63

and the brachial plexus, should be sought, and if presentdivided. This alone may relieve pressure on the lowertrunk of the brachial plexus (Falconer and Weddell 1943,Lawson and McKenzie 1950) as may removal of the cer-vical rib if present. Rogers (1949) drew attention to anotherpossible mechanism-namely, that the posterior scapularartery may arise from the third part of the subclavian

artery and pass between the upper and middle trunks ofthe brachial plexus in such a way as to keep the lowest andmiddle trunks closely opposed to the subclavian arterythereby causing symptoms. Raaf (1955) described twocases in which division of such an anomalous arteryrelieved symptoms.Even in the presence of other possible causes (e.g., an

anomalous posterior scapular artery or a scalenus minimus[case 10]) the surgeon should test for a costoclavicularcompression. To do this he places the tip of his fore-finger between the clavicle and first rib, and then with theother hand depresses the ipsilateral shoulder downwardsand backwards. By this manoeuvre we have found in ourcases, but not in controls (e.g., patients submitted to ligationof the common carotid artery for aneurysms), that theclavicle will approach the first rib so closely that the tip of theforefinger is nipped. Palpation will then show whether thisnipping is compressing the brachial plexus (as in the casesdescribed in this paper), the subclavian artery (Falconerand Weddell 1943), or both. Once this mechanism hasbeen demonstrated as much as possible of the first ribshould be removed (see accompanying figure). To do thisthe scalenus anterior muscle is divided, enabling thesubclavian artery to be retracted anteriorly, while thebrachial plexus is retracted posteriorly. The rib can thenbe removed with rongeurs beneath both the artery andthe brachial plexus. Usually the rib can be removed

anteriorly just short of the costal cartilage and posteriorlyto within 1 to 2 cm. of the tip of the transverse process.Then, when the downward and backward bracingmanoeuvre is repeated, it can be shown that the compres-sion of the brachial plexus has been relieved. Since one ofus (M. A. F.) adopted this manoeuvre in 1943 he has notfound a single case in which he was convinced that thatsignificant compression of the neurovascular bundle couldoccur between the scalenus anterior muscle and a normalfirst rib. He has, however, demonstrated costoclavicularcompression in the majority of cases. Lord (1953)practised complete removal of the clavicle in this syn-drome, and claimed good results; but we have not hadexperience of this procedure.

SummaryEleven cases of " thoracic outlet syndrome " without

cervical rib are reported, in which the brachial plexus wasbeing compressed between the clavicle above and in frontand the first rib below and behind when the shoulder-

girdle was in certain postures.The mechanism which most constantly produced

symptoms was one involving downward and backwardbracing of the shoulders.This mechanism can be used as a clinical test before

operation to provoke or aggravate pain, and also at

operation to test for abnormal approximation of the clavicleto the first rib. The other preoperative clinical sign whichis useful in diagnosis is the production or accentuation ofpain by digital pressure on the brachial plexus just abovethe clavicle where it is usually tender.

In the eleven cases, including two in which bilateraloperations were performed, removal of the first rib

provided relief. In two of these cases anterior scalenotomyhad previously been performed elsewhere without relief.Similarly three patients had earlier undergone carpal-tunnel decompression without improvement. The follow-up period is long enough to show that the benefit ispermanent.At operation the patient’s shoulders should be braced

downwards and backwards on the operating-table to

ascertain whether a costoclavicular compressing mechanismis present.We wish to thank our various colleagues who referred their

patients; Mr. P. H. Schurr, who allowed us to cite his case; andDr. R. D. Hoare for the radiological studies.

REFERENCES

Adson, A. W., Coffey, J. R. (1927) Ann. Surg. 85, 839.Eaton, L. M. (1946) Surg. Clin. N. Amer. 26, 810.Eden, K. C. (1939) Brit. J. Surg. 27, 111.Falconer, M. A., Weddell, G. (1943) Lancet, ii, 539.Gray’s Anatomy (1938) 27th edition (edited by T. B. Johnston); p. 239.

London.Jones, F. W. (1911) J. Anat., Lond. 45, 249.Lawson, F. L., McKenzie, K. G. (1950) Canad. med. Ass. J. 65, 358.Le Vay, A. D. (1945) Lancet, ii, 164.Lord, J. W. (1953) Arch. Surg., Chicago, 66, 69.McGowan, J. M., Valinsky, M. (1949) ibid. 59, 62.Murphy, J. B. (1905) Ann. Surg. 41, 399.Naffziger, H. C., Grant, W. T. (1938) Surg. Gynec. Obstet. 67, 722.Ochsner, A., Gage, M., De Bakey, M. (1935) Amer. J. Surg. 28, 669.Raaf, J. (1955) J. Amer. med. Ass. 157, 219.Rogers, L. (1949) Brit. med. J. ii, 956.Stammers, F. A. R. (1950) Lancet, i, 603.Telford, E. D., Mottershead, S. (1947) Brit. med. J. i, 325.Upmalis, I. H. (1958) Surg. Gynec. Obstet. 107, 521.Walshe, F. M. R., Jackson, H., Wyburn-Mason, R. (1944) Brain, 67, 141.Wright, I. S. (1945) Amer. Heart J. 29, 1.

OBSTRUCTION TO THE EXTRAHEPATIC

PORTAL SYSTEM IN CHILDHOOD

STANLEY SHALDONM.A., M.D. Cantab., M.R.C.P.

LECTURER IN MEDICINE

SHEILA SHERLOCKM.D. Edin., F.R.C.P., F.R.C.P.E.

PROFESSOR OF MEDICINE

ROYAL FREE HOSPITAL MEDICAL SCHOOL, LONDON, W.C.1

Frerichs (1861) recognised the association of gastro-intestinal haemorrhage and splenomegaly with obstructionto the portal venous flow in patients without cirrhosis.The concept of

" portal hypertension "

as the operativefactor was not, however, suggested until the beginning ofthe present century when the term was introduced byGilbert and Villaret (1906). Banti’s (1883) description ofa specific disease process starting with splenomegaly andprogressing to cirrhosis and anaemia in the absence ofportal-vein thrombosis confused many people but alsoproduced a wealth of papers stressing the association ofgastrointestinal haemorrhage, anaemia, splenomegaly, andportal-vein thrombosis in the absence of cirrhosis (Dockand Warthin 1904, Edens 1908, Cauchois 1908, Warthin1910). It became generally accepted that portal venousobstruction could produce this syndrome (Whipple 1945),although the xtiology of the obstruction was not certain.

This syndrome in childhood was first studied by Smithand Howard (1927), who reported the cases of 5 childrenwho had died from gastrointestinal haemorrhage and inwhom the first symptom of the disease was splenomegaly.It was postulated that the condition resulted from sclerosisor phlebitis of the portal veins. Cavernomatous trans-formation of the portal vein was first described by Balfourand Stewart (1868), and subsequently Pick (1909) con-cluded that the lesion was a hamartoma. Klemperer(1928) agreed with this in certain cases, but believed that

64

TABLE I-CLINICAL DATA

G.I. =gastrointestinal. I.S.P. =intrasplenic pressure (mm. Hg): normal range 6-14. W .H. V.P. =wedged hepatic venous pressure (mm. Hg): normal range 3-12

thrombosis of the portal vein might also be responsible.This view has been confirmed by Gibson and Richards(1955) and Parker and Seal (1955), who emphasised thatcavernomatous lesions of the portal vein were neithercongenital nor tumour transformations but were in factsecondary to acquired thrombosis.

Recognition of this syndrome in paediatrics has addedto the long list of causes of splenomegaly. When infections,blood dyscrasias, lipoidoses, reticuloses, and cirrhosis ofthe liver and congenital fibrosis (Kerr et al. 1961) areexcluded there remain some instances in which no obviousdisorder can be demonstrated. We describe here our

experience of extrahepatic portal venous obstruction in16 infants and children in whom no hepatic abnormalitywas seen in liver biopsy. In every instance a lesion of the

extrahepatic portal venous system was demonstrated byportal venography.

aetio1ogy9 children had a definite history of umbilical sepsis in

the neonatal period (see table i). In 6 children this hadnecessitated extension of stay in hospital or admission tohospital and treatment with antibiotics. In 1 patient(case 9) an exchange transfusion had been performed onaccount of hxmolytic disease of the newborn and theumbilical vein had become infected. This child had been

extremely ill with a tender abdomen and enlarged liverbut had completely recovered within six months whenantibiotic therapy was given. In 2 others there was a

history of staphylococcal pneumonia following umbilicalsepsis; and in 1 child a subphrenic abscess had developedduring the neonatal period, again following infection of theumbilicus.

In 2 children there was a history of severe sepsis afterthe neonatal period. 1 child (case 11) had an osteomyelitisof -the left tibia when 4 years old, and the other child(case 10) suffered from pylephlebitis following an appendixabscess when he was 13 years old.

In the other 5 children no preceding history of infectionwas obtained; but in 3 of them details of the birth andneonatal period were not available.

Presentation

There were 8 females and 8 males in the series. In11 children the presenting feature was splenomegaly alone.4 others also had gastrointestinal haemorrhage. When

splenomegaly occurred alone the initial diagnosis wasoften obscure, and 3 cases had been diagnosed as

aleukaemic leukaemia. 3 children were considered to have

hepatic cirrhosis. 9 of the 11 children with splenomegalyalone subsequently bled from oesophageal varices; thetime between presentation and haemorrhage averaging1-3 years.The age at presentation could be related to aetiology, the

average being after three years in those with a history ofumbilical sepsis and eight years in the group with latechildhood infection or without any clear astiological

TABLE II-PORTAL VASCULAR STATE AND OPERATIVE RESULTS

G.o. = gastro-oesophageal. i.M. = inferior mesenteric.

65

factor. 1 child (case 15) presented with ascites after anepisode of gastrointestinal hxmorrhage.

Jaundice, other skin stigmata of chronic liver disease,and hepatomegaly were not seen.

DiagnosisThe interval between presentation and diagnosis

averaged three years and ranged from three months toeleven years, delay being usually due to failure to performsplenic venography.Percutaneous splenic venography (Atkinson et al. 1955)

was performed under general ansesthesia in 15 children,and operative mesenteric venography in 1 child (case 12).The results (table 11) have been considered in terms of thesite of obstruction to the portal vein. In 5 children it wasdemonstrated at the hilum of the liver, the splenic andpart of the portal vein being patent (fig. 1). In 5 childrenthe splenic vein appeared patent, the obstruction beingdemonstrated at the junction of splenic and portal veins;in 1 of these the venographic appearance resembled acavernous transformation of the portal vein (fig. 2). In 6children the splenic vein was blocked, the obstructionbeing demonstrated at the splenic hilum. In every casecollateral vessesls to the oesophagus and stomach weredemonstrated, and in 7 instances there was retrograde

filling of the inferior mesenteric venous channel withcontrast material.

In 13 cases the portal pressure was estimated by takingthe pressure in the spleen (Atkinson and Sherlock 1954).The pressure was elevated (mean 27:6, range 15-42,mm. Hg) above the normal range (10:2 mm. Hg) inall 13 patients (table i). In 4 children the wedged hepaticvenous pressure-an index of postsinusoidal venous

pressure-was normal, the mean being 6 mm. Hg (range4-8 mm. Hg) compared with the normal range of3-12 mm. Hg.

Barium-swallow examination demonstrated oesophagealvarices in 12 of the 16 patients.

Percutaneous needle biopsy of the liver was performedat the same time as the splenic venogram. The hepatichistological appearances were normal in every case.

Routine liver-function tests were essentially normal inall children without recent hxmorrhage. A large hxmor-rhage sometimes resulted in temporary depression of theserum-albumin level. The serum-bilirubin value did notexceed 1 mg. per 100 ml., and the flocculation tests andserum-transaminase values were all normal. The serum-

alkaline-phosphatase concentration was not raised abovethe normal range for the various age-groups. The pro-thrombin value was normal. Hxmatological findings were

Fig. 1-Case 7: splenic venogram, showing obstruction of the portalvein at the hilum of the liver, with obstruction of the vessels.vein at the hilum of the liver, with filling of the left gastric vessels.Fig. 2-Case 1: splenic venogram, showing cavernous transforma-

tion of the portal vein.

66

not helpful in the diagnosis of this condition as they wereeither common to all cases of splenomegaly (" hyper-splenism ") or were those associated with iron deficiency.The leucocyte-count was less than 3000 per c.mm. in only4 cases, and in 10 cases the platelet-count was below100,000 per c.mm. In 11 cases the peripheral bloodshowed the picture of iron deficiency. Marrow studiesrevealed normoblastic erythropoiesis in all cases, usuallywith hyperplasia of the red cell series after a recent

haemorrhage. Iron deficiency without overt bleedingwas common and was invariably associated with positiveoccult-blood tests in the faeces.

Management5 children have been managed with conservative

measures alone. 2 of these (cases 1 and 2) have not yetbled overtly. The splenomegaly has been noted for fiveand six years, and they have intermittently positiveoccult-blood tests in the fxces. Otherwise they are

perfectly well and development is proceeding normally.1 of these (case 2) has an obstruction of the portal veinat the liver hilum with a suitable length of vein availablefor portacaval anastomosis. When he is 8 years old and theportal vein is of sufficient size, it may be necessary to

perform a portacaval anastomosis. The other child

(case 1) has a cavernomatous transformation of the portalvein, and shunt operations will not be possible. In viewof this it is hoped to manage this child without recourse tosurgery even if frank haemorrhage occurs. The 3 otherchildren (cases 7-9) have experienced at least one episodeof gastrointestinal bleeding but have had no further

episode for six months to three years; no surgical pro-cedures have been undertaken. The episode of htmor-rhage has been managed conservatively by adequatetransfusion, occasionally intubation with the oesophagealcompression tube (Read et al. 1960), and more recentlyintravenous administration of vasopressin to lower portalpressure (Shaldon and Sherlock 1960). Once cirrhosishas been excluded there is no risk of hepatic coma andsedation has been liberal. 2 of these children (cases 7and 8) have a suitable length of patent portal vein, andportacaval anastomosis may be recommended when theyare about 8 years old. Case 9 has an obstruction to the

portal vein at the splenic hilum so that portacavalanastomosis is impossible. It is hoped to manage thischild without operative interference.

Case 10 had recurrent gastrointestinal haemorrhage, andsplenic venography showed an obstruction at the hepatichilum. Portacaval anastomosis was performed, and theintrasplenic pressure fell from 27 to 12 mm. Hg. Nofurther gastrointestinal haemorrhage has occurred in thesucceeding six years, oesophageal varices are no longerdemonstrable, and the spleen is impalpable. This is our

only patient in whom we feel that a permanently effectiverelief of portal hypertension has been brought about.The remaining 10 patients have all had hxmorrhage

from oesophageal varices, and all have been subjected tovarious surgical procedures. 3 of them were referredfrom parts of the world where adequate transfusionservices were not available. None had a suitable portalvein for portacaval anastomosis. In 2 (cases 3 and 13)splenorenal shunts were performed, and one to three

years later haemorrage has not occurred although aeso-phageal varices are still apparent by barium-swallowexamination. In the other child (case 11) transection of theoesophagus was performed, but profuse bleeding recurredthree weeks postoperatively. At a second operation

cesophageal varices were ligated and splenectomy wasperformed. This patient has not bled again for two years.In 2 patients (cases 12 and 14) splenectomy was donebut both rebled within six to twelve months. Sub-

sequently 1 (case 12) had an omentopexy, which controlledhaemorrhage for two years; but this patient has sub-

sequently bled again on two occasions. She was managedconservatively and there has been no further overt

haemorrhage during the past six years. The other childwho bled after splenectomy (case 14) was subjected tototal gastrectomy and partial cesophagectomy. She hasnow been followed for six years without further htmor-

rhage ; she is developing normally and there has been noevidence of intestinal malabsorption. 1 child (case 4) withan obstruction to the portal vein at the hilum of the liverhad a severe haemorrhage, and the collateral veinsrunning to the oesophagus were ligated as an emergencyprocedure. She has not bled in the three years since thisoperation, and portacaval anastomosis will probably beconsidered when she is 8 years old. Another child (case 5)had a transaction of the oesophagus done but bled on twofurther occasions. As the obstruction to the portal systemis at the splenic hilum, further surgery is not con-

templated. Case 15 underwent first transection of theoesophagus and later omentopexy, but bleeding recurredin both instances within a year. Anastomosis of thesuperior mesenteric vein with the inferior vena cava wasthen attempted, but the patient has since bled on threeoccasions. The hxmorrhages have been adequatelycontrolled by conservative therapy, and further operationsdo not seem indicated.

Case 6 had an omentopexy performed on account ofrecurrent haemorrhage, and subsequently developedascites. This feature was also seen in case 16 following anepisode of severe bleeding after attempted anastomosis ofthe superior mesenteric vein with the inferior vena

cava. In both, fluid retention has been relieved by strictdietary salt restriction and by diuretic therapy (Shaldon1961).Regular attendance at the outpatient department is

important. Diet has been unrestricted, and alkali medi-cines have not been given. Oral iron supplements havebeen prescribed to those becoming anxmic. In a follow-upof up to ten years, mental and physical development hasbeen normal. School attendance has been broken onlyby episodes of bleeding. There have been no deaths. Thelongest period free from haemorrhage has been in case 10,who had a successful portacaval anastomosis performed.Clinical signs of hepatic failure have not been seen, andliver-function tests have remained within normal limits.

Discussion

That sepsis in the neonatal period and early childhoodmay cause portal hypertension has previously been

emphasised (Hsia and Gellis 1955, Walker 1959, Clat-

worthy and Boles 1959); and this is confirmed in the

present series, 9 of the 16 children having a history ofumbilical sepsis and 2 of sepsis in childhood. Theassociation of an exchange transfusion via the umbilicalvein with subsequent portal venous thrombosis andhypertension has previously been noted in 1 case (Habif1959). In umbilical sepsis an infective thrombophlebitisspreads along the umbilical vein to the left branch of theportal vein and thence to the main portal vein. In sepsiselsewhere the portal vein is presumably involved withinthe liver by abscesses at the hilum or along its course byphlebitis spreading from an intraperitoneal septic focus.

67

Congenital anomalies of the portal vein are probablyrare causes of portal-vein occlusion. This is supported bythe pathological evidence of Gibson and Richards (1955)and Parker and Seal (1955). Cavernous change in theportal vein is neither a hamartoma nor congenital.Cavernous change can even develop after thromboticocclusion of an unsuccessful portacaval anastomosis

(Steiner et al. 1957).The deviation of portal venous blood from the liver has

not affected physical or mental development in any of thesechildren. In the intervals between overt hxmorrhagethey are extremely well, and all milestones have beenreached at the appropriate age. Aspiration liver biopsyshows normal histological appearances. Hepatic failureis never a problem, and the prognosis is quite differentfrom that of children with bleeding from oesophagealvarices associated with cirrhosis of the liver. Patientswith hepatocellular disease are faced with the prospectof hepatic coma and death every time they have a haemor-rhage (Sherlock 1958). This is rarely so in children witha portal-vein block and a normal liver functionally andstructurally. Leucopenia and thrombocytopenia inseveral does not seem to have affected them adversely,and splenectomy has not been indicated to control theseasymptomatic blood changes. Ansemia, if present, hasbeen of iron-deficiency type and related to chronic blood-loss from the gut. It has usually been cured by oral irontherapy and, in the intervals between frank haemorrhage,has not been a problem.Hsia and Gellis (1955) and Clatworthy and Boles (1959)

noted ascites in about a third of their patients. Theascites was often transient and rarely gross, and oftendisappeared spontaneously. Only 2 of our 16 patientsdeveloped ascites, but it tended to be severe and intract-able. It was preceded by operative trauma or haemor-rhage, and presumably followed a lowering of the serum-protein level and hence of the serum colloid-osmotic

pressure. This, in the presence of portal hypertension,was followed by ascites. Both children were extremelyemaciated, and their general condition improved whentheir fluid retention was controlled by diet and diuretictherapy.

Barium-swallow examinations may fail to demonstrate

oesophageal varices, especially in children who may notcooperate well in the examination. No varices weredemonstrated in 4 of our patients. Splenic venographyis essential, and the children have tolerated this pro-cedure well; there have been no complications. It isessential not only for diagnosis but to permit the pre-operative planning of any surgical procedure; muchdepends upon whether sufficient portal vein is availablefor a shunt procedure. Such portal-systemic shuntingoperations are the only treatment likely to be of per-manent benefit; portacaval anastomosis is the most

satisfactory operation (Milnes Walker 1959, Clatworthyand Boles 1959, Habif 1959). Among our 16 patients thisprocedure would be possible in only 5 who have anadequate portal vein, and then only at 7 or 8 years ofage when the vein is of sufficient size to reduce the ten-dency to thrombosis. It is difficult to assess the patencyof splenorenal shunts, which on the whole have proveddisappointing. In our 2 patients submitted to this opera-tion, oesophageal varices were still present postoperatively,suggesting that the shunt was either not patent or notadequate.The results of other operations are usually found to be

disappointing if the follow-up is sufficiently long.Splenectomy, by removal of safe collaterals running fromthe spleen to the diaphragm, may encourage further

haemorrhage. Transection of the stomach and oesophagusmay be useful during episodes of particularly severe

bleeding, but long-term results are again disappointing.Tanner (1961) reports major rebleeding in 4 of 7 patientswith extrahepatic portal hypertension submitted to

portoazygos disconnection with subcardiac transectionof the stomach. Milnes Walker (1960) states that transec-tion operations give far from satisfactory results in thisgroup. Total gastrectomy and partial oesophagectomyhave been recommended by Habif (1959), and 1 of our

patients has not bled again for six years after thissomewhat drastic operation.

Unless a venous-shunt operation can be performed witha reasonable chance of success, we prefer to manage thesepatients without surgical intervention. This policy is

probably justified: none of our patients has died. Thethreat of exsanguinating haemorrhage has been over-

emphasised. Episodes of haemorrhage may become lessfrequent as time allows opening up of collateral vesselsto the renal and lumbar veins and so portal pressure falls.This possibility may be lessened with repeated operativeintervention and removal or transection of collateralvessels. This conservative regimen is probably also

justified because there is no risk of fatal hepatic comadeveloping after the bleed.

Summary16 children with extrahepatic portal venous obstruction

have been followed for from one to ten years. A historyof neonatal umbilical sepsis was present in 9 cases andof severe sepsis elsewhere in 2 others. There were nodeaths. The children are developing normally.

Percutaneous splenic venography under general anaa-thesia is essential both for diagnosis and to determinewhether portacaval anastomosis is possible. Aspirationneedle biopsy is performed at the same time. Delays indiagnosis were attributed to failure to perform theseinvestigations in children with unexplained splenomegaly.

1 patient had a successful portacaval anastomosis. 9others have been submitted to various operations, includ-ing splenorenal anastomosis and transection procedureson the oesophagus and stomach. Results have on thewhole been disappointing, and medical management isadvocated when portacaval anastomosis is impracticable.

This work was supported by the Miles Laboratories. We wish tothank Prof. R. E. Steiner, of the Postgraduate Medical School ofLondon, and Dr. W. B. Young, of the Royal Free Hospital, and theirstaff for radiological advice and assistance.

REFERENCES

Atkinson, M., Sherlock, S. (1954) Lancet, i, 1325.— Barnett, E., Sherlock, S., Steiner, R. E. (1955) Quart. J. Med. 24, 77.

Balfour, G. W., Stewart, T. G. (1868) Edinb. med. J. 14, 589.Banti, G. (1883) Arch. Scuola Anat. Pat. Firenze, 2, 53.Cauchois, A. (1908) Splenomegalie chronique d’origine pylethrombosique.

Thèse, Paris.Clatworthy, H. W., Boles, E. T. (1959) Ann. Surg. 150, 371.Dock, G., Warthin, A. S. (1904) Amer. J. med. Sci. 127, 24.Edens, E. (1908) Mitt. Grenzgeb. Med. Chir. 18, 59.Frerichs, F. T. (1861) A Clinical Treatise on Disease of the Liver. Trans-

actions of the New Sydenham Society, vol II, London.Gibson, J. B., Richards, R. C. (1955) J. Path. Bact. 70, 81.Gilbert, A., Villaret, M. (1906) C.R. Soc. Biol., Paris, 60, 820.Habig, D. V. (1959) Surgery, 46, 212.Hsia, D. Y. Y., Gellis, S. S. (1955) Amer. J. Dis. Child. 90, 390.Kerr, D. N. S., Harrison, C. V., Sherlock, S., Walker, R. M. (1961) Quart.

J. Med. 30, 91.Klemperer, P. (1928) Arch. Path. 6, 353.Parker, R. A., Seal, R. M. E. (1955) J. Path. Bact. 70, 97.Pick, L. (1909) Virchows. Arch. 197, 490.Read, A. E., Dawson, A. M., Kerr, D. N. S., Turner, M. D., Sherlock, S.

(1960) Brit. med. J. i, 227.

68

Shaldon, S. (1961) Proc. R. Soc. Med. 54, 259.— Sherlock, S. (1960) Lancet, ii, 222.

Sherlock, S. (1958) Disease of the Liver and Biliary System. Oxford.

Smith, R. M., Howard, P. J. (1927) Amer. J. Dis. Child. 34, 585.Steiner, R. E., Sherlock, S., Turner, M. D. (1957) J. Fac. Radiol., Lond.

8, 158.Tanner, N. C. (1961) Ann. R. Coll. Surg. Engl. 28, 153.Walker, R. M. (1959) The Pathology and Management of Portal Hyper-

tension. London.— (1960) Thorax, 15, 218.

Warthin, A. S. (1910) Int. Clin. 4, 189.Whipple, A. O. (1945) Ann. Surg. 122, 449.

CARBON-MONOXIDE POISONING

A Comparison between the Efficienciesof Oxygen at One Atmosphere Pressure,

of Oxygen at Two Atmospheres Pressure, andof 5% and 7% Carbon Dioxide in OxygenT. A. DOUGLAS

B. Sc., Ph.D. Glasg., M.R.C.V.S.LECTURER IN

VETERINARY BIOCHEMISTRY

D. D. LAWSONM.R.C.V.S.

SENIOR LECTURER IN SMALL

ANIMAL SURGERY

I. MCA. LEDINGHAMM.B. Glasg.

SENIOR HOUSE-OFFICER, WESTERN

INFIRMARY, GLASGOW

J. N. NORMANM.D. Glasg.

OF THE EXTERNAL STAFF OF THE

MEDICAL RESEARCH COUNCIL

G. R. SHARPM.B. Glasg.

I.C.I. FELLOW IN ANESTHETICS

GEORGE SMITHM.B.E., M.D., Ch.M. St. And., F.R.C.S., F.R.F.P.S., F.A.C.S.

READER IN SURGERY

With the technical assistance ofJBSS WILSON, CARRICK HENDERSON, and KATHLEEN HUME

From the University Department of Surgery at the WesternInfirmary, and the Veterinary Hospital, University of GlasgowTo date, the treatment of carbon-monoxide poisoning

has been by the inhalation of pure oxygen or of Carbogen’mixtures, that is 5% or 7% carbon dioxide in oxygen.Recently the successful use of pure oxygen at two atmo-spheres pressure has been reported by Smith and Sharp(1960) and by Lawson, McAllister, and Smith (1961).The experiments here reported were designed to decidewhether such a method of treatment with pure oxygenat two atmospheres is superior to others in current use.

MethodThis has been described previously (Douglas et al. 1961).

In all twenty dogs were used in two groups of ten. Eachanimal was gassed until the blood-level of carboxyhxmoglobinwas 70%, and then it was resuscitated by the inhalation ofone of the four mixtures to be tested. The experiments withoxygen at pressure were performed in the pressure chamberinstalled in the university department of surgery at theWestern Infirmary, Glasgow. The sequence whereby theanimals were eventually subjected to each of the resuscitationmixtures was a random one. After each gassing and resuscita-tion the dog was allowed to recover for several weeks beforeit was subjected to the next stage of the experiment. The firstten animals were gassed over a period of 45 minutes withcarbon monoxide in oxygen; the resuscitating circuit included aHeidbrink valve and rebreathing bag. In the second group,the animals were slowly gassed with a coal-gas/air mixturewhich contained 0-37% carbon monoxide; the average timeof gassing was 2 hours, and the resuscitation circuit includeda Ruben non-return valve.

Results

The times taken for the blood-level of carboxyhsemo-globin to fall from 70 to 35%, as estimated by the

Hartridge reversion spectroscope, were recorded in allanimals for each of the four methods of resuscitation.These half-clearance times (T/2), in minutes, are set

out in the table.The great superiority of treatment with oxygen at

a pressure of two atmospheres absolute is obvious.I

Discussion

Our results leave no doubt that oxygen at pressure isthe most efficient means whereby the blood may becleared of carboxyhaemoglobin. The use of carbogenmixtures greatly increases the rate of clearance from theblood of carbon monoxide when compared with oxygenat normal atmospheric pressure.

It has always been held that the most important featureof the treatment of carbon-monoxide poisoning is therapid elimination of carbon monoxide from the blood,

HALF-CLEARANCE TIMES (T/2) OF TWENTY DOGS RESUSCITATED BYVARIOUS METHODS

because this liberates haemoglobin for oxygen carriage tothe tissues. Oxygen at two atmospheres pressure expelsthe carbon monoxide (Lawson et al. 1961); but evenbefore this the cellular anoxia is corrected to a largeextent, because a considerable volume of oxygen isdissolved in the plasma and tissue fluids to oxygenatethe tissues without recourse to the haemoglobin-transportmechanism.None of the dogs showed any immediate ill effects

from the experiments, and they remained well in themonths following them.

SummaryTwo groups, each of ten dogs, were gassed with carbon-

monoxide mixtures until the carboxyhaemoglobin levelwas 70%. They were then resuscitated with pure oxygenat two atmospheres pressure, and the time taken for thecarboxyhaemoglobin level to fall from 70 to 35% was

noted.The results were compared with the times for half-

clearance of the blood when the same dogs, gassed inthe same way, were resuscitated with oxygen at normal

atmospheric pressure, or with 5% or 7% ’Carbogen’(carbon dioxide in oxygen).Treatment with pure oxygen at a pressure of two

atmospheres absolute was by far the most efficient. Next