PROXIMAL SKIN NECROSIS AFTER RADIAL-ARTERY CANNULATION

1135 small

to

allow any statistical

analysis

or to

draw any

dogmatic conclusions, they appear to be more encouraging than those reported by the Medical Research Council. An important observation which emerges from this series is the lack of the serious postoperative complications noted by Bromley and Szur,3 who reported their results of combined radiotherapy and resection for bronchial carcinoma. Five of their sixty-six patients developed an empyema not associated with a fistula, and thirteen developed a bronchopleural fistula. Thus their complication rate was 27%-a high figure. It is justifiable to point out that the radiation dosage is not comparable in that the tumour dose employed by Bromley and Szur varied from 3700 to 6000 rad. with an average of 4700 rad., deep X-ray therapy between 190 and 250 Kv having been applied in all cases. A high incidence (13’3%) of postoperative bronchopleural fistulae after preoperative radiotherapy of 4500 rad. was also noticed by Smith-and Pamsingha,4 who

supervoltage therapy (4 MeV) over a period of four weeks. Little attention has been paid to the use of lowdose preoperative radiotherapy and surgery in the treatment of operable malignant disease. Most clinical trials of preoperative irradiation have been of the high-dose variety.5 Five daily doses of 400 rad. were given by Henschke et al.6 before radical neck dissection, and they reported a drop from 33°/ to 20% in the incidence of local recurrence at three years in a controlled clinical trial. On the other hand, in a similar trial Borgstrom and Lindgren7 showed that there was no effect on survival by giving 1500 rad. in four treatments in eight days prior to radical mastectomy and gave

3. Bromley L. L., Szur, L. Lancet, 1955, ii, 937. 4. Smith, L., Parnsingha, T. Thorax, 1969, 24, 457. 5. Glickman, A. S. Rhode Isl. med. J. 1965, 48, 538. 6. Henschke, U. K., Frazell, E. L., Hilaris, B. S., Nickson, J. J., Tollefsen, H. R., Strong, E. W. Radiology, 1966, 86, 450. 7. Borgstrom, S., Lindgren, M. Acta radiol. 1962, 58, 9. 8. Medical Research Council. Lancet, 1973, ii, 63. 9. Nias, A. H. W. Br. J. Radiol. 1967, 40, 166. 10. Shields, T. W., Higgins, G. A., Lawton, R., Heilbrunn, A., Keehn, E. J. J. thorac. cardiovasc. Surg. 1970, 59, 49.

Addendum made a decision to give a higher dose of radiation, and 2500 rad. M.T.D. (cobalt-60) was given preoperatively in ten treatments in eleven days’ overall time. This higher dose was used in twenty-eight patients with no adverse reaction although one patient developed a postoperative bronchopleural fistula. The results were worse and a one-year survival of 25% In 1969

we

recorded. In consequence we have now reverted the original dose of 17S0 rad. A similar finding was observed by Shields et al.,10 who reported a series of three hundred and thirtynine patients with carcinoma of the bronchus, half of whom were given four thousand to five thousand rad. as preoperative radiotherapy. It was noted that the survival-rate decreased as the radiation dose increased. The increased dose of radiotherapy may interfere with the patient’s immune reaction. was

to

PROXIMAL SKIN NECROSIS AFTER RADIAL-ARTERY CANNULATION I. GLAVES D. J. COOPER Cardiothoracic Unit, Northern General Hospital, Sheffield S5 7AU R. WYATT

postoperative radiotherapy. In the M.R.C. ten-year follow-up report 8 the is made that " A patient with oat-celled carcinoma on bronchoscopic biopsy should be ’advised to submit to radiotherapy rather than surgery." This statement is now perhaps open to question, and the organisation of a multicentre random trial on a national basis of radiotherapy alone versus preoperative low-dose radiotherapy and radical surgery to establish statistically valid results should be con-

proximal to the site of radial-artery cannulation are described, a frequency of about 3%. Histological, anatomical, and radiological investigations suggested that the arterial blood-supply closely proximal to the usual site for radial-artery cannulation

sidered. The organisation of such trials is discussed by Nias,9 who suggested that a single preoperative dose of 500 to 1000 rad. should be given on the day of operation, ideally on the way to the theatre. He points

Introduction

statement

that care must be taken to choose only those clinical situations where local and/or freshly disseminated metastases lead to a significant degree of morbidity and mortality. It would seem reasonable to add a rider that the tumour should be of known radiosensitivity even if not radio-curable. out

We are grateful to Dr J. F. Heggie and Dr Walford Harrison for their histological reports. We owe particular gratitude to Dr K. F. W. Hinson for kindly reviewing all the slides. Sister P. Milburn has lent invaluable help with both the patients themselves and the organisation of their treatment. Requests for reprints should be addressed to V. L., Department of Radiotherapy, North Middlesex Hospital, London

Summary

Seven

cases

of necrosis of the skin

makes this site unsuitable for such a purpose. Application of a modified technique has avoided this complication in a further fifty consecutive cannulations.

INDWELLING arterial cannulse

are

of value for direct

blood-pressure monitoring and repeated blood-gas analysis in critically ill patients; they are also a convenient source of other blood-samples. The radial artery is frequently chosen for cannulation because of the extensive collateral circulation to the hand distal to the cannula and ease of insertion and fixation.1 We have seen ischa’mia and necrosis of the skin over the flexor surface of the forearm proximal to the site of cannulation in seven cases in this hospital, the same technique being used in each instance.

N18 1QX. REFERENCES 1. Medical Research Council. Lancet, 1969, ii, 501. Willis, R. A. Pathology of Tumours; p. 366. London, 1967.

2.

Technique The caimulae (18 gaugeMedicut’, Argyle, Sherwood Medical Industries, Crawley, Sussex) were inserted per-

1136

cutaneously of

a

at a

shallow

angle

to

the skin in the

manner

venupuncture, avoiding transfixion of the artery.

haematoma sufficient to occlude the artery, was not noted in any case. Patency was maintained by constant slow infusion (less than 4 ml. per hour) of physiological saline, containing heparin 1 unit per ml. using a roller Samples were withdrawn via a three-way tap, pump. avoiding suction, air entry, or the infusion of any fluid other than that from the pump.

Spasm,

or

Case-reports Case 7

Female, aged 27

years, height 1-63 m., weight 45 kg.; rheumatic mitral-valve disease, for which mitralvalve replacement was performed under cardiopulmonary bypass. Postoperatively she twice required re-exploration for bleeding, became septicaemic, and died 10 weeks later with a septic cerebral embolus. The left radial artery

Case 4

Male, aged 48, height 1-67 m., weight 72 kg.; emergency repair of a dissecting aortic aneurysm followed 32 hours later by aortic-valve replacement and ascending aortic prosthesis. Recovery was slow, isoprenaline infusion and artificial ventilation being required. 7 days after the first operation, at which a left radial artery cannula had been inserted,and 24 hours after its removal, the left forearm became swollen and painful and a 4 x3 cm. area of ischaemic skin, with blistering, developed. This proceeded to full-thickness skin loss, for which skin grafting was required 2 months after cannulation. Case 5

severe

Female, aged 54, height 1-57 m., weight 57’5 kg.; mitral-valve replacement for rheumatic disease, with an recovery. The left radial artery was cannulated at the time of operation. 2 days postoperatively ischsemic patches, 1 x 2 cm. and 2 X 2 cm., appeared on the radial aspect of the forearm. The cannula was removed, and the lesion healed spontaneously, sloughing and then

uncomplicated

granulating. Case 6 m., weight 61 kg.; mitralreplacement for severe rheumatic disease. Postoperatively low cardiac output and renal failure requiring peritoneal dialysis developed. She died 4 weeks later. The left radial artery was cannulated before operation and removed after 5 days when signs of skin ischaemia proximal to the cannula appeared. For 10 days before death there was a large slough, 15 Xcm., extending to the elbow, on the flexor aspect of the left arm.

Female, aged 57, height 1’52

valve

Case 7 Fig. 1-Left forearm

days after radial-artery cannulation in 1, showing skin loss.

22

case

Female, aged 42, height 1’57 m., weight 50 kg.; emeroperation after a cardiac arrest, for aortic regurgitation. An aortic-valve prosthesis and ascending aortic graft gency

inserted with anastomosis of the coronary arteries to the graft. There was good postoperative recovery until sudden death from haemorrhage 18 days later. A left radial-artery cannula was inserted on the day of operation and removed 6 hours later after ischaemic areas of skin appeared 3 cm. proximal to the site of entry of the cannula. 2 days later the skin was oedematous and next day it was blistered. 1 week postoperatively there were three areas of full-thickness skin loss on the left forearm. were

cannulated at the time of the first operation and retained for 13 days, being withdrawn because signs of skin ischaemia 3 cm. proximal to the point of entry of the cannula were noted. Areas of full-thickness skin loss, the two largest being 2 x1 cm. and 2 X 2’5 cm., had developed by the 22nd postoperative day (fig. 1). was

Case 2

Female, aged 56, height 1’55 m., weight 46-6 kg.; aortic-valve replacement for rheumatic disease, the immediate postoperative course being complicated by cardiac tamponade necessitating further surgery. The left radial artery was cannulated before the first operation. 2 days later a solitary blister 2 cm. in diameter was seen The cannula on the radial aspect of the left forearm. was removed, but the blistered area blackened and subsequently a slough formed. The lesion healed spontaneously

Cases 3-7 occurred during 150 consecutive cannulations performed between Jan. 1, 1973, and Dec. 12, 1973, a frequency of 3-3%. Cases 1, 6, and 7 died while in hospital; the lesions healed spontaneously in cases 2, 3, and 5. A skin graft was performed in case 4.

by granulation.

Histology Six specimens

Case 3

Female, aged 43, height 1’65 m., weight 62’5 kg.; mitralreplacement and tricuspid anuloplasty for rheumatic heart-disease, with uncomplicated recovery. The left radial artery was cannulated before surgery, but sampling during the operation was difficult and the circulation to the skin over the tip of the cannula was poor. The canvalve

nula was removed and a brachial-plexus block was performed using 1’5% lignocaine. 2 days later there was an area of ischaemic skin, 3 cm. in diameter, over the radial aspect of the forearm, which blistered 4 days postoperatively and sloughed over the next 3 weeks. Skin grafting was not thought to be necessary, and the lesion healed spon-

taneously.

Investigations were examined from four patients who died after cardiac surgery. The left radial artery had been cannulated for more than 72 hours in each case and the right radial artery had been cannulated less than 48 hours before death in two. Only one case had shown clinical evidence of skin ischaemia and none had shown necrosis. The radial artery, surrounding tissues, and overlying skin were excised en bloc, fixed in 4% formaldehyde and processed in paraffin wax. 5 Jl. sections were cut and stained with heematoxylin-eosin and with Lendrum’s Martius scarlet-blue. All specimens showed recent ischaemic necrosis of

1137

Fig. 4-Radial arteriogram showing small branch proximal

to

cannula.

Fig. 2-Histology.

(A) Adherent thrombus

at

origin of cutaneous branch of radial (B) Ante-mortem thrombus

artery 48 hours after cannulation. in arterioles within the dermis-

the epidermis and underlying dermal tissues. Subendothelial fibrin deposition and adherent thrombus were present to varying extents proximal to the position of the cannula. In two specimens where the initial cannulation attempt had been unsuccessful and the cannula inserted more proximally, thrombus was present at the origin of the cutaneous branch and in the arterioles within the superficial dermis (fig. 2). There was no evidence of pre-existing vascular disease in any case. All specimens showed endothelial erosion and destruction of the internal elastic lamina and adjacent media at the site of entry of the cannula.

Anatomy The arterial supply to the skin over the radial aspect of the forearm was demonstrated in two cadaver limbs. There were at least eight branches, none more than 1 mm. diameter, arising from the radial artery, some of which led to deeper structures. Four branches ran superficially, supplying the skin of the radial side of the forearm. Two of these arose close to the origin of the radial artery, but two arose within 10 cm. of the base of the first metacarpal, as did two of the deep branches. No anastomotic channels could be identified (fig. 3). Fig. 3-Diagram

of a dissection of the right forearm to show the radial artery and its branches. A=radial artery, B=superficial flexor muscles, C=small arteries supplying skin, D=reflected skin flap, E=base of first

metacarpal.

Radiology 7-10 ml. of

50% ’Conray

280’

(meglumine iothala-

injected into the radial-artery cannula in six

mate)

was

cases,

shortly

after its insertion and while the

patients

1138

heavily sedated with opiates and receiving artificial ventilation with nitrous oxide and oxygen, to avoid discomfort. In each case one or two very small branches of the radial artery were outlined, arising 2’5-4’C cm. from the point of entry of the cannula into the artery (fig. 4). None of these patients developed signs of skin ischsemia.

TRANSFORMATION OF HUMAN FIBROBLASTS WITH D.N.A. OF CULTURED HUMAN RHABDOMYOSARCOMA CELLS

were

Modified Technique

as

follows:

(a) The radial artery is cannulated possible. (b) A smaller (20 gauge) cannula is

as

distally

as

used to allow greater flow around the cannula and lessen the risk of

thrombosis. other than for blood-gas analysis reduce the risk of thrombus forming in the three-way tap and subsequently being flushed inwards. (d) Cannulre are removed as soon as possible, rather than being retained for convenience when sampling requirements become infrequent.

(c) Sampling of blood

is avoided,

to

50 consecutive cannulations have now been performed in this way to date; no evidence of skin ischaemia has been seen after careful follow-up.

Factors known

to

increase the risk of ischaemic

complications after arterial cannulation2 include low cardiac output3 (present in cases 4 and 6), prolonged cannulation (in cases 1, 4, and 6), infusion of excessive amounts of fluid, and severe local trauma. An additional factor relevant to the radial artery would be occlusion of the cutaneous end-arteries, by proximal extension of thrombus and subendothelial fibrin

deposition,

or by the cannula itself. All our cases of short stature, suggesting that a shorter distance than usual from the site of cannulation to the origin of the cutaneous vessels makes this complication more likely. Proximal skin necrosis has been observed by others in four cases,4,5 but because of its apparently benign nature other cases may have gone unreported. Investigations are being continued because the possibility of damage to nerve or muscle tissue has not been excluded.

were

We thank Mr G. H. Smith and Dr R. King for permission report on patients under their care, and the nursing staff of the postoperative intensive-care unit of the Northern General Hospital for their assistance. to

Requests for reprints should be addressed

to

R. W.

REFERENCES 1.

Brown, A. E., Sweeney, D. B., Lumley, J. Anesthesia, 1969, 24,

2. 3. 4. 5.

Hall, R. Br. J. Surg. 1971, 58, 513. Dalton, B., Laver, M. B. Anasthesiology, 1971, 34, 194. Robertson, D. S. Personal communication. Johnson, R. W. Personal communication.

532.

was

extracted from cultured

Summary human rhabdomyosarcoma cells which had an abnormal growth pattern, pleomorphic cytology, and highly distorted karyotypes. Skin fibroblasts from a normal human embryo were treated with the D.N.A. from the rhabdomyosarcoma cells. After repeated subculturing for 8 months the uninfected control cells ceased growing. In contrast, the D.N.A.-infected cultures continued to grow rapidly to form dense multilayers. Karyotype analysis at 6 months revealed that the uninfected cultures had a normal karyotype whilst 7.5% of the D.N.A.-treated cells had abnormal karyotypes with chromosomal rearrangements, endoreduplications, breaks, and acentric and dicentric chromosomes. These preliminary observations, together with two earlier reports concerning the isolation of avian and murine sarcoma viruses, both of which could be transmitted through extracted D.N.A. to normal cells, suggest the possibility of isolating viral-coded D.N.A. from human malignant cells.

Introduction viruses have been found to be induction and development of leukaemia and sarcoma in an increasing number of animal species. The D.N.A. of cells which have been transformed by the C-type R.N.A. avian and murine viruses carries the genetic information of the corresponding virus. The viral coded enzyme, R.N.A.directed D.N.A. polymerase, initiates the synthesis of a D.N.A. copy of the viral R.N.A., which integrates into and replicates within the affected cell 1 A biologically active D.N.A. that contained the information for the synthesis of the avian Rous sarcoma virus (R.s.v.) was first obtained from the R.S.v.-transformed rat XC cells.2 Chick-embryo fibroblasts, when inoculated with such D.N.A. preparations, transformed and released an infectious R.s.v. When we infected mouse cells with similar D.N.A. preparations the infected cells also transformed and acquired malignant properties, but did not release R.S.V.’3 We also obtained a biologically active D.N.A. from the nonvirus-producing mouse and hamster cells which have been transformed by murine sarcoma virus (M.S.V,),4 Normal mouse cells treated with this D.N.A. preparation transformed during prolonged culture. In some of the transformed cells, sufficient viral information was integrated into the cells so that the M.S.V. genome could be " rescued " with a helper Rauscher leukaemia virus: in other D.N.A.-treated mouse cells the genome could not be rescued, but the cells were transformed morphologically, they contained abnormal chromosomes, and were highly malignant when inoculated into adult mice.5 It seems, then, that cellular transformation can

THE

Discussion

ELIZABETH TUCKERMAN

Department of Medicine, University of Cambridge D.N.A.

The arterial blood-supply to the skin immediately proximal to the usual site of radial-artery cannulation is of small diameter, scanty, arises directly from the main radial artery, and has no collaterals. This area is therefore susceptible to ischaemia after cannulation of the radial artery, even for less than 48 hours. Since Dec. 12, 1973, the technique of cannulation

has been modified

A. KARPAS

C-type R.N.A. responsible for the