wo found that the red blood corpuscles of netwere included in the total born babies had potassium concentrations a (67) tissue breakdown,

·No text on this page.

·GENERAL DLSCUSSION der 8 meq/L certainly indicate potassfurn value for testing neonatal reactions during depletion, but a high, normal, or slightly the post-operative period. Aubnormal loval might be encountered in a Dogitivo as well as a positive balance phase THE ENDOCRINE RESPONSE As to adults, post-operativo retention of TO INJURY podium and chlorido is common. There are, howover, somo points worth noting in rela It remains for us to discuss briefly the Hon to newborn Infants Sodium and chloride possiblo hormonal control of the metabolic retention does not occur on the day of opera response to surgery in nowborn infants In tion. Storage of sodium and chloride usually order to elucidate this problem we have to starts one or two days after operation As mention somo of the work which has been has been mentioned previously, some noo done on adults and neonates. nates are very prone to acidosis and tend to It was Cannon (1915 1932) who flest di retala considerably moro chlonde than so rocted attention to the neuro-endocrino rodrum. The ensuing acidosis does not appear sponse to injury and stress and Selye (1836, to have any serious clinical effects Retention 1948) who by introducing his concept of the of sodium is thought to be accompanied by "alarm reaction," did so much to stimulate expandon of the extra-cellular space, and research into these problems. certainly the weight changes in some of our Activity of the posterlor pituitary antipatients following operation point towards diuretic hormone was first demonstrated by considerable water retention Gastric and Verney (1946a, b, 1947), and Burnett ot al. fntestinal aspirations of neonates contain a (1949) showed that the hormone is releasod canalderablo quantity of sodlum and even as the result of anaesthesia. Operative trau moro chlorido. Continuous gastric suction ma has the same effect (Ariel and Miller, will therefore depleto the body of these lons, 1950), so has pain (Kelsall, 1949, Chalmers and hypochloraemic alkalosis will result. and Lowis, 1851), and so have morphla and However, in order to produce a serious degree pethidine injections (Habif ot al., 1851) of alkaloris, gastric siction must continue for The anti-diuretic hormone has no effect many day. upon sodium retention and potassium ex In the older neonates (Le,, those over three cretion (Chalmers of al, 1857, Hayes and weaks -- Cases 2, 3, and 8) the sosinophil Coller, 1952) response to trauma resemblod that found in There is considerable evidenco that post adults - La, an immediato post-operativo operativo sodium rotontion and potassium oxdrop to very low lovels, followed by a gradual cretion in adults are adreno-cortical in orgin rise, often to levels above the mitial one. In (Johnson et al. 1950) The eosinophil count talants who were only a few days old the falls and urinary excretion of corticolds and eadinophil response was most frregular and koto-sterolds Increases after operation (Hardy appeared not to have any connection with the ot al., 1953) Administration of these horsoverity of the condition or with clinical mones should therefore increase the atra- Improvement or deterioration. These obser cellular fuld space and decrease the total vations supported the finding of Jaller et al (1851) that the cosinophil response of new body water This was shown to be so in bora infants to ACTH showed wide vartanimal speriments by Gaudino and Lovitt utford It therefore seemed obvious that tho (1949) The secretion of adreno-cortical hortona eosinophil coumt would be of do practical appears to be controlled by secretion of [89]

·No text on this page.

·GENERAL DISCUSSION strow shows that his resistance is high. Whatover the cause of this resistance, be it due to physiological processes in the foetus or to the action of hormones secretod by the mother and conveyod to the foetus through the placenta, ft wears off some days after birth. During this neonatal period, however the Infant shows striking differences in his hormonal equilibrium and metabolism. Ho is endowed with marked resistance to trauma and stress, which is reflected in his metabolic response to surgery

·No text on this page.

·mod following operation by clothing them in thikt layers of Gamgee tissue of cotton wool PRACTICAL APPLICATIONS dngle trauma with gratifying convalescence, nursing them on electric blankets. However, provided the surgeon does nothing to inter there are several theoretical objections to rupt the compensatory mechanism of nature these procedures. First, when a person is Ho stressed the need to leave the patient shocked by operative trauma, circulation to Lood the vital centres is dependent upon a reduced The dangers of over treatment are par blood supply, and dilatation of the subticularly markod in neonatal surgery By far cutaneous vessels by application of hoat there the most common cause of death following fore does not improve his condition. The this type of surgery is pneumonia, and this contrary is the case. Second, a fall in body is not mfrequently due to over-enthusiastic tamperature reduces the basal metabolism Administration of Intravenous infusions and decreases the oxygen consumption (Louw ot al, 1954) on theoretical grounds it is therefore bene On the other hand, unqualified rejection fidal (quite apart from its application to of intravenous therapy in surgical practice cardiac surgery) in prolonged operations on would be a retrograde stop In our opinion, seriously ill patients. Third, as Miller ot al. when complications occur it is not the (1854) have shown, hypothermia increases therapy but the therapist who is at fault. We neonatal resistance to anoxia. For some years therefore believe that it devolves upon the it has been our practice not to protect our surgeon to tako a greater interest in the infants from heat loss durlog operation. Pubject. As Lockwood and Randall (1949) Whilst we do not actively cool tham, the have so aptly stated "The surgeon who is absence of protection from heat loss results ambitious to maintain his mortality at an in a conspicuous lowering of body tempera- Irreducblo minimum must be just as much ture, especially in small infants. This has concerned with the necessity for physiological facilitated anaesthesia and post-operative retold replacement therapy as with technical covery and has certainly not increased the details of the surgical procedure itself" fncidence of post-operative pneumonia. Temperature After operation the babies are placed in incubators to which they can be tended, Nowborn infants in general and premature nursed, and x rayed without change of on infants in particular have comparatively unvironment (Fig. 3 see insert, Chapter o) dovelopod temperaturo-regulating centres This has several advantages (Smith, 1851) Their body temperatures are often inconsistent and tend to fluctuate with 1 A constant temperature (usually 85° F) the environmental temperature. Moreover can be maintained. This allows the fnfant because of the neonato s relatively large body to be nursod naked. As we uso do dress surface, high metabolic rate, and small ings ercopt Inch plastic tape, constant Amount of subcutaneous fat, heat loss from inspection of the abdomen and of the rato the body is more rapid than in adults and and type of respiration can be maintained. Moreover, umrestricted by clothing, the These facts have been realized for a long Infant can move freely 2. Draughts are avoided. tice to protect infants from heat loss durtag 3 A definito concentration of orygon can be maintained if necessary sustounding then with hot water bottles, or 4. Most important of all, an atmosphere of 100 per cent humidity can be maintained. [78] older children House and it has therefore been standard prac-

·No text on this page.

·PRACTICAL APPLICATIONS came this difficulty Todd (1953) tried infu Flold Requirements sloss of 10 per cent invert sagar, which are It is in estimating the post-operative fluid npidly motabolized and less likely to cause requirements of newborn fnfants that most thrombosis of the veins. This sugar bas cer mistakes have been made in tho past. Surtainly proved to be of value in infants suffer goons and paediatricians have often not realing from gastro-enteritis, who aro very much ized how very small are tho newborn babys dehydrated and need large quantities of fold requirements, how little dehydration Balds. We too, have used 10 per cent invert harms him, and how easily ho can be oversagar solutions for neonates during the post transfused. Many an acellently performed operative period. Although wo found it to operation has been marred by subsequently be an improvement on 10 per cent glucoso, drowning the infant with excessivo intrathrombopes sometimos occurred when tho venous therapy Infusion was given at the very slow rato The widely taught rule, that an infant's required by our technique. Furthermore, fluid requirements are 2% ounces per pound even a 10 per cent Invert sugar solution will of body weight does not apply to neonatal not provide sufidant calories when the total surgery or for that matter to the immediate dally fuld intake is small. We have not yet post natal period of normal Infants. The uttod emolsiflod fat infusions, as they are still nary output is very small at first and rises in tho experimental stage in this country A only gradually to what are regarded as normal really matisfactory preparation would be of levels. The fluid requirements during the first great benefit to noonatal surgery weaks of life aro also very mall. They are In our experience it has therefore beon oven smaller, actually and proportionately, in Imposible to provide newborn infants with premature Infants m adequato caloric intako by intravenous Post-operative water retention is not as Infodrom. This fact alono made it imperative markod in noodates as it is in adults but it to commenco oral feeding as soon as possible. does occur and further reduces the already The immediate changes in caloric intake, very small fluid requirements. Very great acce milk foeds were used, are shown in the care must therefore be taken to assessing and causes descrlbod above. Fortunately bocause treating dehydration and replacing fuld of tho tolerance of neonates to low calorlo losses intake and also because we havo soldam had The clinical diagnosis of dohydration is to rely solely on intravenous alimentation for usually not dificult. Dahydration produces longer than ten days at the most, this prob- clinically recognizable signs more rapidly in lem has nover boen a very serious One Tho infants than in adults, although it must be roatino uso of 5 per cent glucose solutions, remembered that when dehydration is obcoupled with occasional blood and plame transfusions, appears on the whole adequate vious, 8 per cent of the body water has al ready been lost (Darrow 1040) Although to tido the baby over the immediato post the blood urea level has proved a reliable operative perlod as far as the caloric intake i concerned. guide to the state of hydration for adults (Homann, 1951) the rise is so rapid in neo- Fmally, we have to mention the posubility nates that it may give an erroneous Impresof providing calories by intravenous infusion slon of the severity of the infants condition of protein hydrolymates. This will be dis cuitsed in some detail in relation to nitrogen A reading of over 100 mg per cent is often encountered in an infunt with minimal clini cal dehydration As has been pointed out 1761 metabolism.

·No text on this page.

·PRACTICAL APPLICATIONS The Nitrogen Requirements point of measuring and charting the quantitia not us drops per minute (an Inaccurate The newborn infant loses weight and method, as the stze of drops is very variable) breaks down proteins for some time after but us ml per hom It is also obvious that at birth and this catabolic phase cannot be re this slow rato intravenous Infusions are very versed by a high protein intako. Operation likely to stop unless there is constant, careful, during this period slightly increases the nitroand skilled mursing supervision and unless a gem excretion. When the post-operativo two-way tap with a syringe attachment is in adreno-cortical phase is short, there is no corporated in the infusion set need to worry about this nitrogen loss, but if Finally, we havo to touch upon the ques It is prolonged, the replacement of nitrogen Homs whether dehydration should be cor becomes of great importance. Our experience roctod pro-operatively and to what extent with the infusions of protein hydrolysates was pre-operative Intravenous therapy should be an unhappy one, since all the preparations wo glvert. Louw et al (1954) have stated that triod were very irritating to nowborn Infants dehydration must be correctod before opera veins. Reconstructed driod plasma has proved Hon. We find that in cases of simple water much more satisfactory Diluted with an loss, as in oesophageal atresia, this is often un equal amount of distilled water in order to necessary Infants five and six days old will lower the electrolyto content, the plasma is often stand the operation without any pre infused In quantities of 50 to 100 ml per day operativo fluid replacement. Infants suffering according to the size of the baby As pointed from intestinal obstruction present a very dif out in a previous chapter, plasma infusion forent problem. Here the losses by vomiting quickly restores the plasma volume in noomust certainly be made good before opera nates and also raises the plasma protein contion can bo contemplated, but the loss of contration, which rapidly falls when tho water is toch less important than the loss of babies are starved. electrolytes (300 below) No intravenous infusion can do more than In view of the great hazards of post-opera tide the child over until it can tako milk tivo infudons, it cannot be over-emphasized orally In those children who cannot tako that the sooner the intravenous infusion is milk (le, certain cases of mecanlam lleus, discontinued and oral feeding started the who are very intolerant to pancreatin by better is the chance of recovery Unfortunato mouth) oral feeding with protein hydrolyly, many abdominal operations upon neonates sates bas occasionally been quite successful. in which tho intestines are opened are fol Under this heading we should like to menlowed by prolonged periods of lleus and in Hon briefly the question of blood replacetravenous therapy must be continued. In this ment which has been previously discussed to connection it should be stressed that great as some detail (Rickham, 1854a) At birth, inare the dangers of Intravenous infusions for fants have a very high haematocrit and newborn infants, the dangers of vomiting haemoglobin concentration. In spite of this, and Inhaling the vomitus during the post blood loss during operation should be meticuoperative period are oven greater Gastric aslously replaced. While over infusion is defi. pirations (and henco Intravenous Infusions) nitely harmful, we have seen so ill-effects should thoroforo never be discontinued until from slight over transfusion during opera tho surgeon is absolutely sure that the flous Hon. The aplanation may lie in the fact that (whether mechanical or paralytic) has been post-operatively nowborn infants can specdly destroy their red blood corpuscles. Wo be [77] Overcome

·No text on this page.

·VV PRACTICAL APPLICATIONS ponses. Each case sults can be obtained within a very fow hours has to be treated on its merits after careful and unless the laboratory staff is ready to Inical and laboratory ovaluation. It is clearly help at any time of the day or night. It is our beyood the scope of many laboratories to firm conviction that unless a surgeon can rely perfamm balance tests such as the ones here on such laboratory facilities he is most unwise descubod, but in practice it has been found to operate upon newbom infants. that only a very few blochemical tests are Decemtary in order to ensure satisfactory post CASE 10 (VIVIAN A) opartive management. Although an occa History domal haemoglobin reading or estimation of The infant was admitted to the Neonatal plasma potassium may be of use, such tests Surgical Unit at the age of eight days, with a pro fnfrequently employed. Experience has history of having vomited bile-stained ma trought us to rely almost entirely on four blo terial since birth. She had passed several chemical tests - nemaly, the blood urea, the meconium stools plasma allal reserve, and the plasma chloride A provisional diagnosis of partial duodenal Rod protein concentrations. If the rules laid obstruction was confirmed by radiography down abovo are borne in mind and the pa The operation was performed on the day Hents intako and output are accurately meas of admission, at which tlme & perforated urod, these four tests are entirely sufficient to deal with the most complicated post-opera septum in the third part of the duodenum was excised and a duodeno daodenostomy tire problems. performed To illustrato this point we have added a Post-operatively large quantities of bile temth case to the present series. The post stained material were obtained by gastric asoperativo metabolic changes of Case 10 were piration, and on tho sixth day it became ob adequately controlled, although only the vious that the anastomosis was not working basic tests mentioned above were routinely Consequently at a second operation a duosoployed. This case was specifically chosen because the patient not only underwent two deno-fejunostomy was performed. After a mejor operations, but also suffered from pro period of paralytic lous lasting three days, the child made an uninterrupted rocovery longed Deus, necessitating continuous gastrio ruction and intravenous therapy for ten days Discussion (Soo Tablo 10) Furthermore, who had suffered from high in- Tho blood samples for chemical analysis testinal obstruction and henco vomited copi were taken each morning The intravenous only befaro operation. We feel that, if it is possible to control an infants blochemistry therapy was planned on the basis of the biomder sich difficult crcumstances, using only chemical data and the clinical findings. On admission the blood urea concentration was a few standard tests, It should be feasible in 47 mg per 100 ml, and mild dehydration was practically all cases. Before discussing this case in more detail, performed after six hours of intravenous It should be polnted out that although the tests wo routinely employ are few in number, they must be performed with accuracy and laboratory with facilities to handle oltra-micro tests. Furthermore, none of these tests are of any practical value unless the retherapy Post-operatively the considerable amount of fluid aspirated from the stomach necessitated a larger intravenous infusson than we usually give With the intravenous régimo outlined in [79]

·No text on this page.

·Appendix The composition of the various fluids used for oral and intravenous administration in o investigation has only been loosely referred to in the text. A more detailed description given in this Appendix. BALINE. When the word saline is mentioned in the text either for oral ar intraveno nise, N/5 saline was used – 1.o, a solution containing 29 1 meq/L. Specific mention made in the text to the few occasions on which N/2 saline (containing 72.7 meq/L) w used. Normal saline was not used. DARROW & BOLUTION The Darrow s solution used during this investigation had the f lowing composition Potassium chloride 357 meq/L Sodium chloride 68.5 meq/L Sodium lactate 53.3 meq/L PLASMA. The plasma infusions referred to in the text consisted of dried plasma reconst tuted with double the usual amount of distilled water BLOOD The blood used was stored blood. In this connection it should be noted that amount of plasma and blood shown in the fluid intake charts refers not to the total amou given but only to the water content. 2016. The milk mistures used were made up from milk powder supplied to us i batches of uniformly mixed powder bulk analysed by the laboratory of the Cow an Gate Company As our studies extended over a lengthy period, it was necessary to r place the original milk powder by a fresh supply These two batches of milk powde varled considerably in their composition. To make up feeds we dissolved 1 gm of the powder in 10 ml of water The resultin mik mlxture is referred to in the text as full-strength mill. Occasionally we used hal strength milk mixturo containing only 0.5 gm of the powder per 10 ml of water The composition of the full-strength mill mixtures was as follows [81]

·No text on this page.

·Bibliography

·No text on this page.

·Bibliography Albright, F., Forbes, A P., and Reifenstein, Barnett, H. L., Perley, A. M, and E. Cn Jr (1946) TT A Am. Physicians HG (1942) Proc Soc Expor Blol 50 221 Mod. 49 90 Allen, J G., Bogardus, G, Egner, W, and Barnett, H. L., and Vesterdal, ) (1959) Phemister D B (1948) Surg, Gynec Pediat 42 99 & Obst 88 604 Barta, L. and Hernadi, (1850) Am. ) Di Allen, J G Egner, W Brandt, M B., and Child. 79 467 Phemister, DB (1950) Am. Surg Bauer, J (1872) Zochr f BioL 8 567 131 1 Beach, E. F, Bernstein, S S., and Macy, I.« Artel, I. M. (1851) Arch. Surg 62 303 (1941) J Pediat 19 190 (1954) Ann. Surg 140 150 Ariel, I. M., Abels, J C., Pack, G T and Beal, J M., Frost, P M, and Smith, J (1953) Ann. Surg 188 842 Rhoads, C. P (1943) J.A.M.A. 123 28 Arial, L. M, and Kremen, AJ (1850) Ann. Beling, C. A, Morton, T V., and Bosch, D Surg 132 1009 (1948) Surg., Gynoc & Obst 87 163 Ariel, 1 M, Kromen, A. J., and Wangensteen, Ballet, S, Nadler, CS, Gazes, P C., O H. (1850) Surgery 27 827 Lanning, M (1949) Am. J Med. 1 Arial, I. M., and Miller, F (1850) Surgery Benda, C. E. (1046) Mongolism and C. 28 716 Lsm. Now York Gruno & Stratton Aronstam, E M., Schmidt, C. H , and Jenkins, Benedict, F G (1915) Carnoglo T E. (1853) Ann. Surg 137 316 of Washington, Publication No 203 Austila, J , and Gammon, G D (1931) Bergstrand, C G Hellström, B and J Clin. Inoestigation 10 287 son, B (1952) Acta paodiał 41 383 Barlow Ay and McCanco, RA (1948) Bernard, C (1878) Loçons sur les Phénom Arch Du Childhood 23 225 ones de la vie communs aux animaur Barnes, R., Richardson, D., Berry, } W. aux cégétau. Paris J B Baillière ot Hood, R. L (1945) Indust á Engin. Berry R. E. L., Iob V, and Campbell, K. Chom. (Analyt Ed.) 17 605 (1948) Arch Surg 57 470 Barnett, H. L. (1850) Podiatrics 5 171 von Bozold, A. (1857) Ztschr f Barbett, H. L., Hare, W K. McNamari, H., Zool. 8 487 and Hare, RS (1948) J Clin. Incosti (1858) Zische f boligensch. Zool. 9? gatlon 27:691 Birhhill, F R., Maloncy, M to, and I Banctt, I. L, Hare, V K. McNamara, H., son, SM (1949) 1 Cun. I and Hare, RS (1948) Proc. Soc. Exper 28 772 Blol b Ned. 09 53 Black, D A K (1953) Lancet 1 305, 353 [85] and

·No text on this page.

·7 BIBLIOGRAPHY Cooko, R E., and Crowley, L G (1952) Davies, J A V (1937) J Pediat 10 802 Now England J Med. 246 637 Dean, RF An and McCance, RA (1947 Cooke, R. E., Pratt, E. L and Darrow, D C. Physiol 106 431 (1950) Am J Dis Child. 79 1128 Deane, N, Ziff, M., and Smith, H W (1952) Cooper, D R, Iob V, and Coller, FA J Clin Inoestigation 31 200 (1049) Ann Surg 129 1 DoGowia, E C, HAITI, ) E., and Plass, E Coppinger, WR, and Goldner MG (1940) JAM.A. 114 855 (1850) Surgery 28 75 DII, D B., Hall, F G, and Edwards, H. Coulson, Rt, and Stewart, CA (1946) (1938) Am. J Physiol. 123 412 Proc Soc Expor Blol. 6 Mod. 61 364 Dingwall, J A, Heinzen, B R, and Pifer, Crandel, L A, Jr., and Anderson, M X (1854) Surgery 36 87 (1834) Am. ) Digest DLS & Nutrition Doradis, S A, Goldfinch, M K., and 11 128 KS (1953) Lancot 2 801 Cuthbertson, DP (1929) Blochom. I Dunger, R. (1910) Münchon med. w 23 1928 schr 57 1942 (1942) Lancet 1 433 Earlo, DP, Bakwin, H., and Hirsch, Dalton, A J, and Selye, H. (1839) Folla (1851) Proc Soo Expor Blol. GM haemat 62 397 76 756 Danowsk, T S (1849) Am J Med. 7 525 Danowild, T S., Austin, A. C., Gow, R. C., Edelman, L. S, Haloy, H. B. Schloerb, P R Sheldon, D B., Friis-Hansen, BJ, SI Mateor, F M., Weigand, F A., Poters, G., and Moore, F D (1852) J H, and Greenman, L (1850) Podl atrict 5 57 Gynoc & Obst 95 1 Dadowald, T S. Greenman, L., Peters, J H., Edmunds, M E (1950) Arch. Dls hood 25.254 Welgand, F A, Mermelstein, H. A, Par sons, W B, and Matcer, F M (1951) Elkinton, J R, and Winkler, A. W (1944 Acta poodlat 40 198 J Clin. Investigation 23 83 Darrow, D C (1940) JAM.A. 114 855 Ellinton, J R, Wikler, A. W, and I (1845) Now England ] Med. 233 01 shd, T S (1848) 1 Clin. I (1846) I Pediat 28 515 27 74 (1848) Buł Now York Acad. Med. Elman, R., Shatz, B , Keating, R. E., 24 147 Weichselbau, T E. (1952) Ann (1850) Now England J Med 242 978 136 111 Darrow, D C., and Cary, M K. (1933) I Ely, R. S, and Sutow, W W (1952) Pe Pediat 3 573 atrics 10 115 Darrow, D C da Silva, M. M., and Steven- Evans E L (1950) Ann Surg 191 945 800, S S (1945) J Pediat 27 43 Evans, G H. (1901) JAM.A. 57 2126 Darrow, D C., Pratt, E. L Flett, J, Jr., Fantus, B (1938) J.A.B.A. 107 14 Gamblo, A. H., and Wiese, H. (1949) Fellers, F X, Barnett, H. L Haro, K., Pediatrict 3 129 MaNamara, H (1949) Podlatrict 3 Darrow, D C, Schwartz, R. M. Iannucci, Findlay, C. W., Jr., and Howes, E. L. (1950 J F, and Coville, F (1948) J Clin In Surgery 28 970 Dedigation 27 188 Flemmer LB, Wido, W S., Proctor, N Darrow, D Cors and Yannet, H. (1835) I Clin. Cowie D B, Vosburgh, G J, and Investigation 14.288 man, L M (1947) ſ Pediat 50 413 [87]

·No text on this page.

·gory 36 580 BBLIOGRAPHY HILS, A G, Forsham, P H, and Finch, CA von Konschegg, A., and Schuster, E. (1915) (1948) Blood 3 755 Doutscho med. Wchnschr 41 1091 Hoffman, W S, Parmeleo, A. H., and Gross Konzelmann, F (1834) Am. ) Dls Child. 47 467 man, A. (1940) Am. ) Dts Child. 77 49 Holman, R. L, Mahoney, E. B., and Whipple Koop, C.E (1853) In Levine, S Z. (editor), G H (1834) | Expor Mod. 59 289 Adooncos in Pediatrics, Vol 6, p 63 Chi Holt, L E. Courtnoy A. M and Fales, H cago Year Book Pubrs L (1918a) Am J Dis Child. 17 38 Krieger, H., Abbott, W E. Levey, S, Babb Holt, L E., Courtney A. M. and Fales, H. L L I, and Holden, W D (1954) Sur (1918) Am. ) Dis Child. 17 241 Halt, L E, Courtney A. M, and Fales, H L Ladd, W E., and Gross, R. E (1941) Ab- (1918) Am. ) Dls Child. 17 423 dominal Surgery of Infancy and Child Homann, R. E. (1951) Am. J Surg 81 10 hood. Philadelphia Saunders Hughes, W E., and Hammond, M L (1948) Lams, H (1907) Compt rond. Soc de Blok J Pediat 32 676 62 488 Hune, D M (1949) J Clin. Inoestigation Lanman, J (1953a) Podlatrics 11 120 28 790 (1953b) Pediatrics 12 62 - (1853) Ann. Surg 138 548 Lans, H S, Stein, L. F, Jr, and Meyer, K. A Ingraham, RC, and Visscher, M B (1833) (1952) Surg, Gyngo & Obst 95 321 Proc Soc. Espor Blol. & Med. 30 464 Laragh, J H, and Almy, T P (1948) Proo Jalles, J W. Wong, A S A., and Engle, E. T Soc Expor Blok & Mod. 69 499 (1851) J Clin Endocrinol 11 186 Latta, T (1832) Lancet 2 274 Jaudon, JC (1946) J Pedlat 29 096 Lopore, M. ) (1831) Proc Soc Expor Blol. Jennings, P B (1952) Brit M J 1 1055 & Med. 29 318 Johnson, H. T, Conn, J W, Iob, V., and Lo Quesme, L P (1953) Ann Roy Coll. Coller, F A. (1850) Ann Surg 132 374 Surgeons England 18 207 Jones, C. M, and Eaton, F B (1833) Arch (19540) Fluid Balance in Surgical Prac Surg 27 159 tice London Lloyd Luke Kelth, N M, Rowntree, L G, and Geraghty (1854b) Lancet 1 172 JT (1015) Arch. Int Med. 16 547 Lo Quesne, L. P, and Lowis, A. AG (1953) Kekwick, A. (1850) Ann. Roy Coll. Surgeons Lancet 1 153 England 7:390 Losser, J H., and Pareira, M D (1953) Ann Kolmell, A. R (1949) J Physiol 109 150 Surg 138 846 Koutman, E. H, Bassott, s H, and Warren, Lovine, S Z., and Gordon, H R. (1942) Am. ) Dis Child. 64 274 SL (1839) J Clin. Investigation von Liebig, J (1842) Dlo organische Chomlo King. EJ (1851) Micro-Analysis in Medical in threr Anwendung auf Physlologlo und Blocheml#try London Churchill Pathologie Braunschweig King. E. J. Wootton, I. D P, Donaldson, R, Lockwood, J S., and Randall, H. T (1949) Bul. Now York Acad. ded. 25 228 Sisson, R. B., and Macfarlane, RG Louw J H. Bul, A. B and Hansen, J DL (1954) S African J Clin. Sc 5 109 Klein, R., and Hanson, J (1950) Pediatrics Lowe, G U. Rourke, M., MacLachlan, E., and Butler, A M. (1950) Pediatrics 6 183 [ 89 ] 18 239 (1948) Lancet 2 971 Klein, R. (1851) J Clin. Investigation 30 818 6:192

·No text on this page.

·1 1 gery S6 580 BIBLIOGRAPHY Hills, A. G., Forbem, P H, and Finch, CA. von Konschegg, A., and Schuster, E (1915) (1943) Blood 3 755 Doutsche med. Wchnscht 41 1091 Hoffman, W S, Parmeles, A. H., and Gross Konzelmann, F (1834) Am. ) Dis Child. men, A (1940) Am J Dls Child. 77 49 47 467 Holmen, R. L, Mahoney, E. B, and Whipple, Koop, C E (1853) In Lovine, S Z (oditor), G H (1834) J Expor Mod. 59 269 Adooncos in Pediatrics, vol 6, p 63 Chi Holt, L E, Courtney, A. M, and Fales, H. cago Year Book Pubts. L (19192) Am. ) Dls. Child. 17 38 Krieger, H., Abbott, W E, Lovey, S., Babb, Halt, L E, Courtney, A. M, and Fales, H. L L I., and Holde, W D (1954) Sur- (1919b) Am. ) Dls Child. 17 241 Halt, L E, Courtney AM, and Fales, H L Ladd, W E, and Gross R E (1941) Ab (1910c) Am J Dls Child. 17 423 dominal Surgery of Infancy and Child Homann, R. E (1951) Am. J Surg 81 10 hood. Philadelphia Saimders Hughes, W E, and Hammond, M L (1948) Lams, K (1907) Compt rond Soc do Blol J Pediat 32 676 62 488 Hume, D M (1949) J Clin. Investigation Lanman, J T (1853a) Pediatrics 11 120 28 790 (1953b) Pediatrics 12 62 -(1953) Ann Surg 138 548 Lans, H. S., Stein, L. F, Jr, and Meyer, K. A. Ingraham, R C. and Visscher, M B (1933) (1952) Surg, Gynec. & Obst 95 321 Proc. Soc Expor Bloh & Med. 30 464 Laragh, ) I, and Almy, T P (1948) Proc Jailer, J W, Wong, A. S H., and Engle, E T Soc Exper Bloh Mod. 09 499 (1851) 1 Clin Endocrinol 11 186 Latta, T (1832) Lancet 2 274 Jaudon, J C (1946) J Pediat 29 898 Loporo, M J (1831) Proc Soc Expor Bioh & Mod. 29 318 Jennings, P B (1952) Brit M J 1 1055 Johnson, H. T. Com, J W. Iob, V, and Lo Quesne, L. P (1853) Ann. Roy Coll. Coller F A. (1850) Ann. Surg 132 374 Surgeons England 13 207 Jones, C. M, and Eaton, F B (1833) Arch (1954a) Fludd Balance in Surgical Prac Surg 27 159 tico London Lloyd Luko Keith, N M., Rowntree, L. G, and Geraghty, (1954) Lancet 1 172 JT (1915) Arch Int Medh. 16 547 Lo Queso, L. P, and Lewis, AG (1953) Eokwick, A. (1850) Ann. Roy Coll. Surgeons Lancet 1 153 England 7 390 Lesser J H, and Paretra, MD (1953) Ann. Kolsall, A. R. (1949) I Physiol. 109 150 Surg 138 848 Koutmann, E. A Bassett, S H, and Warren, Lovine, S Z., and Gordon, A. H (1942) Am. J Dk Child, 84 274 SL (1839) 1 Clin. Investigation von Liebig. J (1842) Dlo organische Chomlo King, E I (1851) Micro-Analysts in Medical in threr Anwendung auf Physiologie und Blochemistry London: Churchill Pathologie Braunschweig hing. E J., Wootton, LDP Donaldson, R., Lockwood, J S., and Randall, F T (1949) Sisson, R. B., and Macfarlane, R. G Bull. Now York Acad. Med. 25 228 (1948) Lancet 2 971 Louw, J H. Bull, A. B., and Hansen, J DL Kleto, R. (1951) 1 Clin Inoestigation 30 318 (1854) S African J Clin Sc 5 109 Kein, R, and Hanson, ] (1850) Pediatrics Lowe, C. U., Rourko, M, MacLachlan, E., and Butler, A. M (1830) Pediatrics 6 183 [89] 18.239 6 192

·No text on this page.

·BIBLIOGRAPHY Poppar www, r, and Flach, E. (1950) Arch Schloerb P R Friis-Hansen, B ), Edelman, Dt. Childhood 25 129 I S, Solomon, A. K., and Moore, FD Pringla, H., Maunsell, R. CB, and Pringle, S (1950) I Clin. Inoestigation 29 1298 (1905) BrH M J 2 542 Schloss, O M, and Crawford, J L (1011) Randal, H. T (1952) S Chn. North Amor Am. ) Dls Child. 1 203 Ica 82 445 Schmidt, C. (1850) Charakteristik der opl- Randal, H. T., Habtf, D V, and Lockwood, demlochon Cholors gegenüber demond Į S (1850) Surgery 28 182 ton Transsudationsanomalion. Leipzig Rendall, H. T., Habif D V, Lockwood, JS, G A Reybar and Werner, S C (1948) Surgery Schoen, I., Strauss, L., and Bay. H. W 28 841 (1853) Surg, Gynec & Obst 96 403 Randolph, T G (1949) | Lab & Clin Mech Schwaiger M, von Lüttichay, E., and Schmel 84 1096 ser, K. (1952) Chirurg 23 150 Road, CH, Venning, E H., and Ripstein, Selye, H. (1838) Naturs, London 138 82 M. P (1850) J Clin Endocrinol 10 845 (1946) J Clin. Endocrinol 8 117 Reardon, H. S, Graham, B D., Wilson, ] Long (1850) Brit M J 1 1383 Baumann, M, L., Tsao M U, and Mura Sherman, H C. (1946) Chomistry of Food yama, M (1950) Podlatrics 6 753 and Nutrttion New York Macmillan Roes, G. J (1854) Personal communication Shohl, A. T (1939) Mineral Motabolism Reeve, E, B, and Veall, N (1948) J Physiol. (American Chemical Society Monograph 108 12 Series No 82) New York. Rolnhold Roffensteto, E. C., Jr., Albright, F and Wells Smith, CA (1851) Physiology of the Nero S L. (1045) 1 Clin. Endocrinol. 5 367 bom Infant Oxford Blackwell Rickham, P P (1852) Lancet 1 332 Smith, C. A., Yudkin S Youmg, W., Minkow (18542) Arch Dls Childhood 29 304 sh, A and Cushman, M (1949) Podt (1954) "Emergencies in tho Neonatal atrics 3 34 Perlod - Surgical Aspects" Locture to Smith, H. P., Amold, H R, and Whipple, tho Liverpool Modical Institution, GA (1021) Am. J Physiol 50 338 Rickham, PP, and Mason, H. R (1953) Snyder H. E. (1847) Surg, Gynoc. & Obst Hospital, London 49 805 84 1125 Ringer S (1883) I Physiol. 4 29 Roche, M, Thorn, G W and Hills, A G Snyder, R. And Katzenelbogen, S (1042) Blok Chom 143 293 (1950) New England J Med. 242 307 Rooten-Aunge E C (1949) Am. ) Dis Snyder W A., Snyder, M A, and Chaffin, L (1854) Arch. Surg 68 546 Child. 77 185 Stanton, R., Lyon, RP, Freis, E D., and Rubin, M L, Bruck, E. Rapoport, M., Spivo Smithwick, R H (1849) Surg, Gynec ly M, Mckay, H., and Baunler, A. & Obst 80:181 (1949) Cun. Investigation 28 1144 Sload, A L (1054) "Somo Aspects of the Rod, F (1947) Acta psychiat et nourol., Musolo Rolnxnnt Surninotironium and its Suppt. 401 Aolion on thio Nowvlom Infant." M.D Rudman, I., and Stewart, JD (1950) SUT Tiosis, University of St Androrys gery 28:170 Stowart, ) D, ani Rourko, G Mi (1838) Santull, T V (1954) I Pediat 44:317 J Clin. Inorstigallon 171418 Sayers, G, and Sayers, M A. (1948) Recent Stowarts ) D., and Rourke, GM (1942) Prog Hormone Research 2:81 J Clin Inurrigation 21:107 (91)

·No text on this page.

·BIBLIOGRAPHY
Wilon, A, Obrist, A R, and Wilson, H Wynn, V., and Rob, C G (1954) Lancet
(1859) Loncot 2 388
1 587
Winfield, J M, For, C L., Jr., and Mers Yllpo, A. (1918) Ztschr f Kindorh 14 288
halmer W L (1951) Ann Surg Young, W F, Hallum, J L., and McCance,
134 628
RA (1841) Arch Dls Childhood
Winter, H. A Hoff, H. E., and Dso, L. 16 243
(1040) Fodoration Proo 8 109
Young, W F, Poyner Wal, P Humphreys,
Wolman, B (1952) Arch Dls Childhood H C., Finch, E, and Broadbent, I
27 283
(1850) Arch. Dls Childhood 25 31
-

·No text on this page.